GENETICS: disposition to a bitch with a similar disposition and
The science of hereditary and variation expect the offspring to be pretty nasty too.
Genetics is a branch of biology concerned with the
study of genes, genetic variation, and heredity in
organisms. Though heredity had been observed for
millennia, Gregor Mendel, a scientist and
Augustinian friar working in the 19th century, was
the first to study genetics scientifically. The word
biology is derived from the greek words /bios/
meaning /life/ and /logos/ meaning /study/ and is
defined as the science of life and living
organisms. An organism is a living entity
consisting of one cell e.g. bacteria, or several cells
e.g. animals, plants and fungi.
Gregor Mendel was not appreciated until after his
death. He is now called the "Father of Genetics,"
but he was remembered as a gentle man who
loved flowers and kept extensive records of
weather and stars when he died.
What is Genetics?
● The Study of similarities and differences
between relatives.
● What is it that elephants have that no other
animal has?
Baby Elephants!
The emphasis here must be on the fact that
genetics studies similarities (as well as
differences) between relatives and not
differences between different species. The
answer to this question places the emphasis on the
similarities, of which there are many more than
there are differences.
Why do we resemble our parents?
❖ Our parents provided most of the
information (in the sex cells) that governs
our appearance, our activity, and our
behavior.
❖ Genetics is also seen as the study of Genes
or genetic variation.
Early Ideas About Inheritance:
Archeological evidence from
8,000 – 1,000 B.C. shows
horses, camels, and oxen had
been domesticated and that
various breeds of dogs had
derived from wolves, through
artificial selection.
It is pretty obvious that people were breeding
animals some 3,000 years ago and had managed,
through selection, to produce what are similar to
today’s oxen, camel, horse and dogs. This wasn’t
too sophisticated; but indicates that they had some
idea of inheritance. If you want a good guard dog,
you would probably mate a male with a nasty
Cultivation of many plants, including wheat, corn
and rice as well as the date palm began as early as
5,000 B.C. The appearance of new varieties from
unconscious attempts to breed and cultivate must
surely have led in time to conscious attempts to
propagate desirable traits and the elimination of
undesirable traits by the breeders.
Plant cultivation probably began as soon as man
stopped his nomadic existence and settled down in
one spot. Early people would have had to have
reliable sources of food planted such as these
listed here and the archeological record shows us
evidence that he was planting crops as far as 7,000
years ago. No doubt there was selection going on
here as well in that seed selection for the next crop
was probably part of the conventional wisdom of
these early farmers.
The Scope of Genetics
❖ Genetics is used for a study of the
mechanism of heredity and variation
❖ Provided tools for the study of the
fundamental biological processes examined
and taught in areas, like plant physiology,
biochemistry, biosystematics, ecology, plant
pathology, microbiology, etc.
➢ medicine, agriculture, forestry,
fisheries, law and religion.
❖ Genetics can be broadly classified in the
following three areas for the convenience of
a discussion on its scope and significance:
• transmission genetics involving study of
transmission of genetic material from one
generation to the other;
• molecular and biochemical genetics, involving
study of the structure and function
of genes
• population and biometrical genetics, involving
study of the behavior and effects of
genes in population, often using mathematical
models.
Application of Genetics
The following points highlight the top four
applications of genetics. The applications are:
1. Taxonomy - from Greek taxis, meaning
arrangement or division, and nomos, meaning law
-- is the science of naming, describing and
classifying organisms and includes all plants,
animals and microorganisms of the world; a branch
of science concerned with classification, especially
of organisms; systematics.
2. Agriculture - The contribution of genetics in the
field of agriculture is remarkable in two ways:
a) Improvement of Crop Plants: Various
principles and methods of genetics have been
applied for the development of plants useful to between them and repeated backcrossing
mankind. Controlled hybridization and artificial
selection have increased usefulness of many
plants. Such applications include improvement in:
✓ Crop,
✓ Quality
✓ Maturity duration
✓ Resistance to insects, diseases, salinity,
drought, frost, lodging, etc
✓ Adaptability.

b) Improvement of Domestic Animals:

✓ The usefulness of many domestic animals has
been increased due to selective breeding.
✓ Milk production in cows and buffaloes, meat
production in sheep’s, goats and pigs and egg
production capacity in poultry have been
significantly
✓ Moreover, many improved breeds of pet
animals like horse, dogs, cats, pigeon Mutagenesis - the genetic information of an
and rabbits have been developed all over the world. organism is changed, resulting in a mutation.

3. Medicine - The advancements made in the field

of genetics have been useful in the field of
Medicine in two main ways as given below:

a) Detection of Hereditary Diseases:

✓ Hereditary diseases can be detected at an
early stage of life -- possible to provide secondary
cures in some cases.
✓ Refined techniques such as amniocentesis
(fetus test) and fetoscopy have made such cures
possible.
✓ Moreover, genetic diseases can be prevented
by advising future parents with the help of family
pedigrees.
Mutagenesis is the process by which mutations
are induced in the cells of organisms. Mutations
can have beneficial effects, deleterious effects, or
no consequences in organisms. Certain mutations
have a positive effect on the organism.
Why are genetics and genomics important to our
health? WHO definitions of genetics and
genomics?
➢ Genetics is the study of heredity
➢ Genomics is defined as the study of genes
and their functions, and related techniques.

b) Production of Antibiotics: The main difference between genomics and

✓ Special genetic strains of fungi and bacteria genetics is that genetics scrutinizes the functioning
have been isolated to greatly increase and composition of the single gene whereas
the yields of antibiotics and other drugs genomics addresses all genes and their
interrelationships in order to identify their combined
4. Evolution - Both natural and artificial selections influence on the growth and development of the
have been responsible for evolution of various crop organism.
plants. However, selection is effective when
sufficient amount of variability exists in the
population in which selection has to be practiced.
Three genetic methods:
❑Polyploidy
❑Introgression
❑Mutagenesis

Introgression - the
transfer of genetic
information from one
species to another as a
result of hybridization
What are some of the new genetic and genomic
techniques and technologies?
❑ Pharmacogenetics and Pharmacogenomics
describing the intersection of pharmacology (the
study of drugs, or pharmaceuticals) and genetic
variability in determining an individual's response to
particular drugs
❑ Stem Cell Therapy also known as
regenerative medicine, promotes the repair
response of diseased, dysfunctional or injured
tissue using stem cells or their derivatives
❑ Cloning the process of producing individuals
with identical or virtually identical DNA, either
naturally or artificially.
_________________________________________
LESSON 2:
THE CHROMOSOME THEORY OF INHERITANCE
Discovery of Cells Common Parts of Cells
• The first time the word cell was used to refer to
these tiny units of life was in 1665 by a British
scientist named Robert Hooke. Hooke was one of
the earliest scientists to study living things under a
microscope. The microscopes of his day were not
very strong, but Hooke was still able to make an
important discovery.
• Soon after Robert Hooke discovered cells in cork,
Anton van Leeuwenhoek in Holland made other
important discoveries using a microscope.
Leeuwenhoek made his own microscope lenses,
and he was so good at it that his microscope was
more powerful than other microscopes of his day. In
fact, Leeuwenhoek’s microscope was almost as
strong as modern light microscopes.
Cell Structure
A. Organelles
• Specialized structures within cells
• Transient residents of the cell
B. Cytoplasm
• The living matter of the cell
Functions of the Cell
• Basic unit of life • Protection and support
• Movement • Communication
• Cell metabolism and energy release • Inheritance
Cell Membrane
• Also called Plasma Membrane.
• The outermost component of the cell.
• It is a Selective Permeable Membrane.
Components:
1. Two layers of Phospholipids
2. Proteins
3. Cholesterol, Carbohydrates, Water, and ions
• While lipids help to give membranes their
flexibility, proteins monitor and maintain the cell's
chemical climate and assist in the transfer of
molecules across the membrane
Its function is to protect the integrity of the
interior of the cell by allowing certain substances
into the cell while keeping other substances out. It
also serves as a base of attachment for the
cytoskeleton in some organisms and the cell wall in
others
Another function of the membrane is to regulate
cell growth through the balance of endocytosis
and ​exocytosis. In endocytosis, lipids and proteins
are removed from the cell membrane as
substances are internalized. In exocytosis, vesicles
containing lipids and proteins fuse with the cell
membrane increasing cell size.
Who figured out that genes are on
chromosomes?
• Walter Sutton and Theodor Boveri generally get
credit for this insight.
• Sutton, an American, studied chromosomes and
meiosis in grasshoppers.
• Boveri, a German, studied the same things in sea
urchins.
• In 1902 and 1903, Sutton and Boveri published
independent papers proposing what we now call
the chromosome theory of inheritance
 Observations that support the chromosome
Theory of inheritance include:
A. Chromosomes, like Mendel's genes, come in
matched (homologous) pairs in an organism. For
both genes and chromosomes, one member of the
pair comes from the mother and one from the father
B. The members of a homologous pair separate in
meiosis, so each sperm or egg receives just one
member. This process mirrors segregation of
alleles into gametes in Mendel's law of segregation.
C. The members of different chromosome pairs are
sorted into gametes independently of one another
in meiosis, just like the alleles of different genes in
Mendel's law of independent assortment.
What is the difference between allele and gene?
• A gene is a stretch of DNA or RNA that
determines a certain trait. Genes mutate and can
take two or more alternative forms; an allele is one
of these forms of a gene. For example, the gene for
eye color has several variations (alleles) such as an
allele for blue eye color or an allele for brown eyes.
THE CELL CYCLE & MITOSIS
• Actively dividing eukaryote cells pass through a
series of stages known collectively as the cell cycle:
two gap phases (G1 and G2); an S (for synthesis)
phase, in which the genetic material is duplicated;
and an M phase, in which mitosis partitions the
genetic material and the cell divides.
The Cell Cycle & Mitosis
• G1 phase. Metabolic changes prepare the cell for
division. At a certain point - the restriction point -
the cell is committed to division and moves into the
S phase.
• S phase. DNA synthesis replicates the genetic
material. Each chromosome now consists of two
sister chromatids.
• G2 phase. Metabolic changes assemble the
cytoplasmic materials necessary for mitosis and
cytokinesis.
• M phase. A nuclear division (mitosis) followed by
a cell division (cytokinesis). The period between
mitotic divisions - that is, G1, S and G2- is known
as interphase.
• MITOSIS is a process of nuclear division in
eukaryotic cells that occurs when a parent cell
divides to produce two identical daughter cells.
• During cell division, mitosis refers specifically to
the separation of the duplicated genetic material
carried in the nucleus.
• Mitosis is conventionally divided into stages
known as: Prophase, Metaphase, Anaphase, &
Telophase
While mitosis is taking place, there is no cell growth
and all of the cellular energy is focused on cell
division.
➢ Prophase
• During prophase, the replicated pairs of
chromosomes condense and compact
themselves.
• The pairs of chromosomes that have been
replicated are called sister chromatids, and they
remain joined at a central point called the
centromere.
• A large structure called the mitotic spindle also
forms from long proteins called microtubules on
each side, or pole, of the cell.
➢ Metaphase
• Spindle fibers align the chromosomes along the
middle of the cell nucleus. This line is referred to as
the metaphase plate. This organization helps to
ensure that in the next phase, when the
chromosomes are separated, each new nucleus
will receive one copy of each chromosome.
➢ Anaphase
• The paired chromosomes separate at the
kinetochores and move to opposite sides of the
cell. Motion results from a combination of
kinetochore movement along the spindle
microtubules and through the physical interaction of
polar microtubules.
➢ Telophase
• Chromatids arrive at opposite poles of cell, and
new membranes form around the daughter nuclei.
The chromosomes disperse and are no longer
visible under the light microscope. The spindle
fibers disperse, and cytokinesis or the partitioning
of the cell may also begin during this stage
➢ Cytokinesis
• cytokinesis results when a fiber ring composed of
a protein called actin around the center of the cell
contracts pinching the cell into two daughter cells,
each with one nucleus. In plant cells, the rigid wall
requires that a cell plate be synthesized between
the two daughter cells.
Phases of Meiosis
• It still needs to separate sister chromatids (the two
halves of a duplicated chromosome), as in mitosis.
But it must also separate homologous
chromosomes, the similar but nonidentical
chromosome pairs an organism receives from its
two parents.
➢ Meiosis I
• Before entering meiosis I, a cell must first go
through interphase. As in mitosis, the cell grows
during G_11start subscript, 1, end subscript phase,
copies all of its chromosomes during S phase, and
prepares for division during G_22start subscript, 2,
end subscript phase.
➢ Meiosis I
Prophase I
differences from mitosis begin to appear. As in
mitosis, the chromosomes begin to condense, but
in meiosis I, they also pair up. Each chromosome
carefully aligns with its homologue partner so that
the two match up at corresponding positions along
their full length.
➢ Meiosis I
Prophase I
the letters A, B, and C represent genes found at
particular spots on the chromosome, with capital
and lowercase letters for different forms, or alleles,
of each gene

