When Will There Be Public Health Warnings That Some Researchers Deemed Called For Many Years Ago? It is not the mother's age.

Schizophrenics have unique genetic mutations: study

People with schizophrenia have high rates of rare genetic mutations which appear to disrupt the developing brain, according to a study released Thursday.

Individuals with the devastating mental condition have three and sometimes four times the number of rare genetic abnormalities that healthy individuals do, and more of them affect genes regulating brain function.

The abnormalities consist of duplicated or deleted strands of DNA and differ from person to person, so much so that the genetic fingerprint of the disease is unique for every individual.

"We speculate that most people with schizophrenia have a different genetic cause," said Mary-Claire King, professor of genome sciences at the University of Washington in Seattle, who collaborated on the study.

"The mutations are individually rare, but share consequences downstream."

Schizophrenia is a chronic psychiatric disorder that afflicts about one percent of the population. People with the illness suffer from hallucinations, delusions, feelings of persecution and disorganized thinking.

Some of the symptoms can be managed with anti-psychotic medications, but there is no cure.

Prior to the publication of this study in Science, it was assumed that genetic studies like this one would trace the origins of the illness back to a cluster of common, or high frequency, genetic mutations.

But this paper suggests the genetic signature of schizophrenia, much like autism, is more complicated than that, involving dozens or even hundreds of genes, whose function has been disrupted by duplications or deletions of DNA.

For this paper, the researchers from University of Washington, Cold Spring Harbor Laboratory in New York and the National Institutes of Health studied a relatively modest number of people: 150 individuals with schizophrenia and 268 healthy patients.

The study implicated 24 different genes in the disease, and yet virtually every single mutation or copy number variation was different, which suggests that studies of larger populations will implicate even larger number of genes.

Many copy number variations are benign, but the researchers looked only at rare abnormalities, and not only were they much more abundant in the people with the disorder, but a preponderance of them were in genes that affect communication between brain cells.

Specifically, 15 percent of schizophrenia patients who developed the illness as adults had these rare DNA errors versus just five percent of healthy controls.

The rate jumped to 20 percent among patients who had a more severe form of the illness that began in childhood or adolescence.

"This is an important new finding in the genetics of schizophrenia," said Thomas Insel, director of the National Institute of Mental Health.

"Identifying genes prone to harbouring these mutations in brain development pathways holds promise for treatment and prevention of schizophrenia, as well as a wide range of other neurodevelopmental brain disorders."

© 2008 AFP

This story is sourced direct from an overseas news agency as an additional service to readers. Spelling follows North American usage, along with foreign currency and measurement units.

Sperm Donation at 44 is Way Too Old For the Health of Future Generations

Childless couple dedicate lives to helping others have families
Louise Hall Health ReporteR
March 30, 2008


Happy donors ... Faith Haugh and partner Glenn Watson Shannon.



BETWEEN them, Faith Haugh and her partner Glenn Watson have made 20 babies.

As an egg donor, Ms Haugh is the biological mother of 17 children - 10 girls and seven boys. She has also raised a 19-year-old daughter, Ashlyn, from a previous marriage.

Mr Watson, 44, has one toddler and another baby on the way through sperm donation.

This remarkable couple have dedicated their lives to helping infertile men and women start a family, and many of the donor children form a large, loosely extended family.

But the couple's desire to have a baby of their own has been dashed, as Ms Haugh was recently diagnosed with liver cancer.

The 37-year-old office worker is now freezing her own eggs to prevent her ending up in the same heartbreaking situation as the infertile women she has helped.

"Once I get through this cancer the first thing I'm going to do is try to get pregnant," she said. "But I'm going to freeze an embryo, just in case."

Ms Haugh's decision to become an egg donor first occurred 15 years ago, when she saw an ad in The Age newspaper placed by an infertile couple. Through an IVF clinic at a public hospital she anonymously donated her eggs to them, which led to the birth of twin girls.

Further donations - each requiring her to undergo hormone injections and a stint in hospital - resulted in a second set of twins to another couple, followed by three more babies.

While the donations were to unidentified couples, Ms Haugh is prepared for the donor children to contact her once they turn 18 as her details were recorded on a central register.

