genetic polymorphism

GENETIC POLYMORPHISM

GENETIC POLYMORPHISMSALWA HASSAN TEAMA

HUMAN GENETIC VARIATION

Difference and variation of genetic make up among individuals.

Genetic polymorphism promotes

diversity within a population.

Genetic polymorphism: A difference in DNA sequence among individuals, groups, or populations.

The DNA of most people is 99.9% the same. Although we are look quiet different from one another.

DNA and Human Diversity

GENETIC POLYMORPHISM .

www.centenary.edu 

A genetic polymorphism is the existence of two or more variants - which may be allelic, phenotypic, chromosomal or general DNA sequence variants - at significant frequencies in a population. A frequency of 1% or more is generally considered to be a polymorphism.

Source: Wikipedia

SOURCE OF GENETIC VARIATION

Mutation include

Single nucleotide polymorphism

Insertions/ Deletions

Structural variation• Copy number variation

• Inversion/Translocation

Sequence repeats Recombination ……………….

Single Nucleotide Polymorphism (SNPs)

Sequence repeatsStructural variation Recombination

SOURCE OF GENETIC VARIATION

www.bmj.com  

SINGLE NUCLEOTIDE POLYMORPHISM

The quality of existing in several different forms

SNP is a source variance in a genome. SNPs are the most simple form and most common source of genetic polymorphism in human genome (90% of all human DNA polymorphism).

SNPs begin their existence as point mutations (nonsense mutation).

Two types of nucleotide base substitutions resulting in SNPs:Transition: Substitution occurs between purines or pyrimidines. Account 2/3 of all SNPs.Transversion: Substitution occurs between purines and a pyrimidines.

Single Nucleotide Polymorphism

DISTRIBUTION OF SNPS

The substitution causes no amino acid change to the protein it produces (silent mutation).

Synonymous

The substitution results in an alteration of the encoded amino acid. A missense mutation changes the protein by causing a change of codon. A non sense mutation results in a misplaced termination codon. One half of all coding sequence SNPs result in non-synonymous codon changes

Non Synonym

ous

CODING REGION SNPS

SNPs may also occur in regulatory regions of genes. These SNPs are capable of changing the amount or timing of a protein production.

PHENOTYPE, GENOTYPE AND HAPLOTYPE

mics.org

INSERTION/DELETION POLYMORPHISM

“Indel,” is a type of genetic variation in which a specific nucleotide sequence is present (insertion) or absent (deletion). While not as common as SNPs, indels are widely spread across the genome

An indel in the coding region of a gene that multiples of 3 nucleotides result in a protein with extra amino acids (insertion) or loss of amino acids (deletion) or is not a multiple of 3 nucleotides results in a frameshift mutation; shifting the reading frame and the DNA transcript sequence may now code for an entirely different set of amino acids or result in a premature stop codon, altering the protein structure and function.

Source: http://link.springer.com/referenceworkentry/10.1007%2F978-1-4419-1005-9_706

SEQUENCE REPEATS

Major categories of repeated sequence or repeats:• Tandem repeats: copies which lie adjacent to each other, either directly or

inverted• Satellite DNA  • Minisatellite  • Microsatellite

• Interspersed repeats (aka. interspersed nuclear elements)• Transposable elements • SINEs (Short Interspersed Nuclear Elements) • LINEs (Long Interspersed Nuclear Elements)

RECOMBINATION

RECOMBINATION

Recombination one mechanism for the generation of genetic diversity through the exchange of genetic material between two homologous nucleotide sequences.

Alternation of the primary structure of the gene lead to alteration of the encoded protein product.

Recombination Homologous recombination, Site-specific recombination and Transposition.

Homologous recombination; the process of genetic exchange that occurs between any two molecules of DNA that share a region (or regions) of homologous DNA sequences. Occurs frequently while sister chromatids are paired during meiosis, it generally involves exchange of large regions of the chromosomes.

Site specific recombination involves exchange between much smaller regions of DNA sequence (approximately 20 - 200 base pairs), events occur primarily as a mechanism to alter the program of genes expressed at specific stages of development.The most significant site-specific recombinational events in humans are the somatic cell gene rearrangements that take place in the immunoglobulin genes during B-cell differentiation in response to antigen presentation.

DNA Transposition is a unique form of recombination where mobile genetic elements can virtually move from one region to another within one chromosome or to another chromosome entirely. Transposition occurs with a higher frequency in bacteria and yeasts than it does in humans.  

Pharmacogenomics The science of understanding the correlation between an individual patient`s genetic make-up (genotype) and the their response to drug treatment.

SNP Diagnostics ; SNPs in Functional Proteomics; SNPs and precancerous conditions and cancer

susceptibility ; GeneTherapy

USE AND IMPORTANCE OF SNP

GENETIC VARIATION AND HUMAN DISEASES

In certain parts of Africa, however, the same allele is polymorphic because it confers resistance to the blood-borne parasite that causes malaria.

ALLELE OF SICKLE-CELL DISEASE

SNP MAPPING• SNP involves identifying SNP sites along the genome

to track disease genes. • A human SNP map specifies the contribution of

individual genes to diseases and other phenotypes.• SNP maps will help them identify the multiple genes

associated with complex ailments such as cancer, diabetes, vascular disease, and some forms of mental illness. These associations are difficult to establish with conventional gene-hunting methods because a single altered gene may make only a small contribution to the diseaseHAPLOTYPE MAP

• The maps purpose is to relate human genetic variation with disease predisposition, specifically common or complex disorders.

MUTATION OR POLYMORPHISM

Use and Importance of SNP

Ali Khalifa. Applied molecular biology; eds: ( Fathi Tash and Sanna Eissa). 109 pages. Egypt. University Book Center. 2002.

Daniel H. Farkas. DNA Simplified: The Hitchhiker's Guide to DNA. 110 pages. Washington, DC: AACC Press, 1996, ISBN 0-915274-84-1. Available in paper copy from the publisher

Innis, David H. Gelfand, John J. Sninsky. PCR Applications: Protocols for Functional Genomics: 566 pages. Academic Press; 1 edition (May 17, 1999). ISBN:0123721865.

Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Molecular Biology of the cell. 1392 pages. Garland Science; 5 edition (November 16, 2007).ISBN. 9780815341055.

Robert F. Mueller, Ian D. Young. Emery's Elements of Medical Genetics: Publisher: Churchill Livingstone. 1995 ISBN. 044307125X.

Robert F. Weaver. Molecular Biology. 600 Pages. Fourth Edition. McGraw-Hill International Edition. ISBN 978-0-07-110216-2.

William B. Coleman, Gregory J. Tsongalis . Molecular Diagnostics. For the Clinical Laboratorian: 592 pages. Humana Press; 4th Printing. edition (August 15, 2005). ISBN 1588293564

• http://www.brooklyn.cuny.edu/bc/ahp/BioInfo/GP/Relationship.htl• http://www.ornl.gov/sci/techresources/Human_Genome/faq/snps.shtml• http://genome.wellcome.ac.uk/doc_wtd020780.html• http://hapmap.ncbi.nlm.nih.gov/whatishapmap.html• http://medicine.jrank.org/pages/1921/Balanced-Polymorphism.html

REFERENCES &FURTHER READING

All images belong to their respective authors Thank You