Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

18.10.2002


Scientists from the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins may have discovered 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 and must be corrected by surgery.



While Apert syndrome itself affects only 1 in 160,000 births, the scientists believe their findings could extend to many of the 20 or so other genetic conditions similarly linked to older fathers. The researchers are scheduled to present their findings Oct. 17 at the annual meeting of the American Society for Human Genetics in Baltimore.

"It makes sense that the mutations causing these diseases would occur more frequently in older men, and indeed that’s what we saw for Apert syndrome," says Ethylin Jabs, M.D., director of the Center for Craniofacial Development and Disorders at Johns Hopkins.


Importantly, disorders linked to advancing paternal age begin to increase rapidly at about the same time as maternal risks increase -- age 33 to 35. Until now, the only evidence for paternal age effects has come from determining how many children with these diseases are born to fathers of various ages.

To obtain the first genetic explanation for these effects, the scientists studied sperm from about 60 men of various ages and looked for two genetic changes responsible for 99 percent of the cases of Apert syndrome. They found that men over 50 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations were not more common in blood samples as men aged.

The scientists say it’s likely that the number of cell divisions that go into making a sperm plays a large role in the link between Apert syndrome and paternal age, and represents a fundamental difference between how aging egg and sperm can impact the health of a child.

"In the men we studied, these mutations had not been inherited, but rather collected over time in the reservoir of primitive cells that become sperm," says first author Rivka Glaser, a graduate student in human genetics at the Johns Hopkins School of Medicine.

Cells that mature into eggs are essentially frozen in time from puberty until the time the egg is signaled to develop. Because of the stage at which they are "frozen," the most likely error in an egg is to have an abnormal partitioning of chromosomes, producing an egg with an extra copy or a missing copy, Glaser says. For example, in Down syndrome, an extra copy of chromosome 21 is inherited from the mother.

Sperm, on the other hand, are continually produced throughout a male’s lifetime from a reservoir of primitive cells. These primitive cells, like other kinds of so-called stem cells, can either replicate themselves or take a step closer to becoming a sperm, a process called differentiation. All told, these cells divide every 21 days after puberty, and at each cell division the opportunity exists for an error in copying the DNA.

"Literally hundreds of millions of sperm are made in each batch, so in most cases there are still many normal sperm available," says Jabs, also a professor of pediatrics. Their study showed that "high levels" of mutations among men who had no children with Apert syndrome amounted to roughly 3 sperm with the mutation among 100,000 sperm.

If an error is made in any of the steps toward becoming a sperm, the only cells affected are the resulting sperm for that batch. However, if an error appears in a primitive cell as it replicates itself and the mistake isn’t fixed, the mutation will continue to be passed on to all of its progeny, including subsequent primitive cells and other batches of semen.

As men age, more of these primitive cells have collected mutations that cause Apert syndrome, leading to more sperm with the mutations in each batch of semen, the scientists suggest. The risk of having a child with Apert is about six times higher for a man age 52 than for someone who’s 27.


Authors on the study are Glaser, Jabs, and Rebecca Schulman, of Johns Hopkins School of Medicine, and Karl Broman, of the Johns Hopkins Bloomberg School of Public Health.

Abstract # 1127 "Molecular evidence for the paternal age effect in sperm." R. Glaser, et al.

Joanna Downer | EurekAlert!
Further information:
http://www.ashg.org
http://www.hopkinsmedicine.org/craniofacial/Home/

More articles from Health and Medicine:

nachricht New nanomedicine slips through the cracks
24.04.2019 | University of Tokyo

nachricht Sugar entering the brain during septic shock causes memory loss
23.04.2019 | Rensselaer Polytechnic Institute

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: Energy-saving new LED phosphor

The human eye is particularly sensitive to green, but less sensitive to blue and red. Chemists led by Hubert Huppertz at the University of Innsbruck have now developed a new red phosphor whose light is well perceived by the eye. This increases the light yield of white LEDs by around one sixth, which can significantly improve the energy efficiency of lighting systems.

Light emitting diodes or LEDs are only able to produce light of a certain colour. However, white light can be created using different colour mixing processes.

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

Proteins stand up to nerve cell regression

24.04.2019 | Life Sciences

New sensor detects rare metals used in smartphones

24.04.2019 | Life Sciences

Controlling instabilities gives closer look at chemistry from hypersonic vehicles

24.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>