Methods in genome wide association studies.Noruacute; Moreno.ppt

Imputation Dealing with missing data points by filling in values. In SNPs: T A G G T ? T G C C T A G C G T Why? Cost-saving Avoid re-genotyping Keep effective sample size SNP comparisons between existing platforms. Imputation High rate of occurrence. ‘Direct’ imputation. T A G G T ? T G C C T A G C G T T A G G T A T G C C T A G C G T Linkage disequilibrium Non-random association of alleles at two or more loci. Imputation LD SNP of interest Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays Homer, et al. The DNA Detective Is an individual genome present in a DNA mixture? Query Mixed DNA // Population DNA Detective We have: Different laboratories different conclusions. Usually not accurate at all. Hard and cannot be automatized. DNA Detective - Methodology Summary: Cumulative sum of allele shifts over all available SNPs. Shift’s sign individual of interest is closer to a reference sample or closer to a given mixture. First genotype a single SNP for a single person, then adapt it to all mixtures and pooled data. DNA Detective – Single SNP, Single person Raw preprocessed data allele instensity (How much of A and how much of B we have). Transform normalized data into a ratio. Yi is the estimate of allele frequency BB AB AA ~0 ~0.5 ~1 DNA Detective - Methodology Use relative probe intensity data. Compare allele frequency estimates from the mixture (M). Assume reference population (Pop) has similar ancestral components interchangeable. Distance measure for individual Yi DNA Detective - Methodology Null hypotheses, individual is not in the mixture, D(Yi,j) ~ 0 Alternative hypotheses, D(Yi,j) 0 More similar to M than Pop D(Yi,j) 0 Yi,jc is more ancestral similar to Pop than to M. DNA Detective - Methodology (Homer, p.4) DNA Detective - Results Accurate findings. Determined if a trace amount (1%) of DNA is present in a DNA mixtur