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

Background: Several studies have demonstrated a lower apolipoprotein E4 (APOE e4) 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...

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Main Authors: Roses, A., Lutz, M., Saunders, A., Goldgaber, D., Saul, R., Sundseth, S., Akkari, Patrick, Roses, S., Gottschalk, W., Whitfield, K., Vostrov, A., Hauser, M., Allingham, R., Burns, D., Chiba-Falek, O., Welsh-Bohmer, K.
Format: Journal Article
Published: Elsevier Inc. 2014
Online Access:http://hdl.handle.net/20.500.11937/15480
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author Roses, A.
Lutz, M.
Saunders, A.
Goldgaber, D.
Saul, R.
Sundseth, S.
Akkari, Patrick
Roses, S.
Gottschalk, W.
Whitfield, K.
Vostrov, A.
Hauser, M.
Allingham, R.
Burns, D.
Chiba-Falek, O.
Welsh-Bohmer, K.
author_facet Roses, A.
Lutz, M.
Saunders, A.
Goldgaber, D.
Saul, R.
Sundseth, S.
Akkari, Patrick
Roses, S.
Gottschalk, W.
Whitfield, K.
Vostrov, A.
Hauser, M.
Allingham, R.
Burns, D.
Chiba-Falek, O.
Welsh-Bohmer, K.
author_sort Roses, A.
building Curtin Institutional Repository
collection Online Access
description Background: Several studies have demonstrated a lower apolipoprotein E4 (APOE e4) 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 e4 or APOE e3 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 e4 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.
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spelling curtin-20.500.11937-154802017-09-13T13:41:03Z African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles Roses, A. Lutz, M. Saunders, A. Goldgaber, D. Saul, R. Sundseth, S. Akkari, Patrick Roses, S. Gottschalk, W. Whitfield, K. Vostrov, A. Hauser, M. Allingham, R. Burns, D. Chiba-Falek, O. Welsh-Bohmer, K. Background: Several studies have demonstrated a lower apolipoprotein E4 (APOE e4) 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 e4 or APOE e3 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 e4 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/15480 10.1016/j.jalz.2014.06.009 Elsevier Inc. unknown
spellingShingle Roses, A.
Lutz, M.
Saunders, A.
Goldgaber, D.
Saul, R.
Sundseth, S.
Akkari, Patrick
Roses, S.
Gottschalk, W.
Whitfield, K.
Vostrov, A.
Hauser, M.
Allingham, R.
Burns, D.
Chiba-Falek, O.
Welsh-Bohmer, K.
African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
title African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
title_full African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
title_fullStr African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
title_full_unstemmed African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
title_short African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
title_sort african-american tomm40'523-apoe haplotypes are admixture of west african and caucasian alleles
url http://hdl.handle.net/20.500.11937/15480