Genetic variation, Evolution and Disease

The long-term research goals of my lab are to understand how evolutionary processes and demographic history have shaped patterns of genetic variation in humans, and how such variation influences differences in disease susceptibility. A major aim is to better understand how common genetic variation is distributed among human populations (i.e., population structure). An important outcome of this work has been a critical analysis of the relationship between genetics and racial classifications commonly used in biomedical research. My lab is also interested in the effects of natural selection on genes, particularly those that encode components of the adaptive immune system and how this information can facilitate finding risk factors for diseases like AIDS, juvenile rheumatoid arthritis, inflammatory bowel disease and neuroinvasive West Nile virus disease. Finally, over the past decade, my lab has identified genetic variants that underlie about a dozen different birth defect syndromes. Much of this work has focused on identifying the genetic and molecular basis of syndromes characterized by limb defects, particularly contractures of the feet (e.g., clubfoot) and hands. We have found mutations that cause such contractures in half a dozen genes (e.g., MYH3, MYH8, MYH2, TNNI2, TNNT3, TPM2). These genes encode proteins of the contractile apparatus of fast-twitch myofibers. However, affected individuals exhibit neither weakness nor postnatal muscle damage, so these syndromes appear to be a new and unique class of congenital muscle disease. The study of these disorders is adding much to our understanding of the types of molecular mechanisms that can cause rare human birth defect syndromes, and we are now carefully studying the role these genes play in more complex birth defects such as idiopathic clubfoot.

Selected Publications:

Guthery S, Salisbury BA, Stephens JC, Bamshad M (2007) The structure of common genetic variation in United States populations. American Journal of Human Genetics 81:1211-31.

Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ (2006) Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nature Genetics 38:561-565.

Wooding S, Stone AC, Dunn DM, Drayna D, Weiss RB, Bamshad M (2006) Independent evolution of bitter-taste sensitivity in humans and chimpanzees. Nature 440:930-934.

Toydemir RM, Brassington AE, Bayrak-Toydemir P, Krakowiak PA, Jorde LB, Whitby FG, Longo N, Viskochil DH,Carey JC, Bamshad MJ (2006) A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome. American Journal Human Genetics 79:935-941.

Bamshad MJ (2005) Genetic influences on health: Does race matter? Journal of the American Medical Association 294:237-246.