On-line Survey for Parents of Children with Autism Spectrum Disorders

Advanced Grandparental Age as a Risk Factor for Autism

This study is currently recruiting patients.
Verified by University of Mississippi Medical Center June 2007

Sponsored by: University of Mississippi Medical Center
Information provided by: University of Mississippi Medical Center
ClinicalTrials.gov Identifier: NCT00464477


Purpose

The Division of Medical Genetics at the University of Mississippi Medical Center is recruiting parents of children with a pervasive developmental disorder (including autism, autistic spectrum disorder, PDD-NOS, Asperger syndrome, childhood disintegrative disorder, and Rett syndrome) to participate in a study to help determine potential causes of the increasing prevalence of these disorders. The study is being conducted using an anonymous on-line survey available to parents through a secure link.

The study consists of approximately 90 questions about the affected child, siblings, parents, and grandparents, which will take roughly 10-15 minutes to complete. Several families will also be invited to participate in a phone interview. Both the survey and the phone interview are conducted using a self-designated code to protect anonymity and patient privacy. No identifying information such as name, date of birth, address, or phone number will be asked. Only questions regarding the year of birth of family members will be asked.

Condition
Autistic Disorder
Pervasive Developmental Disorder
Asperger Syndrome
Childhood Disintegrative Disorder
Rett Syndrome


MedlinePlus related topics: Asperger's Syndrome; Autism; Mental Health; Rett Syndrome
Genetics Home Reference related topics: Rett syndrome

Study Type: Observational
Study Design: Natural History, Cross-Sectional, Random Sample, Retrospective Study

Official Title: Advanced Grandparental Age as a Risk Factor for Autism and Other Pervasive Developmental Disorders

Further study details as provided by University of Mississippi Medical Center:

Total Enrollment: 100
Study start: June 2007; Expected completion: December 2007


Autism is a genetically heterogeneous entity. Although numerous studies have demonstrated a strong genetic basis, no clear etiology has been identified to date. Recently, two studies have demonstrated an increased risk of autism in children born to fathers over the age of 40. However, given the large male-to-female predominance of autism, it is likely that new mutations on the X chromosome account for a significant number of affected cases. Due to the maternal origin of the X chromosome in males, we hypothesize that advanced maternal-grandpaternal age may also be a risk factor for autism. Precedence for this theory exists with other X-linked disorders such as Duchenne muscular dystrophy and Rett syndrome. Additionally, it has been demonstrated that maternal psychiatric illness, but not paternal psychiatric illness, is more prevalent among parents of children with autism. Using anonymous surveys of families with autistic children, we seek to identify the ages of grandparents at the time the parents were born in order to determine if advanced maternal-grandpaternal age is associated with an increased risk for autism when adjusted for advanced maternal and paternal age. Additionally, we will seek out sister-pairs in order to identify any statistical significance between the ages of the maternal grandfather at delivery of each sister. If advanced maternal-grandpaternal age is, in fact, a risk factor, it would help direct molecular researchers towards genes on the X chromosome as potential etiologies for autism. Also, further study of potential mutagenic exposures in the environment of grandparents may help elucidate the reason for the increasing incidence of autism in recent decades.
Eligibility

Genders Eligible for Study: Both
Criteria
Inclusion Criteria:

Individuals of any age with autism, autistic disorder, autistic spectrum disorder, Asperger syndrome, pervasive developmental disorder, PDD-NOS, Rett syndrome, or Childhood disintegrative disorder
Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00464477

Omar Abdul-Rahman, MD 601-984-1900 OAbdulrahman@prevmed.umsmed.edu


United States, Mississippi
University of Mississippi Medical Center, Jackson, Mississippi, 39216, United States; Recruiting
Omar Abdul-Rahman, MD 601-984-1900 OAbdulrahman@prevmed.umsmed.edu



Study chairs or principal investigators

Omar Abdul-Rahman, MD, Principal Investigator, University of Mississippi Medical Center
More Information and to participate in this study



Study ID Numbers: 2007-0023
Last Updated: June 18, 2007
Record first received: April 20, 2007
ClinicalTrials.gov Identifier: NCT00464477
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on June 20, 2007

Hindustan Times Sperm mutations cause genetic disease

I just found this article in the Hindustan Times

"It is curious that although sperm have been around since the beginning of time, we know so little about what is in them, and what makes them tick, er, swim. So scientists spend a lot of their waking hours trying to compare the structure and content of the proteins of sperm in various species, in order to understand their evolution and origin. For instance, the mutated DNA in the genes of the sperm of older fathers is believed to cause many genetic diseases. It is almost as if a man’s biological clock accelerates mutation in sperm cells in his early ’30s."

