Short introduction to Human Variation Lasse Folkersen Center for Biological Sequence analysis Technical University of Denmark
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
33M letters
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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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147M 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
33M letters
147M 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
33M letters
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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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147M letters
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59M letters
73M letters
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SNP: rs16891982 – ethnicity dependent
34M letters
14M letters
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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147M letters
147M letters
59M letters
73M letters
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
33M letters
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SNP: rs16891982 – hair colour associated
1
32
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