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PRESENTED BYBIPUL JYOTI DASM.Sc BIOTECHNOLOGY3RD SEMESTER ROLL NO: 17CENTRE FOR STUDIES IN BIOTECHNOLOGYDIBRUGARH UNIVERSITY

SINGLE NUCLEOTIDE POLYMORPHISM

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Single Nucleotide PolymorphismA Single Nucleotide Polymorphisms (SNP), pronounced

“snip,” is a genetic variation when a single nucleotide (i.e., A, T, C, or G) is altered and kept through heredity. ◦ SNP: Single DNA base variation found >6%◦ Mutation: Single DNA base variation found <1%

C T T A G C T T

C T T A G T T T

SNP

C T T A G C T T

C T T A G T T T

Mutation

94%

6%

99.9%

0.1%

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Mutations and SNPs

Common Ancestor

time present

Observed genetic variations

MutationsSNPs

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Each SNP location in the genome can have up to four versions: one for each nucleotide, A, C, G, and T

A SNP and its distribution in a population might look like the image to the right

Not all single-nucleotide changes are SNPs, though. To be classified as a SNP, two or more versions of a sequence must each be present in at least one percent of the general population

SNPs occur throughout the human genome—about one in every 300 nucleotide base pairs. This translates to about 10 million SNPs within the 3-billion nucleotide human genome

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SNPs and disease-causing mutations: Not the same!

First, to be classified as a SNP, the change must be present in at least 1% of the general population. No known disease-causing mutation is this common

Second, most disease-causing mutations occur within a gene's coding or regulatory regions and affect the function of the protein encoded by the gene. Unlike mutations, SNPs are not necessarily located within genes, and they do not always affect the way a protein functions

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SNPs are divided into two maincategories:

SNPs

Linked SNPs

Causative SNPs

Coding SNPs

Non-coding SNPs

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Linked SNPs

Also called indicative SNPs

They do not reside within genes and do not affect protein function . Nevertheless, they do correspond to a particular drug response or to the risk for getting a certain disease

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Causative SNPs

Causative SNPs affect the way a protein functions, correlating with a disease or influencing a person's response to medication

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Coding SNPs Located within the

coding region of a gene, change the amino acid sequence of the gene's protein product

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Non-coding SNPs Located within

the gene's regulatory sequences, change the timing, location, or level of gene expression

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eSNP ( Expression SNP )SNPs that are not present in the coding - coding

region may still affect gene splicing , transcription factor binding , Messenger RNA degradation, or the sequence of noncoding RNA

Gene expression affected by this type of SNP is referred to as an eSNP and may be present upstream or downstream from the gene

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Finding SNPs in the human genome Scientists approach the problem of identifying ,

cataloging, and characterizing SNPs in two main ways:

Genomic approaches

Functional approaches

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What are the effects of SNPs ?Where Result Effect

In cod-ingregion

May be silent, o.g.,UUG→CUG, leu in both cases

sSNP Usually no change inphenotype

In cod-ing re-gion

May change amino acid sequence, e.g., UUC→UUA,phe to leu, Some characterize these as the least common and most valuable SNPs, Many being patented

cSNP*

Phenotype change(may be subtle depending on amino acid replacement andposition)

In cod-ing re-gion

May create a "Stop"codon, e. g., UCA→UGA, ser to stop

Phenotype change

In cod-ing re-gion

May affect the rate of transcription(up-or down-regulate)

cSNP*

Possible pheno-type Change

Other regions

No affect on gene products(7). May act as genetic markers for multi-compo-nent diseases. These are sometimes called anonymous SNPs and are the most common.

rSNP*

*cSNP – coding *rSNP – regulatory

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SNP analysisAnalytical methods to discover novel SNPs and detect known SNPs include:

DNA sequencingCapillary electrophoresisMass spectrometryElectrochemical analysisGel electrophoresisRestriction fragment length polymorphism etc

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A wide range of human diseases result from SNPs.

