Researchers believe they may be closer to understanding why older mothers have an increased risk of giving birth to children with birth defects characterized by abnormal chromosome numbers.
A team from the Albert Einstein College of Medicine of Yeshiva University, New York, NY, have found that the increased risk of conditions such as Down syndrome could be attributable to the genetic process of recombination, in which pairs of chromosomes exchange genetic material with each other before separating.
At present, maternal age is the only factor known to affect the probability of a child being born with Down syndrome, caused by the presence of an extra chromosome. The new study, published in Nature Communications, provides a clue as to the mechanism behind the increase in risk.
Cells normally contain 46 chromosomes arranged into 23 pairs. When sperm and egg cells are formed, a cell divides in a process called meiosis, forming a new sex cell comprised of 23 chromosomes – one from each pair.
Before the pairs separate, genetic material is exchanged between the chromosomes. This chromosomal shuffling process is referred to as recombination and helps to ensure that sperm and egg cells have new combinations of genetic traits, protecting the species’ genetic diversity.
The new study has found that the process of recombination may be less regulated in older mothers, potentially leading to abnormal chromosome numbers in sex cells (aneuploidy) or large chromosomal rearrangements.
“It’s been known for many years that the rate of recombination varies across the genome, but less is known about how the rate of recombination changes with parental age,” says study leader Dr. Adam Auton, assistant professor of genetics and epidemiology and population health.
For the study, researchers utilized genetic data from more than 4,200 families with at least two children. The participants were customers of the direct-to-consumer genetic testing company 23andMe, who all gave informed consent to provide data for the study.
The researchers analyzed over 645,000 recombination events among the participants. As maternal age increased, so too did the number of recombination events transmitted from mother to child. Recombination events also occurred more closely to each other among older mothers.
“We know there are cellular processes that tightly regulate the process of recombination,” says Dr. Auton. “So the greater rate of recombination we observed in the chromosomes of older mothers could imply that this tight regulation becomes weaker with age. Basically, recombination appears to be a more dynamic process than we previously appreciated.”
No similar age-related effects were observed among the fathers in the study, partly funded by grants from the National Institutes of Health (NIH) and 23andMe.
At present, the researchers state that there are no clinical applications for their findings. They believe the findings could lead to a better understanding of how genetic errors can occur, however.
“Our study adds to the understanding of the basic biology of meiosis and how recombination shapes the evolution of the human species,” explains Dr. Auton. “In the long run, it may help us understand how aneuploidy or certain types of genetic mutation can occur through failures of recombination.”
Down syndrome is the most common birth defect in the US, according to the Centers for Disease Control and Prevention (CDC). To understand more about the potential risk of having a baby with a birth defect, the CDC advise having a discussion with a clinical geneticist or a genetic counselor.
Recently, Medical News Today reported on a study detailing a new form of testing that allows the whole genome of embryos to be scanned via the cells of 10 biopsies. The new technique will allow doctors to detect all new genetic mutations that happen uniquely in an individual, rather than just those inherited from parents.