Association mapping requires linkage disequilibrium (LD) between a disease susceptibility locus and a marker. In non-admixed human populations, significant LD is limited to a few tenths of a centimorgan (cM). A novel method of gene mapping, mapping by admixture linkage disequilibrium (MALD), has been developed to take advantage of the increased LD across 5-25 cM in admixed populations. We focus on African Americans (20% average European ancestry) as a suitable population for MALD mapping of disease genes. An equation for the Fisher information matrix for ancestry fractions from multiple founding populations has been published. We have been able to show that in the case of two founding populations, the information is proportional to the sum of the squares of the allele frequency differences between founding populations divided by the allele frequency in the admixed population. The sum is taken over all alleles at a locus. Since the inverse of the expected value of the information provides the variance of a maximum likelihood estimator, this equation measures the ability of a marker to reduce the variance in admixture fraction estimates. This is highly correlated with the ability of a marker to detect associations between marker genotypes and clinical traits in an admixed population. This measure of the inverse of the admixture fraction variance is being computed for a large number of markers that are being genotyped in European Americans, African Americans, and indigenous Africans.
| Smith, Michael W; Patterson, Nick; Lautenberger, James A et al. (2004) A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet 74:1001-13 |
