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O3‐13‐03: Massive parallel gene panel sequencing in a belgian ftld cohort of causal genes associated with diverse neurodegenerative brain diseases
Author(s) -
Zee Julie,
Robberecht Caroline,
Dillen Lubina,
Sleegers Kristel,
Cruts Marc,
Broeckhoven Christine
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.311
Subject(s) - frontotemporal lobar degeneration , c9orf72 , genetics , exon , biology , gene , frontotemporal dementia , haplotype , trinucleotide repeat expansion , dementia , disease , medicine , allele , pathology
with the previously reported data of genetic linkage analysis in these pedigrees, which identified a set of AD susceptibility chromosomal loci, including 1q25, 1q21, 11q24 and 3q23 loci. Results:We selected rare single nucleotide variations (SNV) and insertion deletion (indel) mutations shared between at least two AD patients in each pedigree branch. We searched only for the rare variations with MAF<0.05 that potentially affect protein structure. We filtered out potential sequencing errors and also removed the SNV/indels found in “controls,” including genomes of centenarians with no AD symptoms (Illumina sequencing data). The deleterious effects were verified by computational programs. In the primary analysis, we selected the genes with SNVs/indels located on 1q25, 1q21, 11q24 and 3q23 loci. In a broader whole-genome scanning, we listed all the rare variations that had an effect on protein structure and which are shared between at least two affected, distantlyrelated individuals. Conclusions: The data suggested that not a single, but many genetic variations may be involved in risk and modulation of AD pathway, even in a genetic isolate with common genetic founders. A set of candidate genes bearing rare variations in AD patients which are involved in Abeta/tau– metabolism and regulation and in neurodegeneration-related biological processes were revealed and their role will be discussed.