Genome wide association analysis in a mouse advanced intercross line.

Area of Science:

• Genetics
• Genomics
• Neuroscience

Background:

• The LG/J x SM/J advanced intercross line (AIL) is a multigenerational outbred mouse population.
• It possesses high minor allele frequencies, a simple genetic background, and fully sequenced genomes, making it ideal for genome-wide association studies (GWAS).

Purpose of the Study:

• To identify genetic associations for traits relevant to human health and disease using the LG x SM AIL.
• To explore the genetic architecture of mammalian behavior and gene expression regulation.

Main Methods:

• Genome-wide association studies (GWAS) were performed on 1,063 LG x SM AIL mice.
• Thousands of cis- and trans-expression quantitative trait loci (eQTLs) were identified in brain regions (hippocampus, striatum, prefrontal cortex) of approximately 200 mice.
• Replication of a previously identified association between locomotor activity and the Csmd1 gene was conducted.

Main Results:

• 126 significant genetic associations were identified for 50 different traits.
• Thousands of cis- and trans-eQTLs were discovered in key brain regions.
• The association between locomotor activity and Csmd1 was replicated, and Csmd1 mutant mice exhibited the same locomotor phenotype.

Conclusions:

• The LG x SM AIL is a valuable resource for genetic mapping and identifying trait-associated loci.
• The study identified numerous novel genetic associations and provided insights into the genetic underpinnings of mammalian behavior and gene expression.