Human/male genetic biological clock

When parents are over 35 years old, man and woman alike,
the following cases become prevalent:

Up to a third of all cases of schizophrenia are linked to increasing paternal age.
Men 40 and older are nearly six times more likely to have offspring with autism than men under age 30.
Other research shows that the risk of breast and prostate cancer in offspring increases with paternal age.
The chances of parents of babies with achondroplasia is higher
Older fathers can cause genetic conditions in their offspring, such as birth defects, autism and schizophrenia.
Increased chances of an older woman having a baby with Down's syndrome has been well documented.




Posted by Neriz at Thursday, August 21, 2008
Labels: pasalubong, science

Do Copy Number Variations Increase With Older Paternal Age, Is That Why Non-Familial Cancers, Autism, Schizophrenia, Autoimmune Diseases Increase

Canadian, British And American Scientists Launch Major New Genome Partnership To Catalogue All Common Copy Number Variations
Main Category: Genetics News


An international team will use state-of-the-art, high-density microarrays and new computer algorithms to improve the detection of variants in the human genome which are implicated in various diseases. The new systems are the foundation of Phase 2 of the Genome Structural Variation Consortium, which was set up in 2004 and seeks to identify structurally variable regions in the human genome.

In 2006, the Genome Structural Variation Consortium, along with other international collaborators, generated a first-generation map of copy number variants (CNVs) covering the human genome. The CNVs that they identified, which in many cases lead to deletion or duplication of genes along chromosomes, tended to encompass large stretches of DNA ranging from thousands to millions of chemical bases of DNA. These changes are part of the normal variability between apparently healthy people, but some may also predispose individuals to disease. The data also suggested that thousands more CNVs exist, but technological limitations associated with that earlier study precluded the discovery of more CNVs.

The new comprehensive map will be critical for studies attempting to identify genes involved in both rare and common diseases. "Our experiments will generate the highest-resolution CNV catalogue of worldwide populations. The initiative will also complement ours, and other efforts to sequence entire genomes", said Dr. Stephen Scherer, Senior Scientist and Director, The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children (SickKids) in Toronto.

In its second phase, this international research collaboration will develop a comprehensive, higher resolution CNV map for the Human Genome - at a level 100-fold finer than the first map. Working with NimbleGen Systems, Inc. of Madison, Wisconsin, USA, the Consortium has designed a novel set of 2.1-million-feature microarrays that will enable genome-wide detection of CNVs with 42 million probes. The set of microarrays have been referred to as "whole-genome oligonucleotide tiling arrays" because they cover almost all DNA along chromosomes, spaced at intervals of only 50 bases, or letters of DNA code.

The international consortium is led by Scherer, Drs. Nigel Carter, Matthew Hurles, and Chris Tyler-Smith of the Wellcome Trust Sanger Institute, and Dr. Charles Lee from Brigham and Women's Hospital and Harvard Medical School.

To better understand CNVs and diseases, researchers and clinicians around the world are now accessing the new CNV maps from the "Database of Genomic Variants" (http://www.projects.tcag.ca/variation/) hosted by SickKids. TCAG is a genomics platform funded by Genome Canada through OGI.

"Copy Number Variation has emerged over the past few years as a novel and productive focus for understanding variation within the human genome as well as other species' genomes," noted Dr. Christian Burks, President and CEO of the Ontario Genomics Institute (OGI). "We are delighted, in conjunction with funding from Genome Canada and Ontario's Ministry of Research and Innovation, to be supporting this work, and to see Ontario and Canada at the forefront of this area of biomedical research."

"From our Phase 1 map, we suspected there remains much more CNV to be discovered," said Dr. Matthew Hurles, Investigator at the Wellcome Trust Sanger Institute. "Because of the higher resolution of the new systems, we will, for the first time, be able to uncover these smaller variants."

