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LSM 1102

MENDELIAN GENETICS

We inherit 2 copies of genes


AO A or O BO B or O

Possibilities: AB, AO, BO, OO

Recommended Text Books


1. Principles of Genetics.
2nd edition, John Wiley

Snustad and Simmons (1999)

2. Principles of Genetics.
7th Edition. McGraw Hill

R. H. Tamarin (2002)

3. Analysis and Principles of Genetics.


Addison Wesley Longman

R. J. Brooker (1999)

4. An Introduction to Quantitative Genetics


4th Edition, Longman

Falconer & McKay (1996)

Mendels Laws, Sex Chromosomes

Terminology
Gene Controls a physical character of an individual Inherited from parents via gametes Allele Alternate forms of a gene
eg components of blood group such as A, B, O.

Locus Site of a specific gene or DNA sequence on a chromosome

Terminology
Genotype Individuals collection of genes The allele combinations in an individual that cause a particular trait or disorder.
For a diploid organism: eg blood group AA, AO, AB,etc

Phenotype Traits visible appearance


Eg Eye colour, height,

Physical expression of genotype (not visible)


- a particular protein form, blood group

Terminology
Homozygote Person having 2 identical alleles at a particular locus on homologous chromosomes
Eg blood groups AA, BB, OO

Heterozygote Person possessing different alleles at a particular locus on homologous chromosomes


Eg blood groups AO, BO, AB

Hemizygote Describes the genotype of males with an Xlinked trait, as males have only one X chromosome

Terminology
Dominant trait An allele that is expressed when present in even one copy
Eg blood group A, B

Recessive trait An allele whose expression is masked by another allele

Terminology
Chromosome A structure within a cell nucleus that carries genes. A chromosome consists of a contiuous molecule of DNA and proteins wrapped around it Autosome A non-sex-determining chromosome. Human has 22 pairs of autosomes Sex Chromosome A chromosome containing genes that specify sex. Human male XY, female XX

GREGOR MENDEL (1822-1884)


- Monk in Augustinian Abbey - Brno, Austro-Hungarian Empire (now Brno, Czech Republic) - Entered monastery to be free from the bitter struggle for existence - Attended and intrigued by results of plant crossbreeding in a course conducted by his Abbot - Left to study math & physics in Univ of Vienna - Returned 2 years later to conduct his own experiments with pea plants.

Experiments by Mendel
Experimental species Garden pea, Pisum sativum 1. Has well-defined characteristics 2. Pure-bred (homozygous) varieties were available 3. Flower hermaphroditic having male and female parts. 4. Self fertilization ordinarily. Cross-fertilization possible 5. Relatively short life cycle 6. Large number of offspring produced from each mating.
Favourite question: EXPLAIN why it was advantageous for Mendel to us the pea plant as an experimental model.

Fig 1. Traits of the Garden Pea.


Klug & Cummins, pg 45

A Monohybrid Cross
P F1 F2 Tall x Short

All tall (selfed) Tall


(787)

Short
(277)

3
P :Parental generation F1: First filial generation F2: Second filial generation

A Monohybrid Cross
(Behind the Scene)
P Tall TT x Short tt all t x
(selfed) Segregation Genes segregate in gamete-formation

P Gametes all T
Gametes fuse

F1

Tall Tt (T

Tall Tt t) tT : tt Short
(277)

t) TT Tt Tall

(T

Gametes fuse randomly

F2

(787)

Punnett Square
Male Gametes

T
Female Gametes

t Tt

TT

tT

tt

Conclusions from the Monohybrid Cross


Inheritance is not a process in which features of the 2 parents are blended together to produce an intermediate results
No medium height in F1

Although F1plants are tall, they must have received from their short parent a factor for shortness which remained hidden in F1 and does not reveal its presence in the outward appearance until F2.
No short plants in F1 but some appeared in F2

Factor for tallness is dominant over factor for shortness, which is recessive
Factor for shortness must have been swamped by factor for tallness

Mendels First Law


Law of Segregation The characteristics of an organism are controlled by genes occurring in pairs. Of a pair of such genes, only one can be carried in a single gamete

