SciTech

UNC-Chapel Hill research suggests RNA from fathers works harder

UNC-Chapel Hill genetics professor Fernando Pardo-Manuel de Villena: A study of mice finds RNA from inherited from male parent has bigger-than-expected effect and, he said, “The basic molecular processes are very similar between humans and mice.”
UNC-Chapel Hill genetics professor Fernando Pardo-Manuel de Villena: A study of mice finds RNA from inherited from male parent has bigger-than-expected effect and, he said, “The basic molecular processes are very similar between humans and mice.” UNC School of Medicine

Half your genes are from your dad and half are from your mom, but a recent study at UNC-Chapel Hill suggests the genes from dad may carry more weight.

“That was completely unexpected,” said Fernando Pardo-Manuel de Villena, a professor of genetics and one of the lead scientists of the study, along with Patrick Sullivan, also a professor of genetics at UNC.

The study was conducted using new strains of genetically diverse mice. “There’s no direct evidence that it’s happening in humans, but I would be extremely surprised if it doesn’t,” de Villena said. “The basic molecular processes are very similar between humans and mice.”

All mice and all humans inherit two complete sets of genes – one set from each parent. Each cell in your body contains both sets, coiled up in long strands called DNA. The DNA directs the production of RNA, which in turn directs the production of proteins, which carry out most of the biological functions in the body. In almost all cases, both sets of genes produce RNA, so if a gene from one parent is defective, the gene from the other parent can do the job.

However, for a small subset of genes (a couple hundred out of about 25,000), only the father’s or the mother’s copy is “turned on” and able to produce RNA. These are called imprinted genes. The UNC team was looking to identify more imprinted genes, and they did find a few. But the more startling outcome concerned the other genes – those that aren’t imprinted. One might expect that the father’s and mother’s genes would each produce about the same amount of RNA, or that perhaps in some cases the mother’s would produce more and in others the father’s would produce more, but that it would generally even out.

Of mice and men

de Villena and his colleagues counted the RNA molecules produced and found that genes from the father produced on average more RNA than genes from the mother. (And remember, RNA directs the production of proteins, which are the workhorses of the body’s development and function.) The implication? “It’s not only what you inherit, but from whom you inherit,” he said.

If the father’s genes have variations in them, those variations (positive or negative) could have a bigger-than-expected effect. This implication may apply particularly to conditions that seem to be caused a group of genes – schizophrenia, bipolar disorder, type 2 diabetes, and obesity to name a few. That’s because the increased expression of the father’s genes might not matter much in a single gene, but it might matter quite a bit when multiplied by a large number of genes.

The results were so unexpected that the team re-analyzed the data. “We took a long time to make sure that data were correct and the conclusions were sound,” de Villena said. Particularly puzzling is the fact that for any particular gene, the father’s copy and the mother’s copy are typically identical: “It’s not the DNA itself, it’s how it’s used.”

In other words, something besides the DNA itself influences what or how much protein is produced by the DNA-to-RNA-to-protein process. He says the study illustrates how far we have to go to really understand the mechanics of genetics.

The UNC study, funded by the National Institutes of Health and published in Nature Genetics in March, focused on brain genes in mice, so the next steps are to look for the same effect in human cells and in other types of genes. de Villena said, “We expect the conclusion to extend to all genes, but it has not been proven yet.”

According to de Villena, this type of project would not have been possible without the skills and perspectives of a wide variety of scientists. Besides co-principal investigator Patrick Sullivan, the team included biostatisticians, biologists and computer scientists. “The future is interdisciplinary,” de Villena said. “You need to talk to people who do things differently than you do.”

New kind of mouse at work

The UNC Chapel Hill study is one of the first based on new populations of mice called the Collaborative Cross. The population, developed over the last 10 years through international collaboration, is housed at UNC. The Collaborative Cross, which will eventually contain 150 genetically diverse lines, allows more complex and precise genetic studies. “Using these mice we are going to learn things that would not be possible using standard mice,” Pardo-Manuel de Villena said.

  Comments