IP: Dra. Estrella Gómez Tortosa

Resumen del proyecto: A few years ago the Genodem project was started with the aim of collecting clinical and genetic information of cases with familial neurodegenerative dementia of the Alzheimer type (DAT). To date, this project has collected clinical information and DNA samples of more than a hundred families with DAT.
A particularly important line of research in this project is the genetic study of an extensive family with late onset pathologically confirmed Alzheimer’s disease inherited across five generations in a genetically isolated population. Microarray studies of this family revealed linkage to a locus on chromosome 8p22-p21.2. A selective sequencing of this locus obtained a 70% coverage of the exome in this region and didn’t point to any genetic marker as the pathogenic cause of the disease. Recently, a wide-screen genome sequencing with a 96% coverage has been conducted in four affected probands. Preliminar analysis of identity by descent (IBD) regions of 1Mb neither shows a candidate gene segregating with the disease in this family, and further analysis with shorter IBD regions is under progress.
However, these genetic studies show that many of the members in this family bear low- frequency variants (<5% in the general population) in SNPs of several genes in both the 8p22-p21.2 locus and other chromosomal regions. These data may suggest new genetic risk markers for DAT.
The objective of this part of the project is to compare these low-frequency genetic variants in a wider population of DAT (stratified by the well known risk factor APOE genotype) and controls, to analyze their relationship with the risk of developing DAT.

Entidad financiadora: Ministerio de Ciencia e Innovación