Dr. Gleeson is a
Professor of Neuroscience and Pediatrics at the UCSD School of Medicine, La
Jolla, California. He also holds joint appointments as Clinical Investigator at
Rady Children's Institute for Genomic Medicine, San Diego, California and
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
The first author of
the paper was Dr. Martin W. Breuss, PhD, who is an Assistant Project Scientist
in Gleeson's lab.
The present study
is based on the findings of recent studies that have shown that disease-causing
harmful de novo
mutations occur in at least 10-30 percent of
. The number of these mutations increases with the
age of the father at the time of conception. These de
mutations usually occur spontaneously in the parents' sperms or egg
before fertilization, as a result of which the mutations spread to every cell
in the baby's body as the fertilized egg undergoes division. Importantly, the
father's sperms have increasingly been suspected to harbor the majority of
these de novo
mutations, with the chance of their
recurrence within the same family, estimated to be around 1-3 percent.
"However, such estimates are not based on actual
knowledge of the risk in an individual family, but instead are based on
frequencies in the general population,"
says Gleeson. "When a disease-causing mutation occurs for
the first time in a family, the probability that it could happen again in
future offspring is not known. Thus, families must make a decision with a great
deal of uncertainty."
Objective of the Study
It is known that of
the approximately 1 in 59 children afflicted by autism,
proportion is caused by de novo
(deoxyribonucleic acid) mutations. However, it is not known when and where
these mutations occur. Hence, the major objective of the study was to find
whether mutations occurring in the father's sperms could result in recurrence
of the same mutations in their children.
Salient Features of the Study
- Sperms of 8 fathers of children with autism were
- Presence of genetic
mosaicism was studied using deep whole-genome
- Genetic mutations in the offspring matched only
those present in the father's sperms
- 15 percent of the father's sperms contained
Future Prospects of the Study
The study findings
could lead to the development of a clinical test that will detect any de novo
mutations in the father's sperms, which will
help to predict the risk of their occurrence in future offspring. This
potential genetic test could play an instrumental role in genetic counseling
"While medical textbooks teach us that every cell in
the body has an identical copy of DNA, this is fundamentally not correct.
Mutations occur every time a cell divides, so no two cells in the body are
He adds: "Mosaicism can cause cancer or can be silent
in the body. If a mutation occurs early in development, then it will be shared
by many cells within the body. But if a mutation happens just in sperm, then it
can show up in a future child but not cause any disease in the father."
The study was
funded by the National Institutes of Health (NIH), the Simons Foundation Autism
Research Initiative (SFARI), the European Molecular Biology Organization
(EMBO), the European Commission, and the Austrian Science Fund.
- Autism Risk in Offspring can be Assessed through Quantification of Male Sperm Mosaicism - (https://www.nature.com/articles/s41591-019-0711-0)