The DNA is broken at the same spot on each

homologue—here, between genes B and C—and
reconnected in a criss-cross pattern so that the
Meiosis homologues exchange part of their DNA.

• MEIOSIS is used for just one purpose in the This process, in which homologous chromosomes
human body: the production of gametes—sex cells, trade parts, is called crossing over.
or sperm and eggs.
Its goal is to make daughter cells with exactly half After crossing over, the
as many chromosomes as the starting cell. spindle begins to
capture chromosomes
Phases of Meiosis and move them towards
the center of the cell
• In many ways, meiosis is a lot like mitosis. (metaphase plate). This
• The cell goes through similar stages and uses may seem familiar from
similar strategies to organize and separate mitosis, but there is a
chromosomes. twist.

Meiosis I
• In anaphase I, the homologues are pulled apart
and move apart to opposite ends of the cell. The
sister chromatids of each chromosome, however,
remain attached to one another and don't come
apart.
• Finally, in telophase I, the chromosomes arrive at
opposite poles of the cell. In some organisms, the
nuclear membrane re-forms and the chromosomes
decondense
Meiosis II
• The cells that enter meiosis II are the ones made
in meiosis I. These cells are haploid—have just one
chromosome from each homologue pair—but their
chromosomes still consist of two sister chromatids.
• In meiosis II, the sister chromatids separate,
making haploid cells with non-duplicated
chromosomes
Meiosis II
• During prophase II, chromosomes condense and
the nuclear envelope breaks down, if needed. The
centrosomes move apart, the spindle forms
between them, and the spindle microtubules
begin to capture chromosomes.
• In telophase II, nuclear membranes form around
each set of chromosomes, and the chromosomes
decondense.
Cytokinesis splits the chromosome sets into new
cells, forming the final products of meiosis: four
haploid cells in which each chromosome has just
one chromatid. In humans, the products of meiosis
are sperm or egg cells.
LESSON 3:
VARIATION IN CHROMOSOME NUMBER
The number of chromosomes in each cell of an
organism is generally fixed and ranges from one in
bacteria to hundreds in some plants and animals.
Most organisms are diploids (2n) since their
somatic cells have a chromosome complement
consisting of two homologous sets. A few species,
however, naturally have only one set of
chromosomes, and they are called haploid or
monoploid (1n). Gametes generated in diploid
organisms by meiosis and gametogenesis also
contain the haploid number of chromosomes. Any
organism with complete sets of chromosomes that
exceed two is a polyploid. The condition of
polyploidy has been established surprisingly often
among organisms, especially in plants. Aneuploidy,
on the other hand, refers to cells or individuals that
have one, two, or a few chromosomes either
absent or in excess of the basic number for that
species; that is, a lesser or higher number exist
than found in complete sets. These differences are
chromosome anomalies, and they can occur in a
variety of ways. In addition, one or more individual
chromosomes can be structurally altered into a
variety of rearrangements. Such changes are called
chromosome aberrations. Deviations from haploidy
in sex cells, diploidy in somatic cells, and normal
chromosome structure are not rare.
Variation in Chromosome Number
Changes in chromosome number can occur by the
addition of all or part of a chromosome
(aneuploidy), the loss of an entire set of
chromosomes (monoploidy) or the gain of one or
more complete sets of chromosomes (euploidy).
Each of these conditions is a variation on the
normal diploid number of chromosomes. As you
would expect each of these can have drastic effects
on phenotypic expression.
• Aneuploidy - the abnormal condition were one or
more chromosomes of a normal set of
chromosomes are missing or present in more than
their usual number of copies (46 is N)
• Monoploidy - the loss of an entire set of
chromosomes (The term monoploid refers to a cell
or an organism that has a single set of
chromosomes)
• Euploidy - an entire set of chromosomes is
duplicated once or several times.
ANEUPLOIDY is the presence of an abnormal
numbers of chromosomes in a cell, for example a
human cell having 45 or 47 chromosomes instead
of the usual 46. It does not include a difference of
one or more complete sets of chromosomes. A cell
with any number of complete chromosome sets is
called a euploid cell.
(ploidy: the number of sets of chromosomes in a
cell, or in the cells of an organism)
(diploid: (of a cell or nucleus) containing two
complete sets of chromosomes, one from each
parent)
The different conditions of aneuploidy are:
• Nullisomy - the loss of both pairs of homologous
chromosomes; individuals are called nullisomics
and their chromosomal composition is 2N-2
• Monosomy - the loss of a single chromosome;
individuals are called monosomics and their
chromosomal composition is 2N-1
• Trisomy - the gain of an extra copy of a
chromosome; individuals are called trisomics and
their chromosomal composition is 2N+1
• Tetrasomic - the gain of an extra pair of
homologous chromosomes; individuals are called
tetrasomics and their chromosomal composition is
2N+2
Chromosome Constitutions in a Normally Diploid
Organism with Three Chromosomes (Labeled A, B,
and C) in the Basic Set
Monosomy
Monosomy is when a diploid organism has only one
copy of one of its chromosomes instead of two.
This is an example of aneuploidy, or having an
abnormal number of chromosomes. A human with
a monosomy would only have 45 chromosomes
instead of 46.
Human monosomy
A. TURNER SYNDROME, a condition that affects
only females, results when one of the X
chromosomes (sex chromosomes) is missing or
partially missing. Turner syndrome can cause a
variety of medical and developmental problems,
including short height, failure of the ovaries to
develop and heart defects.
• Turner syndrome – People with Turner
syndrome typically have one X chromosome
instead
of the usual two sex chromosomes (45 XO).
• The only full monosomy that is seen in
humans—all other cases of full monosomy are
lethal
and the individual will not survive development.
• Turner syndrome is a chromosomal condition
that affects development in females.
What are common treatments for Turner
syndrome?
• Human growth hormone. If given in early
childhood, hormone injections can often increase
adult height by a few inches.
• Estrogen replacement therapy (ERT) can help
start the secondary sexual development that
normally begins at puberty (around age 12).
Turner syndrome cannot be prevented. It is a
genetic problem that is caused by a random error
that leads to a missing X chromosome in the sperm
or egg of a parent. However, there are many
options for treatment.
Psychological tests
Wide Range Achievement Test and the Slosson
Intelligence Test
a) Wide Range Achievement Test (WRAT) is an
achievement test which measures an individual's
ability to read words, comprehend sentences, spell,
and compute solutions to math problems
• The test is appropriate for individuals ages
5–94 years. The WRAT4 provides two equivalent
forms (Blue and Green), which enables retesting
within short periods of time without potential
practice effects that occur from repeating the same
items.
The test was developed in 1941 by psychologists
Sidney W. Bijou and Joseph Jastak.
a) Slosson Intelligence Test provides a quick,
reliable screening measure of cognition for children
and adults, has large, color stimulus items for the
visually impaired, and is administered and scored
simultaneously.
B. CRI DU CHAT SYNDROME (5p minus)
chromosomal condition- a piece of chromosome 5
is missing
Nullisomy
Nullisomy is a genome mutation where a pair of
homologous chromosomes that would normally be
present is missing. Thus, in nullisomy, two
chromosomes are missing, and the chromosomal
composition is represented by 2N-2
“nondisjunction”
• Nullisomy is caused by a nondisjunction during
cell division, particularly meiosis.
• (In mitosis) The failure of sister chromatids to
separate during and after mitosis.
• (In meiosis) The failure of homologous
chromosomes to segregate or to separate during
and after meiosis.
Nondisjunction occurs when the homologous
chromosomes (or sister chromatids) failed to
separate.
• The two of the gametes to have no chromosomal
material, leaving the other two gametes to have
double the amount of chromosomal material
(disomic).
• Due to the lack of genetic information, the
nullisomic gametes are rendered unviable for
fertilization
The number of chromosomes in each cell of an
organism is generally fixed and ranges from one in
bacteria to hundreds in some plants and animals.
Most organisms are diploids (2n) since their
somatic cells have a chromosome complement
consisting of two homologous sets. A few species,
however, naturally have only one set of
chromosomes, and they are called haploid or
monoploid (1n). Gametes generated in diploid
organisms by meiosis and gametogenesis also
contain the haploid number of chromosomes. Any
organism with complete sets of chromosomes that
exceed two is a polyploid. The condition of
polyploidy has been established surprisingly often
among organisms, especially in plants. Aneuploidy,
on the other hand, refers to cells or individuals that
have one, two, or a few chromosomes either
absent or in excess of the basic number for that
species; that is, a lesser or higher number exist
than found in complete sets. These differences are
chromosome anomalies, and they can occur in a
variety of ways. In addition, one or more individual
chromosomes can be structurally altered into a
variety of rearrangements. Such changes are called
chromosome aberrations. Deviations from haploidy
in sex cells, diploidy in somatic cells, and normal
chromosome structure are not rare.
Trisomy
A trisomy is a chromosomal condition characterized
by an additional chromosome. A person with a
trisomy has 47 chromosomes instead of 46. Down
syndrome, Edward syndrome and Patau syndrome
are the most common forms of trisomy.
• A type of aneuploidy characterized by the gain
of an extra copy of a chromosome, and is
designated as 2N+1
• A trisomy is a type of polysomy in which there
are three instances of a particular chromosome,
instead of the normal two.
• A trisomy is a type of aneuploidy (an abnormal
number of chromosomes).
The most common types of autosomal trisomy that
survive to birth in humans are:
• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
 • Trisomy 13 (Patau syndrome)
• Trisomy 9
• Trisomy 8 (Warkany syndrome 2)
Trisomy of sex chromosomes can also occur and
include:
• XXX (Triple X syndrome)
• XXY (Klinefelter syndrome)
• XYY
Trisomy 21 (Down syndrome)
• is a genetic disorder caused by the presence of all
or part of a third copy of chromosome 21
• It is usually associated with physical growth
delays, mild to moderate intellectual disability, and
characteristic facial features.
• The average IQ of a young adult with Down
syndrome is 50, equivalent to the mental ability of
an 8-or 9-year-old child, but this can vary widely
What are the treatments for Down syndrome?
Your physician will help you develop an appropriate
care team for a patient with Down syndrome. The
care team may include:
• Primary care physician to monitor growth,
development, medical concerns and provide
vaccinations
• Medical subspecialists depending on the needs
of the patient (for example, cardiologist,
endocrinologist, geneticist, hearing and eye
specialists)
• Speech therapy to improve the ability to
communicate
• Physical therapy to help strengthen muscles
and improve motor skills
• Occupational therapy to help refine motor skills
and make daily tasks easier
• Behavioral therapy to help manage the
emotional challenges that may accompany Down
syndrome
Tetrasomy
• Is a form of aneuploidy with the presence of four
copies, instead of the normal two, of a particular
chromosome.
• Occurs due to non-disjunction (Table 1.1) when
the cells are dividing (meiosis I or II) to form egg
and sperm cells (gametogenesis). This can result in
extra chromosomes in a sperm or egg cell. After
fertilization, the resulting fetus has 48
chromosomes instead of the typical 46.
The centromere divides each chromosome into two
regions: the smaller one, which is the p region, and
the bigger one, the q region. The p region is
represented in the shorter arm of the chromosome
(p is for petit, French for small) while the q region is
in the larger arm (chosen as next letter in alphabet
after p).
Autosomal tetrasomies
• Cat eye syndrome where partial tetrasomy of
chromosome 22 is present - The name “cat eye
syndrome” is derived from a distinctive eye
(ocular) abnormality that is present in a little over
half affected individuals. This defect, known as a
coloboma, usually appears as a cleft or gap in the
iris below the pupil, and the elongated pupil
therefore resembles the appearance of a cat's eye.
• Klinefelter syndrome - is the set of symptoms
that result from two or more X chromosomes in
males. The primary features are infertility and small
testicles.Klinefelter syndrome is a genetic condition
in which a boy is born with an extra X chromosome.
Instead of the typical XY chromosomes in men,
they have XXY, so this condition is sometimes
called XXY syndrome. Men with Klinefelter usually
don't know they have it until they run into problems
trying to have a child.

