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Lecture One

Mendelism, How it all began

Genetics is the study of genes, the biological information units that control heredity, that is the
way characteristics of organisms are passed on, through successive generations, from parents to
their off-springs and so on.
By the end of this lesson, you should be able to:
Explain why Mendel is the father of genetics
Outline a series of experiments done by Mendel
Use Punnett squares and Decision or Branching diagrams to work out the results of
various crosses
Explain the blending theory of inheritance
Use the product rule of probability to determine chances of happening of various
Denition of key words

Thinking Vocabulary
Sex cells are often referred to as gametes. Hereditary factors are now called genes Alternative
forms of a gene are called alleles, e.g A is allelic to a. A measurable characteristic or distinctive
trait is called a phenotype. A phenotype may be visible to the eye, purple, white, yellow, green,
may require a form of measurement, e.g height with a ruler, tall and short, weight with a balance
or may require special tests e.g human ABO blood groups. A phenotype is due to a gene product
or some environmental effect..All genes possessed by an individual constitute that individual's
A genotype is said to be homozygous when two alleles in a diploid are identical e.g AA or aa. A
homozygous genotype produces only one type of gamete. Individuals that are homozygous are
referred to as pure line or true breeding. A heterozygous genotype is one that carries different
alleles e.g Aa. Different kinds of gametes are produced by a heterozygotes. The word hybrid is
sometimes used synonymously with a heterozygous condition. A monohybrid is a heterozygote
at one gene locus (Aa), a dihybrid is heterozygous at two loci (AaBb), a trihybrid at three loci
(AaBbCc) and so on. Whenever one of a pair of alleles can come to phenotypic expression only
in homozygous genotype we call that allele recessive. An allele that expresses itself in the
heterozygote as well as in the homozygote condition is a dominant allele. Usually a capital
letter is used to symbolise a dominant allele and a small letter is used to designate a recessive
allele. For example albinism in human beings can be shown as follows:
aa an albino homozygous recessive
Aa a normal heterozygous person
AA is a normal person with homozygous with dominant allele
In cases like albinism we sometimes use the word "carrier" to describe individuals heterozygous
for both alleles A and a..We sometimes use the word wild-type to mean the most common allele
in a wild population. Usually mutants with a few exceptions are recessive and wild-types are
dominant. A + sign is used to symbolise wild-type.The specic location of a gene is called a
locus (plural loci)
1.1 Mendel studied garden pea plants (Pisum sativum). Peas are normally self pollinating.
Whenever Mendel wanted pure strains or true breeding strains of the peas he would obtain these
by allowing the plants to self pollinate. Whenever he wanted to crossbreed he removed all
anthers from the owers he wished to pollinate and covered the owers with a container with
pollen he wished to use. A pure line is one that breeds true and constant for a particular character
being studied. For example a true breeding purple owered garden pea plant seeds will all grow
into purple owered plants if the plant self pollinates itself. Mendel worked with eight clearly
dened contrasting pairs of traits of the peas. Each pair was distinct from and had no inuence
over the others:
Seed form (round or wrinkled)
Seed coat form (inated or wrinkled)
Unripe pod colour (green or yellow)
Stem length (tall or dwarf), Tall was taken to be 6-7 feet high and dwarf 9
- 18 inches high.
Seed colour (yellow or green)
Seed coat colour (yellow or green)
Flower position (axial, along the stem or terminal at the tips of the stem)
Gregor Mendel the father of Genetics
Please Note
Mendel used clear contrasting characters e.g. tall or short, yellow or green, round or wrinkled
and so on, that is, opposites with no intermediate traits in between the two extremes.
In one type of experiment he crossed a pure line with tall plants with pure line with dwarf plants.
If the tall plant was pollinated by pollen from a dwarf plant all progeny plants were tall.. The
reciprocal cross, produced the same result. When one of the parents was tall and the other dwarf
all the resulting plants were all tall. He called the rst generation off-springs the rst lial
generation or F
and their parents parental generation or P.
Parents Tall x Dwarf
(Female) (Male)

Filial one generation all Tall (selfed)
Filial two generation ! Tall and " dwarf in ratio 3 : 1

Mendel then selfed the F
plants, that is allowed each ower to self pollinate. He called the
resulting offspring the lial 2 or F
generation. Of the resulting plants of the F
generation the
majority had purple owers but there were a few plants with white owers. He observed that
these occurred with a ratio of about 3 purple to 1 white. He repeated this experiment with the
other seven pea pairs of characteristics and found nearly 3 : 1 ratios in the F
generation for all
of them.
(Tall) (Dwarf)
(Female) (Male)
P TT x tt
Gametes all T all t

all Tt all Tall
x F
Tt x Tt (selng)

Gametes # T , # t #T, # t

" TT, "Tt, "Tt, "tt (genotypes) 1: 2: 1 of TT, Tt and tt

T- tt (phenotypes)
! " in ratio 3 : 1 of T- and tt
Tall Dwarf
Mendel repeated this experiment with the other seven pea pairs of characteristics and found
nearly 3 : 1 ratios in the F
generation for all of them.
Blending theory of inheritance
At this time the popular opinion on heredity was that inheritance of traits was due to blending.
Sex cells were thought to consist of many essences of all tissues, organs and organ systems. On
fertilization these essences were supposed to mix so that a new individual growing from such a
fertilized egg had a blend or mixture of essences for each tissue, organ or organ system. Mixing
or blending was thought to occur to result to a blend or mixture of the constituent essences from
the male and female parents. This blending was thought to be similar to mixing that happens
when two or more different coloured inks are mixed together. The resulting ink colour is
intermediate between the colours of the original inks. Mendels experiments showed that
heredity did not occur this way, he proposed a model of multi-particles of pairs to replace the
blending theory of inheritance. He argued that:
There are units or factors of a particulate nature. Inheritance was due to material that
acted like particles not inks
Each adult pea plant has two factors, one originally inherited from each parent. If the
parents were true breeding for two different but contrasting characteristics the two factors
would be different. Mendel reasoned that the F
plants must have at least one factor for
what he called recessive character because it is masked in F
but reappears in a later
generations. The F
plants also had a factor for what he called dominant character, that is
the one that masks the other in F
and appears in majority in F
Each sex cell pollen grain or egg cell (ovule) has only one factor
During sex cell formation either of the pair of factors of the parent plant passes with
equal frequency into the sex cells.
The union of sex cells to form a new individual or zygote is random, that occurs by
chance alone. The sex cells do not seek each other out or any basis like beautiful, ugly,
rich and so on. Any sex cell of any type has an equal chance with any other sex cell of
fertilizing any opposite sex cell of any type.

Mendel represented this analysis in diagrams as follows:
Using T to represent the dominant factor and t the recessive factor;
(Tall) (Dwarf)
(Female) (Male)
TT x tt
Gametes all T all t Parents
Random mating Tt Filial 1 (F
Using a Punnet Square:
x F
Tt x Tt
Gametes # T , # t #T, # t

# T # t
# T "TT "Tt
# t " Tt "tt
Altogether "TT , #Tt, and " tt in genotypes or ! T- and "tt , tall and dwarf in
Mendel then tested this model by crossing F
purple with white (true breeding). He predicted
and obtained a 1: 1 ratio of purple to white.

Test cross Tt x tt
Gametes #T , #t all t
all t
#T #Tt
#t #tt
Mendels rst law states that:
Factors segregate (i.e separate) from each other during sex cell formation into
equal numbers of sex cells.
Further Readings

1. Suzuki, Grifths and Lewontin, Introduction to Genetic Analysis. Freeman and Company
2. Ayala and Kiger, Modern Genetics.The Benjamin Cummings Publishing Company Inc
3. Redei, Genetics Macmillan Publishing Co. Inc.
Lecture Two
Probability and the law of independent assortment
Probability will help one understand what Mendel did next, he took two or morecharacteristic
pairs at a time to propose the second law of independent assortment.
Probability is the study of random events. It expresses the likelihood that an event will or will
not happen. Outcome of biological events are determined by chance to a very great extent.
Consider meiotic production of gametes, the random union of these gametes in fertilisation and
so on. Chance determines which of the four meiotic products will become functional, and also
determines which one of the millions of sperm cells will fertilise the one mature egg cell in a
mammal to take one example.
Probability is stated in fractions or decimals with limits of 0 on one extreme and 1 on the other
extreme. An event with a probability of 1 will happen without doubt, and one with a probability
of 0 will not happen for sure. For example, if you go swimming you are certain to get wet, that
is the probability of getting wet is 1. Events that may or may not happen have a probability
between 0 and 1. These events are probable, likely, unlikely and so on.
Equally likely events
Probability is related to a set of events which are equally likely to happen. For example in
tossing a true (honest, un biased, un loaded) coin, the chance of it landing with heads face up is
as likely as landing with tails up. Tails or heads up are said to be equally likely events for each
toss. In a cross Bb x Bb, each parent produces an equal number of B and b gametes, therefore
B and b gamete is equally likely to fertilize any of the gametes produced by the other parent.
Again if a card is drawn from a well shufed pack of cards, each of the 52 cards in the pack is
equally likely to be drawn.
Figure 6.3 showing Die / Dice and Coins Head side up and Tail side up
Probability may also be thought of as the relative frequency of a particular even in a large
number of trials.
i.e. Probability (p) = the number of times an even happens (s)
the number of opportunities for it to happen (N)
(or the number of trials)
p = s
The probability of an event not happening is 1-p in cases where the events are mutually exclusive
or alternatives. This is sometimes termed q. Thus p + q = 1.
Do you know what a die is ? Dice (plural) are used in gambling casinos in various games. A die
is also used in children games like "snakes and ladders". A die is a cube of six sides, each side
with a distinct mark. A die is rolled and comes to rest with one of its six sides on top. The die
corners are rounded to make the probability equal for any of the six sides ending up after each
roll. A die that has perfectly rolled corners is said to be unbiased, unloaded, true and honest die.
In rolling a die we expect an even number to occur in three ways out of six equally likely ways,
if the die is rolled many times repeatedly. This is the idea of probability that we shall be
interested in this course.
You have no doubt used subjective probability in discussing the weather, the outcome of
elections or in buying or selling shares and stocks. The subjective probability is based on what
you feel or know about the weather, constituency or a certain stock to assess the likelihood that it
will rain, one of the candidates will win the election or a certain stock price will rise tomorrow.
You use this type of probability when you assess the probability of there being life on mars. This
type of probability is indicated with a ratio like 1: 10, to mean that there is a probability of 1 in
11 (1/11) of an event happening. The value of the probability indicates the degree of certainty of
the assessor. In horse racing the odds might start at 1:10 before the race, rise to 1:4, then 1:2 as
the horses run the race and the horse performs better than initially expected.
The probability of rolling a four on a die in a single trial is 1/6, because a die has six sides.
Combining Probabilities
(i) Product rule
The probability of two independent events occurring simultaneously is the product of each of
their probabilities. Events are said to be independent if the occurrence of any one of them does
not affect probabilities of occurrence of any others.
For example with two dice the probability of rolling two fours is 1/6 x 1/6 or 1/36.
In a cross of a heterozygous black pig Bb and a white one bb i.e Bb x bb, gametes produced by
the heterozygous pig are #B and #b. The homozygous recessive pig gametes are all b. The
resulting progeny are #Bb (black) and # bb (white) piglets. The probability of the rst two
offspring being white is "
Next Mendel crossed peas differing in two pairs of contrasting characters. Again he used true
breeding parental lines in each case, for example:
(green, round) (yellow, wrinkled)
(Female) (Male)
Parents yyRR x YYrr
Gametes all yR all Yr

YyRr (Yellow, Round)
x F
YyRr x YyRr
Gametes "YR ,"Yr, "yR,"yr (and similar gametes from the other parent)
"YR "Yr "yR "yr
9 Y-R- : 3 Y-rr : 3 yyR- : 1 yyrr
Yellow,Round : Yellow,wrinkled : Green, Round : Green, wrinkled
1,2,3,4 ,5,7,9,10,13 6,8,14 11,12,15 16
Using a fork diagram the phenotypic ratios will be:
! R- 9/16 Y-R-
! Y- " rr 3/16 Y-rr
Y-R- x Y-R-
"yy ! R- 3/16 yyR-
"rr 1/16 yyrr

Mendel tested these results like he had done with one pair of traits. He predicted and obtained a
1: 1: 1: 1; ratio.
YyRr x yyrr

