GOOD AFTERNOON

BASIC GENETICS
 GENETICS
Is the science concerned with the
structure and function of all genes in
different organisms.
OR

It is a scientific study of the mechanism

of inheritance and causes of variation in
living organisms related by descent.
THE MOLECULAR BASIS OF
GENETICS

CELL
 CELL

Any of the protoplasmic masses making up

organised tissue ,consisting of a nucleus
surrounded by cytoplasm enclosed in a cell or
plasma membrane.
 CYTOPLAS
Endoplasmic reticulum along with
ribosomes (lipid M
and protein
synthesis).

Golgi apparatus (secretion of

cellular products) .

Mitochondria-energy production.

Peroxisomes and lysozomes-

degradation of toxic molecules.
 MENDELS LAWS OF
GENETICS
o The law of uniformity

o The law of segregation

o The law of independent

assortment
 The law of uniformity
When two homozygotes with different
alleles are crossed ,all the offspring in the
F1 generation are identical and
heterozygous.

TT
tt

Tt(tall)
Mendels breeding
experiment
 The law of independent
assortment
Members of different gene pairs
segregate to offspring independently
of one another.
 The law of segregation
Each individual possesses two genes
for a particular characteristics ,only
one of which can be transmitted at
any one time . T t

T TT Tt

t Tt tt
A punnetts square showing the different ways
In which genes can segregate and combine in
Second final cross .It provides a simple method
For showing the possible gamete combinations
In different matings.
 yR yR Yr yr

YR YYRR YyRR YYRr YyRr

yR YyRR yyRR yYRr yyRr

Yr yyRr YyRr YYrr Yyrr

yr YyRr yyRr Yyrr yyrr

 The dihyrid or double heterozygous
YyRr individual is capable of
producing four types of gametes
relative to these characteristics
YR ,Yr ,Yr ,yr .Because this is a
process involving random
distribution it has been postulated as
the principle of INDEPENDENT
ASSORMENT.
 AUTOSOMAL
MONOHYBRID
INHERITANCE

What is monohybrid
cross?

When a set consisting of two genes

is exclusively and independently
concerned with one
characteristics ,the experimental
 Example

When Mendel crossed a pure tall pea

plant with a pure dwarf pea plant ,the
plants with the seed from this cross
produced were all tall .Thus ,the gene
for tall must be dominant over that
for dwarf ,these plants are known as
the first filial (F-1) generation.
 When plants of the F-1 generation
were crossed with each other
,their seeds produced plants in
the ratio of 3 tall to 1 dwarf .
 What is genotype,
phenotype?
The generic constitution of the various
individuals for height reveals that three gene
combinations are possible;

TT (tall)
Tt (tall)
tt (dwarf)
These are referred as
genotypes
 With respect to the expression of
the genic combination (physical
manifestation of height in this
case ) only observable are ;tall
and dwarf.
These are
known as phenotypes
 HOMOZYOUS
dominant/recessive

WHEN two genes are identical in their

expressiveness as in the genotypes TT
and tt ,the adjective homozygous is used
to modify their dominant or recessive
nature .so TT is homozygous dominant
and tt is homozygous recessive.
In the genotype Tt adjective
heterozygous is used.
 AUTOSOMAL DIHYBRID
INHERITANCE

IN crossing a homozygous dominant

yellow round (YYRR) pea plant with
a homozygous recessive green
wrinkled (yyrr)plant ,only one type
of gamete can be produced by each
YR and yr.
 CHROMOSOMES
The word chromosome is derived from
the Greek word chroma (color) and soma
(body).

Chromosomes are the factors which

distinguish one species from another and
which enable transmission of genetic
information from one generation to other.
 The normal human karyotype is
made up of 46 chromosomes
consisting of 22 pairs of autosomes
and a pair of sex chromosomes.

XX is in the female and XY in the

male.
 HUMAN CHROMOSOMES

Chromotids /sister chromotids

identical strands(as result of DNA
replication)

Centromere

Sister chromotids joined at a

primary constriction known as
centromere

Telomere

Tip of each chromosome ,seals the ends

of chromosomes ,maintains their structral
integrity
 Each chromosomes consists of a short
arm(p) and long arm(q) joined at the
centromere.

