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 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. We have analyzed a large set of single nucleotide polymorphisms (SNPs) from the SNP Consortium allele frequency database and other sources. Markers having at least 20 subjects typed in both African and European Americans were examined with Var(MAPP*) - a measure of affiliation with parental population that takes centrality and directionality of allele frequencies into account. Under reasonable assumptions, about 1,200 cases and an equal number of controls would be required to detect an association between a disease locus with a genotypic risk ratio of two or greater and such a marker located within 2.5 cM. After ongoing verification, these informative SNPs constitute the foundation of a suitable set of markers for genomic MALD scans in African Americans.
| 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 |
