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Thread: Children of older fathers prone to certain disorders, study says

  1. #1
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    Children of older fathers prone to certain disorders, study says

    Children of older fathers prone to certain disorders, study says

    http://www.latimes.com/news/science/...,1730423.story

    Men who become fathers later in life pass on more new genetic mutations to their children, increasing the risk of autism and schizophrenia, researchers find.

    Scientists have pinpointed a likely source for many cases of autism and schizophrenia: Men who become fathers later in life pass on more brand-new genetic mutations to their offspring.

    The finding buttresses observations from population studies that rates of these disorders are more prevalent in children born to older fathers, sometimes by a factor of 2 or more, experts said.

    The research, published online Wednesday by the journal Nature, also should help correct an overemphasis on the riskiness of women giving birth at older ages, some researchers said.

    Although older mothers are more likely to have children with chromosomal disorders such as Down syndrome because of problems with older eggs, the study found that practically all of the novel mutations detected in children came from the father's sperm.

    And the older the father, the more mutations he passed on.

    A man who was 29.7 years old at the time he fathered a child contributed 63 new mutations, on average, to his offspring, while a man who was 46.2 would contribute 126 mutations, the researchers calculated.

    Many of these mutations will have no effect on the children, scientists noted. But some will — and that is significant because more older men have been fathering children in developed countries over the last few decades, said Dr. Kari Stefansson, the study's senior author. Perhaps between the environment, how we live and how we are reproducing we are creating the perfect storm for such epidemics.

    Stefansson, a human geneticist and neurologist at the University of Iceland and chief executive of deCODE Genetics in Reykjavik, noted that the average age of Icelandic fathers at the time of a child's conception was 27.9 years in 1980 and 33 years in 2011.

    "Similar changes have taken place all over the Western world," he said. "It's very likely to have made meaningful contributions to increased diagnoses of autism in our society. What percentage is due to that and what percentage is due to increased focus on diagnosis, I cannot tell you."

    Stefansson and his team sequenced the entire genomes of 78 mother-father-child "trios" to detect cases in which a single "letter" in the DNA code had been altered. Of the children, 44 had received a diagnosis of autism spectrum disorder and 21 had schizophrenia.

    The scientists were able to identify stretches of the children's DNA that came from the father or mother. But they also detected new mutations that did not exist in the genome of either parent.

    The scientists calculated that the age of the father could account for 97% of the variation in these new mutations in children. They also found that the rate at which the father generated new mutations increased with age.

    There's a good biological reason why older fathers contribute more new mutations than older mothers, the researchers said.

    The types of mutations examined in the study tend to occur when DNA is being copied. If this happens in sperm and eggs or in the cells that give rise to them, they can be passed on to the child.

    In the case of a woman, all her eggs are produced to near-readiness before she is even born. In contrast, a man produces sperm in great quantities throughout his adult life. That means DNA is being copied at ages when errors may be more frequent and the mechanisms to chemically correct them may not function as efficiently.

    "It's been known that aged sperm has more mutations," said Dr. Daniel Geschwind, director of UCLA's Center for Autism Research and Treatment. What's striking about the new study, he added, is "the magnitude and extent of the effect."

    With more than half of all genes being active in the brain, there's reason to believe that these mutations would be especially likely to result in brain disorders such as autism and schizophrenia, scientists said.

    But though such disorders were the focus of the study, there is no reason why the effect should be limited to such conditions, Geschwind said. It's known, for example, that rates of non-familial cases of achondroplasia, a type of dwarfism, and a condition known as Alport syndrome that affects kidney function increase with the age of the father.

    Autism is the focus of intensive research efforts, and several DNA-sequencing studies published this spring strongly implicated new mutations from fathers as the cause of some cases of the disorder that don't seem to run in families.

    It's a powerful approach for identifying genes that may be involved in this spectrum of conditions, Geschwind said.
    Older fathers pass on more new genetic mutations to offspring

    http://www.latimes.com/health/booste...,4956716.story

    Men who become fathers later in life pass on more brand-new genetic mutations to their offspring, a study has found — probably contributing to disorders such as autism and schizophrenia in the next generation.