Is Paternal Age Involved in the Genes for Crohn's Type 1 Type 2 Diabetes, Hypertension, Coronary Heart Disease, etc.???

Read the whole article at the Telegraph:
A dramatic genetic breakthrough has paved the way for potential new treatments of seven common diseases that could help more than 20 million people.

The largest ever study of its kind has found 10 new genes linked to seven of the most common ailments: heart disease, rheumatoid arthritis, high blood pressure, type 1 and type 2 diabetes, bipolar disorder and Crohn’s disease.

Some 200 British scientists from 50 research groups collaborated to discover the genes after screening DNA from 17,000 people.

In two years, the £9 million investigation analysed 10 billion pieces of genetic information.

Together the seven diseases affect more than 20 million people across the UK, with coronary heart disease alone claiming the lives of 105,000 people every year, making it the country’s biggest killer. The study has identified, for the first time, some of the genes that trigger these diseases.

Professor Peter Weissberg, medical director of the British Heart Foundation, said the new research held out the hope of a new understanding of heart disease and high blood pressure, that could ultimately lead to new treatments.

The painstaking two-year Wellcome Trust Case Control Consortium investigation is the biggest study of the genetics behind common diseases ever undertaken. It has been likened to trawling the sea with huge nets rather than fishing with a rod and line.

The scientists analysed DNA samples from 2,000 patients per disease, comparing them with 3,000 control samples from healthy volunteers.

One of the most exciting finds was a new link between type 1 diabetes and Crohn’s disease, a type of inflammatory bowel disorder that affects up to 60,000 people in the UK.

A gene called PTPN2 was found to be common to both auto-immune diseases, suggesting that they share similar biological pathways.

Professor Peter Donnelly from Oxford University, chairman of the Consortium, tonight said the new approach - published tomorrow in the journal Nature - would open a new chapter in the study of how genetics influences the development of diseases.

“Our study heralds a new dawn in genetics,” he said.

“It is absolutely clear now that this approach works. The findings are reliable and the whole field is changing, so our understanding of human genetics will be quite different in a year or so.

“By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments.”




Dr Mark Walport, Director of the Wellcome Trust, the UK’s largest medical research charity, was optimistic about the study’s potential.

“Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people,” he said.

“This research shows that it is possible to analyse human variation in health and disease on an enormous scale.

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“New preventive strategies and new treatments depend on a detailed understanding of the genetic, behavioural and environmental factors that conspire to cause disease.”

Professor Weissberg stressed there was still a long was to go before new drugs were developed that could target mechanisms triggered by various genetic factors.

He said: “It might give us a new insight into the mechanisms that produce high blood pressure and heart disease. If we can get to an understanding of new mechanisms, that might lead us to a new drug to target those mechanisms.”

Karen Addington, CEO of the Juvenile Diabetes Research Foundation in the UK, said the “landmark” study could help the lives of around 350,000 people who suffer from type 1 diabetes in the UK.

“For the first time we can pinpoint which genes increase the likelihood of developing type 1 diabetes,” she said.

“The more that we understand how and why the condition occurs, the closer we come to being able to prevent and cure it.”

Andrew Hattersley of the Peninsula Medical School in Exeter, an expert in type 2 diabetes, which affects 1.9 million people in the UK, added: “We now have significantly more pieces to the jigsaw that will help us understand the mechanisms behind type 2 diabetes.

The breakthrough link between Crohn’s disease and type 1 diabetes was also welcomed by doctors. Professor John Todd, University of Cambridge, said: “This is the first time that we have seen a specific genetic link between type 1 diabetes and Crohn’s disease. This new link between the two diseases is a possible new avenue for us to understand how they occur.”

The study is a “major step forward” into understanding rheumatoid arthritis according to Professor Jane Worthington of Manchester University. The disease affects 387,000 mostly elderly people in the UK.



The study's key findings were:

Bipolar disorder: A whole collection of genes were found to be associated with this mental illness, also known as manic depression, which is marked by extreme mood swings. Each on its own makes a small contribution to risk, but together they can have a significant effect. Several of the genes identified play a key role in the way nerve cells in the brain talk to each other. Bipolar disorder affects about 100 million people worldwide.

Coronary heart disease: The study found several new genetic regions that increased the risk of heart disease. Most notable was a site on chromosome 9, one of the paired bundles of DNA in which the genetic code is written, which increased the risk by 50% in people carrying one version of the risk variant. For those carrying both copies of the variant, the risk was almost doubled. Coronary heart disease is Britain's biggest killer, claiming 105,000 lives each year.

advertisementCrohn's Disease: Three new genes were found to increase a person's susceptibility to this illness, which affects between 30,000 and 60,000 people in the UK. One, PTPN2, which is involved in the regulation of the immune system, was also found to be shared with type 1 diabetes. It is the first genetic link between the two diseases to be identified.