• Pallister-Killian syndrome (tetrasomy 12p) - A

child with Pallister-Killian syndrome has 47
chromosomes. This extra chromosome is made up
of two copies of the short arm (p arm) of
chromosome 12 in some cells of the body. In these
cells, there are four copies of this 12p arm of Euploidy
chromosome 12, instead of the usual two copies. • is a condition when a cell or an organism has one
or more than one complete set of chromosomes.
For example, when a human cell has an extra set
of 23 chromosomes, then it is called euploid.

• Euploidy is a chromosomal variation that involves

the entire set of chromosomes in a cell or an
organism and is more tolerated in plants than in
animals

• Tetrasomy 9p - Tetrasomy 9p (also known

tetrasomy 9p syndrome) is a rare chromosomal
disorder characterized by the presence of two extra
copies of the short arm of chromosome 9 (called
the parm), in addition to the usual two.

• Tetrasomy 18p - Tetrasomy 18p is a

chromosomal condition that affects many parts of
the body.
This condition usually causes feeding difficulties in
infancy, delayed development, intellectual disability
that is often mild to moderate but can be severe,
changes in muscle tone, distinctive facial features,
and other birth defects.

Sex-chromosome tetrasomies
• 48, XXXX syndrome - Tetrasomy X (also called
XXXX syndrome, quadruple X, or 48,XXXX) is an
extremely rare chromosomal disorder caused by • Euploidy is a chromosomal variation that involves
the presence of four X chromosomes instead of two the entire set of chromosomes in a cell or an
X chromosomes organism and is more tolerated in plants than in
animals.
• Tetrasomy X is a chromosome disorder that only
affects females and is caused by having four copies • There may be a single set (monoploidy), two sets
of the X chromosome instead of two. Females with (diploidy), or multiple sets (polyploidy, i.e. triploid,
tetrasomy X have a total of 48 chromosomes in tetraploid, pentaploid, hexaploid, etc.) of
their cells, so this condition is sometimes written as chromosomes.
48, XXXX

