Thursday, September 07, 2006

MALD for prostate cancer in African Americans

First a short description of MALD from the paper cited below:

The idea of admixture mapping is to screen through the genome of populations of mixed ancestry such as African American, searching for regions where the proportion of DNA inherited from either the ancestral European or African population is unusual compared with the genome wide average. Admixture mapping requires a relatively small number of markers for a whole genome scan: a couple of thousand, rather than the hundreds of thousands estimated to be necessary in nonadmixed populations. Because the mixture between European and West-African populations occured within the past 15 generations, stretches of DNA with contiguous European and African ancestry have not had much time to break up because of recombination and typically extend millions of base pairs. Admixture mapping therefore studies highly selected SNPs every few million base pairs, rather than every few thousand as with linkage disequilibrium mapping.

and one of the main conclusions from this study:

...we show that the 8q24 locus contributes to a major increased risk for prostate cancer in African Americans with African ancestry at 8q24. The difference between these individuals and African Americans with European ancestry at 8q24 explains a large proportion of prostate cancer in younger African Americans.

Admixture mapping identifies 8q24 as a prostate cancer risk locus in African American men

Matthew L. Freedman, Christopher A. Haiman, Nick Patterson, Gavin J. McDonald, Arti Tandon, Alicja Waliszewska, Kathryn Penney, Robert G. Steen, Kristin Ardlie, Esther M. John, Ingrid Oakley-Girvan, Alice S. Whittemore, Kathleen A. Cooney, Sue A. Ingles, David Altshuler, Brian E. Henderson, and David Reich

PNAS: Early Edition

A whole-genome admixture scan in 1,597 >African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P <> and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P <>-9) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.

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