African‐American TOMM40'523‐APOEhaplotypes are admixture of West African and Caucasian alleles

Male 0301 basic medicine haplotypes Phased Sanger sequencing Poly T Epidemiology Clinical Neurology 610 Black People TOMM40 Caucasian Yoruban White People Cohort Studies Cellular and Molecular Neuroscience 03 medical and health sciences age of onset Apolipoproteins E Developmental Neuroscience Gene Frequency 616 Mitochondrial Precursor Protein Import Complex Proteins Complex disease genetics Humans African-American Phylogenetic analysis Health Policy Membrane Transport Proteins Alzheimer's disease United States Psychiatry and Mental health Africa, Western Population admixture Haplotypes Female Geriatrics and Gerontology APOE
DOI: 10.1016/j.jalz.2014.06.009 Publication Date: 2014-09-26T02:45:45Z
ABSTRACT
AbstractBackgroundSeveral studies have demonstrated a lower apolipoprotein E4 (APOEε4) allele frequency in African‐Americans, but yet an increased age‐related prevalence of AD. An algorithm for prevention clinical trials incorporating TOMM40'523 (Translocase of Outer Mitochondria Membrane) andAPOEdepends on accurate TOMM40'523‐APOEhaplotypes.MethodsWe have compared theAPOEand TOMM40'523 phased haplotype frequencies of a 9.5 kb TOMM40/APOEgenomic region in West African, Caucasian, and African‐American cohorts.ResultsAfrican‐American haplotype frequency scans of poly‐T lengths connected in phase with eitherAPOEε4 orAPOEε3 differ from both West Africans and Caucasians and represent admixture of several distinct West African and Caucasian haplotypes. A new West African TOMM40'523 haplotype, withAPOEε4 connected to a short TOMM40'523 allele, is observed in African‐Americans but not Caucasians.ConclusionThese data have therapeutic implications for the age of onset risk algorithm estimates and the design of a prevention trial for African‐Americans or other mixed ethnic populations.
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