Centromere is responsible for movement of

the chromosomes at cell division.

Telomere seals the end of the chromosomes

and
maintains structural integrity.
 MORPHOLOGICALL
Y
chromosomes

metacentric submetacentric acrocentric

 The female sex chromosome,
being the differential sex
chromosome carried by half the
male gametes and all female
gametes in man and other male
heterogametic species.
 The male chromosome, being
the differential sex
chromosome carried by half
the male gametes and none
of the female gametes.
 METHODS OF
CHROMOSOMAL ANALYSIS

The chromosome constitution

of an individual is known as
karyotype.It is used to
describe a photomicrograph
of an individual
chromosomes,arranged in a
standard manner.
 CHROMOSOME
PREPARATION
Any tissue with living nucleated cells
which undergo division can be used for
studying human chromosomes.
Most Commonly used samples;
Circulating lymphocytes.
Skin
Bone marrow
Cells from amniotic
fluid(amniocytes)
 Peripheral (venous blood)+small
volume of nutrient medium
(phytohaemagglutinin)

T-Lymphocytes
 Stimulated T-Lymphocytes then divide.

The cells are cultured under sterile

conditions at 37 degree for about 3 days
during they divide and colchicine is then
added to each culture .

This drug prevents spindle formation ,thus

arresting cell division during
metaphase(chromosomes are maximally
condensed and therefore most easily
visible.
 Hypotonic saline is then
added which causes red blood
cells to lyse and results in
spreading of the
chromosomes which is then
fixed , mounted on a slide and
stained ready for analysis.
Preparation of a
karyotype
 CHROMOSOME
BANDING
G (giemsa) banding
Most commonly used.
The chromosomes are treated with
trypsin which denatures their protein
content and stained with DNA binding
dye known as Giemsa which gives
chromosomes a characteristic and
reproducible pattern of light and dark
bands.
 Q (quinacrine) banding

Similarto G banding and

requires ultra violet
fluorescent microscope.
 R (reverse) banding

Thechromosomes are heat

denatured before staining
with giemsa ,yielding light
and dark bands which reverse
of G banding.
 C(centromeric
heterochromatin) banding:
If the chromosomes are pretreated
with acid followed by alkali prior to
G BANDING ,the centromeres and
other heterochromatic regions
containing highly repetitive
sequences are preferentially stained.
KARYOTYPE ANALYSIS

It involves first counting the number

of chromosomes present in a
specified number of cells referred to
as metaphase spreads,then careful
analysis of the banding pattern of
each individual chromosome in a
selected cells.
 Detailedanalysis of the banding
pattern of the individual
chromosomes is carried out on
both members of each pair of
homologues in approximately 3-
5 mataphase spreads which
show high quality banding.
 The banding pattern of each chromosomes is
specific and can be shown in the form of a
stylized karyotype known as IDIOGRAM. The
cytogeneticist analyses each pair of
homologous chromosomes either with
microscope or on a photograph of the
metaphase spread.

The karyotype will show each chromosomes

pair in descending order of size.
An idiogram showing the banding
Patterns of individual chromosomes
As revealed by fluorescent and Giemsa
Staining.
CHEMICAL NATURE OF
NUCLEIC ACID

Nucleoprotein are classified as a

conjugated protein and consists of
equal amounts of protein and a non
protein prosthetic group (nucleic
acid) and these components are
associated with each other through
ionic types of linkage.
 COMPOSITION OF DNA
Phosphoric acid is linked
By an ester linkage to the
Nucleotide 5-c of the pentose sugar

Phosphate
Nitrogenous baseSugar molecule
molecule
 NITROGENOUS BASES

They are the derivatives of the N

containing compounds

Purines(adenine and guanine)

Pyrimidines(cytosine,thymine,uracil)
 Pentose sugars ,which can be
either beta D-ribose (RNA) or
beta -2`deoxy D-ribose (DNA).
 NUCLEIC ACID
Two types

DNA(deoxyribonucleic acid)

RNA(ribonucleic acid)-5carbon
sugar
DEOXYRIBONUCLEIC ACID

Deoxy as hydroxyl group at the 2

position 0f the ribose sugar is
replaced by a hydrogen bond.

