Table of ContentsGenomics: sequence and variationGenetics: the inherited contribution to phenotypic variation Example: inherited contribution to risk of type 2 diabetes Correlating biological variation with variation in DNA sequence Available tools work well at finding single genes with a big impact on risk of disease Finding the genes for monogenic diseases PPT Slide PPT Slide Human Genetics 1985 - . . . PPT Slide But little success for common diseases caused by multiple genes and environment And most common diseases are caused by a combination of genes and environment PPT Slide Most DNA variants change a single DNA letter: single nucleotide polymorphism (“SNP”) PPT Slide PPT Slide Question: what is the contribution of rare vs. common variation? PPT Slide Understanding polymorphism rate: Humans are small population, that grew large fast PPT Slide PPT Slide Association studies with common variants offer the greatest statistical power Finding variants that influence function Common variants found in the coding region of 106 human genes (n=114 chromosomes) Regulatory variants: how many? Finding new regulatory elements Can we comprehensively characterize all the common genetic variation across the genome? It will be critical to test variation across each gene, not just in the coding region Disease association: direct and indirect Disease association: direct and indirect Humans are small population, that grew large fast PPT Slide Disease association: Indirect Disease association: Indirect Building a genome-wide catalogue of SNPs An explosion in publicly available SNPs PPT Slide How correlated are nearby SNPs? Extent of SNP correlation: pairs of markers Fine structure of LD in each region Fine structure of LD in each region Patterns of LD across a region reveal block structure PPT Slide PPT Slide Summary of blocks: low historical recombination provisional definition of a‘block’: a set of contiguous SNPs for which all pair-wise comparisons show D’?.8 Haplotype Map of Human Genome LD Mapping in Practice: Inflammatory Bowel Disease PPT Slide PPT Slide PPT Slide The “red” haplotype is a major risk factor for Crohn’s Disease “Candidate Gene” studies Testing previous T2DM associations Testing previous T2DM associations Direct Association Study: Type 2 Diabetes What is PPARg? PPARg P12A and type 2 diabetes Meta-analysis of all published studies Implications Conclusions: potential impact of genetics on medical practice Overall conclusions |
Author: David Altshuler
Email: altschul@genome.wi.mit.edu Home Page: http://theory.lcs.mit.edu/~bab/01-18.417-home.html Other information:
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