Researchers, in a first of its kind study, have shown how mammals inherit genetic variants from their parents and have revealed that mammals are genetically more like their dads.
“This is an exceptional new research finding that opens the door to an entirely new area of exploration in human genetics,” said Fernando Pardo-Manuel de Villena, PhD, professor of genetics at UNC School of Medicine and senior author of the paper published in Nature Genetics.
Researchers show through their study that although offspring inherit equal amounts of genetic mutations from their parents – the mutations that make them who they are instead of some other person – they actually “use” more of the DNA that is inherited dads.
The research has wide implications for the study of human disease, especially when using mammalian research models. For instance, in many mouse models created for the study of gene expression related to disease, researchers typically don’t take into account whether specific genetic expression originates from mothers or fathers.
But the UNC research shows that inheriting a mutation has different consequences in mammals, depending on whether the genetic variant is inherited from the mother or father.
This means that scientists will be able to garner more insight into how diseases and conditions are caused by gene expression of thousands of DNA, of which several hundred imprinted genes – rather than out of the 95 initially thought – could be in favour of the father.
Researchers opted for Collaborative Cross in the latest study. Researchers claim that the Collaborative cross is the most genetically diverse mouse population in the world, which is generated, housed, and distributed from UNC.
Traditional lab mice are much more limited in their genetic diversity, and so they have limited use in studies that try to home in on important aspects of diseases in humans. The Collaborative Cross bred together various wild type mice to create wide diversity in the mouse genome.
Pardo-Manuel de Villena said that this diversity is comparable to the variation found in the human genome. This helps scientists study diseases that involve various levels of genetic expression across many different genes.
For the purpose of the research, three genetically diverse inbred strains of mice that were descended from a subspecies that evolved on different continents were selected. These mice were then bred to create nine different types of hybrid offspring in which each strain was used as both father and mother. When the mice reached adulthood, the researchers measured gene expression in four different kinds of tissue, including RNA sequencing in the brain. They then quantified how much gene expression was derived from the mother and the father for every single gene in the genome.
“We found that the vast majority of genes – about 80 percent – possessed variants that altered gene expression,” said James Crowley, PhD, assistant professor of genetics. “And this was when we discovered a new, genome-wide expression imbalance in favor of the dad in several hundred genes. This imbalance resulted in offspring whose brain gene expression was significantly more like their father’s.”
