The document discusses genetic polymorphism, defined as the presence of multiple forms of a gene in a population, particularly when variations exceed 1% frequency. It explains the structure and function of chromosomes, mutations, and the various types of polymorphisms such as single nucleotide polymorphisms and insertion-deletion polymorphisms. Key examples include the ABO blood group system and the HLA system, highlighting how genetic variations influence traits and biological functions in humans.

1. Genomics Proteomics &
Bioinformatics
Module 1
Topic: Polymorphism & types

2. • Before we begin with the discussion on genetic polymorphism, it is essential that we understand what a
gene is?
• A gene can be defined as a segment of the DNA that specifies the sequence of amino acids in a particular
protein.
• Throughout the life cycle of a cell, it is the DNA that directs the cellular functions and exists in an uncoiled
granular form.
• However, during the life cycle of the cell, the normal activities of the cell might cease and the cell divides.
• Cell division results in the production of new cells.
• At this stage, the DNA is highly coiled and visible under a microscope as a discrete structure called
chromosomes.
• During the early stage of cell division, when the chromosomes become visible, they are made up of two
strands or two DNA molecules that are joined together at a constricted area called the centromere.
• Chromosomes are present in identical sets of two (or in pairs).
• Humans have 46 chromosomes or 23 sets of chromosomes.
• Of these, 22 pairs are autosomes and other two are sex chromosome that is X and Y. The sex
chromosomes determine the sex that is either male or female.
• The autosomes are responsible for all physical characteristics of an individual except primary sex
determination.
• Human cells contain around 28000-30000 genes (Deloukas et al., 1998). These genes code for important
and necessary information that determine molecular traits that are passed on from parents to their
offspring.

3. • Genes encode various traits like hair color, eye color, skin color, hair texture, etc.
• Any change in the DNA sequence brings about change in the genetic information, which brings about
change in the phenotypic expression and also the associated biological function.
• The changes in the DNA sequence is known as a mutation.
• Physical anthropologists are concerned in understanding visible human variations as they are
interested not only in identifying the factors that produce visible physical variation but also the
underlying genetic determinants that dictate it.
• Genetic variations arise due to the differences in the DNA sequence among populations from the wild
type form.
• Each and every individual has two sets of genomes, one maternal and one paternal.
• Therefore, at each genetic location (locus), the alleles from the maternal and the paternal side, can
either have identical DNA sequence or slightly differing DNA sequence.
• The wild type form in a population refers to individuals with normal phenotype. The wild type form is
usually possessed by the majority of the individuals in the population.
• In contrast to this, mutant type refers to individuals with a phenotype that varies from the normal
population.
• These variations can also be referred to as homozygous if the alleles on both the chromosomes are
identical or heterozygous if they differ on any one of the chromosomes

4. POLYMORPHISM
• The term “polymorphism” is a combination of two Greek words “poly” meaning multiple and “morph” meaning
form, can be defined as a mendelian trait, which exists in a population, in at least two different forms. Ford,
1940 defines genetic polymorphism refers to the occurrence together in the same habitat of two or more
discontinuous forms or phases of a species in such proportions that the rarest of them cannot be maintained
by recurrent mutations.
• In simpler words, genetic polymorphism refers to the occurrence in the same population of two or more than
two alleles at the same locus in the same population, such that the frequency of the rarer allele is always
greater than one percent and the rarer allele is maintained in the population, not merely be recurrent
mutations (Cavalli-Sforza and Bodmer, 1971).
• In the nutshell, polymorphisms can be defined as the variations in the DNA sequence that are present in the
population, with the frequency of the variation being greater than 1 percent.
• In other words, it can be said that mutation frequency is more than 1 percent in a population, it is a
polymorphism. Insertions-deletions polymorphisms, single nucleotide polymorphisms, restriction site
polymorphisms or restricted fragment length polymorphism etc. are some of the examples of genetic
polymorphisms.
• Genetic polymorphism refers to the occurrence of multiple forms or variants of a particular gene within a
population. These variations are encoded in the DNA sequences and can manifest through differences in
nucleotide bases or changes in the structure and function of the gene.
• Genetic polymorphism can lead to diverse phenotypic characteristics and traits observed among individuals.

