title: African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles.
abstract: BACKGROUND
  Several studies have demonstrated a lower apolipoprotein E4 (APOE ε4) 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) and APOE depends on accurate TOMM40'523-APOE haplotypes.
  
  
  METHODS
  We have compared the APOE and TOMM40'523 phased haplotype frequencies of a 9.5 kb TOMM40/APOE genomic region in West African, Caucasian, and African-American cohorts.
  
  
  RESULTS
  African-American haplotype frequency scans of poly-T lengths connected in phase with either APOE ε4 or APOE ε3 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, with APOE ε4 connected to a short TOMM40'523 allele, is observed in African-Americans but not Caucasians.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA; Zinfandel Pharmaceuticals Inc, Chapel Hill, NC, USA; Cabernet Pharmaceuticals, Inc., Chapel Hill, NC, USA. Electronic address: allen.roses@duke.edu.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lutz
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Saunders
authors.affiliation: Department of Psychiatry, State University of New York, Stony Brook, NY, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Goldgaber
authors.affiliation: Polymorphic DNA Technologies, Alameda, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Saul
authors.affiliation: Cabernet Pharmaceuticals, Inc., Chapel Hill, NC, USA.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Sundseth
authors.affiliation: Cabernet Pharmaceuticals, Inc., Chapel Hill, NC, USA.
authors.forename: P Anthony
authors.initials: PA
authors.lastname: Akkari
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Roses
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: W Kirby
authors.initials: WK
authors.lastname: Gottschalk
authors.affiliation: Department of Psychology, Duke University, Durham, NC, USA.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Whitfield
authors.affiliation: Department of Psychiatry, State University of New York, Stony Brook, NY, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vostrov
authors.affiliation: Center for Genetic Diseases, Duke University, Durham, NC, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC, USA.
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.affiliation: Zinfandel Pharmaceuticals Inc, Chapel Hill, NC, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Burns
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: Ornit
authors.initials: O
authors.lastname: Chiba-Falek
authors.affiliation: Duke University Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Welsh-Bohmer
mesh_terms: D000354:Africa, Western; D001057:Apolipoproteins E / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011071:Poly T / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human; D011071:Poly T
keywords: APOE; African-American; Alzheimer's disease; Caucasian; Complex disease genetics; Phased Sanger sequencing; Phylogenetic analysis; Population admixture; TOMM40; Yoruban; age of onset; haplotypes