Recombinant inbred systems can advance research in behavioral ecology

Gini, Beatrice; Hager, Reinmar

doi:10.3389/fgene.2012.00198

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…In order to establish the biological networks of our candidate genes we utilized the massive phenotype and expression data sets available for the BXD panel (Gini and Hager, 2012 ; Ashbrook and Hager, 2013 ). Generally, microarray analysis uses a number of probes, targeted at different parts of a gene.…”

Section: Methodsmentioning

confidence: 99%

A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

Ashbrook

Williams

et al. 2015

Front. Behav. Neurosci.

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Bipolar disorder (BD) is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS) have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium's bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis. We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1, and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG, and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG, and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG, and TNR influence intercellular signaling in the striatum.

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Section: Methodsmentioning

confidence: 99%

A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

Ashbrook

Williams

et al. 2015

Front. Behav. Neurosci.

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“…These recombinant litters are then inbred by brother/sister mating for >20 generations to produce a series of fully inbred lines, which are homozygous at every locus but have, across lines, a fixed pattern of two possible alleles (Peirce et al, 2004; Gini and Hager, 2012; Pollard, 2012). …”

Section: Empirical Approachesmentioning

confidence: 99%

Empirical testing of hypotheses about the evolution of genomic imprinting in mammals

Ashbrook¹,

Hager²

2013

Front. Neuroanat.

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The close interaction between mother and offspring in mammals is thought to contribute to the evolution of genomic imprinting or parent-of-origin dependent gene expression. Empirical tests of theories about the evolution of imprinting have been scant for several reasons. Models make different assumptions about the traits affected by imprinted genes and the scenarios in which imprinting is predicted to have been selected for. Thus, competing hypotheses cannot readily be tested against each other. Further, it is far from clear how predictions about expression patterns of genes with specific phenotypic effects can be tested given current methodology of assaying gene expression levels, be it in the brain or in other tissues. We first set out a scenario for testing competing hypotheses and delineate the different assumptions and predictions of models. We then outline how predictions may be tested using mouse models such as intercrosses or recombinant inbred (RI) systems that can be phenotyped for traits relevant to imprinting theories. Further, we briefly discuss different molecular approaches that may be used in conjunction with experiments to ascertain expression patterns of imprinted genes and thus the testing of predictions.

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Recombinant inbred systems can advance research in behavioral ecology

Cited by 2 publications

References 46 publications

A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

Empirical testing of hypotheses about the evolution of genomic imprinting in mammals

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