Dr. Nigel Carter, Senior Investigator at the Sanger Institute added, "The availability of flexible high-density oligonucleotide arrays has made a study of such scope possible. The first data from the 42 million probe set has confirmed the ability of this approach to identify copy number variants at least as small as 500 base pairs in size."

The new arrays will be used to scan DNA samples from dozens of individuals of diverse geographic background, in experiments designed to capture all CNVs with a frequency of five percent or greater in the world. As such, the project will generate more than 1.68 billion data points.

"We also anticipate being able to obtain fine-scale information on the anatomy of individual CNVs" said Dr Charles Lee, Director of Cytogenetics (Harvard Cancer Center), Brigham and Women's Hospital and Harvard Medical School. "Ultimately, the data generated from our Phase 2 studies will be important for disease association studies, cancer biomarker studies, and accurate interpretation of many genetic diagnostic tests."

The Centre for Applied Genomics (TCAG) is located in the Research Institute of The Hospital for Sick Children (SickKids), Toronto, and is a Science and Technology Platform of Genome Canada, funded by Genome Canada through the Ontario Genomics Institute. TCAG provides genomics infrastructure to facilitate a wide variety of research, including human genomics and disease, model organisms, and agricultural and food sciences. The Centre's services are available to all clients in the academic, government or private sectors. TCAG supports a number of large-scale Genome Canada projects, other national and international genomics efforts, as well as hundreds of additional researchers in Ontario, Canada, and worldwide.

http://www.tcag.ca

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992 as the focus for UK sequencing efforts. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms such as mouse and zebrafish, and more than 90 pathogen genomes. In October 2005, new funding was awarded by the Wellcome Trust to enable the Institute to build on its world-class scientific achievements and exploit the wealth of genome data now available to answer important questions about health and disease. These programmes are built around a Faculty of more than 30 senior researchers. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK.

http://www.sanger.ac.uk/humgen/cnv/

Brigham and Women's Hospital (BWH) is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 800 physician-investigators and renowned biomedical scientists and faculty supported by more than $400M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative.

http://www.brighamandwomens.org
http://www.chromosome.bwh.harvard.edu

The Ontario Genomics Institute (OGI) is a private, not-for-profit corporation focused on providing leadership for Ontario in helping build a globally-competitive life sciences sector by creating leverageable genomics resources with top-notch research. Through its relationship with Genome Canada, the Ontario Ministry of Research and Innovation (MRI), and other private and public sector partners, OGI helps Ontario-based scientists secure funding for research in genomics and proteomics as well as for commercialization activities. OGI also focuses on the potential ethical and social issues that can arise with and from such research.

http://www.OntarioGenomics.ca

Children Born to Couples who have IVF are more likely to be autistic, have cancers, cerebral palsy and mental retardation

THE ARTICLE DOESN'T POINT OUT THAT THIS IS DUE TO THE AGE OF THE FATHER IN MOST CASES


Children born
after IVF treatment 'face higher health risks'


Ian Sample in New Orleans
Thursday October 26, 2006
The Guardian


Children born to couples who have undergone fertility treatment are more likely to be diagnosed with autism, cancer and other disorders such as cerebral palsy and mental retardation, researchers claimed yesterday.
The higher risk to child health is believed to be caused by medical problems in the parents, such as diabetes and hypertension, damaging the child in the womb, but doctors conducting the study said IVF and other fertility treatments may also play a role. Medical records of children born after their parents sought fertility treatment showed they were four times more likely to have autism than those born to fertile parents. Childhood cancers including leukaemia and brain tumours also rose.

The risk of more minor problems, such as attention deficit hyperactivity disorder, rose by 40%, and other medical conditions affecting hearing and sight nearly doubled. Children had a 30% higher chance of being admitted to neonatal intensive care units and to stay in hospital for more than three days if they were born following fertility treatment, the study found.

The researchers stressed the figures represent relative risks. In July researchers at Guy's and St Thomas' hospital in London reported the prevalence of autism to be 0.39% in the general population, a figure that will include some children born to parents aided by fertility treatment. A fourfold rise in the risk of autism would see a child's chances of having the condition increase to 1.56%.