Table. Results of three Monohybrid Genetic Crosses carried out by Mendel (1)
Experiment 1
P1 yellow pods green pods F1 all yellow F2 428 yellow, 152 green (total 580) Ratio 2.82 : 1 (ratio obtained by dividing 428 and 152 by 580)

Experiment 2
P1 axial flowers terminal flowers F1 all axial F2 651 axial, 207 terminal (Ratio 3.13 : 1)

Experiment 3
P1 inflated pods constricted pods F1 all inflated F2 882 inflated, 299 constricted (Ratio 2.95 : 1)

Monohybrid Cross
PARTIAL DOMINANCE (Incomplete or semi-dominance) Every genotype has a distinguishable phenotype The heterozygote is intermediate between the two homozygotes
Example: In snapdragons (flower colour) P (cross) RR (Red)

rr (White)

F1 (selfing)

Rr (pink)

F2 phenotypic ratio

1/4 RR 1 (Red)

: 1/2 Rr : 2 (Pink)

: 1/4 rr : 1 (White)

Fig 4. PEDIGREE STUDIES IN HUMANS (albinism) Segregation of single-character differences


Gardner, Simmons & Snustad, pg 27

A Dihybrid Cross
P Tall Coloured Short White

F1 F2

All tall, coloured (selfed) Tall Tall Coloured White 9 : 3 : Short Short Coloured White 3 : 1

Punnett Square
Male Gametes

TC TC
Female Gametes
Tall, Colored

Tc
Tall, Colored

tC TtCC
Tall, Colored

tc TtCc
Tall, Colored

TTCC TTCc TTcC


Tall, Colored

Tc tC tc

TTcc
Tall, white

TtcC
Tall, Colored

Ttcc
Tall, white

tTCC
Tall, Colored

tTCc
Tall, Colored

ttCC
Short, Colored

ttCc
Short, Colored

tTcC
Tall, Colored

tTcc
Tall, white

ttcC
Short, Colored

ttcc
Short, White

Mendels Second Law


Law of Independent Assortment Each member of a pair of alleles may combine randomly with either of another pair

Complete Dominance (Testing Phenotypes)


G (yellow pod) : completely dominant g (green pod) : recessive Phenotype : Genotype : yellow GG, Gg green gg

1. Selfing or self-fertilization
Only possible for self-fertilizing plants and animals (a) homozygote (b) heterozygote GG GG Gg Gg

GG 100% yellow

GG : Gg : gg 3 yellow : 1 green

Complete Dominance (Testing Phenotypes)


2. Testcross Backcross of individual to recessive parent or testcross to homozygous recessive tester stock (a) homozygote GG gg (b) heterozygote Gg gg

Gg 100% yellow

Gg : gg 1 yellow : 1 green

Testcross
Tester stock is homozygous recessive for all gene loci Monohybrid: Aa aa tester stock Dihybrid: Aa Bb aa bb (homozygous recessive) Trihybrid: Aa Bb Cc aa bb cc

Relations among pairs of independent alleles, gametes, and F2 genotypes when dominance is present
Gardner, Simmons & Snustad, pg 33

No. of No. of kinds heterozygous of gametes pairs 2n 1 (Aa) 2 2 (AaBb) 4 3 8 (AaBbCc) 4 16 10 1024 n 2n

No. of F2 genotypes 3n 3 9 27 81 59,049 3n

No. of F2 phenotypes 2n 2 4 8 16 1024 2n

Trihybrid Cross 3 Gene Pairs, Complete Dominance


Garden pea 1. Seed shape : smooth (S) or wrinkled (s) 2. Seed colour : yellow (Y) or green (y) 3. Flower colour : red (A) or white (a)

smooth, yellow, red SS YY AA

wrinkled, green,white ss yy aa

F1

Ss Yy Aa

8 types of gametes SYA, SYa, SyA, sYA, Sya, sYa, syA, sya

Trihybrid Cross 3 Pairs, Complete Dominance


F2 phenotypic ratio
27/64 : 9/64 : 9/64 : 9/64 : 3/64 : 3/64 : 3/64 : 1/64 2 parentals 8 phenotypes 6 recombinants