Gametes: "YR , "Yr, "yR, "yr all yr
Progeny: "Y-R- : "Y-rr : "yyR- : "yyrr
Yellow,Round : Yellow,wrinkled : Green, Round : Green, wrinkled
a 1 : 1 : 1 : 1 ratio
Test cross is now dened as a cross between individual(s) who are heterozygous for one or more
genes with individuals who are homozygous for the same gene(s)
Back cross is one between individual(s) progeny and one of its parents.
Mendel tried this with all other characteristics two at a time and obtain 9: 3: 3: 1 ratio for each
of them. When he checked to nd out whether the ratio of each pair was still the same as that
obtained in crosses involving one pair of genes, he found that the 3: 1 ratio prevailed.
For example, ignoring the round, wrinkled pair of traits, he counted all the seeds that were
yellow and green and found that they were in a ratio of three yellow to one green and ignoring
the yellow, green traits counted those seeds that were round or wrinkled to nd a similar ratio of
three round to one wrinkled. Mendel concluded that the two pairs of traits were independent of
one another and that the 9: 3: 3: 1 ratio is two 3: 1 ratios combined at random. That is (3:1) x
(3:1) = 9: 3: 3: 1
Using arrows or a decision tree try to combine the two ratios as follows:
(3: 1) x (3: 1) to obtain 9: 3: 3: 1
Y- yy R- rr Y-R- yyR- Y-rr yyrr
From these observations Mendel proposed his second law stating that:
Inheritance of one factor is not inuenced by inheritance of another factor, that
is, the factors assort independently in successive generations.
Mendels ndings can be extended as follows:
Number of segregating gene
Number of phenotypic classes Number of genotypic classes
1 2 3
2 4 9
3 8 27
Probability (continued)
(ii) Sum rule
The probability of the occurrence of one out of a set of mutually exclusive events is the sum of
their individual probabilities. Mutually exclusive events are those in which the occurrence of
any one of them excludes the occurrence of the other.
For example with two dice the probability of rolling two fours, and two sixes is 1/36 + 1/36 or
What is the probability of a calf being born either roan or white from a mating of a roan bull and
a roan cow ?
The calf could be born red (RR) or white (rr) when homozygous or roan (red mixed with white)
if heterozygous (Rr).
Therefore from a cross of a roan bull and a roan cow Rr x Rr
Gametes produced by the cow or bull are R and r.
Therefore the probability of a calf being roan is and being white is , therefore the probability of
a calf being either roan or white is + =

Use the Punnet square to combine the bull and the cow gametes.

(iii) Probability of mixtures and combinations
If the probability of one even occurring is p and the probability of an alternative mutually
exclusive even is q, a formula (p + q)
, where n represents the total number of trials. This is the
binomial expression, with the general expression:
(p + q)
= p
+ np
+ n (n -1) P
q..................n(n-1) p q + np
+ p
1 x 2 1 x 2
Other methods exist to help one calculate these expansions:
[ n! ]
[ x ! y! ]
p + q = 1, and x + y = n
n! is read as n factorial and is equal to 1 x 2 x 3 x 4 x 5 .......(n-2) (n-1) x n 1 ! and 0! are equal to
1 by denition.
The extension to more than two events is p
x ! y! z!
where p + q + r = 1 and x + y + z = n
Coefcient of the successive powers of p + q can also be arranged in a triangle array of numbers
called pascals Triangle as follows:
(p + q)
= 1 1
(p + q)
= p + q 1 1
(p + q)
= p
+ 2pq + q
1 2 1
(p + q)
= p
+ 3p
q + 3pq

3 1 3 3 1
(p + q)
1 4 6 4

(p + q)
1 5 10 10
5 1
(p + q)
= 1 6 15 20 15 6 1
Action Exercise: Complete the pyramid and indicate the two gures added in each case to
make each total below.
You will notice that the rst and the last number in each row is 1 in the triangle and that every
number in the array can be obtained by adding the two numbers appearing directly above it, on
the left and the right. These numbers give the binomial coefcients as shown above.
Note also that the coefcients of each succeeding term can be determined by examining the term
just preceding it. You multiply the exponent of p by the coefcient of the term and divide it by
the number of the term e.g.
Term number 1 2 3 4 5
Exponent of term p4 p3q p2q2 pq3 q4
Coefcient of terms p4 4p3q 6p2q2 4pq3 q4
Third term = 1 Second term = n
and third and following terms = p exponent value of the preceding term x its coefcient
number of the preceding term in the expansion
Lecture Three
Extensions of Mendelian Analysis
By the end of this lesson, you should be able to:
Explain the biological signicance of mitosis

Distinguish the different phases of mitosis and meiosis then draw diagrams of the
Show similarities and differences between mitosis and meiosis
Explain the biological signicance of meiosis
By the end of this lesson, you should be able to:
Explain and give at least two examples of incomplete dominance and/or codominance
Using probability product rule work out expected ratios of various crosses involving
codominance and/or incomplete dominance
Differentiate penetrance from expressivity giving appropriate examples.
List and give examples of at least four types of cytoplasmic or extranuclear inheritance.
Mendel's laws form a base for predicting the outcome of most simple crosses. There are many
exceptions, extensions and situations that cannot be explained by these law alone, let us examine
these one at a time.
7.1 Dominance Relations and Gene Inheritance
Mendel observed complete dominance and recessiveness for all the gene pairs he studied. That
is, the phenotypes of the heterozygotes were similar to those of homozygous dominants.
Sometimes the herozygote shows a phenotype intermediate between the dominant and the
recessive homozygotes. In four-o-clock plants, when a pure line with red petals is crossed to a
pureline with white petals, the F
plants have pink petals. An F
x F
cross results in an F
red petals of genotype RR, , pink petals of genotype Rr, and white petals of genotype rr.
The red phenotype and its determining allele R is incompletely dominant over the white
phenotype and its allele r. If the heterozygote shows the phenotypes of both the homozygotes we
refer to this phenomenon as codominance.
E.g MN human blood groups are determined by two codominant alleles, L
and L
result in the three phenotypes L
, L
, and L
Coat colours of the shorthorn breed of cattle is another good example. Red coat colour is
governed by an allele C
and white coat colour by the allele C
. Both allele result in three
phenotypes of C
(Red), C
(Roan, that is a mixture of white and red patches) and
7.2 Modied Ratios
The classical 9:3:3:1 ratio resulting from combining (3:1) (3:1) is obtained in a dihybrid selng
only when at each gene, one allele in each of the two pairs is dominant to the other. Eg in a
dihybrid AaBb, A is dominant to a and B is dominant to b.
If there is codominance at one gene locus, let us say the rst one the ratio is modied to (1:2:1)
(3:1), that is 3:6:3:1:2:1 and if at both gene loci, (1:2:1)(1:2:1) that is 1:2:1:2:4:2:1:2:1.
Modied ratios may also occur due to various types of gene interactions, that is one gene pair
inuencing expression of another gene pair. For example a ratio 12:3:1 occurs in a dihybrid cross
if a dominant allele at one gene locus, let us say A allele, produces a certain phenotype regardless
of the allelic condition of the other locus, that is A-B- and A-bb produce the same phenotype,
whereas aaB- and aabb produce the additional phenotype. This is reffered as dominant epistasis.
9:3:4 ,9:7, 9:6:1, 15:1 etc ratios can also be obtained by other types of gene interactions.
7.3 Penetrance and Expressivity
A gene does not determine a phenotype by acting alone. The environment, which includes other
genes, the external and internal environment play an important part in specifying the phenotype.
Penetrance is dened as the percentage of individuals with a given genotype who exhibit the
phenotype associated with that genotype. A genotype that does not always produce a specic
phenotype is said to be incompletely penetrant. For example extra nger and/or toes, a condition
known as polydactyly in man is produced by a dominant gene P. The normal condition of ve
digits on each limb is produced by the recessive genotype pp. Some heterozygous individuals Pp
are not polydactylous and therefore the dominant gene P is said to be incompletely penetrant.
Expressivity is the degree or extent to which a given genotype is expressed phenotypically in an
individual. For example in the polydactylous condition expressivity may vary as follows; one
may have six ngers on the left hand and the normal ve on the right hand. Another may have
extra ngers on both hands and a third may have extra ngers on the two hands and extra toes on
both feet.
Lack of complete penetrance or expressivity may be due to the other genes or to the internal or
external environment.
Multiple Alleles
ABO Human Blood groups
ABO Blood Group alleles in human beings provide an example of multiple allelism. There are
four blood types in this group, A, B, AB and O. The alleles involved include three major alleles,
, L
and l which can be present in any combination in one individual (Table 3-1). The rst
two are co-dominant to one another and the third is recessive to both. It is possible to have more
than two allelic forms of a gene in a population. Only two of these alleles can exist in a diploid
cell. Whenever more than two alleles are identied at a locus a multiple allele series is said to
occur at the locus.
The human ABO blood group alleles form a multiple allelic series. Three alleles are involved;
, L
and l.
Table 3-1
Blood type Genotype
Ant i ge n on
Antibody in
Donate to Receive from
A anti-B ($) A, AB A, O
or L
B anti-A (%) B, AB B, O
A and B Neither AB A, B, AB,O
O Ll Neither
anti-A and anti-
A, B, AB,O O
Blood type Genotype
Ant i ge n on
Antibody in
Donate to Receive from
A anti-B ($) A, AB A, O
or L
B anti-A (%) B, AB B, O
A and B Neither AB A, B, AB,O
O Ll Neither
anti-A and anti-
A, B, AB,O O
Table 3-1 shows the antigens and antibodies individuals with various blood types have.
Individuals with blood type O are said to be universal donors and those with AB as universal
receivers. An antigen of a particular type cannot be mixed with its own antibody, if this happens,
agglutination occurs. Giving a blood donation of type O seems to add an antibody to its own
antigen when the receiver is of A,B or AB type. This is safe only when the volume of antibodies
in the O blood type individual is low and the donated blood is diluted by the larger receivers
blood volume.
Blood type A is divided into further blood types A
and A
These subgroups are not
important in blood transfusions. Studies have revealed changes in ones A-B-O phenotypes
associated with certain pathologic conditions. The best known is a weakening of A or B antigen
reaction by variable proportions of erythrocytes in persons suffering from acute myelocytic
leukemia and certain bacterial infections. The basis of this change is not well known at present.
Except for such situations ones ABO blood antigen-antibody traits are constant for life.
ABO blood groups can be used for a medical/regal purposes in cases of paternity disputes.
Indicate below the blood types of children expected and those unlikely in each marriage of
partners with indicated blood types.
Marriage Expected Children Unlikely Children
Note 3.1
A suppressor gene for ABO is found among human beings. This is an autosomal recessive,
which when homozygous makes an individual that would normally express A and B seem like
an O individual, and therefore is blood typed as an O
Secretor Trait
Some people of blood type which bear A and or B antigens can be detected in aqueous body
secretions such as from eyes, nose and salivary glands, they produce water soluble antigens.
Several studies have shown that 77 to 78 percent of all people are secretors. Individuals lacking
this trait are said to be nonsecretors and their antigens are alcohol soluble.
The Rhesus factor
Landsteiner and Wiener in 1940 discovered that a rabbit injected with blood of Macacas rhesus
monkey, antibodies were formed by the rabbit. Tests with human beings show that some people
also produce this antigen, people who do as said to be Rh-positive (Rh
) those who do not are
Rh-negative (Rh
Fisher proposed that at least three closely linked pseudoalleles D,d C,c and E,e are involved in
the Rhesus factor. For all medical and regal purposes those with an allele D are considered
positive and those without negative. The antibody D is the most potent among the group.
Erythroblastosis fetalis an improper physical and mental development of foetus caused by
partial destruction of erythrocytes occurs in infants born of Rh-negative mothers who conceive
Rhesus positive children. This is a haemolytic anaemia, often accompanied by jaundice, as liver
capillaries become clogged with red blood cell remains and bile is absorbed by the blood.
Immature erythrocytes are released as their concentration in blood becomes less and less with
This disorder occurs only when the mother is Rhesus negative and the fetus Rhesus positive,
therefore only marriages of Rhesus negative women and Rhesus positive men are involved.
Initially the fetus blood gets into the mothers circulation during birth and may become more and
in the following similar births. The mother forms Rhesus positive antibodies which pass through
the placenta barrier to cause partial destruction of the fetus erythrocytes. Studies have shown that
such a mother can have healthy children in those circumstances up to the fourth and after which
time the volume of Rhesus positive antibodies accumulate to such high concentrations that the
fetus suffer severe erythroblastosis.
Tissue Incompatibility in Humans
The success or failure of a tissue graft or organ transplant depends on the genotypes of the host
and the donor. If the two do not match, reject of the graft or transplant occurs.
Rejection system is determined by two multiple allele series HLA-A and HLA-B (Human
Lymphocyte Antigens A and B). There are eight alleles for HLA-A (designated A1, A2, A3, A9,
A10, A11, A28 and A29), HLA-B also has eight alleles (B5, B7, B8, B12, B13, B14, B18, and
Incompatibility Alleles in Plants
It has been observed for along time some plants do not self pollinate. The same plants will cross
with other plants, showing that they are not sterile. This phenomena is called Self
Incompatibility and is now known to have a genetic basis and has been found in sweet cherries,
tobacco, petunias, and evening primroses. If a pollen grain bears an S allele which occurs in the
ovule then it will not grow. The number of S alleles in a series in one species can be very large
over 50 in the evening primrose and clover and insome cases of more than 100 alleles have been
reported in some species.
Note 3.1
Identication by means of Blood antigens
The ABO, Rh, MN and another dozen other human blood groups can be used for identication for medical or
regal purposes such as migration, crime investigations, parental disputes (and similar groups can be used for
pedigree conrmation in mammals like dogs, horses and cows).These factors are distributed all over the world,
and are called public factors. In addition there are another 13 private factors in specic kindreds. It has been
calculated that there aremore than 57 million different human blood phenotypes that exist and are distinguishable.
Methods now exist for typing blood antigens from saliva and other body uids.
Other blood groups
Many other human blood groups have been described, some are quite rare. They are usually
named after the family name of the individual in whom the antigen or antibody was rst
demonstrated. Examples include, Lutheran, Lewis, Duffy, Kidd, Cellano and, Kell, to be but a
Further Readings