Mary Croughan at the University of California in San Francisco studied 2,000 women who either gave birth naturally after a long period of infertility, or conceived after a variety of fertility treatments, and compared them with 2,000 fertile mothers who gave birth between 1994 and 1998. More than 19,000 medical records were used to build up a picture of the women's pregnancies and deliveries and the health of their children up to six years of age.

The researchers found infertile women had more complications such as pre-term labour and pre-eclampsia, more delivery difficulties and caesarean sections. Children born to infertile women were 20% more likely to have low birth weights and were twice as likely to show evidence of poor growth in the womb. Speaking at the American Association for Reproductive Medicine (ASRM) conference in New Orleans, Dr Croughan said that medical conditions more common in infertile couples may be to blame for the rise in childhood health problems. She said: "The vast majority of children born to infertile couples are healthy, but if a couple has any risk factors that could lead to a child not being born healthy, then those should of course be taken into consideration."

Clare Brown, chief executive of Infertility Network UK, said "continual research" was needed to ensure "treatment is safe for couples and potential children".

Mental Retardation and Cancer CNVs Polymorphisms Germ-line Mutations/ Paternal Age?

Researchers Determine Genetic Causes of Mental Retardation
Marco Marra of the University of British Columbia and Lisa Lit of the University of California, Davis, discuss chromosome copy number in mental retardation.

VANCOUVER, Canada, December 11, 2006 — University of British Columbia scientists, led by Marco Marra and Jan Friedman, have identified chromosomal abnormalities—genetic duplications and deletions as small as 37.6 kb—that are responsible for the development of mental retardation in children. Using whole-genome sampling analysis (WGSA) with Affymetrix Mapping 100K Arrays, the researchers pinpointed the probable genetic causes of mental retardation in at least twice as many children as conventional cytogenetic analysis, and were able to detect smaller abnormalities than can be detected using BAC-tiling-path arrays.

The researchers examined 100 children and their unaffected parents; each of the children had been assessed by clinical geneticists who were unable to identify the cause of the child’s mental retardation. The team found that 11 children harbored genetic alterations, including eight deletions, two duplications and one with additional copies of chromosome nine in approximately 20 percent of cells. Some deletions were not unique—they appeared in more than one individual
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deletions and you’ll see associations of haplotypes of amplifications. In other words, we will begin to see how germ-line polymorphic alleles might be contributing to the cancer that develops. I think that’s one very exciting area which can really only be looked at using the SNP array platform.
Maris: Yes, I agree with that completely. The 500K especially is going to open up a whole new world in terms of doing classic genetic association studies as well as pretty novel cancer-specific genomics. So we’re excited about that as well.

For mainly technological reasons, we have had a very, uni-focal, looking-under-the-lamppost type of approach, and prognostic biomarkers have been assessed one at a time, a deletion here, or an amplification there by itself and correlated with corollary measures, clinical
factors. And it is very clear that it’s the pattern of DNA aberrations across the genome that really gives you a much more refined picture of the phenotype. There are cooperating loci and associations that if you can consider those together, may be more powerful than the uni-focal approach that we have now. So that’s one of the big areas of interest in our lab, what is the pattern of aberrations and can you learn more from the entire profile than you can from the region-by-region approach, considering things one at a time.

The only downside I see is as we’ve gotten higher and higher resolution, we’ve really run into this problem of how complex the human genome is in terms of copy number polymorphisms, and separating out the real signal from the noise is still a bit of a challenge.

Sellers: Some of that will be offset by the scale of
some of the germ-line studies that are planned by the medical population geneticists using the 500K. With researchers running 10,000 normal germ-line DNAs on the 500K, you’re going to have a pretty good map of polymorphisms pretty soon. It’ll never find the ones that are less than one in a thousand, but I think we can count on our medical population genetics colleagues to identify many of these, and that will help us just simply subtract these by database searches.