Sex Chromosomes
In normal mating approximately equal number of male and female offspring are produced sex ratio = No. of male offspring = approx. 1 No of female offspring These results suggest the simplest hypothesis that sex is determined by a single pair of chromosomes called the sex chromosomes The other chromosomes are called autosomes Genes on the sex chromosomes are called sex-linked genes Genes on the autosomes are called autosomal genes

Mechanisms of Sex Determination (examples)


1. XX-XY mechanism a) In man The total number of chromosomes per cell is 23 pairs or 46 chromosomes. 44 are autosomes and 2 are sex chromosomes.
Female (homogametic) : XX + 44 autosomes Male (heterogametic) : XY + 44 autosomes

TDF (testis determining factor on the Y-chromosome). In humans the X-chromosome is larger than the Ychromosome In mammals, the Y-chromosome determines the sex and is required for maleness.

A
Fig 11. Photo of human chromosomes from a single nucleus at metaphase stage. Male karyotype 22 pairs of autosomes 1 pair of sex chromosmes

(A) Metaphase spread of normal male chromosomes showing Q-banding (B) Karyotype of normal human male, Q-banding

Mechanisms of Sex Determination


b) In Drosophila The total number of chromosomes is 4 pairs or 8chromosomes. One pair of sex chromosomes & 3 pairs of autosomes. Female: XX + 3 pairs of autosomes Male: XY + 3 pairs of autosomes The Y-chromosome is J-shaped. Unlike mammals, in Drosophila the Y chromosome does not determine sex. It determines the fertility of males.

Males are neither homozygotes or heterozygotes for genes on the sex chromosomes. They are hemizygous.

Mechanisms of Sex Determination


2. ZZ - ZW MECHANISM Birds, moths, some fishes
Female : ZW (heterogametic) Male : ZZ (homogametic)

3. XX - XO MECHANISM
Found in many insects eg. grasshopper and the bug, In grasshopper: Protenor

Female : XX + 22 autosomes (total 24 chr) Male: X + 22 autosomes (total 23 chr)

Mechanisms of Sex Determination


ENVIRONMENT AND SEX DETERMINATION
In some invertebrates, sex determination is non-genetic. Males and females have the same genotype but environmental factors cause development into one sex or the other. Example: Bonellia viridis, a marine worm
Fig 12. Gardner, Simmons & Snustad, page 77.

Question
A very traditional couple is filing for divorce, and the husband is blaming the wife for did not provide him with a son to carry on his heritage. The couple has 5 daughters. Explain why the husband should be blaming himself as well and not his wife.

The sex chromosome of the different sexes is XX = females; and XY = males. The daughters X chromosomes come from the mother and father, while the sons X chromosome only comes from the mother. The Y chromosome should come from the father. To be able to get a son, the contribution of the Y chromosome is necessary but this can only come from the father, not the mother.

Question
Other factors being equal, what are the chances of a newly wed having a baby girl or of having a baby boy for their first child? And Why. What are the chances of having a baby girl or of having a baby boy for their second child? And Why as well 50%:50%, because to have a girl, the chromosome of the child needs to be XX (one each from each parent) while to have a boy, the chromosome of the child needs to be XY (X from mother while Y from father). The chance of the Y chromosome segregating into the child from the father (who is XY as well) is 50% (i.e., the father either segregates an X or a Y chromosome). The chances of having a baby girl or boy remains 50%:50% for the second (or any consecutive child), for the same reason.

If the couple has 3 child. Chance of having all boys? x x = 1/8 or P = (n!/ x!y!)pxqy where n = total number of individual x = number of individuals in one class y = number of individuals in the other class p = probability of falling into the class with x individuals q = probability of falling into the class with y individuals P = (3!/3!0!)()3()0 = ()3 = 1/8

Sex Linkage
Genes on autosomes are called autosomal genes Genes on sex chromosomes are sex-linked genes In Drosophila and man, where the males are heterogametic, most sex-linked genes are located on the X-chromosome These genes are X-linked The Y chromosome is essentially devoid of genes Few animals carry some genes on the Y-chromosome that has visible effects Such Y-linked or holandric genes are transmitted from father to son and never appear in females

How do we test for sex linkage?


