Father's Age Tied to Intellectual Disability in Offspring

Rare de novo copy number variations paternal in origin, increase with father's age

WEDNESDAY, Oct. 5 (HealthDay News) -- A large majority of rare de novo copy number variations (CNVs) in intellectual disability (ID) have a paternal origin, and certain CNVs are generated with advanced paternal age, according to a study published online Oct. 3 in the Journal of Medical Genetics.

Jayne Y. Hehir-Kwa, from the Radboud University Nijmegen Medical Center in the Netherlands, and colleagues investigated the genomic and environmental factors predisposing the generation of de novo mutations and structural rearrangements in ID. Information from single nucleotide polymorphism microarrays was used to ascertain the parent-of-origin of 118 rare de novo CNVs in 3,443 patients with ID.

The investigators found that 76 percent of these rare de novo CNVs originated on the paternal allele and this paternal bias was independent of the type and length of the CNV. Molecular mechanisms involved in the creation of rare de novo CNVs seemed to be dependent on the parent-of-origin, as the paternal bias was less pronounced for CNVs flanked by segmental duplications (64 percent). Significantly older age of the father was only noted for those CNVs not flanked by segmental duplications.

"Our data provide, for the first time, convincing evidence that CNVs in ID are largely paternal in origin," the authors write. "Both the paternal bias as well as the age effect that we observed can be explained by the continuation of cell divisions of self-renewing spermatogonia in males."

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