Its found mainly in chromosomes.

 About 95% of the total DNA in
the cell is found as chromatin
in the nucleus and the
remaining exists as the
extranuclear DNA in the
mitochondria.
RIBONUCLEIC ACID
(RNA)

5-c sugar

RNA

Cytoplasm
Adenine
Guanine
nucleolus
uracil
 About80% of the total cellular
RNA is associated with
ribosomes as ribosomal RNA
(rRNA),16% exists as transfer
RNA(tRNA) found in the
cytoplasm and 2% as (mRNA)
associated with ribosomes.
 DNA STRUCTURE

In1953 watson and crick

proposed the structure for
DNA molecule which fulfilled all
the essential requirements
based on x-ray diffraction
studies.
 2 chains of nucleotides arranged
in double helix.

Back bone of each chain is formed

by phosphodiester bonds between
3and 5carbons of adjacent sugar.
DNA DOUBLE HELIX
Sugar phosphate backbone and
Nucleotide pairing of the DNA double helix.
 2 chains held by hydrogen bonds between
nitrogenous bases.

5 end determined by 5carbon atom of sugar.

3 end determined by 3 carbon atom of sugar.

5end of one strand is opposite the 3end of the

other- antiparallel orientations.
 Complementary strands base
pairing

Guanine pairs with cytosine

Adenin
pairs with thymine
 Maximum stability of the
double helix results from the
complementary base pairing
as there is maximum number
of hydrogen bonded base
pairs in the DNA molecule.
 DNA REPLICATION

Important as it explains how

information is transmitted from
generation to generation.

During nuclear division , two

strands of the DNA double helix is
separated by DNA HELICASE.
 Each DNA strands directing the
synthesis of complementary DNA
strands via base pairing resulting in
two daughter DNA duplexes (identical
to the original parent molecule).
 THE PROCESS OF DNA
REPLICATION

Its semiconservative

As only one strand of each

resultant daughter molecule is
newly synthesised.
 DNA replication occur at multiple
points

k/a as origin of replication

DNA polymerase

forming bifurcated Y shaped

structure k/a replication forks
 Synthesis of complementary antiparallel
DNA strands occur in 3-5 direction

One strands known as leading strands

which are synthesized as continuous
process.

lagging strands synthesized into pieces

known as okazaki fragments
 OKAZAKI FRAMENTS are joined to
form continous strands

DNA LIGASE
 DNA replication progresses
in both directions from
these point of origin
forming bubble-shaped
structure
REPLICATION BUBBLES

When replication progresses in both

direction from point of origin
forming replication bubbles.

This all occur in S PHASE of cell

cycle
 CHROMOSOME
STRUCTURE

The packaging of DNA into chromosomes

involves several orders of DNA coiling and
folding.

besides primary coiling,there is

secondary coiling around sphereical
histone beads
 NUCLEOSOMES
Teritary coiling of nucleosomes

chromatin fibers
form long loops on a scaffold of
non histone acidic proteins
 chromosome

( solenoid model of
chromosome)
 Chromatin fiber are examples of
nucleoprotein containing basic protein
known as HISTONES and the nucleic
acid ,deoxyribonucleic acid (DNA).

Histones are rich in amino acids, lysine

and arginine.

Non histone proteins part contain

relatively high amount of acidic
aminoacids and regulate the replication
of DNA and transcription of RNA.
 TRANSCRIPTION
The process whereby genetic information
(stored in genetic code) transmitted from
DNA to mRNA

Every base in the mRNA is complimentary to

a corresponding base in the DNA of the gene

Single stranded mRNA is synthesised by the

enzyme RNA polymerase
 If the DNA has a function of duplication, how is this
accomplished ?

It involves a protein-maker known as RNA. RNA is actually an

amino acid. There is one particular type of RNA designated as
mRNA and known as messenger RNA.

