Modes of imprinted gene action in learning disability

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Abstract

Background

It is now widely acknowledged that there may be a genetic contribution to learning disability and neuropsychiatric disorders, stemming from evidence provided by family, twin and adoption studies, and from explicit syndromic conditions. Recently it has been recognized that in some cases the presentation of genetic syndromes (or discrete aspects of disorders) is dependent on the sex of the transmitting parent. Such ‘parent-of-origin effects’ can be explained by a number of genetic mechanisms, a predominant one of which is genomic imprinting. Genomic imprinting refers to the parent of origin-specific epigenetic marking of an allele of a gene, such that for some genes it is mainly the maternally inherited allele only that is expressed, whereas for others expression occurs mainly from the paternal copy.

Methods

Here we discuss the contribution of imprinted genes to mental dysfunction and learning disability, using clinical examples of association studies and explicit imprinting disorders (with particular emphasis to Angelman and Prader-Willi syndromes), and evidence from animal work.

Results

Clinical and animal studies strongly suggest that imprinted genes contribute to brain functioning, and when the genes or epigenetic processes are disrupted, this can give rise to neuropsychiatric problems. Another system to which imprinted genes provide a large contribute is the placenta and foetal development. Epidemiological studies suggest that this is also a key area in which dysregulation can give rise to learning difficulties.

Conclusions

Disruption of imprinted genes, or the epigenetic processes controlling them, can contribute to learning disability. These effects can be divided into two types: direct effects, such as those seen in explicit imprinting disorders such as Angelman and Prader-Willi syndromes, and indirect effects as manifest via changes in foetal programming.

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