SNPs and the Human Genome

Prof. Sorin Istrail

A SNP is a position in a genome at which two or more different bases occur in the population, each with a frequency >1%.

GATTTAGATCGCGATAGAGGATTTAGATCTCGATAGAG

Single Nucleotide Polymorphism (SNP)

• The most abundant type of polymorphism

The two alleles at the site are G and T

tttctccatttgtcgtgacacctttgttgacaccttcatttctgcattctcaattctatttcactggtctatggcagagaacacaaaatatggccagtggcctaaatccagcctactaccttttttttttttttgtaacattttactaacatagccattcccatgtgtttccatgtgtctgggctgcttttgcactctaatggcagagttaagaaattgtagcagagaccacaatgcctcaaatatttactctacagccctttataaaaacagtgtgccaactcctgatttatgaacttatcattatgtcaataccatactgtctttattactgtagttttataagtcatgacatcagataatgtaaatcctccaactttgtttttaatcaaaagtgttttggccatcctagatatactttgtattgccacataaatttgaagatcagcctgtcagtgtctacaaaatagcatgctaggattttgatagggattgtgtagaatctatagattaattagaggagaatgactatcttgacaatactgctgcccctctgtattcgtgggggattggttccacaacaacacccaccccccactcggcaacccctgaaacccccacatcccccagcttttttcccctgctaccaaaatccatggatgctcaagtccatataaaatgccatactatttgcatataacctctgcaatcctcccctatagtttagatcatctctagattacttataatactaataaaatctaaatgctatgtaaatagttgctatactgtgttgagggttttttgttttgttttgttttatttgtttgtttgtttgtattttaagagatggtgtcttgctttgttgcccaggctggagtgcagtggtgagatcatagcttactgcagcctcaaactcctggactcaaacagtcctcccacctcagcctcccaaagtgctgggatacaggtgtgacccactgtgcccagttattattttttatttgtattattttactgttgtattatttttaattattttttctgaatattttccatctatagttggttgaatcatggatgtggaacaggcaaatatggagggctaactgtattgcatcttccagttcatgagtatgcagtctctctgtttatttaaagttttagtttttctcaaccatgtttacttttcagtatacaagactttgacgttttttgttaaatgtatttgtaagtattttattatttgtgatgttatttaaaaagaaattgttgactgggcacagtggctcacgcctgtaatcccagcactttgggaggctgaggcgggcagatcacgaggtcaggagatcaagaccatcctggctaacatggtaaaaccccgtctctactaaaaatagaaaaaaattagccaggcgtggtggcgagtgcctgtagtcccagctactcgggaggctgaggcaggagaatggtgtgaacctgggaggcggagcttgcagtgagctgagatcgtgccactgcattccagcctgcgtgacagagcgagactctgtcaaaaaaataaataaaatttaaaaaaagaagaagaaattattttcttaatttcattttcaggttttttatttatttctactatatggatacatgattgatttttgtatattgatcatgtatcctgcaaactagctaacatagtttattatttctctttttttgtggattttaaaggattttctacatagataaataaacacacataaacagttttacttctttcttttcaacctagactggatgcattttttgtttttgtttgtttgtttgctttttaacttgctgcagtgactagagaatgtattgaagaatatattgttgaacaaaagcagtgagagtggacatccctgctttccccctgattttagggggaatgttttcagtctttcactatttaatatgattttagctataggtttatcctagatccctgttatcatgttgaggaaattcccttctatttctagtttgttgagattttttaattcatgtgattgcgctatctggctttgctctca

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Human Genome contains ~ 3 G basepairs arranged in 46 chromosomes.

Two individuals are 99.9% the same. I.e. differ in ~ 3 M basepairs.

SNPs occur once every ~600 bp

Average gene in the human

genome spans ~27Kb

~50 SNPs per gene

G C T C G A C A A C A GG T T C G T C A A C A G

Two individuals

C A G HaplotypesT T G

SNP SNP SNP

Haplotype

Mutations

Infinite Sites Assumption:

Each site mutates at most once

Haplotype Pattern

0 0 0 01 1 0 10 0 1 00 1 0 1

C A G TT T G AC A T GC T G T

At each SNP site label the two alleles as 0 and 1.

The choice which allele is 0 and which one is 1

is arbitrary.

G T T C G A C T A T T A

G T T C G A C A A C A TA C G T A T C T A T T A

Recombination

G T T C G A C T A T T A

G T T C G A C A A C A TA C G T A T C T A T T A

The two alleles are linked, I.e., they are “traveling together”

?

Recombinationdisrupts the linkage

Recombination

Variations in Chromosomes Within a Population

Common Ancestor

Emergence of Variations Over Time

time present

Disease Mutation

Linkage Disequilibrium (LD)

Time = present

2,000 gens. ago

Disease-Causing Mutation

1,000 gens. ago

Extent of Linkage Disequilibrium