Genetic polymorphisms and their association with brain and behavioural measures in heterogeneous stock mice.

Abstract:

:Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activity, anxiety and cognitive phenotypes. We identified 126 single nucleotide polymorphisms (SNPs) in genes involved in regulation of neurotransmitter systems, nerve growth/death and gene expression, and subsequently investigated their associations with changes in behaviour and/or brain weights in our sample. We found significant associations between four SNP-phenotype pairs, after controlling for multiple testing. Specificity protein 2 (Sp2, rs3708840), tryptophan hydroxylase 1 (Tph1, rs262731280) and serotonin receptor 3A (Htr3a, rs50670893) were associated with activity/anxiety behaviours, and microtubule-associated protein 2 (Map2, rs13475902) was associated with cognitive performance. All these genes except for Tph1 were expressed in the brain above the array median, and remained significantly associated with relevant behaviours after controlling for the family structure. Additionally, we found evidence for a correlation between Htr3a expression and activity. We discuss our findings in the light of the advantages and limitations of currently available mouse genetic tools, suggesting further directions for association studies in rodents.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Janecka M,Marzi SJ,Parsons MJ,Liu L,Paya-Cano JL,Smith RG,Fernandes C,Schalkwyk LC

doi

10.1038/srep41204

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

41204

issn

2045-2322

pii

srep41204

journal_volume

7

pub_type

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