It's imprinted genes day! This companion piece to the earlier post involves the work of Catherine Dulac, at Harvard. They have annotated over 100 imprinted genes in the brain, including 40 newly-discovered genes. "We looked at a single brain area—the cerebellum—in a very rigorous way, and found 115 imprinted genes, more than 40 of which were brand-new," Dulac said. "That is a 30 percent increase in the number of known imprinted genes in the mouse, which is significant, but the other important idea this paper explores is the notion that these imprinted genes provide a way for the diversity of the brain to flourish. In addition to the diversity in our genetic sequence, the question of who are we inheriting these genes from adds to the diversity we see across a population."
Many are specifically imprinted in the brain and are not imprinted in the rest of the body and many are proportionately imprinted, not either switched on or off. "So there may be 70 percent expression from the maternal allele, and 30 percent from the paternal," Dulac said. "It's not all on or all off." To understand whether these biases have biological significance, Dulac and colleagues targeted a gene called Bcl-X, which, in the adult cerebellum, is expressed 60 percent from the paternal genome and 40 percent from the maternal, and helps prevent cell death.
"Our question is, 'Does the brain care about that bias?'" Dulac said. "If it doesn't we could remove either copy of the gene, and it shouldn't matter. But if that bias ― even though it's not particularly strong—is important, when we remove the more highly expressed copy of the gene, we should see a different phenotype emerge. "When we did this, the results were spectacular. When we removed the paternal copy, we obtained mice with brains that were 15 to 20 percent smaller than mice in which we removed the maternal copy or mice which had both copies."