Mc Gill University study: Fathers have a profound effect on the genetics of their children

11 Oct

Benedict Carey reports in the New York Times article, Father’s Age Is Linked to Risk of Autism and Schizophrenia:

Older men are more likely than young ones to father a child who develops autism or schizophrenia, because of random mutations that become more numerous with advancing paternal age, scientists reported on Wednesday, in the first study to quantify the effect as it builds each year. The age of mothers had no bearing on the risk for these disorders, the study found.

Experts said that the finding was hardly reason to forgo fatherhood later in life, though it might have some influence on reproductive decisions. The overall risk to a man in his 40s or older is in the range of 2 percent, at most, and there are other contributing biological factors that are entirely unknown.
But the study, published online in the journal Nature, provides support for the argument that the surging rate of autism diagnoses over recent decades is attributable in part to the increasing average age of fathers, which could account for as many as 20 to 30 percent of cases.

The findings also counter the longstanding assumption that the age of the mother is the most important factor in determining the odds of a child having developmental problems. The risk of chromosomal abnormalities, like Down syndrome, increases for older mothers, but when it comes to some complex developmental and psychiatric problems, the lion’s share of the genetic risk originates in the sperm, not the egg, the study found. Previous studies had strongly suggested as much, including an analysis published in April that found that this risk was higher at age 35 than 25 and crept up with age. The new report quantifies that risk for the first time, calculating how much it accumulates each year.

The research team found that the average child born to a 20-year-old father had 25 random mutations that could be traced to paternal genetic material. The number increased steadily by two mutations a year, reaching 65 mutations for offspring of 40-year-old men.

The average number of mutations coming from the mother’s side was 15, no matter her age, the study found.

“This study provides some of the first solid scientific evidence for a true increase in the condition” of autism, said Dr. Fred R. Volkmar, director of the Child Study Center at the Yale School of Medicine, who was not involved in the research. “It is extremely well done and the sample meticulously characterized.” http://www.nytimes.com/2012/08/23/health/fathers-age-is-linked-to-risk-of-autism-and-schizophrenia.html?emc=eta1

A Mc Gill University study shows that fathers have a profound effect on the genetics of their children.

Science Daily reported in Environmental memories transmitted from a father to his grandchildren:

If you have diabetes, or cancer or even heart problems, maybe you should blame it on your dad’s behaviour or environment. Or even your grandfather’s. That’s because, in recent years, scientists have shown that, before his offspring are even conceived, a father’s life experiences involving food, drugs, exposure to toxic products and even stress can affect the development and health not only of his children, but even of his grandchildren.

But, despite a decade of work in the area, scientists haven’t been able to understand much about how this transmission of environmental memories over several generations takes place. McGill researchers and their Swiss collaborators think that they have now found a key part of the molecular puzzle. They have discovered that proteins known as histones, which have attracted relatively little attention until now, may play a crucial role in the process.

They believe that this finding, which they describe in a paper just published in Science, has the potential to profoundly change our understanding of how we inherit things. That’s because the researchers show that there is something apart from DNA that plays an important role in inheritance in general, and could determine whether a father’s children and grandchildren will be healthy or not….

There’s more than just DNA involved in inheritance

What they discovered was that there were dire consequences for the offspring both in terms of their development e.g. where offspring were prone to birth defects and had abnormal skeletal formation, and in terms of their surviving at all. Moreover, what was most surprising, was that these effects could still be seen two generations later.

“When we saw the decreased survivability across generations and the developmental abnormalities we were really blown away as it was never thought that altering something outside the DNA, i.e. a protein, could be involved in inheritance,” said Sarah Kimmins, from McGill’s Dept. of Animal Science, and one of the lead authors on the paper. Kimmins is also the Canada Research Chair in Epigenetics, Reproduction and Development.

Kimmins added, “These findings are remarkable because they indicate that information other than DNA is involved in heritability. The study highlights the critical role that fathers play in the health of their children and even grand-children. Since chemical modifications on histones are susceptible to environmental exposures, the work opens new avenues of investigation for the possible prevention and treatment of diseases of various kinds, affecting health across generations.” http://www.sciencedaily.com/releases/2015/10/151008142622.htm?utm_source=dlvr.it&utm_medium=facebook

Citation:

Environmental memories transmitted from a father to his grandchildren
Date: October 8, 2015

Source: McGill University

Summary:

If you have diabetes, or cancer or even heart problems, maybe you should blame it on your dad’s behavior or environment. Or even your grandfather’s. That’s because, in recent years, scientists have shown that, before his offspring are even conceived, a father’s life experiences involving food, drugs, exposure to toxic products and even stress can affect the development and health not only of his children, but even of his grandchildren. But, despite a decade of work in the area, scientists haven’t been able to understand much about how this transmission of environmental memories over several generations takes place. Scientists think that they have now found a key part of the molecular puzzle. They have discovered that proteins known as histones, which have attracted relatively little attention until now, may play a crucial role in the process.