These offspring would join the 10 children Ms Haugh has helped procreate to couples she met through classified ads and online infertility networks.

Mr Watson and Ms Haugh have signed agreements with each of the couples they donate to absolving themselves from child support payments or other legal responsibilities.

Ms Haugh's 13-centimetre tumour was discovered by accident while she was undergoing tests to prepare for her next altruistic deed - donating a kidney to a stranger.

As she has successfully donated to 10 different families, the law prevents her from donating any more so she has turned her efforts towards raising awareness about egg donation and linking up potential donors and recipient couples - and hopefully, becoming pregnant herself.

"Glenn says he doesn't mind if we don't have a baby together but I know he'd really like to. He just says we'll get a dog or go overseas," she said.

lhall@sunherald.com.au

Effects of Male Age on Sperm DNA Damage in Healthy Non-Smokers

https://e-reports-ext.llnl.gov/pdf/331470.pdf

1: Hum Reprod. 2007 Jan;22(1):180-7. Epub 2006 Oct 19

The effects of male age on sperm DNA damage in healthy non-smokers.Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, Anderson D, Wyrobek AJ.
Lawrence Livermore National Laboratory, Livermore, CA, USA.


BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.
Labels: alkali-labile sites, caffeine, coffee, DNA, dna damaged, double-strand breaks in dna, germ-line mutations, older fathers, single-strand breaks in dna, sperm

The age of the father is an important determinant of the health of future generations.