Sex-chromosome tetrasomies
• 48, XXYY syndrome - anomaly in which males
have an extra X and Y chromosome.
Structural Variations in Chromosomes
There are two primary ways in which the structure
of chromosomes can be altered:
1. The total amount of genetic information in the
chromosome can change chromosome can change
• Decrease: Deficiencies/Deletions
• Increase: Duplications & Insertions
2. The genetic material may remain the same, but
is rearranged
• Inversions
• Translocations
Structural Variations in Chromosomes
1. Deletion – loss of a chromosomal segment a
small portion of a chromosome resulting in loss of
one or more genes
• Cri-du-chat (“cry of the cat”) syndrome,
resulting from deletion of part of the short arm of
chromosome 5
The breakage may be caused by various agents
such as:
❖ Radiation
❖ Chemicals
❖ Drugs
❖ viruses at any time during the cell cycle
2. Duplication – involves attachment of a
chromosomal fragment resulting in addition of one
or more genes to a chromosome. Whenever there
is duplication in a chromosome, there is a
corresponding deletion in another chromosome.
Following types of duplications are known
Structural Variations in Chromosomes
Inversion – A change in the direction of genetic
material along a single chromosome
• Result when there are two breaks in a
chromosome and the detached segment becomes
reinserted in the reversed order.
• They are classified into two types depending
upon the inclusion or absence of the centromere
within the inverted segment.
• Thus when both breaks occur in one arm of the
chromosome it leads to a paracentric inversion;
when a break occurs in each of the two arms, the
centromere is included in the detached segment
and leads to a pericentric inversion.
Translocation – A segment of a chromosome
becomes detached and unites with another
non-homologous
chromosome.
a. Simple Translocation:
A single break occurs in a chromosome, and the
broken fragment becomes attached to the end of
another chromosome.
b. Shifts:
In this type three breaks are involved. Two breaks
occur in a chromosome to produce an interstitial
fragment. This fragment becomes inserted into one
of the arms of another non-homologous
chromosome in which a single break has produced
two “sticky” ends.
c. Reciprocal Translocations:
The most frequent and extensively studied
translocations. A single break occurs in each of the
two non-homologous chromosomes followed by a
mutual exchange of the broken fragments. This
results in two new chromosomes each having one
segment of the other chromosome.
GENE MUTATION
➢ A gene mutation is a permanent alteration in the
DNA sequence that makes up a gene, such that the
sequence differs from what is found in most people.
➢ Mutations range in size; they can affect
anywhere from a single DNA building block (base
pair) to a large segment of a chromosome that
includes multiple genes.
Gene mutations can be classified in two major
ways:
Hereditary mutations are inherited from a parent
and are present throughout a person’s life in
virtually every cell in the body.
✓ are also called germline mutations because they
are present in the parent’s egg or sperm cells,
which are also called germ cells.
✓ If this DNA has a mutation, the child that grows
from the fertilized egg will have the mutation in
each of his or her cells.
Acquired (or somatic) mutations occur at some
time during a person’s life and are present only in
certain cells, not in every cell in the body.
✓ Changes can be caused by environmental
factors such as ultraviolet radiation from the sun, or
can occur if an error is made as DNA copies itself
during cell division.
✓ Acquired mutations in somatic cells (cells other
than sperm and egg cells) cannot be passed to the
next generation.
Mutations and Disease
Few mutations are bad for you. In fact, some
mutations can be beneficial. Over time, genetic
mutations create genetic diversity, which keeps
populations healthy. Many mutations have no effect
at all. These are called silent mutations.
But the mutations we hear about most often are the
ones that cause disease. Some well-known
inherited genetic disorders include cystic fibrosis,
sickle cell anemia, Tay-Sachs disease,
phenylketonuria and color-blindness, among many
others. All of these disorders are caused by the
mutation of a single gene.
Cystic fibrosis is an inherited disease characterized
by the buildup of thick, sticky mucus that can
damage many of the body's organs. The disorder's
most common signs and symptoms include
progressive damage to the respiratory system and
chronic digestive system problems.
Mutations and Disease
A genetic blood disorder caused by the presence of
an abnormal form of hemoglobin which causes low
oxygen level. When the sickle cells block small
blood vessels, the organs are deprived of blood
and oxygen.
Tay–Sachs disease is a genetic disorder that
results in the destruction of nerve cells in the brain
and spinal cord. The most common type, known as
infantile. It becomes apparent around three to six
months of age with the baby losing the ability to
turn over, sit, or crawl.
Phenylketonuria (PKU) is an inborn error of
metabolism that results in decreased metabolism of
the amino acid phenylalanine. Untreated, PKU can
lead to intellectual disability, seizures, behavioral
problems, and mental disorders. It may also result
in a musty smell and lighter skin.
Color blindness, also known as color vision
deficiency, is the decreased ability to see color or
differences in color
Males are more likely to be color blind than
females, as the genes responsible for the most
common forms of color blindness are on the X
chromosome. As females have two X
chromosomes, a defect in one is typically
compensated for by the other, therefore females
can be carriers
What number do you see? Example of an Ishihara
color test plate.
Mutagenic Agents
• In genetics, a mutagen is a physical or chemical
agent that changes the genetic material, usually
DNA, of an organism and thus increases the
frequency of mutations above the natural
background level.
• DNA changes caused by mutagens may harm
cells and cause certain diseases, such as cancer
Physical mutagens:
• Physical mutagens are X-rays and UV light.
• X-rays, gamma rays, cosmic rays are ionizing
radiation which ionizes water of the cell to release
hydroxyl free radical (OH). The hydroxyl radical is a
powerful oxidizing agent. Higher dose of X-rays can
even causes death of an organism.
• UV light is a non-ionizing radiation. It causes the
formation of thymine dimer (Pyrimedine dimer). If
two thymine occur together in one strand of DNA,
UV light causes fusion to form thymine dimer. At
the site of thymine dimer confirmation of DNA is
changed, so rate of error during DNA replication is
high.
Chemical mutagens:
Three types of chemical mutagens are found.
➢ Intercalating agent: The chemical intercalate or
slip in between two base pair in Double stranded
DNA helix and hence alter the morphology of DNA
at that position. Chances of error during replication
are higher at this position causing mutation.
Examples: Acridine orange, ethidium bromide,
proflavin
➢ Base analogue: These chemical are
morphologically similar to that of normal nitrogen
bases. So during replication these molecules are
incorporated instead of normal nitrogen bases and
hence cause mutation.
Example: 2-aminopurine is analogue to Adenine,
5-bromourcail is analogue to thymine
Base analogs are molecules which have a very
similar structure to one of the four nitrogenous
bases which are used in DNA (adenine, guanine,
cytosine or thymine). They form a structure similar
to one of the DNA nucleotides and then can be
used to form the new strand in semi conservative
replication.
➢ Reacting chemicals: These chemical mutagens
react directly with the nitrogenous bases of DNA
and chemically modify the DNA causing mutation.
Example: Nitrous acid reacts with nitrogenous
bases and remove amino group from purine and
pyriminine.
Biological mutagens:
• Transposons and insertion sequence (IS)
elements are biological mutagens.
Examples: mutator gene, bacteriophage etc.
• Transposons and IS elements are small sequence
of DNA that moves from one site to another along
DNA strand and causes mutation. Also known as
jumping gene, it contains gene which codes the
enzyme transposase which helps in transposition of
these sequence from one site to other.
• Transposon - a chromosomal segment that can
undergo transposition, especially a segment of
bacterial DNA that can be translocated as a whole
Human Pedigree
✓ Pedigrees are used to analyze the pattern of
inheritance of a particular trait throughout a family.
Pedigrees show the presence or absence of a trait
as it relates to the relationship among parents,
offspring, and siblings.
✓ A pedigree chart is a diagram that shows the
occurrence and appearance of phenotypes of a
particular gene or organism and its ancestors from
one generation to the next, most commonly
humans, show dogs, and race horses.
✓ A pedigree chart was used to track the
presence or absence of a given trait (phenotype)
through two or more generations of a family.
✓ Pedigree analysis is also useful when studying
species with a long generation time.
Common mistakes and misconceptions
The presence of many affected individuals in a
family does not always mean that the trait is
dominant. The terms dominant and recessive refer
to the way that a trait is expressed, not by how
often it shows up in a family. In fact, although it is
uncommon, a trait may be recessive but still show
up in all generations of a pedigree.
You may not always be able to determine the
genotype of an individual based on a pedigree.
Sometimes an individual can either be homozygous
dominant or heterozygous for a trait. Often, we can
use the relationships between an individual and
their parents, siblings, and offspring to determine
genotypes. However, not all carriers are always
explicitly indicated in a pedigree, and it may not be
possible to determine based on the information
provided.
Reading a pedigree
Pedigrees represent family members and
relationships using standardized symbols.
By analyzing a pedigree, we can determine
genotypes, identify phenotypes, and predict how a
trait will be passed on in the future. The information
from a pedigree makes it possible to determine how
certain alleles are inherited: whether they are
dominant, recessive, autosomal, or sex-linked.
To start reading a pedigree:
1. Determine whether the trait is dominant or
recessive. If the trait is dominant, one of the
parents must have the trait. Dominant traits will not
skip a generation. If the trait is recessive, neither
parent is required to have the trait since they can
be heterozygous.
2. Determine if the chart shows an autosomal or
sex-linked (usually X-linked) trait. For example, in
X-linked recessive traits, males are much more
commonly affected than females. In autosomal
traits, both males and females are equally likely to
be affected (usually in equal proportions).
Example: Autosomal dominant trait
The diagram shows the inheritance of freckles in a
family. The allele for freckles (F) is dominant to the
allele for no freckles (f).
At the top of the pedigree is a grandmother
(individual I-2) who has freckles. Two of her three
children have the trait (individuals II-3 and II-5) and
three of her grandchildren have the trait (individuals
III-3, III-4, and III-5).
Since freckles are dominant to no freckles,
an affected individual such as I-2 must at least
have one F allele.
The trait shows up in all generations and
affects both males and females equally. This
suggests that it is an autosomal dominant trait.
Unaffected individuals must have two
recessive alleles (ff) in order to not have freckles. If
we notice, I-2 has some children who do not have
freckles. In order to produce children with a
genotype of ff, I-2 must be able to donate a f allele.
We can therefore conclude that her
genotype is Ff.
Example: X-linked recessive trait
Pedigree showing the
inheritance of color blindness
across four generations.
The diagram shows the inheritance of color
blindness in a family. Colorblindness is a recessive
and X-linked trait (Xᵇ). The allele for normal vision
is dominant and is represented by Xᴮ
.
In generation I, neither parent has the trait, but one
of their children (II-3) is colorblind. Because there
are unaffected parents that have affected offspring,
it can be assumed that the trait is recessive. In
addition, the trait appears to affect males more than
females (in this case, exclusively males are
affected), suggesting that the trait may be X-linked.
What is the genotype of individual III-2?
We can determine the genotype of III-2 by looking
at her children. Since she is an unaffected female,
she must have at least one normal vision allele Xᴮ.
Her two genotype options are then XᴮXᴮ or XᴮXᵇ
.
However, her son (IV-1) is colorblind, meaning that
he has a genotype of XᵇY. Because males always
get their X chromosome from their mothers (and
their Y from their fathers), his colorblind allele must
come from III-2.
We can then determine that III-2's genotype is
XᴮXᵇ, so she can pass the Xᵇ on to her son.
Common mistakes and misconceptions
The presence of many affected individuals in a
family does not always mean that the trait is
dominant. The terms dominant and recessive refer
to the way that a trait is expressed, not by how
often it shows up in a family. In fact, although it is
uncommon, a trait may be recessive but still show
up in all generations of a pedigree.
You may not always be able to determine the
genotype of an individual based on a pedigree.
Sometimes an individual can either be homozygous
dominant or heterozygous for a trait. Often, we can
use the relationships between an individual and
their parents, siblings, and offspring to determine
genotypes. However, not all carriers are always
explicitly indicated in a pedigree, and it may not be
possible to determine based on the information
provided.
MENDELIAN GENETICS
Johann Gregor Mendel (1822-1884)
Father of Genetics
Gregor Johann Mendel, who in 1866 put
forward the major postulates of transmission
genetics as a result of experiments with the garden
pea and thereby laid the foundation of modern
genetics. Using the consistent pattern of results in
the monohybrid crosses,
Mendel derived the following three
postulates, or principles of inheritance. Mendel's
Laws of Inheritance: Mendel postulated three laws,
which are now called after his name as Mendel’s
laws of heredity. These are: 1. Law of dominance
and recessive 2. Law of segregation 3. Law of
independent assortment
1. Law of Dominance - When two homozygous
individuals with one or more sets of contrasting
characters are crossed, the characters that appear
in the F1 hybrids are dominant characters and
those do not appear in F 1 are recessive
characters.
2. Law of Segregation (Purity of Gametes) - The
law of segregation states that when a pair of
contrasting factors or genes or allelomorphs are
brought together in a heterozygote (hybrid) the two
members of the allelic pair remain together without
being contaminated and when gametes are formed
from the hybrid, the two separates out from each
other and only one enters each gamete.
3. Law of Independent Assortment - The
inheritance of more than one pairs of characters
(two pairs or more) is studied simultaneously, the
factors or genes for each pair of characters sort out
independently of the other pairs. Mendel formulated
this law from the results of a dihybrid cross.
The genetic experiments Mendel did with pea
plants took him eight years (1856-1863) and he
published his results in 1865. During this time,
Mendel grew over 10,000 pea plants, keeping track
of progeny number and type. Mendel's work and
his Laws of Inheritance were not appreciated in his
time. It wasn't until 1900, after the rediscovery of
his Laws, that his experimental results were
understood.
Definitions of Terms
➢ Monohybrid cross: A cross involving mating
two individuals, each of which expresses only one
of a pair of contrasting traits (e.g. round/wrinkled
peas, yellow/green peas, purple/white flowers,
tall/dwarf stem)
➢ Parental generation (P1): The original parents
➢ First filial generation (F1): Offspring resulting
from parental mating.
➢ Second filial generation (F2): Offspring
resulting from the self-crossing of individuals from
the F1 generation.
Gregor Mendel (1822-1884)
● Augustinian monk in what is now the Czech
Republic
● Kept extremely accurate records of his
experiments with the garden pea
● Restricted his studies to a very few,
discrete, contrasting traits
● Described many of the foundational
principles of trait transmission.
Gregor Mendel and his Postulates and Laws of
Inheritance
The Mendel’s four postulates and laws of
inheritance are:
(1) Principles of Paired Factors
(2) Principle of Dominance
(3) Law of Segregation or Law of Purity of
Gametes (Mendel’s First Law of Inheritance) and
(4) Law of Independent Assortment (Mendel’s
Second Law of Inheritance).
Mendel laid the foundation of the science of
genetics through the discovery of basic principles of
hereditary. He conducted his experiments with
garden pea (Pisum sativum) for over seven years
(1856-1864) and advocated four postulates,
including two important laws of inheritance.
Postulate-I. Principles of Paired Factors
A character is represented in an organism
(diploid) by at least two factors. The two factors lie
on the two homologous chromosomes at the same
locus. They may represent the same (homologous,
e.g., TT in case of pure tall pea plants) or alternate
expression (heterozygous, e.g., Tt in case of hybrid
tall pea plants) of the same character. Factors
representing the alternate or same form of a
character are called alleles or allelomorphs.
Postulate II. Principle of Dominance
“When two homozygous individuals with
one or more sets of contrasting characters are
crossed, the characters which appear in the hybrids
of F1 generation are always the dominant
characters and those do not appear in F1 offspring
are always the recessive characters”.
During the course of investigations of the
principles of inheritance, Mendel crossed plants of
a variety of Pisum sativum six feet tall with plants of
a variety one foot in height on an average, (i.e.,
parents or P generation). When the seeds from this
cross were planted they produced plants not
intermediate between the two parents, as might be
expected, but all tall, like the six-foot parent (Fig.
5.1).
Mendel made crosses to study the
inheritance of six other sets of characters (given
below) and observed that in every case the hybrid
resembled one of the parents with respect to the
character. It follows then that one factor or gene in
a pair masks or inhibits the expression of the other.
Thus, in the cross described, the tall factor masks,
or inhibits the expression of the dwarf factor in the
F1 (first filial generation); therefore, the tall factor is
called the dominant factor, and the dwarf factor is
referred to as the recessive factor, or gene.
Other six sets of characters that Mendel studied
and classified as dominant and recessive were
as follows:
1. Round form of seeds dominant over wrinkled.
2. Yellow color of cotyledons dominant over green.
3. Axillary position of flower dominant over terminal
position.
4. Green color of unripe pod dominant over yellow.
5. Inflated condition of ripe pod dominant over
constricted.
6. Purple color of flower dominant over white.
Postulate III. Law of Segregation or Law of
Purity of Gametes (Mendel’s First Law of
Inheritance)
The two factors (alleles) of a trait which
remain together in an individual do not get mixed
up but keep their identity distinct, separate at the
time of gametogenesis (i.e., gametes formation) or
sporogenesis (i.e., spores’ formation), get randomly
distributed to different gametes and then get paired
again in different offspring’s as per the principle of
probability. Since two alleles remain together in
pure form without mixing, affecting or blending each
other, the law of segregation is also known as “law
of purity of gametes”.
Main features of this law are as follows:
1. When a dominant and a recessive allele of a
gene come together in a hybrid after crossing
between two plants having contrasting characters,
they do not mix or blend together.
2. They separate into different gametes in equal
number. Each gamete has only one type of allele
(say either A or a).
3. Separation of two alleles of a gene during
gamete formation takes place usually due to the
separation of homologous chromosomes during
meiosis (anaphase I), because alleles are located
on the chromosomes.
4. With complete dominance, segregation leads
to phenotypic ratio of 3: 1 in F2 generation for
characters governed by a single gene, and 9: 3: 3:
1 ratio for characters controlled by two genes.
5. If crossing over does not take place,
segregation of genes takes place during anaphase
I. If crossing over occurs, segregation of genes will
take place during anaphase II.
Example: The principle of the law of segregation
can be explained by means of a monohybrid cross.
Analysis of Monohybrid Cross
A cross in which only a
single pair of alleles is
considered is called a
monohybrid cross. Figure
5.2 is a graphic analysis of
the cross between tall and
dwarf peas in terms of
Mendel’s interpretation.
In this, T is the symbol which stands for the
factor or gene controlling tallness, and t is the
symbol used to denote the factor or gene
controlling dwarfness. The factors or genes as also
postulated by Mendel, always occur in pairs. Both
tall and the dwarf plants which are crossed are
homozygous (i.e., both the genes in a pair are
identical). These plants are “pure” for tallness and
dwarfness respectively, and if self-pollinated will
always breed true, producing only tall and dwarf
plants respectively.
In the present monohybrid cross the tall
parent, which is homozygous, is shown as TT, and
the dwarf parent is shown as tt. During the course
of sexual reproduction both kinds of plants produce
gametes; these gametes contain but one factor of
each pair (i.e., either T or t). The gametes produced
by the tall plant contain T gene, while the gametes
of dwarf plant possess t gene.
The fusion of a gamete from the tall plant
with a gamete from the dwarf plant produces a tall
plant in the F1 generation, because the gene for
tallness (T) is dominant over that of dwarfness (t).
The new plant in the F, generation is shown in the
diagram as Tt. It is a heterozygous plant because it
possesses a pair of homologous chromosomes
carrying one allele for tallness and one for
dwarfness.
The heterozygous plants produce two kinds
of gamete or sex cell, male gametes and female
gametes. Half of the male gametes contain T gene
and half possess t gene. Similarly, half of the
female gametes possess T gene and half contain t
gene. During the process of fertilization which
follows these two kinds of gametes (i.e. male and
female) unite at random and produce F2 (second
filial) generation.
As a result of these chance combinations,
an approximate phenotypic ratio of 3 tall plants to 1
dwarf plant (i.e., 3:1 ratio) is normally obtained. All
plants with TT and Tt genes will be tall, and the
plants possessing tt (both recessive) genes will be
dwarf.
Further self-breeding of these plants shows
that the dwarf plants breed true (tt), i.e., produce
only dwarf plants. Amongst tall plants, 1/3 breed
true, that is, yield only tall plants. The remaining 2/3
of the F2 tall plants or 50% of the total F2 plants
behave as hybrid plants and produce both tall and
dwarf plants in the ratio 3: 1. Therefore, the F2
phenotypic ratio of 3: 1 is genotypically 1 pure tall:
2 hybrids tall: 1 dwarf (1: 2: 1 ratio is also called
Mendel’s Monohybrid Genotypic Ratio).
Postulate IV. Law of Independent Assortment
(Mendel’s Second Law of Inheritance)
After being satisfied with monohybrid
crosses, Mendel took into consideration two pairs
of contrasting characters and studied their
inheritance (i.e., di-hybrid cross).
According to this law “the two factors
(genes) of each contrasting character (trait) assort
or separate independently of the factors of other
characters at the time of gamete formation and get
randomly rearranged in the offspring”.
Following are the main features of this law:
1. This law explains simultaneous inheritance of
two plant characters.
2. In F1 when two genes controlling two different
characters, come together, each gene exhibits
independent dominant behavior without affecting or
modifying the effect of other gene.
3. These gene pairs segregate during gamete
formation independently.
4. The alleles of one gene can combine freely with
the alleles of another gene. Thus, each allele of a
gene has an equal chance to combine with each
allele of another gene.
5. Each of the two gene pairs when considered
separately, exhibits typical 3: 1 segregation ratio in
F2 generation. This is a typical di-hybrid
segregation ratio.
6. Random or free assortment of alleles of two
genes leads to formation of new gene
combinations.
Example: The principle or law of independent
assortment can be studied by means of di-hybrid
cross.
Analysis of Di-hybrid Cross
In the di-hybrid cross Mendel crossed pure
(i.e., homozygous) plants of round seed and yellow
cotyledons variety of pea with those having
wrinkled seed and green cotyledons. He had
already studied these characters and had observed
that roundness was dominant over wrinkleless, and
yellow color of the cotyledons was dominant over
green color. As shown in the figure 5.3 one
homozygous parent is expressed as RRYY (Round
seed and yellow cotyledons) and the other is
expressed as rryy (wrinkled seed and green
cotyledons).
The former, as expected, will produce
gametes with YR genes, and the latter will produce
gametes with ry genes. The two kinds of gametes
fuse to produce F1 individual with genetic
constitution RrYy. Phenotypically these individuals
possess round seeds with yellow cotyledons
because roundness is dominant over wrinkleless,
and yellow color is dominant over green. F1
individuals are thus heterozygous round and
heterozygous yellow.
When Mendel self-fertilized the F1
individuals, in F2 generation he observed plants of
four kinds in the following phenotypic frequencies:
Thus, the four categories of plants appeared
in approximate phenotypic ratio of 9: 3: 3: 1. (Called
Mendel’s Di-hybrid phenotypic Ratio) (Fig. 5.3). The
most noteworthy feature of this di-hybrid cross that
struck Mendel was the appearance of two new
categories of plants besides the parental-ones i.e.,
Round Green, and wrinkled yellow. These two new
categories were in fact the re- combinations of the
parental characters. This led Mendel to postulate
the law of independent assortment.
It can also be proved by studying the individual
character of seed color and seed shape
separately:
Seed color:
Yellow (9 + 3 = 12): Green (3 + 1 = 4) or 3: 1
Seed Shape:
Round (9 + 3 = 12): Wrinkled (3 + 1 = 4) or 3: 1
The result of each character is similar to the
monohybrid ratio.
Punnett Squares - Graphics that help determine
the phenotype and genotype outcomes of gamete
fertilization.
Devised by Reginald C. Punnett
Reginald Punnett, in full Reginald
Crundall Punnett, (born June 20,
1875, Tonbridge, Kent, England—
died January 3, 1967, Bilbrook,
Somerset), English geneticist who,
with the English biologist William
Bateson, discovered genetic
linkage.
Through his contact with Bateson, Punnett
came to support the theories of Gregor Mendel, the
founder of modern genetics. Subsequently, he
wrote Mendelism (1905), the first textbook on the
subject. Using poultry and sweet peas, Punnett and
Bateson discovered some of the fundamental
processes of Mendelian genetics, including linkage,
sex determination, sex linkage, and the first
example of autosomal (nonsexual chromosome)
linkage.
Punnett Squares