Hypertension (high blood pressure): A number of genetic signals were found pointing to a higher risk for hypertension. The results suggest that high blood pressure arises because of a wide range of interacting factors, including a large number of genes. More work is needed, but the research takes scientists closer to understanding the mechanisms behind this incredibly common disorder which affects more than 16 million Britons and a billion people worldwide.

Rheumatoid Arthritis: (RA). Several genes were found for the first time to have a possible role in RA. Further work will have to be undertaken to validate the findings and understand how the genes might influence the development and course of the auto-immune disease suffered by 387,000 people in the UK. Scientists hope the research will lead to new cures.

Type 1 Diabetes: The study highlighted four new chromosome regions that increase the risk of type 1 diabetes, another auto-immune disease in which the insulin-producing cells of the pancreas are destroyed. The newly discovered link with Crohn's may provide clues on how to treat type 1 diabetes in the future. The disease affects around 350,000 people, in the UK, including 20,000 children.

Type 2 Diabetes: Research from the consortium has helped identify clear genetic links between obesity and type 1 diabetes. One of these, the gene FTO, influences the risk of diabetes through an effect on weight gain. The work illustrates the fact that type 2 diabetes is not just the result of lifestyle factors, such as poor diet and lack of exercise, but is also gene-driven. An estimated 1.9 million people in the UK have type 2 diabetes.

Bruce Ponder Hunting For Cancer Genes

Bruce Ponder: The gene hunter


The top cancer scientist tells Polly Curtis about his dogged research to find out how the disease strikes

Tuesday April 3, 2007
The Guardian


Professor of oncology Bruce Ponder inside the Li Ka Shing Centre, the Cancer Research UK Cambridge Research Institute. Photograph: Graham Turner



The view from Bruce Ponder's office looks like an artist's impression. A block of impossibly green grass, the crisp angles of new buildings and a sculpture still shiny and new. When the building was being designed, he was asked to pick out the sculpture, but after a while needed some help because it all looked like "chunks of metal" to him.
The Taichi Arch - Gate of Health, a large bronze by the Chinese master Ju Ming, stands outside the entrance to the newly opened Li Ka Shing Centre, home of the Cancer Research UK Cambridge Research Institute on the Cambridge biomedical c ampus, next to Addenbrooke's Hospital. A symbol of the graceful coordination of tai chi is appropriate for the new facility, which brings together scientists and doctors from a broad spectrum of disciplines to unravel the many mysteries of how cancer kills.

Ponder, the new institute's director, is professor and head of the university's department of oncology, and co-director of two other centres on the campus - a cancer research institute and a centre for epidemiological studies of diseases. Until the new centre was ready, he moved between the different centres, at one point working from four offices. Today, he has consolidated what almost amounts to an empire. The aim is to find out how cancer works and, of course, a cure. His angle is the genetics of cancer: how we inherit a risk of developing different cancers.

Ponder's career started in medicine as a doctor, swinging from clinical work to laboratory work - unusual for the time. He had to fight for funding, as well as to be taken seriously as both a doctor and a scientist.

After general medicine and a PhD in molecular biology, he trained for a year in oncology in the US. "With cancer you have the whole spectrum of medicine," he says. "From some poor old guy with cancer of the oesophagus, who would like to die at home and how can you support him and palliate him, to cancer being the outstanding problem in biology. What cancer is, I think, is a breakdown in the way tissues are organised ... If one understood the basic biology, you might understand something about treatments."

With such broad interests, it sounds like people didn't know what box to put him in. "I didn't know what box to put myself in," he laughs. He ended up working in a bladder unit - as good a place as any to examine the way a cancer develops in a lining, he thought. One day, they were a bit busy next door in the thyroid cancer unit, so he mucked in. The move changed his life. He discovered two thick files, case notes, on families who had experienced thyroid cancer again and again through the generations.

The understanding of genetics was in its infancy and very few people were making the link between inherited genetic mutations and cancers, writing off the patterns within families as being caused by shared environment. But the link with thyroid cancer - a very rare cancer - was too strong. It was 1980, and he set out to find the gene.

"Not many of us have big discoveries," he says, but the mapping of the MEN2 gene, responsible for hereditary patterns of thyroid cancer, was his. It was the first discovery of a predisposing gene linked to a form of cancer in the UK. Six years later, they found the gene itself. "With today's technology it wouldn't take much more than six weeks," he says. His group developed the test now used in all families where thyroid cancer is identified to work out the probability of relatives being diagnosed.