Maris: I agree. In the meantime, we are going to be scratching our heads until there is a big database of these copy number polymorphisms

WHAT IF PEOPLE KNEW THAT FATHERING BABIES PAST THE AGE OF 34 CAUSES DE NOVO AUTISM, SCHIZOPHRENIA, CANCERS, DIABETES, MS, LUPUS, ALZHEIMER'S, FIBRO

CSHL Trustee David Rubenstein
and Liz Watson




Hedge fund manager Bruce Kovner, Dr. Bruce Stillman, David Koch

Honoree Bob Wright, Lonnie Ali, Muhammad Ali, Suzanne Wright,
Lab President Dr. Bruce Stillman, Dr. James Watson

November 9, 2006
CSHL RAISES $2.5 MILLION AT INAUGURAL DOUBLE HELIX MEDALS EVENT & LAUNCHES $200 MILLION CAPITAL CAMPAIGN


EFFORT CITED AT INAUGURAL DOUBLE HELIX MEDALS DINNER HONORING MUHAMMAD ALI, BOB AND SUZANNE WRIGHT, PHILLIP SHARP


Presenters include Meredith Vieira, Phil Donahue, Deborah Norville, Dr. James D. Watson



Dr. James Watson Cold Spring Harbor Laboratory (CSHL), the renowned institution where Nobel laureate Dr. James D. Watson gave the first public presentation of the discovery he and fellow scientist Dr. Francis Crick made of the structure of DNA, is launching a $200 million capital campaign to fortify and expand its leadership role in making groundbreaking research discoveries and developing innovative technologies to study the fundamental aspects of human health. The campaign will enable CSHL, home to seven Nobel Prize winners and recently ranked #1 in cited research in molecular biology and genetics by Science Watch, to make substantial increases in laboratory space, create endowed research centers to support innovation and growth, and provide funding to recruit talented scientists.





Bruce Stillman, Evening Presenter "Inside Edition's"
Deborah Norville, Jim Watson, Honoree Dr. Phillip A. Sharp

The campaign was cited at CSHL's inaugural Double Helix Medals Dinner tonight at the Mandarin Oriental New York. The black-tie gala honored boxing legend and humanitarian Muhammad Ali; Bob Wright, chairman and CEO of NBC Universal, and his wife Suzanne; and Nobel laureate Dr. Phillip Sharp of MIT. The double helix refers to the unique structure of DNA molecule, which carries all of life's information. It is central to biological research, and is at the heart of the CSHL's work.




Dr. James Watson Cold Spring Harbor Laboratory (CSHL), the renowned institution where Nobel laureate Dr. James D. Watson gave the first public presentation of the discovery he and fellow scientist Dr. Francis Crick made of the structure of DNA, is launching a $200 million capital campaign to fortify and expand its leadership role in making groundbreaking research discoveries and developing innovative technologies to study the fundamental aspects of human health. The campaign will enable CSHL, home to seven Nobel Prize winners and recently ranked #1 in cited research in molecular biology and genetics by Science Watch, to make substantial increases in laboratory space, create endowed research centers to support innovation and growth, and provide funding to recruit talented scientists.



The campaign was cited at CSHL's inaugural Double Helix Medals Dinner tonight at the Mandarin Oriental New York. The black-tie gala honored boxing legend and humanitarian Muhammad Ali; Bob Wright, chairman and CEO of NBC Universal, and his wife Suzanne; and Nobel laureate Dr. Phillip Sharp of MIT. The double helix refers to the unique structure of DNA molecule, which carries all of life's information. It is central to biological research, and is at the heart of the CSHL's work.



dinner was chaired by Jeff Zucker, CEO of NBC Universal Television Group, and his wife Caryn; Thomas Quick, retired vice chairman of Quick & Reilly/Fleet Securities, Inc., and a Trustee of CSHL; David Rubenstein, a CSHL Trustee who is co-founder and managing director of The Carlyle Group, and his wife Alice; and Roy Zuckerberg, a CSHL Trustee and senior director of Goldman Sachs.

