A novel genetic method """"""""Mapping by Admixture Linkage Disequilibrium"""""""" (MALD) has been proposed and implemented which provides a population- and patient cohort-based approach for disease gene identification. The method uses genetic markers with significant allele frequency differences between racial groups and a population with a recent history of admixture to identify novel disease genes in patient cohorts. This methodology is particularly appropriate for diseases where collecting large families for linkage analysis is difficult or where disease onset involves exposure to a common environmental or infectious agent. We have been collecting samples from African American patients with prostate cancer. The prostate cancer project is currently ongoing and we plan to analyze other diseases such as, end-stage renal disease and focal segmental glomerulosclerosis as sufficient numbers of patient samples and controls are collected. The markers necessary to scan the genome informativeness are being chosen on the basis of maximal differences between African and European Americans. The results of this project have been collected and are currently undergoing analysis. Positive signals for MALD linkage will be followed up by screening of additional markers from the region for confirmation of the signal. Traditional disease gene identification methods which the laboratory has applied before will then be used to identify the genes involved in the etiology of prostate cancer.
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| 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 |