. The mRNA literally attaches to a strand of the helix and creates

a complementary chain with one slight modification. The RNA is
then free to travel out into the cell .
 Thereare two things that actually take place in this
process. There is transcription or copying of the
nuclear message onto a strip of RNA

There also is translation or transformations from

protein into amino acids and then ultimately back to
protein. This means that genetic information travels
in one direction - from DNA to RNA and then to
protein again or duplicated DNA
 The RNA strip is not just like the
original DNA strip however. It is a
complement. Its actually a mirror image
of the original. However, it carries its
message to another source that again
turns the image backwards to form the
duplicate.
 POST TRANSCRIPTIONAL
PROCESSING
It occurs before the mRNA molecule leaves
the nucleus
mRNA splicing

In this non coding introns in the primary

mRNA
are excised and the non contiguous coding
exons are spliced together to form a shorter
mature mRNA before its transportation to
the ribosomes in the cytoplasm for
translation
 5 CAPPING
It is the modification of the nascent mRNA by
the addition of a methylated guanine
nucleotide to the 5 end of the molecule by an
unusual 5 to 5 phosophodiester bond ,the so
called 5 cap.

5cap is thought to;

Facilitate transport of the mRNA to the

cytoplasm and attachment to the ribosomes
Transcription ,post transcriptional ,translation and post
translational processing
 Protects the RNA transcript from
degradation by an endogenous cellular
exonucleases.

Polyadenylation

The cleavage of the 3 end of the mRNA

molecule from the DNA involves the addition
of approximately 200 adenylate residues ,the
so called poly (A) tail .

Poly (A) facilitate transport of the mRNA to

the cytoplasm and translation.
 TRANSLATION

It is transmission of the genetic

information from mRNA to protein. Newly
processed mRNA is transporated from the
nucleus to the cytoplasm where it
becomes associated with the ribosomes
which are the site of protein synthesis.In
the ribosomes the mRNA forms the
template for producing the specific
sequence of aminoacids of a particular
polypeptide.
 TRANSFER RNA

The incorporation of aminoacids into

a polypeptide chain requires the
aminoacids to be covalently bound
by reacting with ATP to the specific
trna molecule by the activity of the
enzyme aminoacyl trna synthetase.

.
 The ribosome ,with its associated
tRNA ,moves along the mRNA ,the
aminoacids linking up by the
formation of peptide bonds through
the action of the enzyme peptidyl
transferase to form a polypeptide
chain
 POST TRANSCRIPTIONAL
MODIFICATION

POST TRANSCRIPTIONAL
MODIFICATION ,before many
proteins attain their normal
structure or functional activity.

.
 It includes chemical modification
of aminoacid side
chains(hydroxylation
,methylation) or addition of
carbohydrate or lipids
moieties(glycolation) or
proteolytic cleavage of
polypeptide(conversion of
proinsulin to insulin)
 IT results in the transport of the
newly synthesized protein to the
specific cellular locations
example the nucleus or their
secretion.
This process of duplication is important as cells
divide. There are two types of duplication.

The first is mitosis. This involves the duplication of

cells in which the chromosome complement is
identical to the master or original cell. This is a one
for one duplication.
The second type of duplication is meiosis.
This involves cell division in which the
original chromosome complement it reduced
by half. The produce of meiosis are gametes
(sperms for a male and eggs for a female) .
 MUTATIONS
Defined as ,heritable alteration or
change in the genetic material

Mutations arising in somatic cell

cannot be transmitted but mutation
of gonadal cell is transmitted to
future generation.
 Mutations are divided
into
single base pair substitutions
insertions
deletions
duplications of part of a gene or DNA
 SUBSITUTIONS
it is replacement of a single nucleotide b
another
most common type

DELETIONS /INSERTIONS
involves the loss or addition of one or
more nucleotides, result in frame shift
mutations
 BIBLIOGRAPHY

Oral histology ;Inheritance and

development by
D. Vincent Provenza

Emerys elements of medical genetics;

Robert
F.Mueller.
Ian D.
Young.
THANK YOU