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1. GENETIC POLYMORPHISM AND
ITS CLINICAL IMPLICATIONS
presented by:
Rabbia Ishaq
04-PHL-S-24

2. CONTENTS
 Introduction
 Types
 Differences
 Types of DNA polymorphism
 Identification
 Clinical implication
 Conclusion

3. INTRODUCTION
 Genetics
 derived from Greek word genetikos meaning
“generative” which in turn derived from
genesis that means “origin”.
 Study of genes, genetic variation and heredity
in living organisms.
 Polymorphism
 Combination of Greek words poly (multiple)
and morph (form).

4. GENETIC POLYMORPHISM
 Multiple forms of a single gene, exists in an
individual or group of individuals.
 Majority are silent , not alter function or
expression of a gene.
 Some polymorphisms are visible.
 For example, dogs E locus , (also called as
wild type allel). There are five different
alleles(E, Em, Eg, Eh, e)contribute to
pigmentation and patterns in dog coats.

5. GENETIC MUTATION
 DNA sequence not present in most
individuals of species either associated with
disease or resulted from damage caused by
external agents.
 These mutations often occur during cell
division and replication, and it can lead to
cancer or they could help humans better
adapt to their environment over time.
 E,g, sickle cell disease.

6. POLYMORPHISM VS MUTATION
 Mutation is permanent
alteration of a nucleotide
sequence of a gene.
 Frequency is less than
1%.
 Sickle cell anemia,
hemophilia, cystic
fibrosis, and turner
syndrome.
 Polymorphism is the
presence of more than
one allele at a
particular locus in a
particular population
 Frequency is greater
than 1%.
 Human gender and
ABO blood group are
result of polymorphism.
Genetic mutation Genetic polymorphism

7. TYPES OF GENETIC POLYMORPHISM
1- DNA polymorphism
 Polymorphisms that detect slight
variations at the level of DNA.
2- Protein/enzymes polymorphism
variations associated with proteins and
enzymes.

8. TYPES OF DNA POLYMORPHISM
DNA
polymorphism
Tandem repeat
polymorphism
Structural
variants
Restriction
fragment length
polymorphism
Single
nucleotide
polymorphism

9. 1-SINGLE NUCLEOTIDE POLYMORPHISM
 SNPs are genetic variation that occur when a
single nucleotide adenine(A), thymine(T),
cytosine(C), or guanine(G) in the genome
sequence are altered.
 Detect in highly automated by using DNA chip.
 (Microarray is a collection of microscopic DNA
spots attached to a solid surface)
 Most common and simple , accounting 90%
human genetic variation.
 May occur in coding and non coding region of
genome.
 They can affect gene function.

10. SNP
 Most SNPs are not responsible for a
disease state.
 Alzheimer’s disease:
 Genes associated are ApoE.
 Two SNPs in 3 alleles for this gene:Ɛ2, Ɛ3,
and Ɛ4.
 Individuals with Ɛ4 allele have greater
chance.
 Two Ɛ4 alleles never but two Ɛ2 alleles may
develop disease.
 Directly responsible for genetic disease.

11. SNPS AND ITS TYPES
 Transition
 Substitution between purine (A,G) or
pyrimidine (C,T).
 Involve bases of similar shape.
 Constitutes 2/3 0f all SNPs.
 Transversion
 Interchange of purine for pyrimidine bases,
 Involve exchange of one-ring and two-ring
structures.

13. 2-TANDEM REPEAT POLYMORPHISMS
 Series of nucleotides sequence repeated in
tandem (i.e; one time after another).
 Short tandem repeat (STRs).
 Microsatellite (2-6base pairs).
 Mini satellite and VNTR (11-60 base pair)
 Cause monogenic disease such as
Huntington’s disease.

16. 3-STRUCTURAL VARIANTS
 Deletion
 Inversion
 Duplication
 Translocation

18. 4-RESTRICTION FRAGMENT LENGTH
POLYMORPHISM
 Variations in DNA sequences at sites
recognized by restriction enzymes.
 Process
 DNA extraction
 DNA fragmentation
 Gel electrophoresis
 Visualization of bands

20. IDENTIFICATION
 Identified in laboratory using variety of
methods.
 PCR amplify sequence of genes.
 PCR steps:
 Denaturation
(process of separating dsDNA into single
strands)
 Annealing
( Joining of two strands together)
 Target sequence copied and amplified at an
exponential rate.

22. CLINICAL IMPLICATION
 Gene mapping
 Agriculture
 Biological research
 Disease identification
 Pharmaco-genomics
I. Pharmacokinetics
II. Pharmaco-dynamics
 Forensics
I. Crime science
II. Paternity

23. CONCLUSION
 It provides opportunity to integrate selection studies
with knowledge about molecular genetics and their
target.
 Polymorphism of gene-regulatory region is one of
major contributors of phenotypic variation between
and within population.
 Future studies in genetics will determine genes
residing in these phenotypes to map gene
functions.

24. THANK YOU
For your attention!