THE AGE OF THE FATHER AND THE
HEALTH OF FUTURE GENERATIONS
Word Count: 903
　
Leslie B. Raschka M.D., Associate Professor (retired),
Department of Psychiatry, University of Toronto
Address: 27 Edgecombe ave, Toronto, Ontario, Canada
M5N 2Xl, Tel. (416) 783-6938
2
Abstract
Purpose: To assess the role of paternal age in the origin of genetic illness in future generations.
Data Sources: All reference data originated in English language international scientific literature and findings of original research conducted by myself.
Study Selection: Original articles published between 1938 and 1998 were selected according to the stated purpose. One article was written by myself.
Data Extraction: The present paper deals with 4 subtopics: andrology, genetics, pathology, and psychiatry.
Results: Nine articles reporting on 1399 patients described the deterioration of the quality of semen related to ageing. Five articles reported an increased mutation rate in the male germ cells as compared to the female germ cell. Twenty-four articles reported on 1230 patients and related studies described paternal age effect on increased mutation rate causing genetic illness. Eight articles reporting on 10,347 patients described increased prevalence of mental illness as related to older paternal age.
Conclusions: cChildren conceived by fathers older than 34 years of age are at increased risk for genetic illness due to recent mutation in the male germ cell.
3The genetic illness of a child could originate in a mutation related to the age of the father or to a mutation in the spermatogenesis caused by ageing in previous generations. The ageing process in the male is an important, probably the most important, cause of genetic illness in human populations.
　Key Words: Age of the father, mutation, genetic illness
4 Demographic changes taking place in the 20th Century have directed attention to all possible determinants of the health of future generations. The relationship between maternal age and Down Syndrome is a currently recognized scientific fact. The study of the reproductive efficiency of the male is also relevant to the health of future generations. Most children are born healthy regardless of paternal age; however, the age of the father is a determinant of ill health for a significant minority in future generations.
　
5 Andrology
Ageing in the male is expressed in a progressive decline both in the quality and quantity of the sperm (1). Changes include a decrease in motility (2), decreased vitality and an increased percentage of malformed sperm (3, 4, 5, 6, 7). The deterioration associated with ageing can be noticed first in men between the ages of 35 to 40 years (8, 9).
　
6 Genetics
The mutation rate is higher in the male than in the female germ cell (10, 11, 12, 13, 14). While the ageing male germ cell is especially sensitive to mutation (15) there is a significant difference in mutation, rates among different genes. There is evidence that mutation frequencies for a number of different genes causing illness increase with advancing paternal age. The rate of increase differs among different genes (16); not all genes are subject to the paternal age effect. Almost all new mutations were reported to occur in the male germ cell; however, paternal age effect is not equally pronounced in all mutations (12). It is operant in recent germline mutations. Inherited illnesses such as hemophilia A have their origins in mutations in earlier generations where, for example, increased maternal grandparental age was found and new germline mutation related to increased paternal age transmitted to future generations can result in hereditary illness. In the development of illness, more than one gene can be involved. The phenotypic expression can be influenced by modifying genes. The importance of mutations for the health of future generations was born out by the Bulletin of the World Health Organization 1986 (17), which states that about 1% of children will be born with a serious genetic disease and another 1% will develop a serious genetic illness later in life.
7 Pathology
The relationship between increased paternal age and pathological conditions of known genetic origin was reported for achondroplasia in nineteen publications (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34); for Apert Syndrome in sixteen publications (15, 19, 20, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35); on Marfan Syndrome in thirteen publications (15, 20, 21, 22, 23, 25, 26, 27, 30, 31, 32, 33, 34); on osteogenesis imperfecta in five publications (16, 19, 24, 25, 29); on basal cell naevus syndrome in three publications (22, 26, 32); in Waardenburg Syndrome in five publications (22, 26, 31, 32, 33); on Crouzon Syndrome in seven publications (22, 26, 28, 31, 32, 33, 35); on oculo-denta; digital syndrome in four publications (22, 26, 31, 32); on thanatophoric dysplasia in three publications (28, 29, 35); on Pfeiffer Syndrome in three publications (28, 32, 35); on tuberous sclerosis in three publications (31, 33, 36); on multiple endocrine neoplasm in three publications (32, 34, 37); on myositis ossificans in nine publications (15, 19, 21, 22, 24, 30, 31, 32, 33); and on Treacher Collins disease, four publications (22, 26, 31, 33). All of these illnesses are transmitted in an autosomal dominant fashion. Increased risk for X-linked conditions associated with increased maternal grand-parental age is known to exist regarding classical hemophilia and was reported in nine publications (15, 17, 23, 25, 26 31, 32, 34, 38). This is also true for Lesch-Nyhan syndrome, reported in five publications (10, 17, 27, 31, 38). The mutation is transmitted to the child through carrier mothers.
8Psychiatry
Mutations occurring in the course of gametogenesis in the male and the association of psychosis was described in one article (39). Older maternal and paternal age in schizophrenia was reported in four articles (39, 40, 41, 42). My own study involving 574 patients has shown that the increased age of the father is a causative factor in a sub-group of the schizophrenic population (43). Two other articles, reporting on 662 and 8000 patients respectively, confirmed my conclusions, as well as indicating that increased maternal age was secondary to increased paternal age (41, 42). Three articles reporting on 1081 patients described increased paternal age in Alzheimer’s disease (44, 45, 46).
　
9 Discussion
All genetic illnesses have their origin in a distant or recent mutation. Paternal age is an important determinant of mutation frequency in new germ cell mutation, causing both autosomal dominant and X-linked recessive illnesses. The role of other mutagenic factors is not the subject of this study. The results of my own research are supported by other information which indicates that the leading cause of genetic illness present in human populations is the ageing process in the male. Conceiving children by men younger than 35 years of age would prevent many genetic illnesses in future generations.
　
10 Bibliography
1. Johnson L, Nguyen H B, Petty C S, et al. Quantification of Human Spermatogenesis: Germ Cell Degeneration during Spermatocytogenesis and Meiosis in Testes from Younger and Older Adult Men. Biol Reprod 1987; 37: 739.
2. Nieschlag E, Lammers U, Freischem C W, et al. Reproductive Functions in Young Fathers and Grandfathers. J Clin Endocrinol Metab 1982; 55: 676.
3. Holstein A F. Spermatid Differentiation In Man During Senescence. In. : Andre J, ed. Proceedings of the Fourth International Symposium on Spermatology; 1982 June; The Hague. Martinus Nijhoff, 1983: 15-18.
4. Homonnai Z T, Fainman N, David M P, et al. Semen Quality and Sex Hormone Pattern of 39 Middle Aged Men. Andrologia 1982; 14(2): 164.
5. Bacetti B, Renieri T, Selmi M G, et al. Sperm Structure and Function in 70 Year Old Humans. In: Andre J, ed. Proceedings of the Fourth International Symposium on Spermatology; 1982 June; The Hague. Martinus Nijhoff, 1983: 19-23.
6. Spira A, Ducot B. Variations physiologiques du spermatogramme. Ann Biol Clin (Paris) 1985; 43: 55.
7. Sternbach H. Age-Associated Testosterone Decline in Men: Clinical Issues for Psychiatry. Am J Psychiatry 1998; 155: 1310.
11
8. Bishop M W H. Aging and Reproduction in the Male. J Reprod Fert 1970; (Suppl. 12): 65.
9. Schwartz D, Mayaux MJ, Spira A, et al. Semen characteristics as a function of age in 833 fertile men. Fertil Steril, 1983; 39: 530.
10. Vogel F. Editorial. A probable sex difference in some mutation rates. Am J Hum Genet, 1977; 29: 312.
11. Haldene J B S. The Mutation Rate of the Gene for Haemophilia and it’s Segregation Ratios in Males and Females. Ann Hum Genet 1947; 13: 261.
12. Vogel F, Motulsky AG. Human Genetics, Problems and Approaches. Berlin: Heidelberg: New York: Springer Verlag, 1979; 282.
13. Crow J F, Denniston C. Mutation in Human Populations. In: Harris H, Hirschhorn K, eds. Advances in Human Genetics. New York: London: Plenum Press, 1985; 14: 59-123.
14. Shimmin L C, Chang B H, Li W. Male-driven evolution of DNA sequences. Nature 1993; 362: 745.
15. Vogel F, Rathenberg R. Spontanious Mutation in Man. In: Harris H, Hirschhorn K, eds. Advances in Human Genetics. New York: London: Plenum Press, 1975; 5: 223-318. 12