Journal Reference:
1. Keith Siklenka, Serap Erkek, Maren Godmann, Romain Lambrot, Serge McGraw, Christine Lafleur, Tamara Cohen, Jianguo Xia, Matthew Suderman, Michael Hallett, Jacquetta Trasler, Antoine H. F. M. Peters, and Sarah Kimmins. Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science, 8 October 2015 DOI: 10.1126/science.aab2006

Here is the press release from Mc Gill University:

The father effect

News

If you have diabetes, or cancer or even heart problems, maybe you should blame it on your dad’s behaviour or environment. Or even your grandfather’s. That’s because, in recent years, scientists have shown that, before his offspring are even conceived, a father’s life experiences involving food, drugs, exposure to toxic products and even stress can affect the development and health not only of his children, but even of his grandchildren.

But, despite a decade of work in the area, scientists haven’t been able to understand much about how this transmission of environmental memories over several generations takes place. McGill researchers and their Swiss collaborators think that they have now found a key part of the molecular puzzle. They have discovered that proteins known as histones, which have attracted relatively little attention until now, may play a crucial role in the process.

They believe that this finding, which they describe in a paper just published in Science, has the potential to profoundly change our understanding of how we inherit things. That’s because the researchers show that there is something apart from DNA that plays an important role in inheritance in general, and could determine whether a father’s children and grandchildren will be healthy or not.

Taking a new direction

In the past, most of the research in this area, which is known as epigenetics, has focused on a process involving DNA and certain molecules (known as methyl groups) that attach to DNA and act a bit like a dimmer switch – turning up or down the expression of specific genes.

The researchers were curious about whether histones might play a role in transmitting heritable information from fathers to their offspring because they are part of the content of sperm transmitted at fertilization. Histones are distinct from our DNA, although they combine with it during cell formation, acting a bit like a spool around which the DNA winds.

So, to test their theory about the possible role of histones in guiding embryo development the researchers created mice in which they slightly altered the biochemical information on the histones during sperm cell formation and then measured the results. (It’s a bit like putting a nick in a spool of thread and seeing how it affects the way the thread then loops around the spool.) They then studied the effects on the offspring.
________________________________________
• Gestational diabetes: A diabetes predictor in fathers
• Expectant dads get depressed too
________________________________________
There’s more than just DNA involved in inheritance

What they discovered was that there were dire consequences for the offspring both in terms of their development e.g. where offspring were prone to birth defects and had abnormal skeletal formation, and in terms of their surviving at all. Moreover, what was most surprising, was that these effects could still be seen two generations later.

“When we saw the decreased survivability across generations and the developmental abnormalities we were really blown away as it was never thought that altering something outside the DNA, i.e. a protein, could be involved in inheritance,” said Sarah Kimmins, from McGill’s Dept. of Animal Science, and one of the lead authors on the paper. Kimmins is also the Canada Research Chair in Epigenetics, Reproduction and Development.

Kimmins added, “These findings are remarkable because they indicate that information other than DNA is involved in heritability. The study highlights the critical role that fathers play in the health of their children and even grand-children. Since chemical modifications on histones are susceptible to environmental exposures, the work opens new avenues of investigation for the possible prevention and treatment of diseases of various kinds, affecting health across generations.”

Experts who have commented or are willing to be interviewed about the paper:
John R. McCarrey, Robert and Helen Kleberg Distinguished Chair in Cellular & Molecular Biology, Department of Biology, University of Texas at San Antonio
Prof. Marisa Bartolomei, Dept. of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania

“While there is substantial evidence that fathers can transmit diseases and adverse phenotypes to their children in the absence of genetic mutations, this is the first study that shows a feasible mechanism by which this can happen. This gives researchers confidence to pursue histone retention in the male germ cells as a mechanism of inheritance….and it also will serve as a reminder to fathers to be diligent protectors of their germline.”

The research was funded by: Canadian Institutes of Health Research (CIHR), Genome Quebec, the Reseau de Reproduction Quebecois, Fonds de recherche Nature et technologies (FRQNT), Boehringer Ingelheim Fond, Swiss National Science Foundation and the Novartis Research Foundation.

Contact Information
Contact:
Sarah Kimmins
Organization:
Dept. of Animal Science
Email:
sarah.kimmins@mcgill.ca
Secondary Contact Information
Contact:
Katherine Gombay
Organization:
Media Relations Office
Secondary Email:
katherine.gombay@mcgill.ca
Office Phone:
514-398-2189

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