Genetic regulatory network analysis for app based on genetical genomics approach

Xusheng Wang, Ying Chen, Xiaodong Wang, Lu Lu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A number of studies have shown that amyloid precursor protein (App) plays a critical role in Alzheimer's disease (AD); however, little is known about the genetic regulatory network. In this study, the authors combined array analysis and quantitative trait loci (QTL) mapping to characterize the genetic variation and genetic regulatory network for App using hippocampus of BXD recombinant inbred (RI) mice. The variation in expression level of App is conspicuous across the 78 BXD RI strains. Moreover, the expression level of App is significantly higher in DBA/2J than the level in C57BL/6J (p.001). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis has further confirmed the significant difference between the two parental strains C57BL/6J and DBA/2J. The authors performed an interval mapping for App gene expression and found that it is cis regulated with highly significant likelihood-ratio statistic (LRS) score (LRS=19; p.05). Four SNPs and two InDels (insertions or deletions) were identified in the promoter, and one of the SNPs is located in the pax2 motif. Genetic regulatory network analysis showed that App coregulated with many AD-related genes, including Gsk3b, Falz, Mef2a, Tlk2, Rtn, and Prkca. The genetical genomics approach demonstrates the importance and the potential power of the expression quantitative trait loci (eQTL) studies in identifying regulatory network that contribute to complex traits, such as AD.

Original languageEnglish (US)
Pages (from-to)79-93
Number of pages15
JournalExperimental Aging Research
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2010

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Amyloid beta-Protein Precursor
Genomics
Alzheimer Disease
Quantitative Trait Loci
Single Nucleotide Polymorphism
Reverse Transcriptase Polymerase Chain Reaction
Network Analysis
Protein
Precursor
Hippocampus
Gene Expression
Genes
Alzheimer's Disease

All Science Journal Classification (ASJC) codes

  • Aging
  • Arts and Humanities (miscellaneous)
  • Psychology(all)
  • Geriatrics and Gerontology

Cite this

Genetic regulatory network analysis for app based on genetical genomics approach. / Wang, Xusheng; Chen, Ying; Wang, Xiaodong; Lu, Lu.

In: Experimental Aging Research, Vol. 36, No. 1, 01.01.2010, p. 79-93.

Research output: Contribution to journalArticle

Wang, Xusheng ; Chen, Ying ; Wang, Xiaodong ; Lu, Lu. / Genetic regulatory network analysis for app based on genetical genomics approach. In: Experimental Aging Research. 2010 ; Vol. 36, No. 1. pp. 79-93.
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