Cookies disclaimer

I agree Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.

Epigenetic inheritance: the influence of variable silencing of the repeat genome. (360G-Wellcome-210757_Z_18_Z)

<p>Evidence from epidemiological studies and experiments in animal models suggests that effects of environment and lifestyle can be transmitted across generations via non-genetic mechanisms. Such mechanisms are challenging to unravel in mouse and man. In mammals, non-genetic inheritance is best exemplified by the<em> Agouti viable yellow</em> (<em>Avy</em>) mouse where phenotypic differences in genetically identical animals are caused by insertion of a retrotransposon - an endogenous retrovirus (ERV) that provides a cryptic promoter driving ectopic expression of <em>agouti</em>. This ERV is variably DNA methylated in different individuals causing inter-individual variation in coat colour &ndash; a non-genetic influence on phenotype. Remarkably, a memory of parental coat colour is transmitted to subsequent generations. Variable expressivity can be modulated by <em>in utero</em> environmental exposures.</p> <p>ERVs represent ~12% of the mouse genome. &nbsp;Inspired by<em> Avy</em>, we propose a research programme, supported by preliminary data, to address the following questions:</p> <p>Aim 1 &ndash; To what extent do mammalian ERVs exhibit variable epigenetic silencing and what is the mechanism?</p> <p>Aim 2 &ndash; Is this transmitted as non-genetic memory across generations?</p> <p>Aim 3 &ndash; Are they sensors of environmental compromise?</p> <p>Aim 4 &ndash; Are there implications for phenotype?</p> <p>Aim 5 &ndash; Does a related phenomenon occur in humans?</p>


10 Apr 2018

Grant details
Amount Awarded 2929851
Applicant Surname Ferguson-Smith
Approval Committee Science Interview Panel
Award Date 2018-04-10T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 210757/Z/18/Z
Lead Applicant Prof Anne Ferguson-Smith
Planned Dates: End Date 2024-12-01T00:00:00+00:00
Planned Dates: Start Date 2018-12-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Additional data added by GrantNav