Reciprocal crosses
Gives identical results in the F1 and F2 generations for autosomal genes Gives different results in the F1 and F2 generations for sex-linked (X-linked) genes All of Mendels experiments involved only autosomal genes

Reciprocal crosses
Example: Reciprocal crosses between the whiteeye flies with red-eye flies, examine phenotypes of the F1 and F2 generations:
Female red-eye Male white-eye Female white-eye Male red-eye

Sex-linkage in Drosophila
Parent gen.
white-eye, w: red eye gene, w+

Cross between red-eye female with white-eye male.

F1 gen.

Brooker, Fig 3.5, pg 55.

F1 gen.

F2 gen.

Brooker, Fig 3.5, pg 55.

Sex-linkage in Drosophila

Parent gen.

white-eye, w: red eye, w+.

Cross between whiteeye female with redeye male.

F1 gen.

Brooker, Fig 3.6, pg 56

Sex-linkage in Drosophila

F1 gen.

white-eye,w: red eye, w+

Cross between white-eye female with red-eye male.

F2 gen.

Brooker, Fig 3.6, pg 56

Example: Sex Linkage in Humans


Red-green colour blindness is due to a recessive gene. The allele for normal vision is dominant C = normal vision; c = red-green colour blindness

Females:XC XC - dominant homozygote (normal vision) XC Xc - heterozygote, (carrier) normal vision Xc Xc - recessive homozygote (colour blindness) Males: XCY - normal vision XcY - red-green colour blindness

Sex Linkage in Humans


Expression of single sex-linked recessive genes in hemizygous males explain the higher incidence of sex-linked disorders in males than females. Example: Caucasian males - 8% colour blind Caucasian females - 1% colour blind Other sex-linked disorders are haemophila, G-6PD deficiency etc

Sex Linkage in Humans


Reciprocal matings: Colour blindness female male female male normal c.b. c.b. normal XC XC XcY Xc Xc XCY

XC Xc : XCY daughters sons normal normal (carrier)

XC Xc : daughters normal (carrier)

XcY sons c.b.

Shows criss-cross pattern of inheritance

Pedigree of haemophilia in Queen Victorias family

Brooker, Fig 3.13, pg 65

Pedigree of haemophilia in Queen Victorias family

How can you tell that it shows recessive sex-linked inheritance?

Brooker, Fig 3.13, pg 65

Sex Chromatin Body Barr body? (M. L. Barr)


Present in: 1. Nerve cells of female cats - the chromatin body is dark spot in the nucleus revealed by DNA staining Not present in nerve cells of male cats 2. Epithelial cells of buccal mucosa of females in humans. What is a sex chromatin body? Heterochromatic body (X-chromosome) found in The nuclei of normal female mammals. Absent in males. Use of the sex chromatin body to differentiate between Males and females in humans. Sex chromatin body = Barr body

Nucleus of cells of human epidermis illustrating the sex chromatin bodies or Barr bodies in females
Fig 19. Gardner, Simmons & Snustad, page 78.

Nuclei of cells with different number of Barr bodies. Hartl, pg 141


One X chromosome = female Turners Syndrome (no Barr body) Two X chromosomes = normal female (one Barr body) Three Xs chromosomes = Superfemale (2 Barr bodies) Four Xs chromosomes = Superfemale (3 Barr bodies)

(a)
57

(b)

(c)

(d)

Sex-Influenced Dominance
The dominance of alleles differs in the heterozygotes of the two sexes. Affected by sex hormones Example: in sheep b = hornless b+ = horned
GENOTYPES b+b+ b+b bb PHENOTYPE MALES FEMALES horned horned horned hornless hornless hornless