A list of books will be provided after each lesson indicating text books that provide materials
covered in the lecture.
Further Readings

Anna C.P and Marcus-Roberts H. 1999. Genetics: Its Concepts and Implications. Prentice-
Hall Inc.
Strickberger, M.M 1969. Genetics. Macmillan Canada.
Thompson M., McInnes, R. and Willard H. 1991. Genetics in Medicine. W.B Saunders.
Lecture Four
Linkage, Recombination and Genetic maps
After reading this lecture you should be able to:
Explain why linked genes do not assort independently
Calculate map distances among genes given recombinants frequencies

Early in the development of the chromosome theory of inheritance it became clear that there are
many more genes than there are chromosomes. Genes found located in the same chromosome are
said to be linked, they compose a linkage group. Such genes are transmitted together more times
than not during gamete formation. The number of linkage groups in an organism corresponds to
the haploid number (n) of chromosomes in its genome. Drosophila melanogaster (a diploid, 2n)
has four pairs of chromosomes, so it has four linkage groups (see gure 1.1 below). Genes can be
linked in an autosomal or a sex chromosome among those organisms like man and Drosophila
melanogaster where there is chromosomal determination of sex. Genes in one linkage group fail
to assort independently (Mendels second law of independent assortment). This fact is used to
nd out whether two or more genes are linked or not.

Figure 1.1: Linkage map of Drosophila melanogaster, showing the location of various genes
Detection of linkage
The simplest method to detect linkage is to compare the number of each observed phenotypic
class with those expected according to independent assortment and then to test the deviation
between these values by a chi-square. A statistically signicant departure fro expected ratio of
1:1 or !;!:1:1 signies linkage.
For example assuming complete dominance a test cross;
Aa x aa results in the rst parent producing the gametes A and a , the second parent gametes a
and therefore combining the two sets of gametes gives the progeny Aa and aa in a 1 : 1 ratio
or equal amounts.
And if we consider two loci, AaBb x aabb test cross, the rst parents give four types of
gametes; AB, Ab, aB and ab each one quarter of the total, the second parent gives only ab
gametes. If we therefore use a four by one Punnet square to combine the gametes we get progeny
of the following genotypes:
"AB "Ab "aB "ab
All (1) ab "AaBb "Aabb "aaBb "aabb

These progeny form a ratio of 1:1:1:1
A statistically signicant departure from a 1:1 or a 1:1:1:1 ratio in the two examples we have
considered, makes us suspect that there is linkage. If not the genes are so far apart that they
assort independently or in other words behave like they are found located in different
chromosomes or some other effect like viability differences that may change the frequencies of
individual gene pairs.
Coupling and Repulsion linkage arrangements
Genes within a pair of homologous chromosomes may be linked in two fashions. The recessive
alleles of two or more genes may be on the same strand and the dominant alleles on the
corresponding homolog. This arrangement is called coupling or cis. On the other hand when the
recessive allele of one gene and the dominant allele of another are associated on the same starnd
and their corresponding dominant and recessive alleles are on the homolog, the arrangement is
called repulsion or trans (gure 1:2 below)
_______a________b_______ ______a_______B_______
_______A_______B_______ ______A______b________
Coupling or cis phase Repulsion or trans phase
One crossover yields 50% recombination
The association of linked genes is not absolute, in a few instances such genes are not inherited
together. Genes change their arrangement (coupling ! repulsion) during crossing over,
resulting in recombination (Figure 1:3). Crossing over between the X and Y chromosome is
limited to their short homologous regions in man and in the majority of species of ies (e.g
Drosophila melanogaster) and of Lepidoptera (e.g silkworm). Linkage is practically complete in
all individuals (males in Drosophila and females in silkworm). Recombination is limited to the
homogametic sex.
Figure 1:3 Crossing over and recombination between two genes on two homologous
chromosomes. Note: Two of the gametes are parental and two are reciprocally exchanged. The
recombination frequency is 2/4 = 0.5
That is (1Ab +1aB)/ (1AB +1Ab + 1aB +1ab) Where a chiasma (plural chiasmata) form, that
is a crossover, there is breakage and re-union.

Genes located in the same chromosome may show linkage: however, they may appear
independent if the frequency of recombination reaches its maximal value of 50%. Crossing over
takes place at the four letter strand stage early in meiosis. At any time any particular location of
the chromatids only two of the four strands are involved in the exchange. So that a single
crossing over between two genes results in two reciprocally recombined and two parental
chromatids. Recombination values exceeding 50% can be observed only if some types of
gametes are favoured or discriminated against by post-meiotic selection.
Genetic Maps
Frequencies of recombination between two linked gene loci are used as a measure of genetic
distance between them. One percent recombination represents one map unit (m.u.)or one centi
Morgan(cM). In general the genetic map distances between pairs of genes in a series of linked
factors are additive in a specic gene order.
Denition of genetic distance:
Map distance (map units, m.u or centi Morgans cM) = 100 x crossover gametes
Total gametes
Two point Test-cross:
The easiest way to detect crossover gametes in a dihybrid is through testcross progeny. For
example, assuming complete dominance a test cross:

AB x ab
ab ab
Female parents produce gametes AB
ab parentals
aB Single cross overs
and the male parent ab gametes
Combining the two sets, the following are phenotypes of progeny and their frequencies:
A-B- 37%
Aabb 37%
A-bb 13%
aaB- 13%
The map distance between A/a and B/b is (13 +13 / 100) x 100 = 26 map units.
In a two point linkage experiment the greater the distance (i.e without segregating loci) between
two genes, the greater the chance of double crossovers occurring without detection. The most
reliable estimate of the amount of crossing over is that of closely linked genes. Double
crossovers do not occur within a distance of 10 to 12 map units in Drosophila melanogaster.
The minimum double crossover distance will vary between different species. Within this
minimum distance, recombination percentage is equivalent to map distance. Outside this
minimum distance, recombination percentage and map distance become non-linear. The true
(physical) map distance will be underestimated by the recombination fraction and at large
distances they virtually become independent of each other.
The frequency of crossing over usually varies in different segments of the chromosome.
Therefore the actual physical distances between linked genes bears no direct relationship to the
genetic map distances calculated on the basis of crossover percentages. The linear order however
is identical in both cases.
Interference and Coincidence
In most higher organisms the formation of one chiasma (plural, chiasmata) actually reduces the
probability of another chiasma forming in an immediate region of the chromosome. This
reduction in chiasma forming is due to a physical inability of the chromatid to bend back upon
themselves within certain minimum distances.
The net result of this interference is observation of fewer double crossovers than would be
expected. The strength of interference varies in different segments of a chromosome and is
expressed in terms of a coefcient of coincidence or the ratio between observed and expected
double crossovers:
Coefcient of Coincidence (CC) = Observed double crossovers
Expected double crossovers
Coefcient of Coincidence is the complement of Interference that is:
Coefcient of Coincidence + Interference = 1
When interference is complete (= 1) no double crossovers are observed and Coefcient of
Coincidence is zero. On the other hand when all double crossovers expected are observed,
Coefcient of Coincidence is one and Interference is zero.
Genetic maps have the following properties:
Distance is proportional to frequency of crossovers classes ( this approximation actually
holds true for short distances of less than 20 cM or m.u
Distances are approximately additive
Maps are internally consistent and concise
The rst genetic map was constructed in 1911 by Alfred Sturtevant when he was a student in
Morgans lab.
It is important to remember that genetic distances are measured using genetic recombination
that varies from one organism to another. The relationship between genetic distance in cM
and physical distance in base pairs (bp) depends on the recombination rate and is different for
different organisms.
For example: Human 1.3cM/Mbp
Yeast: 360cM/Mbp
Sometimes recombination rates in the male and female of a species are different. In
Drosophila melanogaster there is no recombination in the male so the genetic distance
between markers on the same chromosome are always zero when examined by meiosis in the
male. In humans the recombination rate ( and therefore map distances) in the female are
twice that of the male.
If the measured distance in a cross is statistically indistinguishable from 50 cM then we say
that the genes are unlinked. But this does not mean that distances greater than 50 cM cannot
be obtained. By adding intervals, lager distances that are meaningful can be obtained. For
example, if all the intervals between linked genes in the human genome are added together
the total length of the genome (in males) is 2,500 cM.-

Estimating linkage intensities from F
Product ratio method
Linkage can be calculated in F
by the product ratios of the phenotypic classes in repulsion
( when for example the F
constitution is Xy/xY) and coupling (eg XY/xy) phase. The four
phenotypic classes are designated:
XY (a)
Xy (b)
xY (c)
xy (d)
The repulsion products are a x d / b x c
And coupling products are b x c / a x d
In the Product ratio products table, Repulsion or Coupling, locate the decimal nearest to the
calculated product ratio; the frequency of recombination can be read on the same line, under
Crossover Value. See part of the table below:

Square root method
Assuming complete dominance at each gene locus consider these two sets of crosses:
Coupling Repulsion
AB x AB Parents Ab x Ab
ab ab aB aB
Parentals AB and ab (each .4) Ab and aB (each .4)
Single crossovers ab and aB (each .1) AB and ab (each .1)
Frequency of ab/ab is .16 .01
Therefore in coupling data given the double recessive frequency, parentals frequency equals to:
2 x &double recessives ie, 2 x .4 = .8, therefore recombinants frequency equals .2
For repulsion data, recombinants frequency equals 2 x &double recessives ie, 2 x .1 = .2
Completely sex linked genes
In organisms where sex is determined by chromosomes for example the XY/XX and X0/XX
systems, parental and recombinant gametes can be observed directly in F2 males (in cases of
heterogametic males) regardless of the genotype of the F1 males.
For example in Drosophila melanogaster, considering two gene loci, scute bristles (Sc) and
vermillon eye colour (V);

ScV x ++


++ x ScV
males +-+- wild type
ScV Scute bristles vermillon eyes Parentals
+-V Vermillon eyes
Sc+- Scute bristles Recombinants

Further Readings

A list of books will be provided after each lesson indicating text books that provide materials
covered in the lecture.
Lecture Tive
Quantitative and Population Genetics
After reading this lecture you should be able to:
Explain why linked genes do not assort independently
Calculate map distances among genes given recombinants frequencies

The characters Mendel studied were discontinuous, such traits are said to be qualitative. Mendel
could clearly draw a line for example between tall and dwarf pea varieties, one was nearly two
meter tall the other less than a half meter, green seeds were clearly different from yellow ones,
there were no traits between the two.
Not all inherited traits are expressed in this discontinuous fashion, for example height in humans
is a genetically determined trait, but an attempt to classify a random sample of students in a class
results in continuous phenotypic variation. Where does one draw the line between phenotypic
classes? Should these classes be ten centimeters apart, a centimeter and so forth? Many other
traits are expressed in a similar fashion; egg production in chicken, milk production in cows, and
human skin colour to mention but a few examples.
In an effort to determine whether the mechanism of polygenic inheritance is the same as that of
qualitative traits, several simplifying assumptions are made:
There is no dominance, rather there exists pairs of contributing and noncontributing
Each contributing allele in the series produces an equal effect
There is no epistasis ( masking of the phenotype) among genes at different loci
There is no linkage
Environmental effects are absent or are so controlled that they may be ignored.
In Mendelian Genetics if monohybrid F
was selfed, only one fourth of the F
were as
extreme as either of the original parent. If information for one, two, and three pairs
ofpolygenes is tabulated, a pattern is obtained:
Number of pairs of
polygenes in which
two parents differ
Fraction of F
either parent
Number of
genotypic F
Number of
phenotypic F
phenotypic ratio
= coefcients of
1 " 3 3
(a + b)
2 1/16 9 5
(a + b)

