Dataset Information

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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Publications

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]

PMID: 30406174

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Project description:Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. CONCLUSION: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-010-9063-2) contains supplementary material, which is available to authorized users.

Dataset Information

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

Introduction

Methods

Results

Discussion

Publications

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

Similar Datasets

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