    The finding, published online Wednesday in the journal Nature, buttresses earlier observations that rates of autism and some other disorders are more prevalent in children born of older fathers, sometimes by a factor of two or more, experts said. Though this has been observed for years from population studies, scientists had not known what lay behind it.

    The new research, made possible by recent advances in DNA-sequencing technology, also should help correct an overemphasis on the riskiness of women giving birth at older ages, some researchers said.

    Although older mothers are at higher risk for complications such as diabetes during pregnancy and are more likely to have children with chromosomal disorders such as Down syndrome, the study found that practically all of the new mutations detected in children came from the father.

    And the older the father, the more mutations he passed on.

    A man aged 29.7 at the time he fathered a child contributed 63 new mutations on average to his offspring, the authors found, and a man aged 46.2 contributed 126 mutations — a doubling, the authors calculated.

    Many of the mutations would confer no effect either for good or ill on the children, scientists noted. But some would — and that is significant because in developed countries there has been a shift over the decades toward older men fathering children, said study senior author Dr. Kari Stefansson.

    Stefansson, who is a human geneticist and neurologist at the University of Iceland and the company deCODE Genetics in Reykjavík, noted for example that the average age of Iceland's fathers at the time of a child’s conception was 34.9 in 1900, falling to 27.9 in 1980, then rising back up again to 33 in 2011.

    “Similar changes have taken place all over the Western world,” Stefansson said. “It’s very likely to have made meaningful contributions to increased diagnoses of autism in our society. What percentage is due to that and what percentage is due to increased focus on diagnosis, I cannot tell you.”

    Stefansson and coauthors sequenced the entire genomes of 78 so-called “trios” — father, mother and child — many times over to detect tiny mutations in which a single “letter” in the DNA code had been altered. Of the children, 44 had received a diagnosis of autism spectrum disorder and 21 had schizophrenia. The genetic codes of five grandchildren were sequenced, too.

    The scientists were able to identify stretches of DNA that had come from the father or mother. But they also could detect new mutations in the child that did not exist in the genome of either parent.

    To be sure that these were bona fide new mutations and not an error of DNA sequencing, the genome of each person was sequenced many times over and the genomes of 1,859 other Iceland residents were sequenced as well to exclude mutations that already existed in the general population.
    I think we have had discussions about this before. Some interesting findings in these articles. I think more research needs to be done but perhaps we are beginning to peel back the layers of the onion. Hopefully we begin to put more and more resources into studying the human genome.
    Last edited by DDNYjets; 08-23-2012 at 07:15 AM.

  2. #2
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    Given that, guys who aren't married and ready for children by 25-28 should prolly freeze some sperm for later use.

  3. #3
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    And yet hardly anyone is willing to look at environmental factors, which are cheaper to study and have more tangible results. The hungry mouth of genetic research eats up more NIH funding than anything else I think, if not it's certainly close to the top. Still no effective treatments, though. And all these population studies on stuff like this, yet no one can come to a consensus on increased prevalence? It would be funny if it wasn't so tragic.

    We're at 1 in 88 for ASD in this country using cohorts of kids born 12 years ago, classified by a DSM that has remained largely the same for almost 20 years. But don't worry, the new DSM will redefine ASD and half those people will lose their diagnosis, so no more denied epidemic. SCIENCE!

    The state of scientific study, especially in this country is deplorable. It's all about proving hypotheses and justifying research grants. Shame.

    /rant

  4. #4
    I had three kids at 38, 40 and 45 and my kids are great. Secret is I don't have rusty sperm. I kept my pipes clean since 18 by banging lots of broads.

  5. #5
    Quote Originally Posted by Alkrotraz View Post
    Secret is I don't have rusty sperm. I kept my pipes clean since 18 by banging lots of broads.
    That's quite enough, Pee Wee Herman. Thanks.

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