Question
Sometimes an animal, possibly even humans, has eyes of two different colors. Another example is the calico cat with fur that comes in patches of different colors (black and/or orange). Why isnt the fur of the calico uniform black or white or orange? What is a possible explanation for this trait.
The various colour patches (or eye colour) arose from cells early in development that expresses either a gene for one or the other colour. In the case of the calico cat, the trait for fur colour is carried on the X chromosome. In female mammals however, one of the X chromosome is inactivated, forming a condensed mass, called a Barr body. Thus, the nuclei of a normal XX female will have one barr body and the other the active X chromosome. Which X chromosome is activated or becomes a barr body is entirely random. Thus, in a calico cat (usually only in females), the X chromosome carries the gene for either black or orange in either one of the chromosome. The inactivation of one of these in a particular cell makes it produce the colour trait of the other active chromosome. This mosaic formation is a result of the early activation or deactivation of genes sitting on a particular chromosome.

Single-gene Disorders
Aka Mendelian disorders Mutation in single gene Well characterized genetic etiology Usually very rare Examples: Thalassaemia, Duchene Muscular Distrophy, haemophilia

Modes of Inheritance
Mendelian Autosomal dominant Autosomal recessive X-linked dominant Uniparental disomy X-linked recessive Y-linked Non-Mendelian Maternal Inheritance Complex inheritance (linkage)

Modes of Inheritance
Autosomal dominant The inheritance pattern of a dominant allele on an autosome. Phenotypes can affect both males and females Does not skip generations

Modes of Inheritance
Autosomal recessive The inheritance pattern of a recessive allele on an autosome. Phenotypes can affect both males and females Can skip generations

Modes of Inheritance
X-linked dominant Affects hemizygous males and heterozygous females Excess of affected females Eg Vit D resistant rickets In some conditions, the disorder is lethal in hemizygous males. In this case, fewer males in family, all healthy, excess of females, half affected XX Female XY Male

Modes of Inheritance
X-linked Dominant
Congenital Generalised Hypertrichosis (CGH) ape man

Modes of Inheritance
X-linked recessive Both males and females can be affected Manifest in the female only when recessive allele is in double dose (homozygous state) In male, mutant allele is always manifested since there is no normal allele to counteract the effect Transmitted by affected males and healthy female carriers Eg colour blindness, haemophilia A, B

Modes of Inheritance
Y-linked (Holandric Inheritance) Only males are affected Affected male transmits the trait to all his sons but to none of his daughters Eg hairy ears

Pedigree Symbols

/ Carrier

Question
Study the following pedigree. Deduce the method of inheritance and the genotype of the relevant individuals.

Question
Study the following pedigree. Deduce the method of inheritance and the genotype of the relevant individuals.

I II
1 2 3 4

III IV

Penetrance and Expressivity


Penetrance
The proportion of genotype that express a trait, even if mildly

Expressivity
Variation in severity/intensity in different individuals of a particular genotype.

Penetrance and Expressivity


Example of trait displaying both incomplete penetrance and expressivity:
Polydactyly (extra fingers,toes)
Dominant allele Some with the allele have normal number of fingers and toes Some with polydactyly have an extra digit on both hands and a foot, some have 2 extra digits on both hands and both feet, some may have only 1 extra digit on finger

Pleiotropy
A gene with multiple effects, different subsets of which may occur in different individuals
Example: sickle cell gene causes the syndrome called sickle cell anaemia The effects include: abnormal haemoglobin, sickleshaped red blood cells with tendency to clump and clog in small blood vessels. This result in heart, kidney, liver, spleen and brain damage.
Normal red blood cells

Normal red blood cells

Sickle-shaped red blood cells

Pleiotropic Effects
The sickle cell gene
Mutant Gene - Gut Abdominal pain - Spleen Splenic infarction - Extremities Limb pain Bone tenderness Rheumatism

Abnormal -polypeptide in HbS

Ischaemia viscosity & clumping Thrombosis Osteomyelitis Infarction of cells - Brain Cerebrovascular accident - Kidney Haematuria Low solubility Renal Failure of reduced HbS Sickling - Lung Pneumonia - Heart Heart failure Destruction Anaemia of sickle cells - Splenomegaly - Weakness - Lassitude - Abnormal skull radiographs