A novel genetic method 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 and analyzing samples from African American patients for HCV clearance, HIV-1/AIDS, focal segmental glomerulosclerosis, and end-stage renal disease. The projects are currently ongoing with MALD mapping genotypes collected from 1929 patients totally 4,901,589 genotypings for 2541 loci. Analysis of this data and the diseases of HCV clearance, HIV-1/AIDS, focal segmental glomerulosclerosis is progressing utilizing the ANCESTRYMAP program we described last year.
Chretien, J-P; Coresh, J; Berthier-Schaad, Y et al. (2006) Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans. J Med Genet 43:917-23 |
Smith, Michael W; O'Brien, Stephen J (2005) Mapping by admixture linkage disequilibrium: advances, limitations and guidelines. Nat Rev Genet 6:623-32 |
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 |