Preliminary study of Alzheimer's disease related genes by using genetical genomics approach

摘要

Alzheimer''s disease (AD), the most common type of dementia is characterized by the progressive loss of specific neuronal populations and accumulation of the intraneuronal inclusions. The genetic factors contributing to AD are largely unknown. To date, we have collected 366 AD related genes based on bioinformatics analysis. Genetical genomics have been used to dissect the genetic modulators of these AD related genes by combination of gene expression profiling in the hippocampus of BXD RI mice in combination with linkage analysis. Of the 366 AD related genes, we identified 126 probe sets that target 76 genes that have a significant linkage score (LRS > 15). Approximately 60% of these expression differences are caused by potential cis-acting quantitative trait loci (QTLs). The expression of the genes modulated by 30 of the putative cis-QTLs have a fold-difference higher than 1.7 between the parental strains of the BXD — C57BL/6J and DBA/2J. This study provided the baseline data for the accuracy analysis of genetic networks associated with AD that would be of great value for revealing the molecular mechanisms of AD.