The next step

MichaeL Moore on Oprah Talking About "Sicko" Part 1 and Part 2

This is the best interview

Effects of age on DNA double-strand breaks and apoptosis in human sperm*

Male factor

Effects of age on DNA double-strand breaks and apoptosis in human sperm*1

Narendra P. Singh M.B.B.S., M.S.a, , , Charles H. Muller Ph.D.b and Richard E. Berger M.D.b
a Bioengineering, University of Washington, Seattle, Washington, USA
b Department of Urology, University of Washington, Seattle, Washington, USA
Received 6 February 2003; revised 30 April 2003; accepted 30 April 2003. ;

Available online 3 December 2003.

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Source: University Of Washington
Date: November 27, 2002
More on: Fertility, Stem Cells, Brain Injury, Prostate Cancer, Pregnancy and Childbirth, Nervous System

Research Reveals A Cellular Basis For A Male Biological Clock
Science Daily — Researchers at the University of Washington have discovered a cellular basis for what many have long suspected: Men, as well as women, have a reproductive clock that ticks down with age.



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A recent study revealed that sperm in men older than 35 showed more DNA damage than that of men in the younger age group. In addition, the older men's bodies appeared less efficient at eliminating the damaged cells, which could pass along problems to offspring.

"When you talk about having children, there has been a lot of focus on maternal age," said Narendra Singh, research assistant professor in the UW Department of Bioengineering and lead researcher on the study. "I think our study shows that paternal age is also relevant."

Charles Muller, with the UW Department of Urology and a collaborator on the study, recently presented the findings at the annual meeting of the American Society for Reproductive Medicine in Seattle.

In the study, researchers recruited 60 men, age 22 to 60, from laboratory and clinical groups. A computerized semen analysis was performed for each of the subjects, looking for breaks in sperm cell DNA and evidence of apoptosis, or cell suicide. Normally, when something goes irreparably wrong in a cell, that cell is programmed to kill itself as a means of protecting the body.

The researchers found that men over age 35 had sperm with lower motility and more highly damaged DNA in the form of DNA double-strand breaks. The older group also had fewer apoptotic cells an important discovery, Singh said.

"A really key factor that differentiates sperm from other cells in the body is that they do not repair their DNA damage," he said. "Most other cells do."

As a result, the only way to avoid passing sperm DNA damage to a child is for the damaged cells to undergo apoptosis, a process that the study indicates declines with age.

"So in older men, the sperm are accumulating more damage, and those severely damaged sperm are not being eliminated," Singh said. "That means some of that damage could be transmitted to the baby." More research is needed to determine just what the risks are. Other reseachers in the study included Richard E. Berger, UW professor of urology. The work was supported by the Paul G. Allen Foundation for Medical Research.


Note: This story has been adapted from a news release issued by University Of Washington






Abstract

Objective

This study was designed to explore the relationship between men's age and DNA damage and apoptosis in human spermatozoa.

Design

Semen samples were collected from men between the ages of 20 and 57 years. Sperm DNA double-strand breaks were assessed using the neutral microgel electrophoresis (comet) assay, and apoptosis was estimated using the DNA diffusion assay.

Setting

Academic medical center.

Patient(s)

Sixty-six men aged 20 to 57 years were recruited from infertility laboratory and general populations and consented to donate a semen sample. Recruitment was determined by time and day of analysis; the only exclusions were for azoospermia, prostatitis, or prior cancer therapy.

Intervention(s)

None.

Main outcome measure(s)

DNA damage and apoptosis in human sperm.

Result(s)

Age correlated with an increasing percentage of sperm with highly damaged DNA (range: 0–83%) and tended to inversely correlate with percentage of apoptotic sperm (range: 0.3%–23%). For example, percentage of sperm with highly damaged DNA, comet extent, DNA break number, and other comet measures was statistically significantly higher in men aged 36–57 years than in those aged 20–35 years, but percentage apoptosis was statistically significantly lower in the older group. Semen analysis showed percentage motility to be significantly higher in younger age groups.

Conclusion(s)

This study clearly demonstrates an increase in sperm double-stranded DNA breaks with age. Our findings also suggest for the first time an age-related decrease in human sperm apoptosis. These novel findings may indicate deterioration of healthy sperm cell selection process with age.

Author Keywords: DNA double-strand breaks; apoptosis; human sperm; aging; Comet assay


Corresponding author. Reprint requests: Narendra P. Singh, M.B.B.S., M.S., Department of Bioengineering, Box 357962, University of Washington, , Seattle, Washington 98195-7962, , USA (FAX: 206-685-2060).

*1 Supported by the Paul G. Allen Foundation for Medical Research.

Authors Singh, Muller, and Berger contributed equally to this work.