5. Definition:
Genetic polymorphism is a term used in genetics to describe multiple forms
of a single gene that exist in an individual or among a group of individuals
(Philips, 2016).
Causes of genetic polymorphism
Deletion and duplication of millions of base pairs of DNA.
Changes in one or a few bases in the DNA located between genes or
within exons.
Sequence changes may also be located in the coding sequence of genes
themselves and result in different
protein variants that may lead in turn to different phenotypes.

6. Mutation and polymorphism
 The main difference is of frequency
If frequency more than 1 % : polymorphism
If frequency less than 1 % : mutation
So we can infer that the mutation give rise to polymorphism
 The other difference is in effect
Mutation give rise to diseases
Polymorphism is sometimes neutral while some time dangerous.
HUMAN GENE POLYMORPHISM
When a nucleotide change is very rare, and not present in many individuals, it is often called a
mutation. In contrast to mutations, genetic polymorphisms are usually considered normal variants
in population. When a specific allele occurs in at least 1% of the population, it is said to be a
genetic polymorphism

8. Examples of Genetic Polymorphism
• ABO Blood Group System: The ABO blood group system is a classic example of genetic polymorphism. It is
determined by variations in the ABO gene, which results in the expression of different surface antigens on
red blood cells. The system includes four main blood types: A, B, AB, and O, with individuals having different
combinations of antigens, leading to diverse blood groups.
• Human Leukocyte Antigen (HLA) System: The HLA system is a highly polymorphic group of genes involved
in the immune response. Variations in HLA genes influence an individual's susceptibility to certain
autoimmune diseases, transplantation compatibility, and defense against infectious agents.
• Melanocortin-1 Receptor (MC1R) Gene: The MC1R gene is responsible for determining the production and
type of melanin, influencing hair and skin pigmentation. Genetic polymorphism in the MC1R gene
contributes to variations in hair color, ranging from red and blond to brown and black.
• CYP2D6 Gene: The CYP2D6 gene encodes an enzyme involved in drug metabolism. Genetic
polymorphism in this gene affects an individual's ability to metabolize certain medications, leading to
variations in drug response and potential adverse effects.

9. Causes of Genetic Polymorphism
• Mutation: Genetic mutations, such as point mutations, insertions, deletions, and chromosomal
rearrangements, are a fundamental source of genetic polymorphism. These mutations can occur
spontaneously or due to environmental factors, chemical exposure, or errors during DNA
replication.
• Genetic Drift: Random changes in allele frequency within small populations can lead to the
emergence and maintenance of genetic polymorphism. Genetic drift is particularly significant in
isolated populations or those with limited gene flow.
• Natural Selection: Environmental factors and selective pressures can favor certain alleles over
others, influencing the prevalence of genetic polymorphism. For instance, alleles that confer
advantages in adapting to specific environments or provide resistance to diseases may become
more common in a population over time.
• Gene Flow: Gene flow occurs when genetic material is exchanged between different populations
through migration and interbreeding. It can introduce new alleles into a population, contributing
to genetic polymorphism.
• Non-random Mating: Certain mating patterns, such as assortative mating (choosing partners with
similar traits) or disassortative mating (choosing partners with dissimilar traits), can lead to
genetic polymorphism by altering the distribution of alleles within a population.