3 1/64 27 7
(a + b)
2n +1
(a + b)
2nNumber of pairs of
polygenes in which
two parents differ
Fraction of F
either parent
Number of
genotypic F
Number of
phenotypic F
phenotypic ratio
= coefcients of
1 " 3 3
(a + b)
2 1/16 9 5
(a + b)

3 1/64 27 7
(a + b)
2n +1
(a + b)
As the number of of polygenes governing a particular trait goes up, the progeny very quickly
form a continuum of variation in which class distinctions become virtually impossible to make.
Dividing the total quantitative difference by the number of contributing alleles indicates the
amount contributed by each effective allele.
Further Readings

A list of books will be provided after each lesson indicating text books that provide materials
covered in the lecture.
7. Population Genetics
After reading this lecture you should be able to:
Explain why linked genes do not assort independently
Calculate map distances among genes given recombinants frequencies

Population genetics deals with natural populations and a population is dened as an

interbreeding group of individuals that share a common gene pool. This gene pool is the total
genetic information possessed by the reproductive members of the population.
The theory of population genetics is largely mathematical. A mathematical theory that could take
into account all the relevant phenomena of even the simplest population would be impossibly
complex. Therefore it is necessary that simplifying assumptions are made so that a model that
accounts for all important facts and ignores trivial details and suggests important concepts.
Starting with a simple model one can extend it to more complicated, but more realistic,
A population differs with an individual in that:
The life of an individual is limited in length of time, a life span, a population is
practically immortal
The genetic make up of an individual is xed throughout its life (except where mutations
occur, rare events), genetic composition of a population may change from generation to
generation, suddenly or gradually or remain constant.
An individual is one, populations are made up of many individuals, and therefore have
characteristics that an individual lacks like, distribution ( over a wide area or limited
area), may a a small population (a few hundreds or thousands) or big, hundreds of
thousands or millions)
Gene frequencies
Assume there are two codominant alleles A and a at a particular locus and suppose that there
are N individuals of which D of them are homozygous AA and H are heterozygous Aa and R
are homozygous aa. D + H + R = N
These N individuals have 2N genes altogether if they are diploid. Since each AA individual
has two A and each Aa indidual has one A, the total number of A genes in this group is 2D +
H and therefore the proportion of A genes ( let us call it p) in this group is:
p = 2D +H
= D +#H
This is known as the gene frequency of A in this group. The frequency of the gene a (let us
call it q) in this group is similarly:
q = 2R +H
= R +#H
p + q = 1
For example in a group of 40 individuals (2,12,26, AA, Aa and aa respectively)
P = 2 + 6/40 and = 0.20 and q = 26 + 6/40 = 0.80.
Hardy Weinberg Law
In the absence of disturbing forces ( for example migration, mutation and selection) gene
and genotypic frequencies remain constant ( in equilibrium) from generation to
generation, in a large, randomly mating population.
If such a population is not in equilibrium, it comes to equilibrium in one generation of
random mating. For example populations: .05 .3 .65, .01 .38 .61, .18 .04 .78,
0 .4 .6 all become .04 .32 .64 after one generation of random mating and remain so
unless there occurs a disturbing force.
Random Union of gametes:
(p + q)
= p
+ 2pq + q
= 1
2pq Aa
1 2 3
2pq Aa 4 5 6
7 8 9
AA Aa aa
Union 1 AA x AA = p
4 -------
2 AA x Aa = 2p
q p
q p
q ----
3 AA x aa = p
---- p
2 ------

4 AA x Aa = 2p
q p
q p
q ----
5 Aa x Aa = 4p
2 p
6 Aa x aa = p
---- p
2 ------
7 AA x aa = p
---- p
2 ------
8 Aa x aa = p
---- p
2 ------
9 aa x aa = q
--- ---- q
Totals p
+ 2pq + q
) 2pq(p
+ 2pq + q
) q
+ 2pq + q
Conditions of Equilibrium
Panmictic, random mating, (noun panmixia)
Large population
No selection, no differential mortality and no differential reproduction. The number of
breeding individuals is the same for all lines and in all generations.
No immigration from another population and no emigration to another population, that is
mating is restricted to members of the population and no individual is allowed to refuse
or fail to breed.
Meiosis is normal, there is meiotic drive
Generations are distinct
Changes in gene frequencies
Changes in gene frequencies are due to systematic (migration, mutation and selection) or
dispersive processes. Systematic processes are those changes that results in predictable amounts
and predictable direction. These act in both large and small populations.
Dispersive processes are those changes whose results cannot be predicted in direction but only in
mount. They act only in small populations where sampling errors occur, that is gene frequencies
uctuate randomly because of sampling errors, that is samples of gametes fail to be
representative of the whole population because of their relatively small numbers.
Variations /differences
From mutations
Intrageneic or point mutations;
Intrachronosomal changes -
e.g. delations;
Whole chromome mutations,
e.g. aneuploidy;
- monosomic (2n-1);
- Trisomics (2n+1);
- Tetrasomic (2n+2);
-Nullosomic (2n-2);
- Euploidy;
e.g. Triploids;
These bring about at organism level;
- anatomical feature variations;
- cytological variations;
- histological;
- physiological;
- behavioural;
- biochemical;
Variation may be quantitative or qualitative;
Sources of variation
Gene ow
Recurrent mutation. If all variations have to be maintained by recurrent mutations,
the mutations would have to be extraordinarily high;
Density dependent traits. It is known that individuals enjoy certain environments that are
unavailable to the general population;
Heterosis, over dominance, or hibrid vigour accounts for maintenance of some variation.
Heterosis alone cannot maintain all variations known to exist as the deaths considered
necessary cannot be conpensated for by adequate births;
Frequency dependent selection or minority effects, that is a trait in minority is selected
for much more compared with a trait in a majority of individuals.... add scores for
belonging in minority categories, e.g education, wealth, ......for human beings
Some form of balancing selection, for example an allele selected for in one sex and not in
the other, for in one season and not the other, at one developmental stage and against at
another developmental stage.
Genetic load
Genetic load is dened as the proportional amount by which the average tness (or any other
measurable trait) of a population is reduced relative to that of the optimal genotype. The optimal
genotype is the one with the highest tness, or other, value depending on the prevailing
environment or conditions. A population that possess genetic variation in respect to tness must
possess or carry a genetic load.
L = W
- W
Where L is the genetic load, W
is optimal or maximal tness and W is the average tness
Remember the environment is always changing in time ( day and night, seasons ) and space
(land, sea, atmosphere). Think of environment also in social, political terms and in other ways.
Individuals experience their own individual environments which changes from time to time.
Try to justify that a population that is practically immortal must carry genetic loads in all areas to
ensure its long time survival. Socially human beings must tolerate criminals, social mists who
could be useful in a changed environment ( like war, prolonged adverse conditions, out break of
a new disease)
Discussions of genetic load takes man to be a special case as man well being and values is
unique and different from other organisms.
Further Readings

A list of books will be provided after each lesson indicating text books that provide materials
covered in the lecture.
Lecture Six
Physical Basis of Heredity
Mendelian analysis can be used to interpret and make predictions of data and information
obtained from various matings very successfully. The question however remains: What structure
or structures within a cell correspond to Mendelian factors or what we now call genes? These
structures are chromosomes.
By the end of this lesson, you should be able to:
Explain the biological signicance of mitosis
Distinguish the different phases of mitosis and meiosis then draw diagrams of the
Show similarities and differences between mitosis and meiosis
Explain the biological signicance of meiosis
Before rediscovery of Mendels work in 1900 cytologists had observed and recorded existence of
thread like chromosomes in cells. They had observed their structures and numbers and also
observed their behaviour during cell divisions.
8.1 Mitosis Cell Division
When a cell starts to undergo division by mitosis each of its chromosomes consists of a pair of
identical sister chromatids, joined at the centromeres. During mitosis each of the daughter cells
receives an identical number of chromosomes with a complete set of genetic information.
Biological signicance of mitosis:
It plays the role of asexual reproduction in both plants and some animals.
It is the main mode of reproduction in one-celled organisms
Body/ somatic cells divide by this method
It passes genetic information to daughter cells without alteration
Interphase. This is the period between divisions. Immediately after mitosis a cell goes to a
phase where there is no DNA synthesis, the phase is called G
(Gap or Growth 1). Some cells
spend a very long time at this phase, days or even years. In G
, others pass this phase in hours.
is followed by S phase, the time the DNA is synthesised, during this time each chromosome
duplicates. The next phase is G
(Gap or Growth 2), RNA and proteins are produced and the cell
gradually enlarges eventually doubling in mass before the next mitosis begin.
In a typical growing cell interphase takes 16 to 24 hours, whereas mitosis lasts only 1 to 2 hours.
However there is a great variation in the length of the cell cycle, which ranges in human beings
from a few hours in rapidly growing cells, such as those of the dermis of the skin to months in
other types of cells. Some of the cell types, such as neurons and red blood cells, do not divide at
all once they are fully differentiated, they are permanently stopped during G
in a phase known
as G
. Other cells may enter G
but eventually return to continue through the cell cycle.
Figure 8-1 Cell cycle
Prophase. This stage is marked by gradual condensation of the chromosomes by folding and
coiling. This makes the chromosomes shorter and thicker and to be visible under the light
microscope. The chromosomes have duplicated into identical sister chromatids. The nuclear
membrane starts to disintegrate, the centriole duplicates and each starts to migrate to the opposite
Metaphase. The chromosomes reach maximum condensation, the nuclear membranes have
broken up and allowed chromosomes to disperse within the cell. The chromosomes move to the
equatorial plane of the cells, spindle forms and microtubules get attached the chromosomes
kinetochores (centromeres)
Anaphase. This stage starts when chromosomes separate at their centromeres, allowing each
chromatid of each chromosome (now independent daughter chromosome) to move to opposite
poles of the cell.
Figure 8.2 Shows names of chromosomes types depending on their centromere positions
Telophase. The chromosomes are assembled at the poles, they begin to decondense and return to
their interphase condition. A nuclear membrane forms around each of the two daughter cell
nuclei and each gradually resumes the interphase appearance.
Figure 3 Mitosis: Diagramatic representation showing two chromosome pairs in mitotic
stages: Interphase, prophase, metaphase, anaphase and telophase
Meiosis is sometimes called meiotic mitosis, it halves the number of chromosomes. In organisms
that are haploid for most of their life cycle life meiosis occurs after fertilization. In higher
organisms that are diploid most of their life cycle meiosis occurs before fertilization for
production of sex cells, in the human, egg cells in females and sperm cells in males.
The number of chromosomes is halved as a result of two divisions of the nucleus accompanied
by only one division of the chromosomes. Meiosis therefore results in the separation of
homologous chromosomes and the halving of the chromosome numbers.
8. 2 Biological signicance of meiosis
The main process of sexual reproduction in both plants and animals
Reduces the number of chromosomes by half, therefore allowing the union of male and
female gametes to form a diploid organism
Leads to variation due to recombination or crossing over. This is an important tool for
Conserves a constant number of chromosomes in organism from one generation to the
8.3 Stages of meiosis
Prophase is the rst stage of meiosis, as in mitosis but in meiosis it lasts longer and is more
complicated. Meiotic prophase is further divided into a number of sub-stages: Leptotene,
zygotene, pachytene, diplotene, and diakinesis.
Figure 6-2 Meiotic prophase 1. Showing Leptotene, Zygotene, Pachytene and Diplotene
Leptotene. The word leptotene means thin ribbon. Chromosomes appear thin, long and single
threads at this stage. They contain chromomeres that show as dense granules of irregular sizes
along the extended lengths of the chromosomes.
Zygotene. Homologous chromosomes begin to pair. Homologous chromosomes are so called
because they resemble each other in length, position of centromeres (or kinetochore) and even in
the positions of chromomeres arranged along them. Pairing is followed by synapsis to form
bivalents. Synapsis is precise pairing, chromomere to chromomere and gene to gene. Synapsis
may be complete or incomplete depending on the degree of homology between the bivalent
members,that is depending on specic locality or occurrence of the genes. The mechanism by
which this specic pairing takes place and the nature of the attractive forces involved are not yet
fully understood.
Figure 6-3
Pachytene. The word pachytene means thick ribbon. Chromosomes shorten and thicken by
coiling and folding. At this stage chromosomes appear double. In certain regions there are
apparent exchanges of segments between homologous chromatids known as chiasmata.
Chiasmata are assumed to represent the physical basis of crossing over, since it has been
demonstrated that genetic exchange also involve chromosome exchange.
Diplotene. At diplotene chromosomes in each pair begin to come apart
Diakinesis. Chromosomes move further away from each other. Pairs of homologous
chromosomes are still held together at their chiasmata but elsewhere separated. The nucleolus
disappear during this stage, but may persist usually in reduced size until anaphase.
Metaphyase-I . Metaphase begins after the nuclear membrane disappear and spindle formation
starts. Pairs of chromosomes (bivalent or tetrads) line up on the equatorial plate with
homologous centromeres (kinetochores) oriented towards opposite poles.
Anaphase-I. Homologous chromosomes move towards opposite poles and assume
characteristic shapes (V-shaped for metacentric chromosomes, J-shaped for submetacentric
chromosomes and rod shaped for acrocentric and telocentric chromosomes)
Telophase-I. Chromosomes regroup at each of the two poles, they de-condense and return to the
interphase condition.
Interkinesis. This is the interphase stage between the two meiotic divisions. This stage may be
of relatively long duration in which case a cell wall is laid down between the nuclei to give a two
celled or dyad stage. Sometimes it may be such short duration as to be practically nonexistent. In
this case a cell wall is seldom laid down and the chromosomes go through the second division
relatively unchanged morphologically.
Prophase-II . If there is no inter-kinesis this stage is eliminated. In any event it appears to be
rapid. Chromosomes contract by coiling and folding therefore shorten and thicken.
Metaphase II. The chromosomes line up at the cell equator.
AnaphaseII. Sister kinetochores separate and start moving to the poles, assuming characteristic
shapes and pulling with then the chromatids to which they are attached.
Telophase II. This stage involves the reconstitution of the interphase nuclei and the laying
down of cell walls to give four cells, known as tetrad in plants. In animals there are four separate
cells in the male. In the female a microcyte called the polar body is usually bubbed off after the
rst division and a second polar body after the second division, so that the end product of
meiosis is a reduced egg and two or three polar bodies. The nal result of these two divisions is
four cells, each with a complete chromosome set and half the somatic number of chromosomes.
In animals the end products of meiosis become gametes, while in higher plants a number of
purely somatic type division occurs to give the gametophytic generation.
Figure 6-4
8.4 Variations
Chiasma formation seems to be absent in meiosis of the males of certain insects. A good
example of such an insect is those of the genus Drosophila . The fruit ies, Drosophila
melanogaster we keep in stock in our laboratories belong to this group of insects.
Endomitosis is duplication of chromosomes without cell or nuclear division. Chromosomes
become multi-stranded. This occurs in diptera insects salivary glands and some regions of the
gut. The resulting chromosomes are known as polytene chromosomes. Sometimes they are
referred to as giant or salivary gland-type chromosomes.
Further Readings

