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Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics.

TitleFine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics.
Publication TypeJournal Article
Year of Publication2004
AuthorsLee, JH, Mayeux, R, Mayo, D, Mo, J, Santana, V, Williamson, J, Flaquer, A, Ciappa, A, Rondon, H, Estevez, P, Lantigua, R, Kawarai, T, Toulina, A, Medrano, M, Torres, M, Stern, Y, Tycko, B, Rogaeva, E, St George-Hyslop, P, Knowles, JA
JournalMol Psychiatry
Date Published2004 Nov
KeywordsAged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Caribbean Region, Chromosome Mapping, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 18, Dominican Republic, Female, Genetic Linkage, Genetic Predisposition to Disease, Genotype, Hispanic Americans, Humans, Lod Score, Male, New York, Pedigree, Puerto Rico

Familial Alzheimer's disease (AD [MIM 104300]) has been a focus of intense investigation, primarily in Caucasian families from Europe and North America families. Although the late-onset form of familial AD, beginning after age 65 years, has been linked to regions on chromosomes 10q and 12p, the specific genetic variants have not yet been consistently identified. Using a unique cohort of families of Caribbean Hispanics ancestry, we screened the genome using 340 markers on 490 family members from 96 families with predominantly late-onset AD. We observed the strongest support for linkage on 18q (LOD=3.14). However, 17 additional markers (chromosomes 1-6, 8, 10, 12, and 14) exceeded a two-point LOD score of 1.0 under the affecteds-only autosomal dominant model or affected sibpair model. As we previously reported the fine-mapping effort on 12p showing modest evidence of linkage, we focused our fine-mapping efforts on two other candidate regions in the current report, namely 10q and 18q. We added 31 family members and eight additional Caribbean Hispanic families to fine map 10q and 18q. With additional microsatellite markers, the evidence for linkage for 18q strengthened near 112 cM, where the two-point LOD score for D18S541 was 3.37 and the highest NPL score in that region was 3.65 (P=0.000177). This narrow region contains a small number of genes expressed in the brain. However, at 10q (134-138 cM), the NPL score decreased from 3.15 (P=0.000486) to 2.1 (P=0.0218), but two broad peaks remained overlapping with previously reported peaks. Our results provide modest support for linkage on 10q and 12p in this cohort of Caribbean Hispanic families with familial Alzheimer's disease, and strong evidence for a new locus on 18q.

Alternate JournalMol. Psychiatry
PubMed ID15241431
PubMed Central IDPMC1578737
Grant ListP50 AG008702 / AG / NIA NIH HHS / United States
P01 AG007232 / AG / NIA NIH HHS / United States
R01 AG015473 / AG / NIA NIH HHS / United States
AG07232 / AG / NIA NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
AG15473 / AG / NIA NIH HHS / United States
AG08702 / AG / NIA NIH HHS / United States
RF1 AG015473 / AG / NIA NIH HHS / United States