A new study from a team of University of North Carolina (UNC) School of Medicine researchers suggests that that mammals are genetically more like their dads than their moms. Specifically, the research suggest, although we inherit equal amounts of genetic mutations from our parents – the mutations that make us who we are instead of some other person – we actually “use” more of the DNA that we inherit from our dads.
The research, published in the journal Nature Genetics this month (March, 2015) has wide implications for the study of human disease, especially when using mammalian research models. For instance, in many mouse models used to study 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 in mammals, inheriting a mutation has different consequences, depending on whether the genetic variant is inherited from the mother or father.
Fernando Pardo-Manuel de Villena, PhD, UNC professor of genetics is the senior author of the paper. He said:
We’ve known that there are 95 genes that are subject to this parent-of-origin effect. They’re called imprinted genes, and they can play roles in diseases, depending on whether the genetic mutation came from the father or the mother. Now we’ve found that in addition to them, there are thousands of other genes that have a novel parent-of-origin effect.
These genetic mutations that are handed down from parents show up in many common but complex diseases that involve many genes, such as type-2 diabetes, heart disease, schizophrenia, obesity, and cancers. Studying them in genetically diverse mouse models that take parent-of-origin into account will give scientists more precise insights into the underlying causes of disease and the creation of therapeutics or other interventions.
Pardo-Manuel de Villena said:
These diseases are driven by gene expression, not of one gene but of hundreds or thousands of genes.
Gene expression connects DNA to proteins, which then carry out various functions inside cells. This process is crucial for proper human health. Mutations that alter gene expression are called regulatory mutations.
For the Nature Genetics study, the team selected three genetically diverse inbred strains of mice that were descended from a subspecies that evolved on different continents. These mice were 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.
The study’s first author is James Crowley, PhD, assistant professor of genetics at University of North Carolina. He said:
We found that the vast majority of genes – about 80 percent – possessed variants that altered gene expression. 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.
Pardo-Manuel de Villena said:
We now know that mammals express more genetic variance from the father. So imagine that a certain kind of mutation is bad. If inherited from the mother, the gene wouldn’t be expressed as much as it would be if it were inherited from the father. So, the same bad mutation would have different consequences in disease if it were inherited from the mother or from the father.
Bottom line: A new study published in the journal Nature Genetics this month (March, 2015) suggests that that mammals are genetically more like their dads than their moms. The research has wide implications for the study of human disease.