Mapping by admixture linkage disequilibrium (MALD) is a theoretically powerful, although unproven, approach to mapping genetic variants that are involved in human disease. MALD takes advantage of long-range haplotypes that are generated by gene flow among recently admixed ethnic groups, such as African-Americans and Latinos. Under ideal circumstances, MALD will have more power to detect some genetic variants than other types of genome-wide association study that are carried out among more ethnically homogeneous populations. It will also require 200-500 times fewer markers, providing a significant economic advantage. The MALD approach is now being applied, with results expected in the near future. We determined allele frequencies for 1,913 short tandem repeat (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 single nucleotide polymorphism (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 |