16. Evans HJ. Mutation as a cause of genetic disease. Phil Trans R Soc Lond 1988; 319: 325.
17. Berg K, Bochkov N P, Coutelle C, et al. Bull WHO 1986; 64(2): 205.
18. Penrose L S. Parental Age and Mutation. The Lancet 1955; 2: 312.
19. Modell B, Kuliev A. Changing paternal age distribution and the human mutation rate in Europe. Hum Genet 1990; 86:198.
20. Murdoch J L, Walker B A, Hall J G, et al. Achondroplasia-a genetic and statistical survey. Ann Hum Genet 1970; 33: 227.
21. Rogers J G, Danks D M. Birth defects and the father. Med J Austr 1983; 2: 3.
22. Karp L E. Older Fathers and Genetic Mutations. Am J Med Genet 1980; 7: 405.
23. Tunte W. Human Mutations and Paternal Age. Hum Genet 1972; 16: 77.
24. Modell B, Kuliev A. Impact of public health on human genetics. Clin Genet 1989; 36: 286.
　
　
13
25. Carothers A D, McAllion S J, Paterson C R. Risk of dominant mutation in older fathers: evidence from osteogenesis imperfecta. J Med Genet 1986; 23: 227.
26. Jones K L, Smith D W, Sedgwick Harvey M A, et al. Older paternal age and fresh gene mutation: Data on additional disorders. J Ped 1975; 86: 84.
27. Hook EB. Paternal Age and Effects on Chromosomal and Specific Locus Mutations and on Other Genetic Outcomes in Offspring. In: Mastroianni L Jr, Paulsen C A, eds. Aging, Reproduction and the Climacteric. New York and London: Plenum Press, 1986: 117-145.
28. Wilkin D J, Szabo J K, Cameron R, et. al. Mutations in Fibroblast Growth -Factor Receptor 3 in Sporadic Cases of Achendroplansia Occur Exclusively on the Paternally Derived Chromosome. Am J Hum Genet 1998; 63: 711.
29. Orioli J M, Castilla E E, Scarano G, et. al. Effect of Paternal Age in Achondroplasia, Thanatophoric Dysplasia and Osteogenesis Imperfecta. Am J Med Genet 1995; 59: 209.
30. Erickson D, Cohen M M Jr., A Study of parental age effects on the occurrance of fresh mutations for the Apert syndrome. Ann Hum Genet 1974; 38: 89.

