New Approach Permits Revelation of Diverse Allelic Effects in Mammalian Brain That Are Not Caused by Imprinting or Genetic Variation

For over a century, scientists have thought that most of our cells express genes from both parents' chromosomes relatively equally throughout life. But the biology is more nuanced, say scientists who invented a screen to measure the activity of specific genes from both parents. In Neuron on February 23, 2017, researchers report that in rodent, monkey, and human brains, it's not unusual for individual neurons or specific types of neurons to silence genes from one parent or the other. The article is titled “Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain.” Surprisingly, the differential activation of maternal and paternal gene copies was observed most often in the developing brain, impacting about 85% of genes. Gradually, as the brain matures, neurons increasingly express both parents' genes equally. However, for at least 10% of genes, maternal and paternal copies continue to be differentially expressed in the adult brain, revealing that this imbalance exists throughout an organism's lifetime for many genes in the brain. "This story has its roots in understanding why we reproduce sexually--normally, having two copies of a gene acts as a protect buffer in case one is defective," says senior author Dr. Christopher Gregg, a neurobiologist at the University of Utah School of Medicine and a New York Stem Cell Foundation Robertson Investigator. "Our findings suggest that periods when the healthy gene copy is turned off could be critical windows during which cells are particularly vulnerable to a mutation in the other copy."
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