Monday, August 16, 2010

A custody battle for the mind - brain genes from different parents

Relatively few genes (∼100) have previously been shown to be imprinted such that their expression in progeny derives from either the maternal or paternal copy. Two papers by Gregg et al. now expand this number by an order of magnitude, and reveal complex patterns of parent-of-origin bias in gene expression in the brain that are developmentally and regionally restricted, and in many cases, sexually dimorphic. They uncovered over 1300 loci with maternal or paternal allelic bias. Comparison of the parent-of-origin allelic expression bias in the adult hypothalamus and cortex, and in the developing brain, revealed spatiotemporal and sex-specific regulation. Here are a few clips from the first and the second articles:
...Many imprinted genes are expressed in neural systems associated with feeding and motivated behaviors, and parental biases preferentially target genetic pathways governing metabolism and cell adhesion. We observed a preferential maternal contribution to gene expression in the developing brain and a major paternal contribution in the adult brain. Thus, parental expression bias emerges as a major mode of epigenetic regulation in the brain.
...Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Moreover, analysis of the cortex and hypothalamus identified 347 autosomal genes with sex-specific imprinting features. In the hypothalamus, sex-specific imprinted genes were mostly found in females, which suggests parental influence over the hypothalamic function of daughters. We show that interleukin-18, a gene linked to diseases with sex-specific prevalence, is subject to complex, regional, and sex-specific parental effects in the brain. Parent-of-origin effects thus provide new avenues for investigation of sexual dimorphism in brain function and disease.
I found some background given in a review of this work by Tollkuhn et. al. to be useful. Some clips:
Genomic imprinting is a phenomenon in which either the maternal or paternal copy of a gene is expressed preferentially in all progeny. This curious phenomenon, which violates classical Mendelian genetics, appears to occur only in mammals among vertebrates....An imprinted gene renders the organism functionally haploid at that locus, and permits the expression of phenotypes from mutations that would normally be recessive. In other words, imprinting precludes the protection of a back-up copy afforded by a diploid genome. It has been postulated therefore that the existence of imprinting in mammals must confer a selective advantage. What this selective pressure might be remains to be settled, but the most widely accepted explanation is that imprinting is a consequence of parental conflict over resource allocation to the progeny. Briefly, it is in the father's interest to maximize maternal resources devoted to his progeny, whereas the mother might wish to allocate resources more equitably to current and future progeny, who might conceivably result from matings with other males. This conflict is particularly acute in placental mammals, in whom the progeny develop in utero and often for prolonged gestational periods, requiring greater maternal investment. As applied to imprinting, the conflict theory predicts that paternally expressed genes should increase the use of maternal resources to produce more fit offspring. By contrast, maternally expressed genes should quell the effects of such paternally expressed genes.

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