July 11, 2010
In Mice Many Brain Genes Active From Only One Parent

With the exception of X and Y chromosome genes in men, we have copies of each gene from both parents. Researchers find that in mice (and likely in humans as well) specific genes from one or the other parent are silenced so that only one parent contributes to resulting phenotype (visible appearances and functionality).

The new findings, reported in two papers that appear in the early online edition of the journal Science on July 8, 2010, suggest that imprinting has a significant influence on brain development and behavior. It also likely contributes to diseases of the brain, since imprinting occasionally shuts down the only good gene in a pair.

Howard Hughes Medical Institute investigator Catherine Dulac led the team of scientists who conducted the ambitious analysis. Christopher Gregg, a postdoctoral fellow in her Harvard University lab, is the lead author on both of the publications.

“Essentially what we found with these two studies is that imprinting is not only very extensive but also seems to be subject to a lot of regulation, throughout the life of an individual and even according to brain region and gender,” says Dulac. “And that makes the phenomenon absolutely fascinating.”

This result helps explain why genetic causes of disease, IQ, physical appearances, and other qualities are so hard to track down. The simple Mendelian model of inheritance works in some cases. But for the genes identified in this study the Mendelian model doesn't predict what happens.

Whether the gene from mother or father gets expressed depends on the specific gene, whether the offspring is female or male, and even on stage of development.

Another striking finding was that paternal and maternal imprinting isn’t evenly mixed: About 60 percent of the imprinted genes in the mouse embryonic brain turned out to be maternal, while about 70 percent of the imprinted genes in the adult brain are paternal. Thus, in early life, it appears that imprinting mostly reflects the mother’s influence, and later gives way to the father’s. “But the majority of the genes that we found are imprinted during development, which is when mothers have the greatest influence,” says Dulac.

In their second paper, Dulac and her team reported that the gene imprinting in an animal can vary depending on whether the animal is male or female. Throughout the genome, they found 347 genes that appeared to be imprinted in adult female mice but not males, or vice versa. This sex-specific imprinting was particularly evident in females in the hypothalamic region of the brain, which mediates maternal and mating behaviors. One example of the complexity they encountered is the gene Mrpl48, which they found has a paternal expression bias in the hypothalamus of females, but not males.

Geneticists need to identify for about 20,000 human genes whether their maternal or paternal version is always active or suppressed in each tissue type at each stage of development and do this for men and women and across races.

Share |      Randall Parker, 2010 July 11 10:29 PM  Brain Genetics

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