Methods for high-density admixture mapping of disease genes.

摘要: Admixture mapping (also known as “mapping by admixture linkage disequilibrium,” or MALD) has been proposed an efficient approach to localizing disease-causing variants that differ in frequency (because of either drift selection) between two historically separated populations. Near a disease gene, patient populations descended from the recent mixing more ethnic groups should have increased probability inheriting alleles derived group carries disease-susceptibility alleles. The central attraction is that, since gene flow occurred recently modern (e.g., African and Hispanic Americans past 20 generations), it expected admixture-generated disequilibrium extend for many centimorgans. High-resolution marker sets are now becoming available test this approach, but progress will require (a) computational methods infer ancestral origin at each point genome (b) empirical characterization general properties due admixture. Here we describe statistical estimate locus on basis composite genotypes linked markers, show accurately estimates states along genome. We apply strong extends, average, 17 cM Americans. Finally, present power calculations under varying models risk, sample size, proportions ancestry. Studying ∼2,500 markers patients provide detect regions contributing common disease. A particularly important result study be nearly same wide range mixture scenarios: proportion 10%–90% both