Epigenetic inheritance through meiosis at the agouti locus in mice

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/107204

Funding Status
Closed

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Funded Activity Summary

The manifestations of many genetic traits do not conform to the rules of Mendelian inheritance. In humans, some alleles give a completely predictable phenotype, while others display a wide range of phenotypes, described as differences in penetrance and expressivity. As the phenotype associated with a particular gene in humans may be modified by the genotype at unlinked modifying loci and by environmental factors, it is difficult to determine to what extent any single factor is responsible for variability. In mice, however, a number of examples of variable expressivity have been reported in conditions where genetic background and environment have been controlled. For example, the phenotypes of mice with mutations at the agouti locus can vary substantially between genotypically identical littermates. Epigenetic modifications such as DNA methylation are known to be involved. Furthermore, the phenotypes of the offspring are related to the phenotype of the mother and recent experiments carried out in our laboratory suggest that this is the result of inheritance of the epigenetic state of the allele through the female germline. This is the first report of epigenetic inheritance at an endogenous gene in mammals. The experiments described in this project should help to clarify the mechanisms involved in variable expressivity and epigenetic inheritance. Variable expressivity in combination with epigenetic inheritance may be viewed as an alternative method of inheritance of genetic traits which does not involve DNA mutation, but which can be carried from generation to generation in a semipermanent way. Understanding the mechanisms underlying these phenomena is a challenge for contemporary genetics.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $182,699.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gene Expression

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

DNA methylation | diabetes | epigenetics | eukaryotic gene expression | genetic diseases | genomic imprinting | mouse transgenes | obesity

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