George Redei.1982 Genetics. Macmillan Co. Inc. New York.
Hurt F.B 1964 Animal Genetics. Ronald Press, New York
Gerald Karp 1979. Cell Biology. MacGraw-Hill Inc.
Lecture Seven
Chemical Basis of Heredity

By the end of this lesson, you should be able to:
Explain various experiments that aided in the discovery of DNA and RNA
Explain the chemical and physical structure of DNA and RNA molecules
Distinguish between the structure, location and function of DNA and RNA
Dene the role of DNA and RNA
Tell the occurance, structure and function of mRNA, rRNA and tRNA
Explain DNA replication and transcription
Identify chemicals and organelles involved in translation
Outline stages involved in protein biosynthesis
Primary Genetic Material
Many Scientic Experiments have proved that DNA (Deoxyribonucleic Acid ) is the primary
genetic material. With the exception of some viruses DNA is the start of protein biosynthesis,
further even in those viruses that have RNA as their genetic material convert it to DNA rst
before the proteins are synthesised.
Experiments that led to identication of the DNA as primary genetic material
(1) Grifth Effect ( Bacteria Transformation)
In 1928 Frederick Grifth conducted an experiment using a bacteria Diplococcus pheumoniae on
mice. He used two strains of the bacteria III S and II R strains, the two strains -differ in the
characteristic shown in the table below:
III S-strain II R-strain
Colonies on agar Smooth edges Rough edges
Size of colony Large Small
Virulence or pathenogenicity Non-virulent Virulent
Polysaccharide Capsule
enclosing cell wall
Have Lacks
The II R-strain had mutated from the III S-strain . When Grifth injected a mixture of heat
killed II R-strain and III S-strain, mice died. After extracting body uids from the dead
Fig. 7.1 Transformation of one bacteria strain to another
mice, it showed living III S-strain. He concluded that the presence of the heat killed III S-strain
caused transformation to the II R-strains giving them ability to form a polysaccharide capsule.
However he couldnt understand the transforming substance. This is reffered to as the Grifth
effect or bacteria transformation.
In 1944, the transforming substance was identied by Oswald Avery, Colin Mcleod and Maclyn
McCarthy. They used chemicals and enzymes to degrade proteins, lipids, polysaccharides and
RNA in the heat killed III S-strain before mixing it with the II R-strain. They noticed that
transformation occurred in absence of these chemicals. When they degraded DNA using
deoxyribonucleases there was no transformation. They concluded that DNA is the transforming
substance in Pneumococci.
Hershey and Chase Bacteriophage experiment.
In 1952, Alfred D.Hershey and Martha Chase conducted an experiment to proof that DNA and
not proteins is the carrier of genetic information. They knew that bacteriophage T2 protein
contained sulphur but lacked phosphorous while bacteriophage DNA had phosphorous but
lacked sulphur.
Fig. of experiment
(III) Discovery of DNA as the genetic material in some viruses.
In 1957 Heinz Fraenkel- Conrat and B. Singer worked on tobacco mosaic virus (TMV) to prove
that RNA and not proteins was the genetic material in TMV. TMV has several genetically
different strains that are distinguished by their symptoms on tobacco leaves. They also difer in
their amino-acid content. A TMV particle is made up of a helical RNA core surrounded by a
mass of protein subunits.
Fig TMV viral particle
Fraenkel and Singer isolated the RNA and protein components of two distinct TMV strains and
reconstituted (formed) RNA of one type with the protein of the other type and vise versa.
Fig. Reconstitution experiment
They discovered that the progeny TMV resembled the RNA in the protein coat and did not
ressemble the protein. They concluded that RNA is the substance that was used in transferring
the genetic information.
(IV) James Watson , Francis Crick and Maurice Wilkins experiment
The three compiled knowledge that existed at that time and came up with the structure of the
DNA molecule. They worked in the laboratory owned by Rosalid Franklin and Maurice Wilkins.
X-ray diffraction method was used to come up with the DNA structure.
In 1953, together with Wilkins they published a paper in which they proposed the structure of a
model DNA. They used cans and wires to demonstrate their ndings. The model DNA has the
following features:
Has two polypeptides (wires) wound round each other in a right-handed double helix.
Diameter of 2 nm
Two strands running in an antipararell direction (5! - 3 and 3 5 ).
Sugar-phosphate backbones are on the outerside while nitrogen bases are on the inside
perpendicular along the central axis.
Bases on the opposite strands are held by weak hydrogen bonds.
After every 10 base pairs the helix makes a complete turn (360 ). The distance between
two base pairs is 0.34 nm. This means that each base pair is twisted 36 clockwise with
respect to the previous base pair.
Because of the way bases bond with each other, the sugar-phosphate backbone is not
equally spaced along the helical axis. This results to formation of minor and major
Physical-chemical structure of a DNA molecule
Several biochemical and biophysical studies have helped in identifying the structure of a DNA
molecule. These studies include: chromatography, DNA diffraction, X-ray crystallography.
A DNA molecule is a complex biological polymer made up of repeated nucleotides

Fig. Sugar, base, phosphate joined together
Carbons are usully numbered from right to left. In order to differenciate carbon atoms in bases
from those in sugars, those from sugars are denoted with a prime e.g. 1, 4, 5.
Nitrogen base:
Fig. Structure of pyrimidines and purines
Pyrimidines ( Cytosine, Uracil, Thymine)
Purines ( Adenine and Guanine)
Pyrimidine Uracil is found only in RNA where it replaces Thymine
Purines do not pair with Purines neither do Pyrimidines pair with Pyrimidines.
In a DNA molecule, phosphates join sugars at the 3 and 5 end while nitrogen bases join sugars
at the rst carbon (1)
DNA replication in prokaryotes.

An essential property of the genetic material is the ability to make exact copies of itself. This is
referred to as replication. Replication takes place at interphase in the S-phase. It results in
doubling of both DNA and histones.
Fig. Replication fork
Comparing DNA with RNA
Just like DNA, RNA is a long chain of macromolecules of nucleic acid but it differs from DNA
in the following important properties:
In the nucleotides of RNA the sugar component is ribose and not deoxyribose.
The nitrogenous base Thymine is found in DNA but does not occur in RNA. Instead it is
replaced with Uracil in RNA.
RNA is usually single stranded and does not form a regular helical structure.
RNA is generally shorter than DNA
Protein Biosynthesis
Protein synthesis is also referred to as translation. This is because it involves the transfer of
information from one language (sequence of nucleotides ) to another (sequence of amino-acids).
In both prokaryotes and eukaryotes, translation involves three main stages:
Initiation of translation
Elongation of polypeptide chain
Termination of translation.
Initiation of translation
In both prokaryotes and eukaryotes translation begins at the AUG initiator codon of the mRNA.
In few mRNAs translation can begin at GUG codon. In prokaryotes , the mRNA is not
processed so it is modied by addition of formyl group to form formyl-methionine (fmet).
Enzyme transformalase catalyses addition of formyl group to form a fmet_tRNA.fmet.
Prokaryotic mRNA has a purine rich region that binds to a pyrimidine rich region of the 16S
rRNA. This sequence is called the Shine-Dalgarno sequence named after its discoverers John
Shine and Lynn Dalgarno. Shine-Dalgarno sequence appears between the 5! end and the
initiator codon. It orientates the ribosomes in the correct reading direction during translation.
Eukaryotes do not have the Shine-Dalgarno sequence . They recognise the cap at the 5! end
of mRNA. The small ribosomal subunit binds to the mRNA at the site of initiation codon
followed by the large ribosomal subunit.
Elongation of polypeptide chain
After initiation, a second charged tRNA moves in the site A- site while fmet remains at the P-
site. The ribosome puts the second tRNA in the correct position so that a peptide bond is formed
between the two amino acids. This reaction is catalysed by enzyme peptidyl transferase. The
ribosome moves along the mRNA towards the 3 end in a process called translocation. When
several ribosomes are translating a single mRNA, it is referred to as a polysome or
Fig. Elongation
Termination of translation
The end of a polypeptide chain is signalled by one of the three stop codons (AUG,UAA or
UGA). Ribosomes recognise stop codons by help of proteins called termination factors or release
factors. Release factors initiate a series of specic termination events as follows:
Release of polypeptide from the tRNA at the P site
tRNA is released from the ribosome
Ribosomal subunits dissociate and leave the messenger RNA
The initiator codon is cleaved from the completed polypeptide.
Fig. Termination
Self-assessment questions (SAQ)
How do riboses differ from deoxyriboses?
Which Nitrogen Base is found only in DNA and not RNA?
What is the role played by tRNA?
How does replication differ from transcription?
Why is an RNA molecule usually smaller than a DNA molecule?
Further Readings

1. Norman Rothwell. 1979. Understanding Genetics, Oxford University Press.
2. Wagner R., Judd B., Sanders B. and Richardson, R. 1980. Introduction to modern Genetics,
John Wiley & Sons, New York.
3. Christine Birkett 1979. heredity, Development and Evolution. Macmillan Education..
Lecture Eight
Genetics of Sex
By the end of this lesson, you should be able to:

