REDUCED EXPRESSION OF DNA REPAIR GENES IN THE BLOOD OF AUTISTIC CHILDREN OF YOUNGER FATHERS
Abstract
Objective. The purpose of this study was to evaluate whether genes in the five human DNA repair pathways, namely Base Excision Repair, Mismatch Repair, Homologous Repair, and Non-homologous End Joining are underexpressed in autistic children of younger fathers, since they would inherit fewer DNA mutations in their sperm than those with older fathers. Background. Autism and autism spectrum disorder are complex neurodevelopmental disorders whose prevalence has increased 30% in recent years. A known risk factor for autism is advanced paternal age, which is known to be associated with high rates of de nova mutation in sperm. Methods. First, we designed sets of probes for all of the primary genes in the five human pathways of DNA repair. We then performed a secondary data analysis on gene expression microarray data archived in the GEO database by Alter et al. (2001) PLos One 6: e16715 on blood lymphocytes from patients and controls with fathers of known ages. Results. Genes from all five DNA repair pathways were significantly underexpressed in samples from patients with younger fathers. There was also significant skewing towards underexpression of all the genes in the three base repair pathways. Conclusion. Our data support the concept that increased somatic mutation, affecting either specific genes or the entire genome, is involved in the etiology of autism. In patients with older fathers, these mutations are inherited. In patients with younger fathers, the patients themselves are more susceptible to developing mutations from genotoxic exposures and replication errors. Grants. None
REDUCED EXPRESSION OF DNA REPAIR GENES IN THE BLOOD OF AUTISTIC CHILDREN OF YOUNGER FATHERS
Melnick Auditorium
Objective. The purpose of this study was to evaluate whether genes in the five human DNA repair pathways, namely Base Excision Repair, Mismatch Repair, Homologous Repair, and Non-homologous End Joining are underexpressed in autistic children of younger fathers, since they would inherit fewer DNA mutations in their sperm than those with older fathers. Background. Autism and autism spectrum disorder are complex neurodevelopmental disorders whose prevalence has increased 30% in recent years. A known risk factor for autism is advanced paternal age, which is known to be associated with high rates of de nova mutation in sperm. Methods. First, we designed sets of probes for all of the primary genes in the five human pathways of DNA repair. We then performed a secondary data analysis on gene expression microarray data archived in the GEO database by Alter et al. (2001) PLos One 6: e16715 on blood lymphocytes from patients and controls with fathers of known ages. Results. Genes from all five DNA repair pathways were significantly underexpressed in samples from patients with younger fathers. There was also significant skewing towards underexpression of all the genes in the three base repair pathways. Conclusion. Our data support the concept that increased somatic mutation, affecting either specific genes or the entire genome, is involved in the etiology of autism. In patients with older fathers, these mutations are inherited. In patients with younger fathers, the patients themselves are more susceptible to developing mutations from genotoxic exposures and replication errors. Grants. None