1 / 11

Mark de Pristo

What fraction of human genetic variation has now been described?. Mark de Pristo. But 1-2% of 3 billion is still a lot! . The fraction of variants that is novel varies by type. 3-4,000,000 variants per individual 97.8% of variants in NA12891 are in pilot data

giulio
Télécharger la présentation

Mark de Pristo

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. What fraction of human genetic variation has now been described? Mark de Pristo But 1-2% of 3 billion is still a lot!

  2. The fraction of variants that is novel varies by type • 3-4,000,000 variants per individual • 97.8% of variants in NA12891 are in pilot data • 10-11,000 nonsynonymouschanges • 95% of this class in NA12891 are in pilot data • 80-100 premature stop codons • 88% of this class in NA12891 are in pilot data • 50-100 HGMD “recessive disease causing” mutations • 85% of this class in NA12891 are in pilot data 1000 Genomes Project pilot paper

  3. Functional variants are more likely to be rare

  4. Individuals in outbred populations will still carry many variants not in the 1000GP and other similar data sets • Exponential population growth in last 10,000 years gives long tips to the tree • In “big” populations, tips are hundreds of generations long, so tens of thousands of private variants per sample, hundreds functional

  5. This behaviour is very dependent on population structure.In genetic isolates the tree relating haplotypes is smaller, and the tips are shorter

  6. Isolates share recently diverged chromosomes with long shared haplotypes

  7. Case study: Kuusamo • Settled by 34 families in 1680s • Small indigenous Lapp population disappeared rapidly • Very little immigration after initial settlement • Current population ~20 000 • Enriched phenotypes, e.g. scizophrenia

  8. Fit population simulation modelto genotype data from a fixed sample “Nx plot”: x% of new sample DNA is shared in segments of length >y Best fit model With ~2% migration per generation 100 founders, no migration 4 generations with 2x growth, 8 generations with 1.25x growth KimmoPalin

  9. Orcades population simulation 20 subpopulations (parishes), constant size 1/3 of census 1841 size, endogamy within parishes >~50% from records, 40 generations, immigration generations 20-29 (1400-1670) KimmoPalin

  10. How much variation do we cover with how much sequence? In the end, each individual carries private mutations • Kees Albers, KimmoPalin, KarolaRehnstrom,Leopold Parts, AylwynScally, Jared Simpson,Weldon Whitener

More Related