Work described in this story was made possible in part by federal funding supported by taxpayers. At Harvard Medical School, the future of efforts like this - done in service to humanity - now hangs in the balance due to the government's decision to terminate large numbers of federally funded grants and contracts across Harvard University.
- By CATHERINE CARUSO
Genetic changes that create ever-expanding numbers of identical sperm cells are more widespread than previously thought, according to a new study led by researchers at Harvard Medical School.
The team identified genes underlying these so-called clonal expansions and linked the mutations that result - which can be harmful when passed onto offspring - to a number of single-gene diseases, including certain neurodevelopmental disorders.
The findings, published Oct. 8 in Nature, could improve understanding of genetic diseases driven by clonal expansions in sperm. This, in turn, could lead to better genetic screening tests for newborns.
"Clonal expansions in sperm were a known phenomenon, but we figured out that they are surprisingly common and can be caused by dozens of different genes," said senior author Shamil Sunyaev, professor of biomedical informatics in the Blavatnik Institute at HMS.
The results also reveal how evolutionary forces can shape genetic mutations at both the individual and population levels, the researchers said.
In a complementary study in Nature, also published on Oct. 8, a team led by researchers at the Wellcome Sanger Institute mapped how harmful genetic changes in sperm stem cells - including clonal expansions - increase as men age.
A common phenomenon
Clonal expansions occur when mutations in stem cells confer a growth or survival advantage. As a result, the affected stem cells can produce large quantities of genetically identical mature cells that outcompete stem cells without the genetic changes. Sperm that arise from clonal expansions are thus more likely to be passed on to offspring - along with the mutations they contain.
"These mutations are like a double-edged sword: They help sperm stem cells thrive, but they can result in devastating disorders in children," said co-first author Mikhail Moldovan, research fellow in biomedical informatics at HMS.
Scientists previously thought that clonal expansions in sperm - which are difficult to detect - were limited to specific types of mutations in a small number of genes. Sunyaev and his team decided to delve deeper into these genetic alterations to understand how often they actually occur, which genes cause them, and how they can lead to disease.
The researchers analyzed DNA from more than 54,000 parent-child trios and 800,000 healthy individuals in an existing public dataset.
They identified 40 genes that cause clonal expansions via different mechanisms, giving the affected sperm stem cells a competitive edge. Many of these mutations have been linked in other studies to rare developmental disorders and cancers.
