Mapping by admixture linkage disequilibrium (MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with about 100 times fewer markers than are required for whole-genome haplotype scans. However, MALD studies require a dense map of validated markers known to have large frequency differences between the founding populations. We previously assessed the allele frequencies for 744 short tandem repeat (STR) polymorphisms in African Americans, European Americans, Hispanics and Asians. In addition, we have experimentally confirmed the frequencies for promising single nucleotide polymorphism markers (SNPs) selected from databases containing a total of around 450,000 markers. This allowed us to propose a set of 3,011 SNPs as a MALD map with 1.2 cM average spacing. However, STR markers have a theoretical advantage over SNP markers because, being multialleleic, they have a higher average information content as compared to random SNPs. In order to make use of this potential advantage, we determined allele frequencies for 1,913 STR markers in European-derived populations as well as in African Americans. These allele frequencies allowed us to compute several measures of ethnic population frequency differences including composite delta, Fisher information content, and Shannon information content. Two hundred seventy-eight (14.4%) of the STR markers were found to have a Shannon information content value between Europeans and Africans of greater than or equal to 0.2. Only the top 42% of the highly selected SNP MALD map markers equal or exceed this amount. This demonstrates that accurate assessment of allele frequencies for STR markers in genetically distinct ethnic populations represents an efficient method for the identification of MALD markers. Markers selected from the new set of 1,913 STR markers are being merged with the 744 previously reported STR markers to provide an STR-based MALD map that can enhance the SNP-based MALD map.
| 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 |