10. Types of polymorphism
•Single nucleotide polymorphism (SNP)
•Insertion and deletion polymorphism (indel)
•Nucleotide repeat polymorphism / Variable
number of tandem repeats (VNTR)/ Microsatellite
variation

11. Diagramatic representation
…....

12. Single nucleotide polymorphism
• A Single Nucleotide Polymorphism is a source variance in a genome.
• A SNP (”snip”) is a single base mutation in DNA.
• SNPs are the most simple form and most common source of genetic polymorphism in the human genome
(90% of all human DNA polymorphisms).
• The most common form of polymorphisms is the single nucleotide polymorphism, which is a change in a
single base pair (bp) in the genomic DNA. Single nucleotide polymorphisms can affect gene function. For
example, a single nucleotide polymorphism located in a promoter region may influence the amount of
mRNA produced
• Human genome, that is the complete genetic material in a cell consists of about 3 billion base pairs. SNP
occurs in every 300 nucleotides, meaning that there are around 10 million SNPs that are present in the
human genome.
• All individual humans share genome sequences that are approximately 99.9%the same. 0.1% variable
region is responsible for the genetic diversity betweenindividuals.

13. • . e.g. SNP might change the DNA sequence ATGCCTA to
ATGCTTA.Individuals may be homozygotes (e.g. T/T or C/C),
or heterozygotes with different bases (e.g. T/C) at
polymorphic sites. For a variation to be considered a SNP it
must occur in at least 1% of thepopulation. ~7 million
common SNPs with a population frequency of at least 5%
across theentire human population.
• There are two types of nucleotide base substitutions
resulting in SNPs:
• • A transition substitution occurs between purines (A,
G) or between pyrimidines (C, T). This type of
substitution constitutes two thirds of all SNPs.
• • A transversion substitution occurs between a purine
and a pyrimidine.

14. CODING REGION SNPS
Synonymous : The substitution causes no amino acid change in the protein
that it produces
Non synonymous : The substitution results in an alteration of the
encoded amino acid. A missense polymorphism changes the
protein by causing a change of codon. It results in a misplaced
termination codon. One half of all coding sequence, SNPs result
in non-synonymous codon changes
SNPs may also occur in regulatory regions of genes. These SNPs are
capable of changing the amount or timing of a protein production.

15. Variable Number of Tandem Repeats (VNTR)
Nucleotide repeat polymorphism
• These are arrays of 2 or more base pair core units, located in the non- coding region of the
genome, adjacent to each other.
• Variable number of tandem repeats refer to a condition where the number of nucleotides in the
core unit is variable or is not known.
• On the basis of the size of the core unit, they can be categorized as either
• a) mini-satellites (10-60 bp) is a collection of moderately sized arrays, usually 10-60 base pairs of
tandemly repeated DNA sequences that are dispersed over considerable portions of the nuclear
genome.
• For example: GATACCCCAAAG GATACCCCAAAG GATACCCCAAAG is an array of 12
nucleotide repeats from 3-20 kbp.
• b) microsatellites or short tandem repeats is a small array of tandem repeats of a simple
nucleotide sequence which is usually less than 10 base pairs. For example, GATA GATA GATA
GATA GATA GATA has 4 bases repeated 6 times. TA TA TA TA TA TA is a dinucleotide repeat and
TAT TAT TAT TAT TAT is a trinucleotide repeat. The STRs were first used in the Persian Gulf War
in 1991 for identification of human remains.

16.  :
Another class of polymorphism is the simple sequence repeats, of which of 1 – 4bp

17. Insertion and deletion polymorphism:
• Another category of gene polymorphism involves insertions or deletions. Insertions and
deletions can be as small as 1 base, in which case they may also be classified in the category of
single nucleotide polymorphisms, but can also consist of a few bases, one or more exons, or
even a whole gene.
• These refer to genetic variations in which a sequence of DNA is either inserted or deleted from
the gene.
• The frequency of the occurrence of the insertion deletion polymorphism is only about one tenth of
the frequency of the SNPs.
Studies have shown that around 90 percent of the insertion deletions are of 1-10 nucleotides only.
• Around 9 percent have sequences involving 11 to 100 nucleotides, whereas only 1 percent have
sequences greater than 100 nucleotides (Mullaney et al., 2010).
• the common forms are the dinucleotide and trinucleotide repeats.

18. Microsatellite variation (tandem repeat