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 for Hepatitis C virus (HCV) clearance, HIV-1/AIDS, focal segmental glomerulosclerosis, end-stage renal disease and prostate cancer. The projects are currently ongoing. The markers necessary to scan the genome informativeness were recently published for African Americans (Smith et al., 2004). Additionally we also published a Bayesian analysis methodology (Patterson et al., 2004) back to back in the American Journal of Human Genetics in April 2004. From that work a panel of 3,000 MALD markers has now been developed for genotyping on the high-multiplex ParAllele system. Application of those markers to disease in African Americans is now underway in the LGD.
| 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 |
