A team of researchers, including Matthew Hahn, a professor of computer science at the Luddy School of Informatics, Computing, and Engineering, have published a study that suggests that paternal age at conception for offspring of rhesus macaques explains most of the variation in their rate of mutations at a level similar to that of humans.
The paper, “Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability,” has been published in Genome Research, an international, continuously published, peer-reviewed journal that features outstanding original research providing novel insights into the genome biology of all organisms, including significant advances in genomic medicine. The project is part of the Precision Health Initiative, the first recipient of the funding from IU’s Grand Challenges Program, and features postdoctoral fellow Richard Wang, who is supported by the PHI, as the first author.
“The mutation discovery was part of the original PHI proposal that aimed to understand how new mutations affect various medical outcomes,” said Hahn, who also is the director of the Center for Genomics and Bioinformatics at IU. “This is especially a problem as parents have children later in life since they are leaving more mutations to their children.”
The team at IU collaborated with researchers at the California National Primate Research Center, who had been tracking social behaviors in young macaques. Since macaques and humans both transmit more mutations to their offspring at a similar rate as they get older, the PHI researchers decided to study the sociability, a proxy for normal neurodevelopment, of the offspring of older macaques.
“The California National Primate Research Center work seemed like the perfect study system to understand the effects of these mutations in relation to autism in humans,” Hahn said.
The researchers observed 203 male rhesus monkeys at the Center over the course of four summers, but they found no link between paternal age and negative social behavioral outcomes in offspring despite an increasing number of mutations with paternal age in rhesus macaques.
“We hoped to understand why older human parents tend to have children at a much higher risk of autism,” Hahn said. “The work tells us that the basis for increased risk is not due to the new mutations passed down from older fathers. It’s important because it determines where researchers should look for genes that affect autism.”
PHI researchers plan to continue to study non-human systems to test different hypothesis that have been proposed to explain why human males pass on more mutations to their children as they age.
"Studies like this are so important to the process of building our understanding of genetics," said Kay Connelly, the associate dean for research at Luddy. “The Precision Health Initiative is so critical to advancing the treatment and health interventions for so many areas, and this kind of collaborative work is a great example of the world-class research being conducted at Luddy.”