Although Mendel published his work, it
didn't get recognized for its importance during his
lifetime. It was only once his papers were
rediscovered in the early 20th century that
scientists realized his findings applied to and
explained many observed patterns of inheritance.
Mendel studied the results of crossing
different traits in pea plants, which show relatively
simple inheritance patterns can be broken down
into Mendel's three laws of inheritance:
a. Law of Segregation: The law of segregation
states that everyone has two versions (called
alleles) for each trait, one from each parent, and
that these alleles segregate randomly during
meiosis.
b. Law of Independent Assortment: The law of
independent assortmentstates that genes for
different traits segregate independently of each
other. It means that traits can be are separately
inherited. This is because during meiosisthe
chromosomes line up randomly before the cell
divides, allowing for gamete formation.
c. Law of Dominance: The law of dominance
states that there are dominant and recessive traits.
Dominanttraits are well-defined as whichever
phenotype is expressed in an organism that is
heterozygousfor the trait.
After the rediscovery of the Mendelian
principle of genetics, various scientists started
working on a different combination of crosses in
different plants. Few crosses followed Mendelian
principle of genetics but mostly not and various new
principles of inheritance were given by scientist. In
this lesson student will be able to differentiate the
following:
• Incomplete Dominance
• Codominance
• Multiple Alleles
• Lethal Alleles
• Sex-linked, Sex-limited, & Sex- influenced
Inheritance
Modification of Mendelian Ratios
I. Complete dominance
Complete dominant allele creates full phenotype
either by:
● Producing half the amount of protein found
in homozygous dominant individual but that
is sufficient to produce the full phenotype
(haploinsufficient alleles).
● Or when the dominant allele completely
covers up the recessive allele.
II. Incomplete Dominance
● refers to a genetic situation in which one
allele does not completely dominate another
allele, and therefore results in a new
phenotype.
● is a form of intermediate inheritance in
which one allele for a specific trait is not
completely expressed over its paired allele.
This results in a third phenotype in which
the expressed physical trait is a combination
of the phenotypes of both allele
➢ Neither is DOMINANT nor RECESSIVE
➢ When heterozygous are crossed, a 3rd
phenotype appears
➢ The traits BLEND/MIX together
• This type of relationship between alleles, with a
heterozygote phenotype intermediate between the
two homozygote phenotypes, is called incomplete
dominance
• We can still use Mendel's model to predict the
results of crosses for alleles that show incomplete
dominance.
For example, self-fertilization of a pink plant would
produce:
• Alleles are still inherited according to Mendel's
basic rules, even when they show incomplete
dominance.
III. Codominance
• Closely related to incomplete dominance is
codominance, in which both alleles are
simultaneously expressed in the heterozygote
• We can see an example of codominance in the
MN blood groups of humans (less famous
than the ABO blood groups at Table 1)
• Incomplete dominance is a blending of traits, in
co-dominance an additional phenotype is produced
and both alleles are expressed completely.
• Homozygotes (LᴹLᴹ and LᴺLᴺ) have only M or an
N markers, respectively, on the surface of their red
blood cells.
• Heterozygotes (LMLN) have both types of
markers in equal numbers on the cell surface.
• The best example of co-dominance is AB blood
type inheritance. Blood type is determined by
multiple alleles recognized as A, B, or O and in
blood type AB, both phenotypes are fully
expressed.
Antigen is any substance that causes your immune
system to produce antibodies against it. This
means your immune system does not recognize the
substance, and is trying to fight it off. An antigen
may be a substance from the environment, such as
chemicals, bacteria, viruses, or pollen.
Antibodies are Y-shaped proteins that bind to the
body's foreign invaders and signal the immune
system to get to work. Antibodies are specialized,
Y-shaped proteins that bind like a lock-and- key to
the body's foreign invaders — whether they are
viruses, bacteria, fungi or parasites.
IV. Multiple alleles
• Multiple alleles are a type of non-Mendelian
inheritance pattern that involves more than just the
typical two alleles that usually code for a certain
characteristic in a species.
• With multiple alleles, that means there are more
than two phenotypes available depending on the
dominant or recessive alleles that are available in
the trait and the dominance pattern the individual
alleles follow when combined together.
• As an example, let’s consider a gene that
specifies coat color in rabbits, called the C gene.
● The C gene comes in four common alleles:
C, cᶜʰ,cᶜ, and c:
● a CC rabbit has black or brown fur
● a cᶜʰcᶜʰ rabbit has chinchilla coloration
(grayish fur).
● A cʰcʰ rabbit has Himalayan (color-point)
patterning, with a white body and dark
● ears, face, feet, and tail
● A cc rabbit is albino, with a pure white coat.
Pleiotropy and lethal alleles
Epistasis - the interaction of genes that are not
alleles, in particular the suppression of the effect of
one such gene by another.
Pleiotropy - occurs when one gene will code and
control the phenotype or expression of several
different and unrelated traits. Pleiotropy (from
Greek "more", and tropos, "way") occurs when one
gene influences two or more seemingly unrelated
phenotypic traits. (A single gene controlling or
influencing multiple phenotypic traits)
Most lethal genes are recessive. Examples of
diseases caused by recessive lethal alleles are
cystic fibrosis, Tay-Sachs disease, sickle-cell
anemia, and brachydactyly. These are alleles that
prevent survival when homozygous or
heterozygous (prenatally or any time after birth).
Lethal alleles are usually a result of mutations in
genes that are essential for growth or development.
They may be recessive, dominant, or conditional
depending on the gene or genes involved.
So how can the wild-type phenotype of the
heterozygote be explained?
There are two possible explanations
1. 50% of the normal protein is enough to
accomplish the protein’s cellular function
2. The heterozygote may actually produce more
than 50% of the functional protein
The normal gene is “up-regulated” to compensate
for the lack of function of the defective allele

