African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles

作者：Roses Allen D^*; Lutz Michael W; Saunders Ann M; Goldgaber Dmitry; Saul Robert; Sundseth Scott S; Akkari P Anthony; Roses Stephanie M; Gottschalk W Kirby; Whitfield Keith E; Vostrov Alexander A; Hauser Michael A; Allingham R Rand; Burns Daniel K; Chiba Falek Omit; Welsh Bohmer Kathleen A

来源：Alzheimer's and Dementia, 2014, 10(6): 592-601.

DOI：10.1016/j.jalz.2014.06.009

• Phased Sanger sequencing
• Phylogenetic analysis
• Population admixture
• APOE
• TOMM40
• haplotypes
• African-American
• Alzheimer's disease
• Yoruban
• Caucasian
• Complex disease genetics
• age of onset

Background: Several studies have demonstrated a lower apolipoprotein E4 (APOE epsilon 4) 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 epsilon 4 or APOE epsilon 3 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 epsilon 4 connected to a short TOMM40'523 allele, is observed in African-Americans but not Caucasians.
Conclusion: 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.

• 出版日期2014-11