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Linkage analysis of multiplex Caribbean Hispanic families loaded for unexplained early-onset cases identifies novel Alzheimer's disease loci.


ABSTRACT: Introduction:Less than 10% of early-onset Alzheimer's disease (EOAD) is explained by known mutations. Methods:We conducted genetic linkage analysis of 68 well-phenotyped Caribbean Hispanic families without clear inheritance patterns or mutations in APP, PSEN1, and PSEN2 and with two or more individuals with EOAD. Results:We identified 16 (logarithm of odds > 3.6) linked regions, including eight novel loci for EOAD (2p15, 5q14.1, 11p15.1, 13q21.22, 13q33.1, 16p12.1, 20p12.1, and 20q11.21) and eight regions previously associated with late-onset Alzheimer's disease. The strongest signal was observed at 16p12.1 (25 cM, 33 Mb; heterogeneity logarithm of odds = 5.3), ?3 Mb upstream of the ceroid lipofuscinosis 3 (CLN3) gene associated with juvenile neuronal ceroid lipofuscinosis (JNCL), which functions in retromer trafficking and has been reported to alter intracellular processing of the amyloid precursor protein. Discussion:This study supports the notion that the genetic architectures of unexplained EOAD and late-onset AD overlap partially, but not fully.

SUBMITTER: Cheng R 

PROVIDER: S-EPMC6215058 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Linkage analysis of multiplex Caribbean Hispanic families loaded for unexplained early-onset cases identifies novel Alzheimer's disease loci.

Cheng Rong R   Tang Min M   Martinez Izri I   Ayodele Temitope T   Baez Penelope P   Reyes-Dumeyer Dolly D   Lantigua Rafael R   Medrano Martin M   Jimenez-Velazquez Ivonne I   Lee Joseph H JH   Beecham Gary W GW   Reitz Christiane C  

Alzheimer's & dementia (Amsterdam, Netherlands) 20180827


<h4>Introduction</h4>Less than 10% of early-onset Alzheimer's disease (EOAD) is explained by known mutations.<h4>Methods</h4>We conducted genetic linkage analysis of 68 well-phenotyped Caribbean Hispanic families without clear inheritance patterns or mutations in <i>APP</i>, <i>PSEN1</i>, and <i>PSEN2</i> and with two or more individuals with EOAD.<h4>Results</h4>We identified 16 (logarithm of odds > 3.6) linked regions, including eight novel loci for EOAD (2p15, 5q14.1, 11p15.1, 13q21.22, 13q33  ...[more]

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