Sexes range from two (male amd female) in higher plants and animals to many in lower
in lower organisms, e.g Paramecium bursaria with eight sexes or mating types all
morphologically identical. Each mating type is incapable (physiologically of conjugating
with its own type, but may exchange genetic material with any of the other seven other
types. In higher organisms sexes are two, male and female. Sexes may reside in different
individuals or within the same individual: an animal which has both male and female sex
organs is said to be hermaphroditic, in plants the term used is monoecious ( that where
the male, staminate and female, pistillate, owers occur in the same plant). Only a few
higher plants, angiosperms are dioecious, that is having the male and female sex organs
in different individuals. In higher animals hermaphrodites are a minority but in higher
plants monoecious are a majority.
Sex as a form of reproduction has the advantage of providing a mechanism which
provides for a great amount of genetic variability, through recombination and therefore
provides material on which evolution and adaptation depends.
8.1 Sex Determining mechanisms
8..1.1. Sex Chromosome mechanisms
(a) Heterogametic males
(i) XY/XX system
Examples of this type of sex determining system include man and other mammals, most dipteran
insects e.g Drosophila, some angiosperm plants e.g in the genus Lychnis.
In this system male diploid cells have two types of sex chromosomes X and Y and female diploid
cells have similar X sex chromosomes. Males therefore produce two types of haploid gametes,
those bearing an X sex chromosome and those having a Y sex chromosome (heterogametic).
Females on the other hand produce haploid having only an X sex chromosome (homogametic).
(ii) XX/XO system
Examples of this type of sex determining system include some insects especially those of the
orders: Hemiptera (bugs and beetles), Orthoptera ( e.g cockroaches, praying mantis,
grasshoppers, crickets), Spiders, Myriapods and Nematodes.
The female is homogametic and the male is heterogametic for sex chromosomes. The male
produces two types of haploid gametes, one an X sex chromosome, one type without a sex
chromosome (O or zero).
(b) Heterogametic females
(i) ZZ/ZW system
Examples of this type of sex determining system include a large group of animals including
betteries, moths, silkworms, some birds and shes.
The female is heterogametic (ZW) and the male homogametic (ZZ), that is the female produces
two types of haploid gametes, one type with a Z sex chromosome and the other with a W sex
chromosome, the male produces one type of haploid gamete with a Z sex chromosome.
(ii) ZZ/ZO system
Examples of this type of sex determining system include domestic chicken.
The male is homogametic and the female is heterogametic for sex chromosomes. The female
produces two types of haploid gametes, one a Z sex chromosome, one type without a sex
chromosome (O or zero).
8.1. 2.Autosomal Chromosomes sex determination
In some organisms sex is affected by autosomal chromosomes in addition to the sex
chromosomes, e.g in Drosophila melanogaster
Number of X
Number of
chromosome sets (A)
X/A ratio Sex
3 2 1.50 Super female
4 3 1.33 Triploid Super female
4 4 1.00 Female
3 3 1.00 Female
2 2 1.00 Female
3 4 0.75 Tetraploid intersex
2 3 0.67 Triploid intersex
1 2 0.50 Male
1 3 0.33 Triploid Supermale
1 4 0.25 Tetraploid Supermale
Number of X
Number of
chromosome sets (A)
X/A ratio Sex
3 2 1.50 Super female
4 3 1.33 Triploid Super female
4 4 1.00 Female
3 3 1.00 Female
2 2 1.00 Female
3 4 0.75 Tetraploid intersex
2 3 0.67 Triploid intersex
1 2 0.50 Male
1 3 0.33 Triploid Supermale
1 4 0.25 Tetraploid Supermale
It has been estimated that in D. melanogaster each haploid set of autosomes carries factors with a
male determining value equal to one, and each X chromosome has female determining factor of a
value equal to 1.
E.g a normal male AAXY, has male-female determinants in the ratio 2:1, with the balance in
favour of maleness, while a normal female AAXX has male-female determinants in the ratio 2:3
and therefore the balance is in favour of femaleness.
Super males and females are weak, sterile, underdeveloped and die early.
Intersexes are sterile and display secondary sex characteristics of both male and female.
8.1.3. Haplodiploidy
This form of sex determination occurs in some insects of the order Hymenoptera that includes
ants, bees and wasps.
Males arise parthenogenetically, that is without fertilization, they have a diploid number of
chromosomes. e.g in honey bees, a male (drone) has 16 chromosomes, the queen bee and
workers are females and arise from fertilized (diploid) eggs.
8.1.4. Single gene effects
Complementary sex factors
At least two members of the insect order Hymenoptera are known to produce males by
homozygosity at a single gene locus as well as by haploidy,
e.g (a) Parasitic wasp Bracon hebetor (common name, Habrobracon) and also in honey bees.
At least nine multiple sex alleles are known at this locus in Bracon hebetor and may be
represnted by S
All females are heterozygous ( e.g S
) and males are homozygous ( S
) for the
alleles. Such homozygous individuals develop into diploid male which is sterile. In case of bees
such diploid males are eaten or otherwise destroyed by other bees as soon as they are recognized.
(b) Maize
Maize is monoecious, the tassel consists of staminate (male) owers and the ear pistillate
(female) owers. Two pairs of genes are known to inuence the distribution of the male and
female owers in maize:
Bs/bs , baren stale, such that bs bs results in plants which are staminate (lacking the female parts,
silks, ears ...) but a normal staminate tassel is present.
Ts/ts, tassel seed, such that ts ts converts the tassel to pistillate (female) owers (become small
Bs-Ts- normal
bsbs Ts - Staminate
Bs-ts ts Pistillate (ears terminal and lateral)
bs bs ts ts Pistillate ( ears terminal only)
(c) Transformer gene of Drosophila
A recessive gene (tra) on the third chromosome (an autosome) when homozygous transforms a
diploid female into a sterile male. These males X/X tra/tra resemble normal males in external and
internal morphology with the exception that the testes are much reduced in size. The gene tra has
no observable effect in hetrozygous condition on either males or females.
(d) Mating types in microorganisms, e.g in Chlamydomonas and also in fungi such as
Neurospora and in yeast, sex is under the control of a single gene. Haploid individuals
possessing the same allele of this mating type locus usually cannot fuse with each other to form a
zygote, haploid cells of opposite (complementary) allelic constitution at this locus may fuse.
8.1.5. External Environments /non genetic factors of sex
Males and females have similar genotypes but an environmental source initiates their
developments towards one sex or other.
e.g (a) Marine worm Bonellia, the male is small and lives within the
reproductive tract of the larger female. Extracts made from the female probosis
inuences young worms towards maleness.
(b) In another marine worm Dinophilus sex seems to be related to the size of eggs,
large eggs produce females, small ones males.
(c) In a plant called Equisetum, the plant will grow into female if raised under good
growth conditions and into male when raised under poor conditions.
(d) Freemartins in cattle. Where a cow conceives non identical twins, a male and a female,
sometimes the twins blood vessels become interconnected, both develop into sterile intersex
called Freemartins.
(e) Sex reversal in chicken. If testes of a male chicken are destroyed by disease it
becomes a female.
8.1. 6. Episome
Episome or fertility (F) factor determines sex in bacteria. In conjugation between two cells a
cytoplasmic bridge through which one cell donates to the other, part all of its single chromosome
The donor cell may be thought as analogous to a male, the recipient a
Maleness is determined by possession of n episome or fertility factor (F),
femaleness by its absence.
The F factor may be located in the cytoplasm or integrates into the
If the F factor episome is transferred during conjugation the recipient is
converted from female to male.
Sex determining mechanisms
1. Sex Chromosome mechanisms
(a) Heterogametic males
(i) XY/XX system
(ii) XX/XO system
(b) Heterogametic females
(i) ZZ/ZW system
(ii) ZZ/ZO system
2. Autosomal Chromosomes sex determination
3. Haplodiploidy
4. Single gene effects
5. External Environments
6. Episome
8.2 Gynandramorphs and mosaics
Sometimes an individual organism has a mixture of male and female sex cells. These cells may
be in patches or mosaics or in case of gynandramorphs one half of an individual becomes male
and the other female (bilateral gynandromorph). Mosaics and gynandromorphs are common
among Drosophila and also in man.
A human cell that has a Y chromosome is male and one without is female. It is possible for an
individual to have a body with a mixture of the two types of cells. If the two types are scattered
throughout the body such individual is said to be a sex mosaic. If the cells types are such that one
type is on the left side of the body the other type on the right or one type on the lower half of the
body the other type on the upper side the individual is said to be a gynandramorph. Externally a
sex mosaic or a gynadramorph will exhibit a mixture of internal and external sex organs or show
male or female traits depending on the type of cells that occur in the pelvic area of the body.
Many people who are sex mosaics or gynandramorphs turn up in the sex tests administered to
participants in Women teams in the Olympic games. One such person raised as female turned
out to be an XYY/XO mosaic. (S)he probably started life as a male XY zygote and very early,
perhaps at the rst mitotic division, nondisjunction of the Y chromosome produced the two cell
types: XY > duplicated to XXYY, but during divison one Y became stranded in the middle of
the cell, making it be wrongly included, that instead of two cells with XY and XY, two cells were
formed with XYY and XO. The XO tissue became located in such a way that at birth on
inspection s(he) was declared a female.
8.3 Compound sex chromosomes
This is when the total number of chromosomes in a male differs from that in females. A good
example is in nematodes (Ascaris incurve) where the number of autosome pairs is 13 but the
number of compound sex chromosomes is 8. There are 35 chromosomes in males and 42
chromosomes in females.
8.4 Sex linked Inheritance
E.g in Human beings or Drophila malanogaster (XX/XY , XX/XO or on the analogous ZZ/ZW ,
ZZ/ZO systems) ... a gene is said to be sex linked if found located on the nonhomologous
portion of chromosome X (or Z).
In human Y chromosome is small, like chromosome 22, X chromosome is bigger like
Chromosome 14/15. Chromosome Y has a portion with genes similar to those found in a
homologous portion of X chromosome. Y contains genes in the non homologous portion,
holandric portion, that are not found in the X chromosome, e.g hairy ears.
Unlike inheritance involving autosomal genes, reciprocal crosses do not
yield similar results:
(Female) (Male)
ww x +Y
Gametes w + , Y
w+ wY
normal female white eyed male
Reciprocal cross
(Female) (Male)
++ x wY
Gametes + w , Y
w+ +Y
noramal female normal male
this happens due to the fact that the Y chromosome carries no alleles
homologous to those at the white locus on the X chromosome
In most organisms the Y chromosome has no known genes
Males carry only one allele for sex linked traits, a condition termed
a human character governed by sex linked recessive gene usually is:-
- found more frequently in the male than in the female
- that it fails to appear in females unless it also appeared in the paternal parent
- that it seldom appears in both father and son, then only if the maternal parent is
a human character governed by sex linked recessive gene usually is:-
- found more frequently in the female than in the male the species
- found in all females offsprings of a male of the male with the gene
- that it fails to be transmitted to any son from a mother who did not exhoibit the
trait herself.
Genes found located on the homologous segments of the X chromosome are said to be
incompletely sex linked or partially sex linked. Genes located on the the non homologous portion
of the X chromosome are said to be completely sex linked.
In man a few genes are known to reside in the non homologous portion of the Y chromosome. In
such cases the character is expressed only in males and is transmitted from father to son. Such
completely Y linked genes are called holandric genes.
8.4.0 Examples of Sex linked traits in man
Nearly 250 traits in human beings appear to be due to be sex linked. These include various types
of colour blindness, haemophilia, Lesch-Nyhan syndrome, Ducheme muscular dystrophy and
Ichthyosis. Let us discuss some of these conditions in more details.
8.4.1. Colour blindness
This involves inability to distinguish between red and green colours. The gene involved in
recessive and sex linked, that is it is found located in the nonhomologous portion of X
chromosome . A marriage between a colour blind man and a woman homozygous for normal
colour vision results in all their daughters being carriers or heterozygous but their son being of
normal vision.
Parents: Colour blind male x Normal vision female
Genotypes X
Gametes X
and Y all X