Sex-linked, Sex-limited, and Sex-influenced

For example, phenylketonuria is a disease caused
by pleiotropy. is an inborn error of metabolism that
results in decreased metabolism of the amino acid
phenylalanine hydroxylase. (Chromosome
12q24.1). Untreated, PKU can lead to intellectual
disability, seizures, behavioral problems, and
mental disorders. It may also result in a musty
smell and lighter skin.
Symptoms
➢ A musty odor in the breath, skin or urine, caused
by too much phenylalanine in the body.
➢ Neurzlogical problems that may include
seizures.
➢ Skin rashes (eczema)
➢ Fair skin and blue eyes, because phenylalanine
can't transform into melanin — the pigment
responsible for hair and skin tone.
➢ Abnormally small head (microcephaly)
Inheritance
Sex-linked traits are determined by genes located
on the sex chromosomes. Sex-limited traits are
determined by genes located on autosomes and
express only in one sex. While these traits are
responsible considerably for sexual dimorphism,
sex-influenced traits do not show distinctive
expression between women and men.
A. Sex-linked Inheritance
● Inheritance because of a recessive gene
found in sex chromosomes (the X
chromosome of the XY chromosomes) is
called sex-linked inheritance.
● Generally, color blindness occurs in a male
child born to a carrier X′X female and a
normal XY male

PKU can be easily detected with a simple blood

test. All states in the United States require a PKU
screening test for all newborns as part of the
newborn screening panel. The test is generally
done by taking a few drops of blood from the baby
before the baby leaves the hospital.

