Greater Risk of Autism and Schizophrenia in the Offspring of Older Fathers

A recent study conducted by Dr. Flatscher-Bader and colleagues may shed light on why children with older fathers face an increased risk of autism spectrum disorders (ASD). A significant body of research has revealed that offspring of older fathers are at a greater risk of developing disorders such ASD and schizophrenia; however, the underlying cause of this occurrence is not well understood. For this reason, Dr. Flatscher-Bader and colleagues used a rodent model to investigate the effects of paternal age on offspring’s genes.

Flatscher-Bader and colleagues were particularly interested in what are called de novo copy number variants (CNVs). CNVs refer to genetic mutations in which particular areas of chromosomes are either missing (i.e., deleted) or repeated (i.e., duplicated). Research has found specific CNVs to be related to a variety of disorders including autism and schizophrenia. In some cases, CNVs are inherited from a parent who also carries the gene mutation. Other times, CVNs are de novo, meaning new. De novo CNVs result from mutations that occur when genetic material is copied from a parent to their offspring (i.e., genetic mutations in the sperm or egg). In this study, the occurrence of de novo CNVs was compared in the offspring of older and younger male mice.

Two groups of offspring were bred for this study. The younger group consisted of the offspring of 3-month-old males and 3-month-old females, while the older group consisted of the offspring of 12 to 16-month-old males and 3-month-old females. Both parents and offspring were genetically screened for CNVs to determine whether the CNVs detected in the offspring were inherited or de novo. Behavioral tests and brain scans were also conducted to determine if specific CNVs were associated with differences in behavior or brain anatomy.

A total of six de novo CNVs were identified in the offspring of the older male mice, while no de novo CNVs were found in the offspring of the younger male mice. Moreover, two of de novo CNVs were found to be associated with differences in behavior and brain anatomy. To relate these findings back to humans, the de novo CNVs identified in this study have been linked to a variety of human disorders including ASD and schizophrenia.

Rodent models are a useful research method in that they allow for the study of human disorders without risking harm to human subjects. However, conclusions drawn from rodent models are limited by the inability to exactly reproduce human disorders in rodents. For instance, using a rodent model to study ASD, a disorder that commonly affects communication and language in humans, is complicated by the fact that mice do not have language. So when interpreting this study, please note that Flatscher-Bader and colleagues did not find the offspring of older male mice to be more likely to develop disorders like ASD and schizophrenia; rather, they found an increased incidence of de novo CNVs, a number of which have been linked to disorders like ASD and schizophrenia in humans.

Using a rodent model, Flatscher-Bader and colleagues identified de novo CNVs in the offspring of older male mice, which may explain why children with older fathers face an increased risk of developing ASD and other disorders. Over the years, there has been an emerging trend of parents having children later. According to Flatscher-Bader and colleagues, this trend may be increasing the incidence of de novo CNVs in children. Furthermore, since de novo CNVs can in turn be passed on to offspring, future generations may also be affected.

If you are interested in reading the full article, you can access it here.

References

Flatscher-Bader, T., Foldi, C. J., Chong, S., Whitelaw, E., Moser, R. J., Burne, T. H. J, … McGrath, J. J. (2011). Increased de novo copy number variants in the offspring of older males. Translational Psychiatry, 1. doi: 10.1038/tp.2011.30

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