According to the latest issue of Translational Psychiatry, scientists at the Queensland Brain Institute (QBI) have discovered a genetic change that could explain the reason for children of older fathers being more susceptible to developing schizophrenia or autism.

Researchers compared the offspring of 3 month-old male mice with those fathered by older mice (14 to 16 months) using genome-wide micro-array screening technology, and discovered that offspring of older parents had an increased amount of new copy number variants (CNVs) in their DNA. CNVs are able to delete or repeat entire ‘paragraphs’ of genetic code compared to some genetic changes that involve just one ‘letter’ changes.

According to lead author QBI Professor John McGrath and his colleagues Professor Emma Whitelaw (Queensland Institute of Medical Research), and QBI’s Claire Foldi and Traute Flatscher-Bader, these results suggest first experimental evidence that offspring of older males are subject to an increased risk of the novo (new) CNVs.

McGrath explained:

“While we’ve known for some time that the children of older fathers are more likely to develop schizophrenia or autism, this study provides the first evidence of the biological mechanism that may be responsible.”

In Australia approximately one in a-hundred adults suffers from schizophrenia and one in two hundred children is affected by autism. Babies of fathers aged 50 years or older have a two times higher risk of developing these neuro-developmental disorders compared with those in their early twenties.

Professor McGrath explains that the male germ line, the precursor of sperm, has significantly more cell divisions during adulthood than the female germ line, the precursor of the oocyte, thus, the higher the number of genetic changes in the sperm of older fathers, the higher is the chance of error with increasing age.

He stated that these findings support the suggestion that men should also think about their biological clock when considering parenthood, saying, “Because many people are delaying parenthood, it’s feasible that the incidence of paternal-age related mutations will increase over time.”

The study also offered new, significant indicators regarding the causes of brain disorders, such as autism and schizophrenia.

According to McGrath, these findings pave the way for larger research projects that will examine whether these age-related CNVs are more likely to affect brain-related genes.

He commented:

“Obviously, this isn’t a study we can conduct on humans, but understanding the impact of advanced paternal age on offspring health could have important implications for future public health.”

Written by Petra Rattue