14
2. Bordson B L, Leonardo VS. The appropriate upper age limit for semen donors: a review of the genetic effects of paternal age. Fertil Steril 1991; 56: 397.
1. Sankaranarayanan K. Ionizing radiation and genetic risks IX. Estimates of the frequencies of mendelian diseases and spontaneous mutation rates in human populations: a 1998 perspective. Mutat Res 1998; 411: 129.
2. Friedman J M. Genetic Disease in the Offspring of Older Fathers. Obstet Gynecol 1981; 57: 745.
3. Carlson K M, Bracamontes J, Jackson C E, et al. Parent-of-Origin Effects in Multiple Endocrine Neoplasia Type 2B. Am J Hum Genet 1994; 55: 1076.
4. Moloney D M, Slaney S F, Oldridge M, et al. Exclusive paternal origin of new mutations in Apert syndrome. Nat Genet 1996; 13: 48.
5. Osborne J P, Fryer A, Webb D. Epidemiology of Tuberous Sclerosis. Ann NY Acad Sci 1991; 615: 125.
6. Schuffenecker I, Ginet N, Goldgan D, et al. Prevalence and Parental Origin of De Novo RET Mutations in Multiple Endocrine Neoplasia Type 2A and Familial Medullary Thyroid Carcinoma. Am J Hum Genet 1997; 60: 233.
　
15
7. Crow J F. How Much Do We Know About Spontaneous Human Mutation Rates? Environ Mol Mutagen 1993; 21: 122.
8. Crow T J. Editorial. Mutation and psychosis: A suggested explanation of seasonality of birth. Psychol Med 1987; 17: 821.
9. Gordon A. The Incidence of Psychotic Disorders in Individuals Whose Parents Married at an Advanced Age. Med Records 1938; 148: 109.
10. Kinnell H G. Parental Age in Schizophrenia. Br J Psychiatry 1983; 142: 204.
11. Hare E H, Moran PAP. Raised Parental Age in Psychiatric Patients: Evidence for the Constitutional Hypothesis. Br J Psychiatry 1979; 134: 169.
12. Raschka L B. Parental Age and Schizophrenia. Magyar Andrologia-Hungarian Andrology 1998/2; III: 47.
13. Bertram L, Busch R, Spiegl M, et al. Paternal age is a risk factor for Alzheimer disease in the absence of a major gene. Neurogenetics 1998; 1: 277.
14. Whalley L J, Thomas B M, Starr J M. Epidemiology of Presenile Alzheimer’s Disease in Scotland (1974-88). 11. Exposures to Possible Risk Factors. Br J Psychiatry 1995; 167: 732.
16

3. Urikami K, Adachi Y, Takahashi K. A Community-Based Study of Parental Age in Alzheimer-Type Dementia in Western Japan. Arch Neurol 1988; 45: 375.
http://diabetes.diabetesjournals.org/cgi/content/full/54/2/563

Diabetes age of parents etc risk factor 2005

CMJ_netprints
- [ Translate this page ]
Infant Mortality in Remote and Poverty-stricken Areas in China: A ... THE AGE OF THE FATHER AND THE HEALTH OF FUTURE GENERATIONS (Leslie B. Raschka M.D.) ...www.aiabeijing.org/netprints/01/02/0102.htm - 14k - Cached - Similar pages




Labels: advancing paternal age and sporadic disorders/new

that some of these rearrangements were found in sperm much more frequently than expected

Mutant sperm guide clinicians to new diseases
Submitted by BJS on Mon, 2007-12-03 10:30. Topic: bioscience and medicine


Research published today in Nature Genetics shows that some rearrangements of the human genome occur more frequently than previously thought. The work is likely to lead to new identification of genes involved in disease and to improve diagnosis of genomic disease.

The scientists from the Wellcome Trust Sanger Institute looked at four unstable regions in the genome where rearrangements cause genetic diseases, so-called 'genomic disorders', and found that that some of these rearrangements were found in sperm much more frequently than expected. In work published in November 2006, the team, led by Dr Matt Hurles, showed that losses or duplication of 'chunks' of the human genome occurred frequently in apparently healthy people. These losses or gains of DNA regions are called Copy Number Variants (CNVs), and can be found all over the genome in every individual.

