Testicular tumors may explain why some diseases are more common in children of older fathers

October 25, 2009,

A rare form of testicular tumour has provided scientists with new insights into how genetic changes (mutations) arise in our children. The research, funded by the Wellcome Trust and the Danish Cancer Society, could explain why certain diseases are more common in the children of older fathers.

Mutations can occur in different cells of the body and at different times during life. Some, such as those which occur in 'germ cells' (those which create sperm or eggs), cause changes which affect the offspring; those which occur in other cells can lead to tumours, but are not inherited.

In work published today in , researchers at the University of Oxford and Copenhagen University Hospital describe a surprising link between certain severe childhood genetic disorders and rare testicular tumours occurring in older men: the that make the mutant gene-carrying sperm seem to be the same cells that produce the tumour.

Although the original mutations occur only rarely in the sperm-producing cells, they encourage the mutant cells to divide and multiply. When the cell divides, it copies the mutation to each daughter cell, and the clump of mutant sperm-producing cells expands over time. Hence, the number of sperm carrying this mutation also increases as men get older, raising the risk to older fathers of having affected children.

Professor Andrew Wilkie from the University of Oxford, who led the study, explains: "We think most men develop these tiny clumps of mutant cells in their testicles as they age. They are rather like moles in the skin, usually harmless in themselves. But by being located in the testicle, they also make sperm - causing children to be born with a variety of serious conditions. We call them 'selfish' because the mutations benefit the germ cell but are harmful to offspring."

The work helps to explain the origins of several serious conditions that affect childhood growth and development. These include achondroplasia and Apert, Noonan and Costello syndromes, as well as some conditions causing stillbirth. The research links these conditions to a single pathway controlling cell multiplication, and will be valuable to doctors explaining to parents why the disorder has arisen, and informing them about the risks of it occurring again: in most cases, future children are unlikely to be affected.

The findings may also help explain one of the mysteries of genetics: why scientists have yet to account for much of the genetic component of common diseases. Common diseases tend to be caused by the interaction of many genes, but despite powerful genome-wide association scans to search for these genes, relatively few have been uncovered. Several of these diseases, including breast cancer, autism and schizophrenia, seem to be more frequent in the offspring of , but the reasons are unknown. Professor Wilkie suggests that similar - but milder - mutations might contribute to these diseases.

"What we have seen so far may just be the tip of a large iceberg of mildly harmful mutations being introduced into our genome," he explains. "These mutations would be too weak and too rare to be picked up by our current technology, but their sheer number would have a cumulative effect, leading to disease."

Further research is needed to find other genes that are affected by this process. However, DNA sequencing technology has recently undergone a step change in capacity, enabling more sequence to be obtained in one day than was possible in a whole year just a decade ago. As the sequencing data emerge over the next decade, we should discover just how vulnerable we are to men's selfish mutation factories.

Source: Wellcome Trust (news : web)

Explore further: Human testes may multiply mutations

Related Stories

Human testes may multiply mutations

August 28, 2007
The testes in humans may act as mutation multipliers that raise the odds of passing improved DNA to offspring – but that can also backfire by increasing the frequency of certain diseases.

Mutant testis cells behind genetic disorder have survival advantage

July 14, 2008
In a cruel irony, testis cells carrying the mutation that causes Apert's syndrome are fitter than normal cells, even though children born from sperm derived from those cells are weakened by fused fingers, toes and skulls, ...

Why is Apert's syndrome so common when mutation rate is so low?

August 28, 2007
Aperts syndrome is a condition caused by a mutation that produces fused fingers and toes, and alters cranial development in affected children. It arises spontaneously, but why the mutation that causes this syndrome appears ...

New model for autism suggests women carry the disorder and explains age as a risk factor

July 24, 2007
A new model for understanding how autism is acquired has been developed by a team of researchers led by Cold Spring Harbor Laboratory (CSHL) and Albert Einstein College of Medicine. Autism is a developmental disorder, characterized ...

Children of older fathers more likely to have bipolar disorder

September 1, 2008
Older age among fathers may be associated with an increased risk for bipolar disorder in their offspring, according to a report in the September issue of Archives of General Psychiatry.

Connecting cancer genes

May 15, 2008
A large genetic study in mice has identified hundreds of genes involved in the development of cancer by examining the DNA of more than 500 lymphomas to find the cancer causing mutations.

Recommended for you

A study suggests that epigenetic treatments could trigger the development of aggressive tumours

November 20, 2018
A study headed by the Institute for Research in Biomedicine (IRB Barcelona) and published in the journal Nature Cell Biology examined whether the opening of chromatin (a complex formed by DNA bound to proteins) is the factor ...

Redefining colorectal cancer subtypes

November 20, 2018
There is a long-standing belief that colorectal cancer (CRC), which causes some 50,000 deaths in the United States each year, can be categorized into distinct molecular subtypes. In a paper published recently in the journal Genome ...

Mutation that causes autism and intellectual disability makes brain less flexible

November 19, 2018
About 1 percent of patients diagnosed with autism spectrum disorder and intellectual disability have a mutation in a gene called SETD5. Scientists have now discovered what happens on a molecular level when the gene is mutated ...

Progress in genetic testing of embryos stokes fears of designer babies

November 16, 2018
Recent announcements by two biotechnology companies have stoked fears that designer babies could soon be an option for those who can afford to pick and choose which features they want for their offspring. The companies, MyOme ...

Gene editing possible for kidney disease

November 16, 2018
For the first time scientists have identified how to halt kidney disease in a life-limiting genetic condition, which may pave the way for personalised treatment in the future.

DICE: Immune cell atlas goes live

November 15, 2018
Compare any two people's DNA and you will find millions of points where their genetic codes differ. Now, scientists at La Jolla Institute for Immunology (LJI) are sharing a trove of data that will be critical for deciphering ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.