Short introduction to Human Variation

Lasse FolkersenCenter for Biological Sequence analysis

Technical University of Denmark

Human 1AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 4AGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 5ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTTGA

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SNP

Human 1AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 4AGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 5ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTTGA

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SNP1 SNP2 SNP3?

SNP

Human 1AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 4AGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 5ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTTGA

33M letters

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SNP1 SNP2 SNP3?(50%) (0.1%)(1%)

SNP

Human 1AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3AGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 4AGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 5ACGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTTGA

33M letters

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SNP: One nucleotide difference occuring in at least 1% of a population

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rs2278007 rs16891982 mutation

1.0.01% (eg. 300k)

2.0.1% (eg. 3 million)

3.1% (eg. 30 million)

4.10% (eg. 300 million)

Question: How many SNPs differ on average between two people?

Human: 3 billion base-pairs~ one base pair out of every 1,000 will be different between any two individuals

Another similar project?

Human 1: European ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2: Mixed ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3: Asian ancestryAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

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SNP: rs16891982 – ethnicity dependent

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C-frequency Scandinavia2%

C-frequency China:99.9%

Practically no Chinesehave GG

Human 1: European ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2: Mixed ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3: Asian ancestryAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

GorillaAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

DogAGGAAAACACGGAATTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAATTGATGCA G AAGCCCCAACATCCAACCTCGA

33M letters

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SNP: rs16891982 – ethnicity dependent

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Human 1: European ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 3: Asian ancestryAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

GorillaAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

DogAGGAAAACACGGAATTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAATTGATGCA G AAGCCCCAACATCCAACCTCGA

33M letters

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SNP: rs16891982 – non-synonymous coding

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E V G C W G F/L C I N S V F SAmino acids:

Human 1: European ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGA

Human 2: Mixed ancestryAGGAAAACACGGAGTTGATGCA G AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

Human 3: Asian ancestryAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGAAGGAAAACACGGAGTTGATGCA C AAGCCCCAACATCCAACCTCGA

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SNP: rs16891982 – hair colour associated

1

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Unravelling a hair-colour SNP

Hair colour and genome-wide association studies (GWAS)

Results from largest hair colour GWAS: there are many hair-colour SNPs

Hair colour and genome-wide association studies (GWAS)

Results and conclusions

Human 1 Phenotype: average scandinavianGenotype-rs16891982 : light homozygousGenotype-others: mixed

Human 3Phenotype: blackGenotype-rs16891982 : dark homozygousGenotype-others: almost all light colour

Human 2Phenotype: average scandinavianGenotype-rs16891982 : heterozygousGenotype-others: half mixed, half complete light