Some of the mechanisms thought to produce CNVs would be expected to produce about one duplication for every deletion: however, clinical records for genomic disorders show only a few duplications, compared with hundreds of deletions.

"There was no direct, global measure of the relative rate at which human DNA is gained or lost, a study that requires many thousands of human genomes," explained Dr Matt Hurles, Investigator at the Wellcome Trust Sanger Institute, "so we carried out a study on four clinically important regions using human sperm cells as our population of genomes.

"Sperm cells give us an unbiased snapshot of CNVs: using our new highly-sensitive assays we can detect one rearrangement in a million cells."

The team looked at regions known to be affected by rearrangement in Williams-Beuren Syndrome, Charcot-Marie-Tooth disease Type 1A, Smith-Magenis Syndrome, and a deletion (AZFa) that causes male infertility. Their study showed that duplications are about half as frequent as deletions. By contrast, the two types of CNV are similarly common in healthy adults, suggesting that some deletions are too detrimental for the genome to tolerate.

"It is likely that deletions are more harmful than duplications, perhaps because a vital gene is removed, and so less likely to survive," explained Dr Hurles. "However, for some of the genomic regions we looked at, duplications can cause milder symptoms. Perhaps we can improve diagnosis with improved understanding of the possible consequences of duplications."

In Williams-Beuren Syndrome, loss of a genomic region (which can vary in size) can have very severe effects, including narrowing of arteries, facial and other skeletal deficiencies and impaired mental development. By contrast, duplications of the same regions have a milder effect, resulting most commonly in delay of speech development. With the results of this study, the team suggest that improved diagnosis might result from examining speech-delay for CNVs in this region.

"Although some of these CNVs arise much more frequently than anyone thought, they are still comfortingly rare: we see them in about 1 in 50,000 sperm cells," explained Dr Hurles. "These are unfortunate accidents of the essential shuffling of our genetic deck of cards, a process essential to human life. We need a new deal for each new person."

The method should also be able to detect rearrangements where none was suspected and to predict new disease-causing variants. Indeed one of the duplications that was detected in sperm has not yet been observed in the clinic, and yet it can be expected to cause disease, because smaller duplications of the same region cause Potocki-Lupski syndrome. Clinical genetics usually proceeds from observations in a patient down a long road to identify the gene involved. The new CNV work opens a new and possibly quicker, route of using new mutations found in sperm to lead to disease-causing mutations in patients.

In their work in 2006, the team has developed the CNV map for apparently healthy people: many of these are unlikely to cause disease. By looking across the entire genome for novel CNVs in human sperm, they will be able to predict where CNVs are likely to play a possible undiscovered role. In this 'reverse genetics', the new methods move from genome to prediction of consequences for patients.

This work complements the systematic cataloguing of CNVs that do cause disease by the Institute's DECIPHER consortium.

From http://www.sanger.ac.uk

5 Things You Didn't Know: Men By Ross Bonander

2- "Men have their own biological clock
We do indeed have a biological clock of sorts, although instead of one that stops, ours becomes increasingly unreliable over time.

As men age they lose approximately 1% of testosterone every year. The consequence of this deficit is that sperm production decreases, and those that are produced are of a lower quality. For this reason, the older we get the greater the chances that the children we spawn suffer from conditions such as autism, schizophrenia and Down syndrome, to name a few.

To explain why, fertility experts point to cell division: About every 16 days the cells that create sperm and determine their genetic code go through the process of dividing. By the age of 50 that division has happened hundreds and hundreds of times, and each time it did the genetic code was vulnerable to changes that can augment genetic deterioration, making birth defects increasingly likely."

From 1999 to 2004, the number of new fathers aged 40 or over rose by a third.

