Genetic regulatory network analysis for app based on genetical genomics approach

Area of Science:

• Genetics
• Neuroscience
• Genomics

Background:

• Amyloid precursor protein (App) is crucial in Alzheimer's disease (AD).
• The genetic regulatory network of App remains largely unknown.
• Understanding App's genetic regulation is key to unraveling AD pathogenesis.

Purpose of the Study:

• To characterize the genetic variation and regulatory network of App.
• To investigate the genetic control of App expression in the hippocampus.
• To identify genes co-regulated with App in the context of AD.

Main Methods:

• Utilized array analysis and quantitative trait loci (QTL) mapping in BXD recombinant inbred (RI) mice.
• Performed quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for validation.
• Conducted interval mapping to identify cis-regulation and analyzed genetic regulatory networks.

Main Results:

• Significant variation in App expression was observed across BXD RI strains.
• App expression was significantly higher in DBA/2J compared to C57BL/6J mice.
• App gene expression is cis-regulated, with identified SNPs and InDels in the promoter region, including one in the pax2 motif. App was found to coregulate with several AD-related genes.

Conclusions:

• App's genetic regulation is primarily cis-driven.
• App is part of a complex genetic regulatory network involving other AD-associated genes.
• Genetical genomics and eQTL studies are powerful tools for dissecting complex traits like AD.