F1 generation X
Carrier daughters Normal vision sons

If a carrier daughter marries a normal man show the proportion of their sons and daughters
expected to be of ;
Normal vision
Colour blind
What general conclusions can you come to from your results (hint: Read notes above on
characteristics of sex linked traits)
8.4.2 Genetic abnormalities involving sex chromosomes
Please Note
Chromosomal variations that involve changes in number are of two types: euploidy, variations
that involve entire sets of chromosomes; and aneuploidy, variations that involve parts of a
chromosome set.
e.g Type Number of homologous Example
Chromosome sets (n)
Monoploid one (n) 1,2,3,4......
Diploid two (2n) 11,22,33,44,.....
Polyploids- Triploid three (3n) 111,222,333,444,.....
Tetraploid four (4n) 1111,2222,3333,4444,......
Pentaploid ve (5n)
Hexaploid six (6n)
Septaploid seven (7n)
Octaploid eight (8n)
Monoploid also called haploid organisms contain the basic chromosome number, that is each
kind of chromosome is represented only once. Lower organisms such as fungi, bacteria are
haploid. Gametes of higher organisms are also haploid. Monoploid higher organisms are smaller
and less vigorous normal diploid,
Diploid (2n), where there are two sets of basic chromosome per cell. This is the typical normal
condition for higher organisms, plants and animals,
Polyploid, ploidy levels higher than diploidy
Variation of chromosomes that involve parts of a set. Aneuploids have either fewer or more
number chromosomes. Such extra or missing chromosomes are less than a complete set
e.g Type Number of homologous Example
Chromosome sets (n)
disomic (normal) 2n 11,22,33.....
monosomic 2n - 1 11,22,3,.....
nullisomic 2n - 2 11,22,.........
Polysomic extra chromosome
(a) trisomic 2n + 1 11,22,333....
(b) double trisomic 2n + 1 + 1 11,222,333...
(c) tetrasomic 2n + 2 11,22,3333
(d) pentasomic 2n + 3 11,22,33333
hexasomic, septasomic, etc Turners Syndrome
Turners syndrome is an abnormal female condition, each of their cells lack one sec
chromosome, their karyotype is- 45,X0, that is monosomic for X chromosome.
Their secondary sexual characteristics (breasts, pubic hair etc) fail to develop, unless sex
hormones are administered to them starting at an early age. Their ovaries do not develop and
because of this reason they cannot have children of their own. This condition occurs in one out of
5,000 live births or 1/2,500 among female babies. As adults they are short in stature have widely
spaced nipples (described as having a shield chest) and as infants they have a webbed neck, that
with folds of skin at the neck. In older children this will show as a aring of the neck as it joins
the shoulders. People with Turners syndrome have normal intelligence. Klinefelters syndrome
This condition is caused by trisomy of either an X or Y chromosome or tetrasomy for X and/or
Y chromosome. Let us discuss a few examples:
Mild Klinefelters syndrome of karyotype 47,XXY male is trisomic . This is the most common
Klinefelters syndrome, with an incidence of one out of 500 male births (or 1 out of 1,000 live
births).One is male but with a tendency to femaleness, for example have sparse body hair, have
no beard, pubic hairs and show partial breast development, have altered set of bodily proportions
( e.g narrow shoulders and larger hips than a typical male), have small testicles ( not exceeding 2
cm in length, have high pitched voice and are sterile. Their intelligence is slightly below normal
at IQ of about 90.
An extreme Klinefelters of karyotype 48, XXXY is also male but tetrasomic for sex
chromosomes and shows more extreme abnormalities compared to the trisomic case descibed
above. For example they have greater degree of mental retardation IQ 25 -50, lesser degree of
sexual development, testicles undescended, small penis. They also show heart defects, and knock
knees is common
A trisomic Mild Klinefelters of karyotype 47,XYY male is also known. They occur in one out
of 500 male births, taller and more malethan normal, they generally antisocial, they live and
relate aggressively and are over-represented in prisons, many have normal intelligence but a few
are mentally retarded.
A female Mild Klinefelters syndrome person of karyotype 47,XXX is also known. They are
usually mentally retarded, commonly infertile, have abnormal ear shapes, small hips and club
feet, small nose and a receding mandible. Those females who have the Extreme Klinefelters
48,XXXX are more extreme, the more X one has the worse the condition.
Please Note
A normal male karyotype is 46, XY and female is 46, XX
46 indicates the 2n number of chromosomes, that is 23 pairs. 22 pairs of autosomal
chromosomes 1 to 22 and a pair of sex chromosomes
A person of IQ (Intelligence Quotient is of normal intelligence, below IQ 100 is
considred below normal in intelligence IQ 30-50 indicates severe mental retardation.
IQ 120 to IQ 150 indicated giftedness and talentedness and above IQ 180 indicates
genius abilities. Sex- linked haemophilia
This disease is also called bleeders disease. The blood of a person who is haemophylic. Takes
an abnormally long time to clot. In the event of event a small cut, there is prolonged bleeding
that could lead to death. Haemophilia is caused a sex linked recessive gene. Most cases are found
in men than in women. It affects the production of prothrombin proteinase, an enzyme necessary
for clotting of blood.
Show the types and proportions of children expected fro the following marriages.
Normal man married to a carrier woman for haemophilia
Haemophylic man and carrier woman
Other examples include: Brown teeth, caused by a dominant sex linked gene, Rickets due to
vitamin D resistance also by a dominant gene, and Ducheme's muscular dystrophy caused by a
recessive gene.
8.4.3 Albinism
Albinism is a lack of pigmentation and is a X-linked recessive trait. Melanin is a derivative of the
amino acids phenylalamine and tyrosine, and is symthesised through a series of reactions. In
human albinism a mutation causes a breakdown during synthesis of pigment melanin. Lack of
pigment leads to white hair, pink skin and pink eyes.
8.4.4 Muscular Dystrophy
This disorder is characterized by wasting of muscles. The most common form, Ducheme
muscular dydtrophy is due to an X-linked recessive gene. Affected individuals though normal at
early childhood shows a progressive wasting away of their muscles, symptoms such as gait, toe
walking, frequent falls and difculty in rising may appear as soon as the child starts to walk.
Muscular weakness intensies until the individual is conned to a wheel chair and death usually
occurs during the teenage years.
Recently the gene responsible was isolated. It is involved in formation of a protein dystrophin in
turn the protein controls the release of calcium in muscle bres. Lack of the protein causes
leakage of calcium into the cells, which promotes the action of an enzyme that dissolves muscle
bres. When the body attempts to repair the tissue, brosis occurs and cuts off the blood supply
so that more and more cells die for lack of nutrient and oxygen supplies. There is now a test to
detect carries of Ducheme muscular dystrophy.
8.5 Y-linked genes or holandric genes
One of the genes found in the non-homologous portion of Y chromosome causes hairy ears in
8.5 Sex inuenced characters

Sex inuenced characters are those that are expressed differently in the two sexes male and
female, e.g Pattern Baldness in man (recessive in women, dominant in males). A man with this
dominant gene that causes baldness loses hair from the forehead in a pattern, a woman with such
a gene, on the other hand loses hair all over the head evenly but not in a pattern.
Sometimes expression of dominance or recessiveness by the alleles of sex inuenced loci is
reversed in males and females due in large part to the inuence in the internal environment
provided by sex hormones.
8.6 Sex assignment
Sex is usually assigned to a new born through casual observation of external sex organs. In cases
of ambiguity sex is assigned by parents and medical personnel by a process of counselling and
tests. In Kenya this has to be done at birth. In some other countries they allow one to choose to
continue to be a bisexual until 18 years of age when they choose to be male or female.
8.7 Sex limited traits come to expression in one of the sexes only e.g egg production in
chicken, milk production in cows.
Some genes may only come to expression in one of the sexes either
because of differences in internal hormonal environment or because of anatomical
dissimilarities, e.g a bull have genes for milk production that they transmit to their
daughters, but the bull cannot express these genes
8.8 Dosage Compensation
In man and all mammals cell nuclei have densely staining chromosomes called Barr bodies
(named after their discoverer Murray Barr). The Barr body indicates a chromosome that has
coiled and folded. In this condition genes located in such a chromosome are inactivated or
switched off so to speak.
The number of Barr bodies is always one less than the number of X-chromosomes found in a
cell. Because of this it has been suggested (Lyons hypothesis by Mary Lyon in 1961) that this
serves to compensate for gene dosage to overcome the number of sex chromosomes differences
between males and females.
Barr bodies are now used to separate male and female Olympic athletes. If a Barr body is
detected in a cell taken from any part of the body one is assigned to be female and no Barr bodies
are evident in any of the cell samples taken one is taken to be male. This decision is arrived at
regardless of whether or not one has been raised male or female.
A woman in an Olympic team showed that she was a mosaic for cell types X0 and XYY,
for that reason she was classied as male for the purpose of the games. Explain what could
have gone wrong from the time she started at day one as a single cell.
Self-assessment questions (SAQ)
Indicate the number of Barr bodies in each cell of a person with the following condition:
Turners syndrome of karyotype 45,X0
Mild Klinefelters syndrome man of karyotype 47,XXY
Normal female, karyotype 46,XX
Extreme Klinefelters 48,XXXX
8.9 Human Sex ratios
Studies have shown that the secondary human sex ratio, that is at life birth is slightly favourable
to the male at between 107 : 100 to 104: 100 boys to girl infants. Studies of premature abortions
at various months indicate that at conception the primary sex ration at conception could be as
high as 300 : 100 boy to girl foetuses.
The ratios after birth show that the number of boys to girls become equal at about 20 years of age
and from then on girl numbers increase compared to those of boys. It seems that from before
birth boys die off in bigger numbers do and this continues throughout life with life expectancies
of male and female ranging from 5 to more than 11 years in various countries.
Secondary sex ratio is an important issue with family planning and birth control in many
countries. Male child preference is blamed for high population growth among many
communities. If a couple can reliably choose the sex of their children it has been suggested there
would be no need to have as many children as they now do.
The following observations have been made in population studies:

Boys are born in more numbers than girls in early fertile marriages;
Boys births outnumber those of girls during war in warring countries (and
also in neutral neighbouring countries);
Girls outnumber boys in illegitimate children births;
Boys are born in more numbers than girls among rural folk than in town or
urban dwellers;
The explanation has been that;
Just before ovulation the body temperature rise by a few tenth of a degree
and then dips, a feeling of a fever is felt. If intercourse occurs in the next within
24 hours the Y bearing sperm cells which swim faster get to the egg in greater
numbers than X chromosome bearing sperm cells, increasing the probability of a
boy child birth;
Human females produce eggs with X chromosomes. Males produce half of
the sperm cells bearing Y chromosomes and the other half bearing X
chromosomes ;
Sperm cells bearing Y chromosomes are smaller, more agile but remain
alive for only 48 hours, while X bearing sperm cells can last for 72 hours;
Fertilization occurs at approximately the outer one third of the fallopian
tube, the egg reaches that position in less than a day, in about 12 or more hours.
Further Readings

1. Norman Rothwell 1979. Understanding Genetics, Oxford University Press.
2. Strickberger, M.W. 1969. Genetics. Macmillan Canada.
Lecture Nine
Recombinant DNA Technology
After reading this lesson you should be able to:
Explain some of the techniques that are commonly used in recombinant DNA technology
Describe how these techniques are used to clone and characterize genes
Describe how these techniques may be applied in agriculture, industry, forensic science
and medicine.
Recombinant DNA technology is now known popularly as genetic engineering as coined by the
press. The major scientic development that occurred at the same time are cornerstones of this
Ability to introduce DNA into Escherichia coli (called transformation) and subsequently
to select the transformed bacteria.
Ability to purify plasmids DNA in high yield
Discovery and purication of restriction enzymes
5.1 Transformation
Many bacteria have the ability to take up DNA naturally, only a small proportion of a bacterial
population has this ability. Bacteria that are able to take up DNA are said to be competent. In
Escherichia coli competent cells do not occur naturally, but they may be made so by treatment
with cold calcium chloride solution, mixed with DNA and followed by a brief heat shock
treatment. After this they are allowed to recover. This process is not very efcient but 10
transformed per microgram of DNA introduced.
Non bacterial cells can also be transformed. Plant cell walls act as barriers to cells
transformation. First of all cell walls are therefore removed using enzymes to leave intact
protoplast which can take up DNA readily. A special technique called electroporation in which
cells are subjected to a short electrical pulse induce pores in the cell wall that can allow DNA to
pass through.
There are also two physical methods that can assist transformation:

Microinjection uses ne pipettes to inject DNA directly into the cell nucleus of a cell and
Biolistics or micro-projectiles bombard cells with high velocity micro-projectiles, usually
particles of gold or tungsten that have been coated with DNA. This is done with a particle
Generally transformation of whole organisms for plants is easy, whole plants can grow from a
single transformed cell, they are totipotent. With animal cells, e.g. mammal cells, a fertilized egg
is taken out transformed and then re-implanted in the mother to be.
5.2 Plasmids
Plasmids are self sustaining pieces of DNA that are often found in bacteria and some lower
eukaryotes. Plasmids are not essential for growth, but they confer some unusual properties to the
cells that harbour them. Plamids replicate independently of the main chromosome and are
sometimes described as extra-chromosomal DNA. Most plasmids are circular, but a few a linear.
Properties conferred by plasmids are varied, the rst plasmid to be identied in Escherichia coli
confers the ability to participate in simple conjugal exchange genetic information. This plasmid
is known as the F factor ( F for fertility). The F plasmid carry tra genes, that give the ability to
promote conjugal transfer of plasmids.
The F factor is large, 96,000 base pairs and is transmissible, that is, it has the ability to promote
the act of conjugation and be transferred from one cell to another. The other plasmids which are
similar and insome cases related to the F factor are:
R factors (R for resistance). These carry genes conferring on the host bacterium resistant
to one more antibacterial agents, such as chloraphenical, ampicillin and mercury. R
plasmids are very important in clinical microbiology as their spread through natural
populations can have profound consequences in the treatment of bacterial infection.
Degradative plasmids allow the host bacterium to metabolize unusual molecules such as
toluene, salicylic acid and so on, for example TOL plasmids allow Pseudomonas putida
to degrade toluene and use it as a carbon source. Related plasmids allow degradation of
xylene and camphor. Similar plasmids has allowed development of bacteria with the
ability to mop up after accidental oil spillage by tankers.
Col plasmids Col is a code for colicins) colicina are proteins that kill other bacteria that
do not have them. ColE1 is plamid of Eschechia coli.
Virulence plasmids confer pathogenesity on the host bacterium, e.g. Ti plamid of
Agrobacterium tumefaciens. A rhizobium bacterium that induces crown gall disease on
dicotyledonous plants. The Ti plasmid confers the ability to x nitrogen and form
symbiuotic association with leguminous plants.
Examples of plasmid sizes
Generally plasmids size range from 1.kb for the smallest to over 250kb for the largest plasmids.
Ti plasmid is 300kb in length, it exists as one or two copies per cell. Purifying such plas
mids is difcult and yields are poor.
TOL is 117 kb
pBR 345 is 0.7kb
ColE1 6.36 kb
pBR 322 4.362 kb
Plasmids of less than 10kb are known and are usually transmissible, they confer a simple
phenotype on the host bacterium, and are frequently 20-40 copies per cell and they can readily be
Plasmids in organisms other than bacteria
Although plasmids are widespread in bacteria they are not so common in other organisms. The
best known plasmid is the 2'm circle that occur in many strains of the yeast Saccharomyces
cerevisiae this plasmid has been used to construct many vectors for cloning gene with industrial
Search for plasmids in other eukaryotes (fungi, plants, animals) have not been successful so far.
Purication of Plasmid DNA by caesium chloride density centrifugation
Cells are broken (lysed) to liberate all the cellular contents. Much of he chromosomal DNA
remains in large fragements and forms a gelatinuous mass which can be removed by simple
centrifugation. This also removes many proteins and cell wall debris. The remaining solution
contains small fragments of chromosomal DNA, RNA, proteins and plasmid DNA. This is then
made almost saturated with CsCl and a dye called ethidium bromide is added. This dye
intercalates between the bases of DNA and causes it to unwind. It also increases the density of
the DNA. Plasmid DNA being circular cannot unwind so much and so does not become so dense.
This crude DNA is then centrifuged for many hours at approximately 140,000g. The CsCl forms
a gradient of increasing density down the tube and the protein rises to the top as it is not very
dense. The RNA sediments at the bottom. The two types of DNA concentrate into two bands in
the middle of the tube. Chromosomal DNA being the more dense is lower in the tube. The
plasmid DNA is then siphoned off and dialysed to remove CsCl. This leaves a pure solution of
5.3 Restriction enzymes
Restriction enzymes are more accurately known as restriction endonucleases. Enzymes that cut
and join DNA are of two types; endonucleases ( cut) and ligases ( join). These enzymes were
discovered when it became apparent that bacteria could recognize foreign DNA and degrade it,
while DNA from the same strain was not degraded. This is because self DNA is modied usually
by attachment of methyl groups to specic bases such that it is no longer hydrolyzed by the
restriction enzymes. Table 9 below lists DNA manipulating enzymes:
Table 9 DNA manipulating enzymes
Nucleases cut , shorten or degrade DNA molecules
Ligases join nucleic acid molecules together
Polymerases make copies of DNA molecules
Modifying enzymes remove or add chemical groups
Topoisomerases introduce or remove supercoils from covalently closed circular DNA
Nucleases degrade DNA by breaking the phosphodiester bonds that link nucleotides together,
one to the next in a DNA strand. There are two kinds of nucleases, exonucleases which remove
nucleotides one at a time from one end of a DNA molecule, and endonucleases which break
internal phosphodiester bonds within a DNA molecule.
Each bacterial species has a restriction enzyme that recognizes a different sequence and some
species have more than one restriction enzyme. In a vast majority of cases the sequence that is
recognized is a palindrome or a sequence of dyad symmetry, that is a sequence in which bases
are repeated on the opposite strand when read in the same direction. Let me list a few examples:
----- T-----C------G-------A---
----- A-----G------C-------T---
----- G-----A---A--T---T---C---
----- C-----T----T-- A--A---C---
Over 1,200 different restriction enzymes has now been characterized.
Table 10 below shows examples of restriction endonucleases, their origin and points where cuts
occur shown with arrows.
Table 10 Some restriction endonucleases and their origin
Blunt ends and sticky ends
Some restriction enzymes make a simple double stranded cut in the middle of the recognition
sequence resulting in a blunt or ush end. Most make cuts that are not at exactly the same
position, instead the cleavage is staggered, usually by two to four nucleotides, so that the
resulting DNA fragments have short single stranded overhangs at each end. These are called
sticky or cohesive ends, as base pairing between them can stick the DNA molecule back
together. One important feature of sticky ends is that restriction enzymes with different
recognition sites may produce the same sticky ends.

Genetic engineering
A piece od DNa is cut by a restriction enzyme that creates a cohesive or sticky ends. The piece
od DNA will tend to rejoin again because the cohesive ends have complementary sequences and
can therefore base pair. The broken DNA is rejoined by DNA ligase. All pieces of DNA cut by
the same restriction enzyme will have the same complimentary ends, and so may be joined
5.5 Application of genetic engineering
In Medicine
Application of recombinant DNA technology to the production of proteins of
medical signicance, e.g Insulin was normally prepared from bovine or porcine pancreas, some
people become allergic to these types of insulin and therefore require human insulin, human
insulin is difcult to obtain as there is no regular supply of human pancreas and chemical
manufacture of insulin is not feasible. In the islets of Langerhans, insulin accumulates in
secretory vesicles as a single polypeptide chain pro-insulin, the rst third (B chain) and the nal
(A chain) of pro-insulin are joined together by disulphide bridges. Before secretion into the blood
stream the middle third (C chain) of the pro-insulin molecule is excised
leaving the A and B chains joined by disulphide bridges as the active insulin.

In genetic engineering the A and B chains are synthesised separately and then joined together, the
gene for A chain has been fused to the $-galactosidase gene (lac Z) of E. coli, the whole lac Z
chain fusion is cloned into pBR322 ( a plasmid), bacteria with this plasmid synthesise $-
galactosidase with the insulin A chain at the carboxyl-terminal end, insulin A chain can be
separated from $-galactosidase by a simple chemical treatment, B chain is produced in an
identical manner, After purication of the two chains they are mixed, oxidized and then reduced
which allows the disulphide bridges to form and active insulin to be produced.

Human growth hormone
This is used to treat pituitary dwarsm, only the human form is active in humans,
this poses a problem in that there is only a limited supply of human pituitary tissue from
cadavers and this contains only a small amount of the growth hormone, human growth
hormone has been expressed in E. coli, the cDNA for human growth hormone, including its
signal peptide (that allows a protein to be secreted) have been fused to a powerful promoter
and cloned into pBR322. E. coli harbouring this plasmid produce large quantities of human
growth hormone, the hormone is secreted without the signal peptide and is fully active, it is
released from bacteria by a simple osmotic shock, the bacteria are removed by centrifugation,
leaving behind the almost pure growth hormone;
Further Readings

A list of books will be provided after each lesson indicating text books that provide materials
covered in the lecture.
- In Agriculture
Many plants species can be transformed,. at present, the major cereal crops, wheat, maize
and rice cannot be transformed;
crops such as soya, potato, rape and tobacco are easy to transform
the bacterium Agrobacterium tumefaciens naturally genetically engineers such
dicotyledonous plants. Agrobacterium tumefaciens has a large plasmid (Ti, or tumour-
inducing plasmid), that produces a tumorous growth, or callus, of undifferentiated plant
cells, these cells produce specialized compounds called opines, upon which the bacteria
feed, to achieve this transformation part of the Ti plasmid, the T-DNA, is transferred from
the bacteria to plant cells, where it integrates at random into a plant chromosome, the T-
DNA then directs the metabolism of the cell to differentiate and to produce opines, the
callus can be maintained in tissue culture free of bacteria and then made to differentiate
back into a normal plant, all of the cells in this plant will carry the T-DNA. Foreign genes
can be cloned into the T-DNA and then transformed into Agrobacterium tumefaciens.
The bacteria will then conveniently transform plant cells, taking in the foreign gene as
well as the T-DNA, many different genes have been introduced into plants by this method,
the aim of agricultural industry is to produce healthier plants which are resistant to
pesticides and selective herbicides, one particular protein that has enormous potential is the
(-endotoxin (B.t. toxin) produced by the bacterium Bacillus thuringensis, this toxin is
lethal to certain types of insect, but is harmless to all other animals and plants, the gene for
B.t toxin has been introduced into some plants using Agrobacterium tumefaciens, when the
gene is fused to a strong plant promoter, the cells in the plant produce the toxin,
transformed plants are completely resistant to insect attack, a similar strategy has been
adopted with a protein that inhibits the enzyme trypsin, the protein and its corresponding
gene have been isolated from the tropical legume cowpea;
The trypsin inhibitor (CpTI) has been shown to disrupt the digestion processes of
insect larvae, such that they starve to death, plants that express the CpTI gene are
therefore resistant to insect attack;
In Forensic science
DNA ngerprinting is used for identication and pedigree conrmation.
The genetic make up of every human being is different, therefore DNA extracted from
traces of blood or tissue can be characterized and the results obtained used to match up with the
DNA of victims or suspects in criminal cases, also the parentage of children may be established
beyond doubt by matching a child's ngerprint which those of its parents,minisatellite DNA are
found in abundance throughout the chromosomes of higher organisms, a large portion of the
DNA in such organisms does not carry genetic information but consists of simple (apparently)
nonsense sequences repeated many times, some repetitive DNA consists of tandem repeats of a
30 -40 bp sequences, not all repeats are identical, but within the 30 -40 bp there appears to be a
core sequence of 10-15bp that are highly conserved and found at most sites, the different
chromosomal locations (loci) at which the core DNA is found are numerous, they are also found
at the same locus on the two members of a pair of chromosomes, the two copies at the same
locus are not identical in size but are allelic to one another.
If the DNA carrying the allelic pair of repeats is cut with a restriction enzyme that does
not cut within the repeat, then two fragments of different size will be generated due to the
different number of repeats within the fragment, the same is true for all the other chromosomal
loci where repetitive DNA occurs, inheritance of the repetitive DNA is by Mendelian fashion,
only one chromosome is inherited from each parent by an individual, the other copy is inherited
from the other parent, if DNA is extracted from some easily available tissue (like white blood
cells) and then digested with a restriction enzyme like HinfI
many thousands of DNA fragments will be generated, most of which have nothing to do with the
repetitive DNA, all of these fragments are then separated from each other by electrophoresis on
an agarose gel, Southern blotting is used to detect specic DNA fragments from amongst many
hundreds of others, each individual has a different fragments that can be identied, the matching
of tissue sample to be individual can thus be made unambiguously with the help of a DNA
ngerprint, the parents of each individual can also be identied with certainty because half of the
fragments will be common with those of the father and half with those of the mother, and there
should be no unaccountable bands;
The chance of occurrence of band matching:
4 250 to 1
6 4,000 to 1
8 65,000 to 1
10 1 million to 1
12 17 million to 1
14 268 million to 1
16 4300 million to 1
18 68,000 million 1
20 1 million million to 1
4 250 to 1
6 4,000 to 1
8 65,000 to 1
10 1 million to 1
12 17 million to 1
14 268 million to 1
16 4300 million to 1
18 68,000 million 1
20 1 million million to 1
In Industry
There are many examples of proteins with industrial applications being produced from
recbonant micro-organisms. Thaumatin and chymosin both of which may be produced by
genetically engineered yeast cells.
Thaumatin- is a plant protein which on a weight for weight basis is 2,00 times sweeter than
Chymosin (Rennin) is used in cheese industry. Previously it was puried from stomachs of
calves. Chymosin can now be produced by genetic engineering means.