Researchers grasp wider role for genetic variation in regulatory elements of genome

Complex traits such as height and susceptibility to common diseases like diabetes and heart disease usually stem from a complicated mix of genetics and lifestyle. While changes in many genes themselves play a role, small variations in DNA sequences near genes that control when and how much a gene is turned on and off, or expressed, are often extremely important for gene activity.

To paint a clearer picture of how such variation affects gene activity, Fernando Pardo Manuel de Villena, Ph.D., at the University of North Carolina, Chapel Hill, and his colleagues crossbred several strains of mice and examined regulatory DNA and gene activity in brain and other tissue. They found that more than 80 percent of the mouse genes had variations in the nearby regulatory DNA that affects gene activity. Genes are inherited in pairs, or alleles, with one allele from each parent. When the researchers compared gene activity due to the genetic contributions from either parent, they found that expression in 95 genes in the brain depended more on being inherited from one parent than the other – a process called imprinting. They also unexpectedly discovered that for thousands of genes in the brain, there was a slightly greater expression of genes inherited from the father than from the mother.

The findings, reported online March 2, 2015 in the journal Nature Genetics, provide new insights into the effects and roles of genetic variation and parental influence on gene activity in mice and humans, as well as the cause of complex traits and disease in both species.

More information:
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Provided by National Institutes of Health