Lethal Alleles
Lethal alleles are usually a result of mutations in
genes that are essential for growth or development.
Lethal alleles may be recessive, dominant, or
conditional depending on the gene or genes
involved. Some lethal alleles exert their effect later
in life = Late age of onset
e.g. Huntington disease (progressive degeneration
of the nervous system, dementia and early death;
onset between 30-50 yrs old
Inheritance of X-Linked Recessive Genes
In criss-cross inheritance, an X-linked
recessive gene is transmitted from P1 male parent
(father) to F2 male progeny (grandsons) through its
F1 heterozygous females (daughters), which are
called carriers and different F1 and F2 results
(ratios) in the reciprocal crosses.

Huntington's disease is a progressive brain

disorder caused by a single defective gene on
chromosome 4 —one of the 23 human
chromosomes that carry a person's entire genetic
code. This defect is "dominant," meaning that
anyone who inherits it from a parent with
Huntington's will eventually develop the disease.

In a simple dominant/recessive relationship, the

recessive allele does not affect the phenotype of
the heterozygote.
 ● Dominant X-linked genes are detected more
frequently found in the female than in the
male of the species.
● The affected males pass the condition on to
all of their daughters but to none of their
sons.
● Females usually pass the condition
(defective phenotype) on to one-half of their
sons and daughters.
● An X-linked dominant gene fails to be
transmitted to any son from a mother which
did not exhibit the trait itself.
● One example is hypophosphatemia
(vitamin D-resistant rickets).
Another example includes hereditary enamel
hypoplasia (hypoplastic amelogenesis imperfecta),
in which tooth enamel is abnormally thin so that
teeth appear small and wear rapidly down to the
gums.
Inheritance of Y-Linked Recessive Genes
Genes that are carried by either sex chromosome
are said to be sex linked. Men normally have an X
and a Y combination of sex chromosomes, while
women have two X's. Since only men inherit Y
chromosomes, they are the only ones to inherit
Y-linked traits.
C. Sex-influenced Inheritance
Sex-influenced traits are autosomal traits that are
expressed based on the influence of the sex, in
particular the sex hormones(testosterone in males
and estrogen and progesterone in females). Sex-
influenced traits are those that are dominant in in
one sex but recessive in the other. This due to the
different cellular environments in males and
females provided by the sex hormones.
Examples: Male Pattern Baldness, Length of index
finger , Body hair Muscle mass
The phenotypic characteristic or trait such as male
pattern baldness that is expressed differently in
males and females, usually because its expression
depends on androgens or oestrogens, and that is
controlled by a single gene that is dominant in
males but recessive in females, so that, for
example, men who inherit the gene from either
parent lose hair as they age, whereas women do so
only if they inherit it from both parents and are thus
homozygotes.

Disorders in Human
❖ Color-blindness
It is a defect in which a person cannot distinguish
between red, green or both the colors from other
Colors.
❖ Haemophilia (Bleeder’s disease)
Hemophilia is called a royal disease and known as
the most serious of all the diseases. A person
suffering from this disease have the inability of their
blood to clot normally even after a minor
injury. It is due to the lack of a blood protein called
clotting factor VIII and clotting factor IX.

B. Sex limited inheritance

Sex limited inheritance refers to the inheritance of

traits that are expressed only in either the male
or the female offspring due to their expression
being influenced by differences in the anatomy of
males and females

The phenotypic expression of a number of

autosomal and sex linked genes will be either
dominant if the individual is a male or recessive if
the individual is a female. These genes are known
as sex influenced traits. A classic example is the
pattern baldness in man or beard in males. A male
shows this trait more than a female, because a
male is bald if he has only one gene, whereas a
woman must receive two genes to be bald. This is
because a single gene can operate in the presence
of a male hormone.
 DNA: THE PHYSICAL BASIS OF LIFE
In 1868, T. H. Huxley described
protoplasm as the “physical basis of life”.
Protoplasm is clear, colorless and jelly-like
substance which seemed to make up the contents
of the cell. It was also described as “substance of
life” or “living material”. It is slimy to the touch
and slightly heavier than water and coagulates on
heating. It can be stretched like a thread which
returns to its original position when released.
The most important physical characteristic
of protoplasm is its colloidal nature to which it
owes most of its properties. Protoplasm is a
complex mixture of two types of aqueous solution.
a. A colloidal solution of organic compounds
(proteins, fats, starches).
b. A molecule solution of both inorganic & organic
substances (salts & sugars).
The term “protoplasm” has lost its original
significance of being a special substance with the
qualities of life. Today, protoplasm is simply a
collective term for the components of the living part
of a cell. It does not have an independent identity.
Nucleic Acids: DNA and RNA
Nucleic acids are naturally occurring
chemical compounds that serve as the primary
information-carrying molecules in cells. They play
an especially important role in directing protein
synthesis. The two main classes of nucleic acids
are deoxyribonucleic acid (DNA) and ribonucleic
acid (RNA).
Deoxyribonucleic acid (DNA) and
Ribonucleic acid (RNA) are perhaps the most
important molecules in cell biology, responsible for
the storage and reading of genetic information that
underpins all life. They are both linear polymers,
consisting of sugars, phosphates and bases, but
there are some key differences which separate the
two. These distinctions enable the two molecules to
work together and fulfil their essential roles. Before
we delve into the differences, we take a look at
these two nucleic acids side-by-side at the
comparison chart.
What are the key differences between DNA and
RNA?
1. Function
DNA encodes all genetic information, and is
the blueprint from which all biological life is created.
And that’s only in the short-term. In the long-term,
DNA is a storage device, a biological flash drive
that allows the blueprint of life to be passed
between generations. RNA functions as the reader
that decodes this flash drive. This reading process
is multi-step and there are specialized RNAs for
each of these steps. Below, we look in more detail
at the three most important types of RNA.
What are the three types of RNA?
❖ Messenger RNA (mRNA) copies portions of
genetic code, a process called transcription, and
transports these copies to ribosomes, which are the
cellular factories that facilitate the production of
proteins from this code.
❖ Transfer RNA (tRNA) is responsible for bringing
amino acids, basic protein building blocks, to these
protein factories, in response to the coded
instructions introduced by the mRNA. This
protein-building process is called translation.
❖ Finally, Ribosomal RNA (rRNA) is a component
of the ribosome. These complex structures, which
physically move along an mRNA molecule, catalyze
the assembly of amino acids into protein chains
2. Sugar
Both DNA and RNA are built with a sugar
backbone, but whereas the sugar in DNA is called
deoxyribose (left in image), the sugar in RNA is
called simply ribose (right in image). The ‘deoxy’
prefix denotes that, whilst RNA has two hydroxyl
(-OH) groups attached to its carbon backbone,
DNA has only one, and has a lone hydrogen atom
attached instead. RNA’s extra hydroxyl group
proves useful in the process of converting genetic
code into mRNAs that can be made into proteins,
whilst the deoxyribose sugar gives DNA more
stability.

