Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Disease-causing genetic mutations in sperm increase with men’s age

20.08.2003


There’s a lot said about a woman’s ticking biological clock, but male biology doesn’t age as gracefully as men might like to think.



By analyzing sperm from men of various ages, scientists from the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins have discovered that older men’s sperm is more likely to contain disease-causing genetic mutations that also seem to increase a sperm’s chances of fertilizing an egg.

The findings, which appear in the advance online section of the American Journal of Human Genetics, emerged during efforts to explain why a rare genetic disease is more common in children born to older fathers. The disease, Apert syndrome, leads to webbed fingers and early fusion of the skull bones, which must be surgically corrected.


The researchers found that mutation rates in sperm increased as men aged, but not enough to fully account for the increased incidence of Apert syndrome in children born to older fathers, leading to the suspicion that the disease-causing mutations confer some benefit to the sperm, despite the mutations’ effects on the resulting baby.

"Mutations causing this disease occur more frequently in the sperm of older men, but the mutation rate isn’t quite as high as the incidence of Apert syndrome," says Ethylin Jabs, M.D., director of the Center for Craniofacial Development and Disorders at Johns Hopkins. "For some reason, a sperm with one of these mutations is more likely to be used to make a baby than normal sperm."

While Apert syndrome itself affects only 1 in 160,000 births, the scientists believe a combination of increased mutation rate and "mutation advantage" might also be behind some of the 20 or so other genetic conditions linked to older fathers, including achrondroplasia dwarfism. These disorders begin to increase rapidly with the father’s age at about the same time as maternal risks increase -- age 33 to 35. Most of the evidence for paternal age effects has come from determining how many children with these conditions are born to fathers of various ages.

For the current study, the Hopkins scientists studied sperm from 148 men of various ages and looked for two genetic changes that are responsible for 99 percent of Apert syndrome cases. They found that men over 60 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations didn’t appear in the men’s blood.

"Men over age 52 are six times more likely than a 27-year-old to have a child with Apert syndrome, so the mutation rate alone can’t account for the condition’s link to paternal age," says first author Rivka Glaser, a graduate student in the human genetics and molecular biology program at Johns Hopkins.

"Literally hundreds of millions of sperm are made in each batch, so in most cases there are still many normal sperm available," adds Jabs, also a professor of pediatrics. "Because the few mutated sperm are more likely to be used to make a baby than would be expected, the mutation must provide them some competitive advantage over their normal counterparts."

The two genetic mutations that cause most cases of Apert syndrome affect a protein called fibroblast growth-factor receptor-2 (FGFR2). The mutated versions of FGFR-2 don’t bind to its usual targets with the same affinity, perhaps contributing to the sperm’s likelihood of fertilizing an egg, the researchers suggest.

The scientists looked for the two FGFR2 mutations in sperm from two groups of men who did not have children with Apert syndrome. These controls -- 57 from a Johns Hopkins study and 76 from an ongoing study at Lawrence Livermore National Laboratory -- were asked to provide sperm and blood samples and to complete a health survey. They also analyzed sperm from 15 fathers of children with Apert syndrome.


The research was funded by the National Institutes of Health, the Environmental Protection Agency and the Department of Energy. Authors on the study are Glaser, Jabs, and Rebecca Schulman of Johns Hopkins School of Medicine; Karl Broman of the Johns Hopkins Bloomberg School of Public Health; Brenda Eskenazi of the University of California at Berkeley School of Public Health; and Andrew Wyrobek of Lawrence Livermore National Laboratory.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/
http://www.hopkinsmedicine.org/craniofacial/Home/
http://www.journals.uchicago.edu/AJHG/journal/issues/v73n4/40284/brief/40284.abstract.html

More articles from Health and Medicine:

nachricht Finding new clues to brain cancer treatment
21.02.2020 | Case Western Reserve University

nachricht UIC researchers find unique organ-specific signature profiles for blood vessel cells
18.02.2020 | University of Illinois at Chicago

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

NUI Galway highlights reproductive flexibility in hydractinia, a Galway bay jellyfish

24.02.2020 | Life Sciences

KIST researchers develop high-capacity EV battery materials that double driving range

24.02.2020 | Materials Sciences

How earthquakes deform gravity

24.02.2020 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>