According to research published in the Journal of Medical Genetics, the association of chromosomal abnormalities with intellectual disability can be traced back to the father, especially to those who are older at the time of conception.
Chromosomal abnormalities can be inherited or arise anew. They are a common cause of intellectual disability caused by copy number variations (CNV’s), which are structural differences that result in DNA sequences in cells that are missing, inverted, repeated or misplaced. So far, little knowledge exists about the formation of CNV’s with questions remaining open as to whether they occur more often on the DNA sequence passed on by the mother or father, or if parental age plays a role.
Researchers conducted a study in which they systematically examined the incidence of rare CNV’s in almost 3,500 intellectually disabled individuals during a study period from 2006 to 2010.
They discovered that 227 cases of intellectual disability had newly arisen instead of being inherited. This demonstrates that the occurrence is approximately two times as common in the group of intellectually disabled individuals compared with those suffering from autism and three times more common as among people with asthma.
Researchers further evaluated data from 118 individuals where data was available to establish the parental origin of the CNV’s, which revealed that 90 CNV’s came from the father and three quarters showed missing DNA sequences.
After comparing the father’s age at time of birth in the group with CNV’s with people that were not intellectually disabled, the researchers adjusted their findings for ethnicity and birth dates to establish whether cultural or social factors may play a role, but discovered no differences in paternal age between the two groups.
Participants with CNV’s where then split into two categories. The first group consisted of individuals with CNV’s occurring in regions of the genome with highly repetitive DNA sequences, whilst the other group contained those with CNV’s occurring in non-repetitive DNA sequences. Both groups’ paternal ages were compared with those who had no intellectual disability.
In the group of CNV’s in non-repetitive DNA sequences researchers discovered a substantial increase in the father’s age. This group accounted for most CNV’s, and according to the authors, this discovery is a vital key to understand how and why disease-causing CNV’s are formed.
The authors continue to say that these findings also suggest that newly arising CNV’s originate more often from the father’s DNA than the mother’s and that the father’s age is of significance and write, “In conclusion, our data provide for the first time convincing evidence that CNV’s in intellectual disability are largely paternal in origin.”
According to the researchers, both the gender and age bias can be explained by ongoing cell divisions of self-renewing sperm cells during the fetal development of boys in which mistakes can occur, and also because of impaired DNA genesis and repair as a consequence of the ageing process.
Written by Petra Rattue