3. Bases
The nitrogen bases in DNA are the basic
units of genetic code, and their correct ordering and
pairing is essential to biological function. The four
bases that make up this code are adenine (A),
thymine (T), guanine (G) and cytosine (C). Bases
pair off together in a double helix structure, these
pairs being A and T, and C and G. RNA doesn’t
contain thymine bases, replacing them with uracil
bases (U), which pair to adenine.
DNA, the Genetic Material
DNA, deoxyribonucleic acid, is the genetic
material in your cells. It was passed on to you from
your parents and determines your characteristics.
The discovery that DNA is the genetic material was
another important milestone in molecular biology.
Genes are segments of deoxyribonucleic acid
(DNA) that contain the code for a specific protein
that functions in one or more types of cells in the
body. Chromosomes are structures within cells
that contain a person's genes. Genes are
contained in chromosomes, which are in the cell
nucleus.
DNA Structure DNA contains the
“information” needed for life. This information
enables cells to grow and divide. It is responsible
for your physical characteristics, such as your
height, skin tone, and eye color. Human DNA
contains about three million deoxyribonucleotide
residues. Eukaryotic cells, which are cells having
membrane-bound nuclei, have most of their DNA in
the nucleus, and small amounts in other organelles
such as chloroplasts and mitochondria. The DNA of
prokaryotic cells is contained in the cytoplasm.
Molecular Structure of DNA and RNA
DNA is composed of Polynucleotide
Chains. The most important feature of DNA is that
it is usually composed of two polynucleotide chains
twisted around each other in the form of a double
helix (Figure 6-1). The upper part of the figure (a)
presents the structure of the double helix shown in
a schematic form. Note that if inverted 180° (for
example, by turning this book upside-down), the
double helix looks superficially the same, due to the
complementary nature of the two DNA strands. The
space-filling model of the double helix, in the lower
part of the figure (b), shows the components of the
DNA molecule and their relative positions in the
helical structure. The backbone of each strand of
the helix is composed of alternating sugar and
phosphate residues; the bases project inward but
are accessible through the major and minor
grooves
RNA contains Ribose and Uracil organic
base and is usually single-stranded. We now turn
our attention to RNA, which differs from DNA in
three respects (Figure 6-26). First, the backbone of
RNA contains ribose rather than 2-deoxyribose.
That is, ribose has a hydroxyl group at the 2
position. Second, RNA contains uracil in place of
thymine. Uracil has the same single-ringed
structure as thymine, except that it lacks the 5
methyl group. Thymine is in effect 5methyl-uracil.
Third, RNA is usually found as a single
polynucleotide chain. Except for the case of certain
viruses, RNA is not the genetic material and does
not need to be capable of serving as a template for
its own replication. Rather, RNA functions as the
intermediate, the mRNA, between the gene and the
protein-synthesizing machinery. Another function of
RNA is as an adaptor, the tRNA, between the
codons in the mRNA and amino acids. RNA can
also play a structural role as in the case of the RNA
components of the ribosome.
Organization of DNA in Chromosomes and
Genes
We turn now to the question of how DNA
molecules are organized within cells into the
structures we observe as chromosomes. Because
the total length of cellular DNA in cells is up to a
hundred thousand times the cell’s length, the
packing of DNA into chromosomes is crucial to cell
architecture.
DNA is the chemical basis of heredity.
Within its sequence is the information necessary for
cells to live, grow, differentiate, and replicate. It is
the DNA that provides both consistency (all
humans generally look the same) and variability
(height, eye, and hair color) among organisms.
While the human genome is extremely polymorphic
and the majority of deviations in DNA sequence are
thought to be benign, variations in its sequence can
and do lead to genetic disorders. Although we
currently understand the roles of only a small
percentage of the total number of genes, great
strides are being made toward elucidating the
physical and molecular structure and function of the
human genome. Through this knowledge we can
more fully appreciate the complex physiology of the
human organism.
Chromatin and Chromosomes
In eukaryotic organisms (plants, animals,
and fungi), the DNA double helix coils into a more
compact structure, as illustrated in the figure on the
right.
In the coiling process, the double helix
wraps around histone proteins, as shown in figure
on the right. The DNA/histone further condenses
into a fiber that is called chromatin.
Depending on the cell life cycle, chromatin
can undergo further coiling. For example, before a
cell divides chromatin is coiled into its tightest, most
compact shape, which is called a chromosome.
The amount of chromosomes that a cell
contains depends on the organism. Humans have a
total of 46 chromosomes per cell, 23 from each
parent. Dogs have a total of 78 chromosomes, 39
from each parent. Fruit flies have a total of 8
chromosomes. The smallest human chromosome
contains about 50 million base pairs, and the
largest one contains about 250 million base pairs.
DNA Replication
DNA replication is the process by which
DNA makes a copy of itself during cell division. The
first step in DNA replication is to ‘unzip’ the double
helix structure of the DNA molecule. This is carried
out by an enzyme called helicase which breaks the
hydrogen bonds holding the complementary bases
of DNA together (A with T, C with G).
The separation of the two single strands of
DNA creates a ‘Y’ shape called a replication ‘fork’.
The two separated strands will act as templates for
making the new strands of DNA. One of the strands
is oriented in the 3’ to 5’ (3 prime to 5 prime)
direction (towards the replication fork), this is the
leading strand. The other strand is oriented in the 5’
to 3’ direction (away from the replication fork), this
is the lagging strand. As a result of their different
orientations, the two strands are replicated
differently:
DNA replication is the process by which DNA
makes a copy of itself during cell division.
1. The first step in DNA replication is to ‘unzip’ the
double helix structure of the DNA molecule.
2. This is carried out by an enzyme called helicase
which breaks the hydrogen bond holding the
complementary bases of DNA together (A with T, C
with G).
3. The separation of the two single strands of DNA
creates a ‘Y’ shape called a replication ‘fork’. The
two separated strands will act as templates for
making the new strands of DNA.
4. One of the strands is oriented in the 3’ to 5’
direction (towards the replication fork), this is the
leading strand. The other strand is oriented in the 5’
to 3’ direction (away from the replication fork), this
is the lagging strand. As a result of their different
orientations, the two strands are replicated
differently:
8. Once all of the bases are matched up (A with T,
C with G), an enzyme called exonuclease (an
enzyme which removes successive nucleotides
from the end of a polynucleotide molecule) strips
away the primer(s). The gaps where the primer(s)
were are then filled by yet more complementary
nucleotides.
9. The new strand is proofread to make sure there
are no mistakes in the new DNA sequence.
10. Finally, an enzyme called DNA ligase seals up
the sequence of DNA into two continuous double
strands.
11. The result of DNA replication is two DNA
molecules consisting of one new and one old chain
of nucleotides. This is why DNA replication is
described as semi-conservative, half of the chain is
part of the original DNA molecule, half is brand
new.
12. Following replication the new DNA
automatically winds up into a double helix.
DNA Mutation and Repair
Most biological molecules have a limited
lifetime. Many proteins, lipids and RNAs are
degraded when they are no longer needed or
damaged, and smaller molecules such as sugars
are metabolized to compounds to make or store
energy. In contrast, DNA is the most stable
biological molecule known, befitting its role in
storage of genetic information. The DNA is passed
from one generation to another, and it is degraded
only when cells die. However, it can change, i.e. it
is mutable. Mutations, or changes in the nucleotide
sequence, can result from errors during DNA
replication, from covalent changes in structure
because of reaction with chemical or physical
agents in the environment, or from transposition.
Most of the sequence alterations are repaired in
cells.
Sequence alteration in the genomic DNA is
the fuel driving the course of evolution. Without
such mutations, no changes would occur in
populations of species to allow them to adapt to
changes in the environment. Mutations in the DNA
of germline cells fall into three categories with
respect to their impact on evolution. Most have no
effect on phenotype; these include sequence
changes in the large portion of the genome that
either codes for protein or is involved in gene
regulation or any other process. Some of these
neutral mutations will become prevalent in a
population of organisms (or fixed) over long
periods of time by stochastic processes. Other
mutations do have a phenotype, one that is
advantageous to the individuals carrying it. These
mutations are fixed in populations rapidly. Other
mutations have a detrimental phenotype, and these
are cleared from the population quickly. They are
subject to negative or purifying selection.
Mutations commonly are substitutions, in
which a single nucleotide is changed into a different
nucleotide. Other mutations result in the loss
(deletion) or addition (insertion) of one or more
nucleotides. These insertions or deletions can
range from one to tens of thousands of nucleotides.
Often an insertion or deletion is inferred from
comparison of two homologous sequences, and it
may be impossible to ascertain from the data given
whether the presence of a segment in one
sequence but not another resulted from an insertion
of a deletion (in this case, it can be referred to as
an "indel"). One mechanism for large insertions is
the transposition of a sequence from one place
in a genome to another.
Types of mutations
Any time DNA is replicated or divided, there is an
opportunity for mutation.
a. Point mutations occur when there is a chemical
change to a single base pair.
b. Substitutions occur when one nucleotide is
replaced with a different nucleotide. Since there is
redundancy in the genetic code (multiple base pair
triplets can code for the same amino acid, see table
at right), a base pair substitution may not affect
which nucleotide is added to the DNA strand.
These substitutions are called silent mutations.
For example, a section of DNA that has mutated
such that its transcribed mRNA strand reads as
GUU rather than GUA would still code for the
amino acid valine during protein synthesis. The
structure of the DNA molecule is affected, but the
structure of the resulting protein is not.
c. Missense errors occur when the mutated DNA
can still code for an amino acid, but not the correct
amino acid. If the rest of the genetic code is intact,
the mutated DNA may still produce a functional
protein, albeit with a different structure and
properties.
d. Nonsense errors occur when the mutated DNA
produces a stop codon too early, terminating
polypeptide synthesis. Usually, these shortened
polypeptide chains cannot fold into functional
proteins.
e. Insertions occur when an extra nucleotide is
added to the DNA strand. The insertion of
additional base pairs may lead to frameshifts
depending on whether or not multiples of three
base pairs are inserted.
f. Deletions occur when a nucleotide is removed
from the DNA strand. Both insertions and deletions
are referred to as frameshift mutations, because all
the nucleotides downstream are grouped
incorrectly.
Mutagen
A mutagen is a physical or chemical
substance that disrupts DNA, causing a permanent
change in the nucleotide sequence.
Ultraviolet radiation is a common physical
mutagen. It causes neighboring thymines to form
dimers, changing the shape of the double helix.
Sunburns occur when too many of these dimers
form, and they cannot all be repaired, and the cells
die instead. Nucleotide sequence errors are
sometimes introduced into the DNA sequence as
the damage is repaired, and an error may result in
unchecked cell growth, leading to skin cancer.
Causes of Mutations
➢ Errors in DNA Replication - On very, very rare
occasions DNA polymerase will incorporate a
noncomplementary base into the daughter strand.
During the next round of replication the
missincorporated base would lead to a mutation.
This, however, is very rare as the exonuclease
functions as a proofreading mechanism recognizing
mismatched base pairs and excising them.
➢ Errors in DNA Recombination - DNA often
rearranges itself by a process called recombination
which proceeds via a variety of mechanisms.
Occasionally DNA is lost during replication leading
to a mutation.
➢ Chemical Damage to DNA - Many chemical
mutagens, some exogenous, some man-made,
some environmental, are capable of damaging
DNA. Many chemotherapeutic drugs and
intercalating agent drugs function by damaging
DNA.
➢ Radiation - Gamma rays, X-rays, even UV light
can interact with compounds in the cell
generating free radicals which cause chemical
damage to DNA.
Methods of DNA Repair
When examining completed DNA
molecules, errors in DNA replication appear rare;
they occur in approximately 1 of every 10 billion
nucleotides copied. However, errors between the
template strand and the single nucleotides being
added to the daughter strand are far more
common: 1 in 100,000.
Mismatched nucleotides that are not
detected by DNA polymerase or that result from
damage after the strand has been synthesized are
corrected by special enzymes in a process called
mismatch repair. Nucleotide excision repair takes
advantage of DNA base-pairing to correct problem
segments. The damaged section is removed by the
enzyme nuclease, and the gaps are filled in by
the polymerase and ligase enzymes, following the
template of the undamaged strand.