Sickle–cell anemia β Thalassemia Cystic fibrosis etc

Sickle–cell anemiaSickle cell disease (SCD): a recessively

inherited chronic hemolytic anemia

Caused by a single nucleotide substitution in the β globin gene on chromosome 11

Hemoglobin S (most common): GTG GAG

results in substitution of valine (hydrophobic) for glutamate (hydrophilic)

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Applying SNP profile to drug choices

The drug Albuterol is commonly prescribed to relieve the symptoms of asthma

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Albuterol effectively relieves asthma symptoms in some people but not in others. Scientists are currently studying how people with different SNP profiles respond to treatment with albuterol.

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Albuterol acts on the beta -2 adrenergic Receptor ( beta 2AR protein) to relieve asthma attacks.

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The beta2AR protein is encoded by the ADRB2 gene.

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In analyzing a 3000 base pair stretch of the ADRB2 gene , scientists have identified 13 locations where SNPs exists.

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Scientists have looked at this region of DNA in many different people , and have identified 12 different haplotypes , which are unique combination of these 13 SNPs.

A set of closely linked genetic markers present on one chromosome

which tend to be inherited together (not easily separable by

recombination)

HAPLOTYPE

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We need to remember that Haplotypes come in pairs ( one from mother and one from father ). Each distinct haplotype pair represents a unique SNP profile.

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This pie chart shows the frequencies of several common SNP profiles found in people with Asthma.

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When scientists administer to the five most common SNP profiles. Albuterol helps people with profiles B and E a great deal , while people with profile D were not helped at all.

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In the future , a physician will be able to determine a patient profile, compare it with known data, and predict whether the patient will respond to the drug Albuterol.

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The physician can then design the patients treatment accordingly . This will be great improvement over a trial and error method physicians used today.

Recent Research Association of interleukin-1β–511 C/T polymorphism with tobacco-

associated cancer innortheast India: a study on oral and gastric cancer

M Lakhanpal, DS Yadav, TR Devi, LC Singh, KJ Singh… - Cancer genetics, 2014 - Elsevier

A pilot study evaluating genetic alterations that drive tobacco-and betel quid-associated oral cancer in Northeast India

DS Yadav, I Chattopadhyay, A Verma, TR Devi… - Tumor Biology, 2014 - Springer

Accumulation of mutations over the complete mitochondrial genome in tobacco-related oral cancer from northeast India

R Mondal, SK Ghosh - Mitochondrial DNA, 2013 Molecular diagnosis of Wilson disease using prevalent mutations

and informative single-nucleotide polymorphism markers A Gupta, M Maulik, P Nasipuri… - Clinical …, 2007 - Am Assoc Clin

Chem

References^ Nachman, Michael W. (2001). "Single nucleotide polymorphisms and recombination rate in humans". Trends in genetics 17 (9): 481–485. (https://www.ncbi.nlm.nih.gov/pubmed/11525814).

^ Sachidanandam, Ravi; Weissman, David; Schmidt, Steven C.; Kakol, Jerzy M.; Stein, Lincoln D.; Marth,Gabor; Sherry, Steve; Mullikin, James C. et al. (2001). "A map of human genome sequence variation containing1.42 million single nucleotide polymorphisms". Nature 409 (6822): 928–33. (https://www.ncbi.nlm.nih.gov/pubmed/11237013).

^ Fareed, M., Afzal, M (2013) "Single nucleotide polymorphism in genome-wide association of humanpopulation: A tool for broad spectrum service". Egyptian Journal of Medical Human Genetics 14: 123–134..

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References

Websites https://www.ncbi.nlm.nih.gov/pubmed/88735 http://en.wikipedia.org/wiki/Single-nucleotide_polymorphism http://www.nature.com/nrg/journal/v5/n2/glossary/

nrg1270_glossary.html http://www.SNPedia.com http://sickle.bwh.harvard.edu/scd_background.html http://ghr.nlm.nih.gov/handbook/genomicresearch/snp

THANK YOU !