Genetic polymorphism Genetic polymorphism is the inheritance of a trait controlled by a single genetic locus with two alleles, in which the least common allele has a frequency of about 1% or greater. Genetic polymorphism is a difference in DNA sequence among individuals, groups, or populations. Types of polymorphisms Protein/enzyme polymorphisms In the early days of human genetics, majority of polymorphisms were those associated with proteins and enzymes. To detect the polymorphism and a person’s genotype, one performed assays for the gene product, i.e., the protein or enzyme produced by the genetic blueprint. DNA polymorphisms The large class of polymorphisms are those that detect Slight variations at the level of DNA nucleotides. Single nucleotide polymorphisms A single nucleotide polymorphism or SNP is a sequence of DNA on which humans vary by one and only one nucleotide . Because humans differ by one nucleotide per every thousand or so nucleotides, there are millions of SNPs scattered throughout the human genome. Tandem repeat polymorphisms A tandem repeat polymorphism consists of a series of nucleotides that are repeated in tandem (i.e., one time after another). The polymorphism consists of the number of repeats. Restriction Fragment Length Polymorphism (RFLP) Restriction Fragment Length Polymorphism (RFLP) is a type in which organisms may be differentiated by analysis of patterns derived from cleavage of their DNA. If two organisms differ in the distance between sites of cleavage of a particular restriction endonuclease, the length of the fragments produced will differ when the DNA is digested with a restriction enzyme. Applications of Genetic Polymorphism The study of polymorphism has many uses in medicine, biological research, and law enforcement. Genetic diseases may be caused by a specific polymorphism. Scientists can look for these polymorphisms to determine if a person will develop the disease, or risks passing it on to his or her children.

1. Genetic Polymorphism
Awais Ali
(Email; awaismalik0306@gmail.com)
University of Agriculture Faislabad,
Pakistan

2. •History
•Introduction
•Differences
•Types
•Identification
•Clinical Significance
•Applications
•Conclusion
•References
Contents

3. •Originally defined by Ford in 1940.
•E. B. Ford and his co-workers from(1920-70s) worked on
it.
•Later Cavalli-Sforza & Bodmer defined in 1971.
•Occurrence of multiple alleles at one locus in same
population, where at least two alleles occur with
minimum frequency is 1%.
History

4. •Genetics derived genetikos meaning
"generative" derived , genesis meaning "origin".
•Study of Genes ,Genetic variation and Heredity in
living organisms.
➢Polymorphism
•Combination of Greek words poly (multiple) and
morph (form).
•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 .
Introduction

5. •Some polymorphisms are visible.
•e.g dogs E locus, five different alleles(E, Em, Eg, Eh,
e)contribute to pigmentation and patterns in dog coats.
➢ Genetic Mutation
• DNA sequence not present in most individuals of species
either associated with disease or resulted from damage
caused by external agents.

6. Types of Genetic Polymorphism
1.DNA Polymorphism.
Polymorphisms that detect Slight variations
at the level of DNA .
2. Protein/Enzymes Polymorphism
DNA Polymorphism
Single Nucleotide
Polymorphism
Tandem repeat
polymorphism
Structural variants
Restriction
Fragment Length
Polymorphism
(RFLP)

7. Types of DNA Polymorphism
1.Single Nucleotide Polymorphism
•A single nucleotide (A,T,C,G) in genome sequences is
altered .
• Detect in highly automated by using DNA ‘Chip’
•Most common and simple , accounting 90% human
genetic variation.
•500-1,000 bases to several millions SNPs in human
population.
• May occur in Coding and Non Coding region of
genome.
•May cause disease, used to search and isolate disease-
causing gene.

8. GCA
T
GCG T A
GCA
T
T C G T A
GCA
T
ACG T A
TCTAAGTCCGTATAA
AGATTCAGGCATATT
TCTAAGTCCGTATAA
TCTAAGTCCGTATAA
AGATTCAGGCATATT
TCTAAGTCCGTATAA
TCTAAGTCCGTATAA
AGATTCAGGCATATT
TCTAAGTCCGTATAA
Green
Yellow
Red
Normal
Carrier
Disease
A C T C A G T T T A
Single Nucleotide polymorphism
SNP
These are position in a genome where some individual have
one nucleotide (e.g.a.G) and others have different nucleotide
(e.g.a. C)
AGATTCAGGCATATT
AGATTCAGGCATATT
AGATTCAGGCATATT
Each SNP could,potentially,have
four alleles
(because there are four
nucleotides)
A C T C A G T T G A
General population
96%

