Older fathers are more likely to pass on new mutations to their offspring than older mothers, researchers from Iceland reported in the journal Nature today. They added that this could partly explain why a higher percentage of children today are born with an autism spectrum disorder, went on to be diagnosed with schizophrenia, or other potentially hereditary syndromes, illnesses or conditions.
Previous studies have pointed to several common factors which raise the risk of schizophrenia, bipolar disorder and autism.
At the time of conception – when the sperm fertilizes the egg – the single largest contributor to passing on genetic defects comes from the father’s older age, and not the mother. The scientists explained that their study examined the world’s largest whole genome sequencing project which linked diseases with uncommon defects in the genome.
The genome refers to all the genetic data a living being has. Each creature has a different genetic makeup or genome. A bacterium’s genome is different from an ants’, the human genome is slightly different from a chimpanzee’s.
Genome sequencing is putting the four letters we used (A, C, D and T) into the right order of DNA nucleotides or bases in a genome. The human genome consists of approximately 3.4 billion sequences of these genetic letters.
Lead author Kari Stefansson, M.D., Dr. Med., CEO of deCODE Genetics, said:
“Strikingly, this study found that a father’s age at the time a child is conceived explains nearly all of the population diversity in new hereditary mutations found in the offspring. With the results here, it is now clear that demographic transitions that affect the age at which males reproduce can have a considerable impact on the rate of certain diseases linked to new mutation.”
Decode Genetics, a company based in Reykjavik, Iceland, is a world leader in analyzing and understanding the human genome.
The team gathered data on 78 families with children which had had a diagnosis of schizophrenia or autism. All the families lived in Iceland. The average age of the fathers in this group was 29.7 years. They sequenced their genomes, as well as the genomes of another 1,859 Icelandic citizens (a larger comparative population).
Below are some of their highlighted findings:
- For every extra year in the father’s age, there was a two-mutation per year rise in offspring
- They also identified the genetic characteristics associated with autism and schizophrenia in the genomes of families with diagnoses of schizophrenia or autism
- In an autism patient subgroup, they identified two defective genes – EPHB2 and CUL3
Dr. Stefansson said:
“Our results all point to the possibility that as a man ages, the number of hereditary mutations in his sperm increases, and the chance that a child would carry a deleterious mutation that could lead to diseases such as autism and schizophrenia increases proportionally.
It is of interest here that conventional wisdom has been to blame developmental disorders of children on the age of mothers, whereas the only problems that come with advancing age of mothers is a risk of Down syndrome and other rare chromosomal abnormalities. It is the age of fathers that appears to be the real culprit.”
The average Icelandic father today at the time of conception is about 33 years old; much older than in the past. The authors explained that epidemiological studies carried out in Iceland have demonstrated that schizophrenia or autism risk in offspring is considerable greater the older the father is.
Previous studies have linked genetic mutations with autism spectrum disorders. Experts say that several genes are involved. A team of researchers in Seattle earlier this year identified three gene mutations – AKT3, PIK3R2 and PIK3CA – which were linked to enlarged brain size, autism, epilepsy, and cancer.
Written by Christian Nordqvist