The age of parenting has been increasing in the Western world in the past two decades, in parallel with the increase in rates of autism.Dr Reichenberg Explains


Research project up for THES award28 September 2007, PR 145/07Dr Avi Reichenberg, Institute of Psychiatry, has been shortlisted for the Research Project of the Year Award in the prestigious Times Higher Awards for his work on paternal age and autism. His was the first project to examine the relationship between older father's age and risk of autism in children.‘I am delighted to be shortlisted for a Times Higher Award. It acknowledges the importance of my research in helping us to better understand the origins of autism and related disorders,' comments Dr Reichenberg. He also recently received the College's inaugural King's Award for Research Project of the Year 2007.From 1999 to 2004, the number of new fathers aged 40 or over rose by a third, which led the Times Higher to note ‘This is why research on autism by a team led by Abraham Reichenberg has important benefits in public health as well as scientific advancement.'Autism is a severe disorder of social and language development, and repetitive patterns of behaviour. The incidence of autism has increased dramatically over the past decade, and it is now estimated that the disorder will affect one in every 150 newborn children. Despite extensive efforts, the causes of autism, and the reasons for the recent increase in its incidence, remain unknown.The age of parenting has been increasing in the Western world in the past two decades, in parallel with the increase in rates of autism.Dr Reichenberg explains: ‘The associations between advancing maternal age and birth defects such as Down's syndrome have long been recognised, but paternal age has been largely ignored. Recent research has shown that the offspring of older fathers are at increased risk of neurological and psychiatric disorders, and this inspired me to test for a similar effect in autism.'Collaborating with Israeli and American researchers, the team found that children born to fathers aged 40 or older were almost six times more likely to have autism and related disorders than those born to fathers under 30. Interestingly, the age of the mother did not affect the risk of autism.The project was conducted using unique Israeli population registers, and it has since been replicated by three other research groups. The finding is important because it may offer an insight into the genetic causes of autism.

Dads and Birth Defects: The Inside Story by Christina Jeffery

Conclusion
The secret to a healthy family is in the hands of the father as well as the mother. The new research that has been carried out has shown how much a father can affect the life of his unborn child. Alcohol consumed months before conception can cause defects in the sperm. Since sperm cells are made continuously throughout a man's life, they are at more risk of mutation, thus increasing the chance that the baby may have problems. A male should plan ahead for a healthy family. Good steps would be to quit smoking, drinking, and using drugs, and also do as much to protect oneself from exposure to harmful chemicals at work. Such actions will not only lengthen a person's life span, but will also increase the possibility of having healthy children in the future.

7 Disadvantages of Mobile Phones-Male Infertility

An interesting new website

An Unsafe Safety Standard (see below)
Negative Health Effects
Male Infertility
The Effect on Children
Mobile Phones and Driving
Increased Stress Level
The Effect on the Environment

Hopefully The Simons Foundation Can Get This Research Done and then the Word Out to the Public

Father's advanced age feeds autism risk
Helen Pearson
25 February 2008 09:00:00 EST

