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
AUTHORS (16)
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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CITATIONS (32)
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