Haplot的ype analysis.pptVIP

Haplotype analysis Shaun Purcell shaun@ MGH, Boston A a M aM m am This individual has aa and Mm genotypes and am and aM haplotypes Haplotypes A a M AM m Am This individual has AA and Mm genotypes and AM and Am haplotypes A a M AM m am This individual has Aa and Mm genotype and AM and am haplotypes… A a M AM m am This individual has Aa and Mm genotype and AM and am haplotypes… but given only genotype data, consistent with Am/aM as well as AM/am Haplotype analysis Estimate haplotypes from genotypes Associate haplotypes with trait Haplotype Freq. Odds Ratio AAGG 40% 1.00* AAGT 30% 2.21 CGCG 25% 1.07 AGCT 5% 0.92 * baseline, fixed to 1.00 Measuring haplotypes Expectation – Maximisation algorithm Applicable in situations where there are more categories than can be distinguished i.e. ‘incomplete data problems’ Complete data = ( Observed data , Missing data ) Haplotype data = ( Genotype data , Phase data ) Measuring haplotypes Genotypes Haplotypes A/A B/b C/c ABC / Abc or Phases ABc / AbC E-M algorithm 1. Guess haplotype frequencies 2. (E) Use those frequencies to replace ambiguous genotypes with fractional haplotype counts 3. (M) Estimate frequency of each haplotype by counting 4. Repeat (2) and (3) until convergence Dataset to be phased 4 individuals genotyped for 2 diallelic markers ID1 A/A B/B ID2 A/a b/b ID3 A/a B/b ID4 a/a b/b Dataset to be phased 4 individuals genotyped for 2 diallelic markers ID1 A/A B/B AB / AB ID2 A/a b/b Ab / ab ID3 A/a B/b AB / ab ? Ab / aB ID4 a/a b/b ab / ab E-step E-step E-step E-step M-step M-step M-step M-step M-step Haplotype counts, frequencies from complete data Count Freq AB 2.5 0.3125 aB 0.5 0.0625 Ab 1.5 0.1875 ab 3.5 0.4375 Sum 8.0 1.0000 back to