کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5623997 | 1406234 | 2015 | 10 صفحه PDF | دانلود رایگان |
IntroductionWe performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants.MethodsWe selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association.ResultsWe identified 26 regions linked to LOAD (HLOD â¥3.6). We validated 13 of the regions (HLOD â¥2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLODmax = 4.7, Pjoint = 6.6 Ã 10â6), a locus located â¼2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835: HLODmax = 4.9, Pjoint = 1.2 Ã 10â5), a region harboring genes associated with the nervous system (GARS, GHRHR, and NEUROD6).DiscussionFuture sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations.
Journal: Alzheimer's & Dementia - Volume 11, Issue 12, December 2015, Pages 1397-1406