9. •Most SNPs are not responsible for a disease state.
➢Alzheimer’s disease:
•Genes associated are ApoE.
•Two SNPs in 3 alleles for this gene: ε2, ε3, and ε4.
•Individual with ε4 allele have greater chance.
• Two ε4 alleles never but two ε2 alleles may develop
disease.
• Directly responsible for genetic disease
SNPs and Its Types
➢Types of SNPs:
▪ Transition
Substitution between purine (A, G) or pyrimidine (C,
T). Constitutes 2/3 of all SNPs.
▪ Transversion:
Substitution occurs between purine and pyrimidine

10. 2.Tandem repeat polymorphisms
•Series of nucleotides Sequence
repeated in tandem (i.e., one
time after another).
•(6.6×109bp in genome)
• GATA sequence.
•Simple sequence repeat (SSR).
•Short tandem repeat (STR).
•Microsatellite(2-6 base pairs).
•Mini satellite and VNTR(11-
60 base pairs).
…CTAGAGATAGATAGATAGATACTAG…
…CTAGAGATAGATAGATAGATAGATAGATAGATAGATACTA
G…
…CTAGAGATAGATAGATAGATAGATAGATAGATAGATAGATACTAG…
4 allele
Repeat
8 allele Repeat
11allele Repeat
Tandem repeat region
Repeat unit
Sequence

11. 3.Structural variants
Slight variation of nucleotide sequence.
➢Deletion
➢Inversion
➢Duplication
➢Translocation

12. A B C D E
A B
B
B
A
A
C
C
C
D
D
D
E
E
E F G H
F G H
F G H
F G H F G H
F G H
F G H
F G H
A B C E
A B C B C D E
A B D C E
M N O C D E
A B P Q RM N O P Q R
DELETION
DUPLICATION
INVERSION
TRANSLOCATION
D

13. 4.Restriction Fragment Length Polymorphism (RFLP)
➢Process
• Analysis.
•Enzyme(restriction
endonuclease).
• Length Variation.
• Identification.
➢Applications:
•Criminal cases.
•Disease status.
•Biotechnology

14. Gene of
interest
Environmental
microbe sample
(Single community)
Extract
Total DNA
PCR amplify
Gene of interest
Add fluorescent
primer
Copy & label
Restriction
digest
Different sizes of labeled
fragments
Electrophoresis
Laser
detection
Fragment length
Electropherogram
Fluorescenceintensity

15. 2.Protein/Enzyme Polymorphism
•Majority associated with proteins
and enzymes.
•Detection of polymorphism and
genotype.
•Detection of blood group,
•A,B,AB or O etc
•Phenotype and Rhesus factor
•Blood transfusion
•Modren genetic research

16. •Identified in laboratory using variety of
methods.
•PCR amplify sequence of gene.
•Amplification of specific DNA sequence.
• Polymorphism and mutation detected
by DNA sequencing.
•PCR Steps:
•Denaturation.
•Annealing.
•Synthesis.
•Target sequence copied and amplified at an
exponential rate.
•Qualitative method for identifying DNA.
Identification

17. Thermal Cycler PCR Cycle
Taq Polymerase
PCR Tube
Primer
G
T
C
A
Nucleotides
DNA Sample
C
95C - Strand Separate 1-Denaturation
2-Annealing
3-Extension
55C - Primer bind strand
72C – Synthesis new strand

18. Clinical Significance
➢Lungs Cancer
Polymorphism discovered in multiple XPD exons.
•‘XPD’ involve DNA repair mechanism during
replication
•Two common polymorphism
•Asp312Asn
•Lys751Gln
•Both result in a change of single Amino acid
➢Asthma
•Inflammatory disease of lungs
•There are many genes for asthma as, one is CD14
•Cause polymorphism in which increase of CD14
protein with low IGE serum

19. Applications
•Gene Mapping
• Pharmacogenomics.
(I) Pharmacodynamics
(II) Pharmacokinetics
•Forensics.
(I) Crime Scene
(II) Paternity
•Agriculture.
•Biological research.
•Disease Identification.

20. •Role of genome in drug response.
•Pharmaco-genomics reflects
combination
of pharmacology and genomics.
•Genetic makeup of an individual affects
his response to drugs.
•Genomics and epi-genetics dealing with
effects of multiple genes on drug
response.
Pharmacogenomics

21. •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 genes functions.
Conclusion

22. 1. Chanock,stephen (2017) technologic issues in
GWAS and follow-up studies.
2. Karki,Roshan,cristiano(2015) Medical genomics.
3. March ME,sleiman PM,(2013) Genetic
polymorphism and associated susceptibility to
asthma
4. "Genetic Testing Report” National Human Genome
Research Institute (NHGRI).
5. Articles
http://medicine.jrank.org/pages/2665/Polymorphis
ms-Uses-Polymorphisms.html.
6. Sheppard, Philip M. 1975. Natural Selection and
Heredity (4th ed.) London: Hutchinson.
References