Some $2.5 million was raised at the dinner to benefit CSHL's groundbreaking biomedical research, innovative technologies and educational initiatives seeking to understand and identify therapeutic approaches and cures for devastating diseases such as cancer, autism, schizophrenia, Alzheimer's and Parkinson's, among others.


“Cold Spring Harbor Laboratory has long been recognized for its excellence in research in the biological and biomedical sciences,” said Dr. Bruce Stillman, president. “Our $200 million capital campaign will enable us to expand our stellar research and continue to teach the next generation of scientists.”


Added Dr. Watson: “Never before has biology and medicine had the capacity to move so rapidly. I excitingly look forward to keeping Cold Spring Harbor Laboratory in its long valued leadership role.”


CSHL has already raised $130 million in the silent phase of the capital campaign. It is customary for institutions to have about one-third to one-half of the campaign completed before making a public announcement.


Major capital and endowment gifts include: $20 million from New York State for campus construction; $15 million from the Starr Foundation, which will go toward cancer genetics; $10 million from the DeMatteis Family, whose name will appear on a building for human genetics research; $10 million from Donald Everett Axinn for research into cognitive disorders; and $10 million from David H. Koch for biomathematics research.



“Cold Spring Harbor Laboratory's work in determining the causes of diseases like cancer through the study of genetics is second to none,” said David H. Koch, a former trustee of the Laboratory who has been a generous supporter of biomathematics at the Laboratory. “I am proud to have my name affiliated with an institution that has made, and will continue to make, important discoveries in the treatment of genetic diseases through outstanding biomedical research.”


“It gives me a great sense of pride to help Cold Spring Harbor Laboratory expand its facilities for groundbreaking research in Parkinson's, Alzheimer's, autism and schizophrenia,” said Donald Everett Axinn, who has made a contribution toward research on cognitive disorders.

DO COPY NUMBER VARIATIONS FOUND IN SPORADIC AUTISM EXIST IN THE SPERMATAGONIA OF THE FATHERS? WILL ANYONE LOOK FOR THEM?

Jonathan Sebat and colleagues found the key to sporadic autism and it seems they will fail to follow up and look for the same CNVs in the father's sperm and spermatagonia. ESPECIALLY BE WARNED ABOUT AUTISM IF YOU HAVE AUTOIMMUNE DISORDERS OR YOUR CLOSE RELATIVES DO. DISEASE CAUSING MUTATIONS ACCUMULATE IN SPERM MAKING CELLS BETWEEN 33-35. YOUR RISK IS MUCH GREATER IF THERE IS ANY AUTISM OR OTHER BRAIN RELATED DISORDERS IN THE FAMILY. TRY TO FATHER YOUR BABIES BY 35-40 AT THE LATEST. IF YOU ARE ABLE TO AND YOUNGER THAN 35 CRYOPRESERVE YOUR SEMEN FOR ANY LATER FATHERING OF BABIES.

CANCERS, ALZHEIMER'S, AUTOIMMUNE DISEASES/ALL OF THEM, AUTISM, SCHIZOPHRENIA, AND MANY OTHER DISORDERS CAN BE CREATED DE NOVO IN OFFSPRING THROUGH SPONTANEOUS MUTATIONS IN SPERM MAKING CELLS. THESE MUTATIONS INCREASE WITH INCREASING PATERNAL AGE.



Finding the genes responsible for autism is one of the goals that Sebat and his colleagues have set for their next project. "We'll be screening at least 2,000 families over the next three years using a much higher resolution platform," Sebat said. He added that he hopes the data will provide a better estimate of the frequency of CNV in sporadic autism, as well as a view of a larger array of genes involved than when researchers restricted their studies to inherited cases. "I think this will be a study that really tips the balance in the field towards using technologies that can directly detect mutations, [and] focusing on the majority of cases that are sporadic."