Children of fathers aged 40 or older are nearly six times morelikely to have autism.
Are older fathers more likely to have children with autism? A series of epidemiological studies is giving credence to the idea, suggesting that, with age, sperm may accumulate damage that increases risk in the next generation.
Advancing age of the father is known to be a significant risk factor for schizophrenia1. These studies — along with anecdotal suggestions that fathers of autistic children tend to be older than average — prompted Avi Reichenberg of Mount Sinai School of Medicine, New York, to launch one of the first thorough epidemiological investigations into a link between the two.
Reichenberg and his colleagues had access to a vast database of health information collected from more than 132,000 Israeli adolescents who underwent draft board assessment, including psychiatric screening, before entering the army. The researchers were able to identify those who were diagnosed with autism spectrum disorders (ASD), along with the age of their parents.
Children of fathers in their 30s are about 1.6 times more likely to have ASD than children of fathers below age 30, the study found2. Compared with the youngest group, children of fathers aged 40 or older were nearly six times more likely to have ASD. “It was much stronger than we had thought,” Reichenberg says.
Since then, a handful of other epidemiology studies have backed the autism-paternal age connection. In one of these3, a team led by Lisa Croen of Kaiser Permanente Northern California Division of Research in Oakland, California, mined a health database of more than 130,000 births and found that each decade of paternal or maternal age increased risk of autism spectrum disorder by around 30%.
Paternal age “is still a relatively small contributor,” Croen says, “but when you see something that keeps coming up in different populations and study designs you start thinking there must be something to this.”
The link may be real, but researchers have yet to explain what causes it. Perhaps, says Croen, older parents are simply more attuned to the development of their children and therefore more likely to get a diagnosis. “It could be an artifact,” she says. “We don’t have enough data yet to really rule that out.”
Genetic origins
Another simple explanation is that fathers who themselves have autism or mild social deficits are likely to marry and have children at a later age than other men, and these children inherit factors putting them at high risk of developing the condition themselves.
But Reichenberg says that in his studies he has found no link between traits such as shyness, sensitivity and aloofness in parents and the age at which they have children. “It’s not definitive but the evidence is definitely against such an explanation,” he says.
Many researchers instead favor a genetic origin for the phenomenon. Male germ cells go through multiple rounds of division to manufacture sperm throughout a man’s life and, according to one idea, they may accumulate DNA damage as the molecule is copied again and again.
Sperm produced by older men are more likely to carry genetic defects, and these defects could boost their children’s risk of autism. Female germ cells divide far fewer times.
It is also possible that older sperm are more likely to acquire epigenetic defects: ones that do not change the DNA sequence itself, but that alter the activity of genes due to structural or chemical changes to DNA such as methylation.
These genetic changes arise in the egg or sperm rather than being inherited from the parents. Both concepts fit with the knowledge that the majority of ASD cases have a genetic cause, even though they are also the first in a family.
For precedent, geneticists point to a condition called achondroplasia, a common cause of dwarfism and the textbook example of a genetic condition associated with paternal age. The risk of sperm carrying a single point mutation in the gene for a growth factor receptor is thought to increase with the age of the father.
“It would be overwhelmingly logical,” for something similar to be going on in some cases of autism, says human geneticist Arthur Beaudet at Baylor College of Medicine in Houston, Texas. Perhaps just one or two of the many genes associated with the disorder are susceptible to detrimental point mutations as the germ cells age.
Beaudet says he would like to see genetic and epigenetic analyses of single sperm to see if mutation rates differ in the fathers of autistic children, and between younger and older men. “That would be the approach I’d be enthusiastic about,” he says. Reichenberg says that he is pursuing such studies.
Because there are few clearly defined genes for autism risk, it’s not yet clear where to look for these increased mutation rates. And genome-wide studies looking for differences in the rates of point mutations in many sperm are still too expensive and laborious.
Copy numbers
Last year, molecular studies showed that mutations called copy number variations (CNVs) — genomic chunks that can be deleted or duplicated from one person to the next — appear to be major contributors to sporadic autism.
A group led by Michael Wigler and Jonathan Sebat at the Cold Spring Harbor Laboratory in New York looked for CNVs that were present in autistic individuals, but not in their parents. They found CNVs in 10% of children with sporadic autism, 2% of those with familial autism and 1% of controls4.
This suggests that many more cases of sporadic autism may be attributable to spontaneous mutations — either CNVs or more subtle mutations — than had been realized.
Sebat has not examined whether the frequency of these CNV mutations increases in aging germ cells — but he suspects it might. “We don’t have data one way or the other,” he says, “but it’s a very tantalizing hypothesis.”
Many of the cellular systems that protect DNA from mutation might begin to fail in aging germ cells, so that their mutation rate increases, Sebat suggests. He is planning to test in a larger group of autistic individuals whether the CNV mutations are more common in children of older parents.
Reichenberg and his colleagues are also testing these hypotheses. In one study, they are trying to compare old and young fathers of autistic children, looking for differences in the rate of new mutations and their association to genetic hotspots previously linked to autism.
They are also doing mouse studies to explore whether offspring of older males tend to suffer more behavioral problems that mimic autism.
There remains some debate about whether the mother’s age is as important a risk factor as that of the father, and studies have differed in their findings. A maternal age effect is harder to tease out, partly because women have children within a more limited age range than men: very few over-40 women have children.
In her study, Croen found that maternal age is just as important and says that other studies have lacked the statistical power to tease this out. “Our data show that maternal age is also in the mix,” she says.
The fact that schizophrenia risk also increases with age leads some researchers to wonder whether some of the same genes may contribute to both disorders – and perhaps to other psychiatric conditions as well.
It’s a “feasible hypothesis”, Reichenberg says, “and I believe a worthwhile one to pursue.”
References:
Malaspina D et al. Arch. Gen. Psychiatry 58, 361-367 (2001) PubMed ↩
Reichenberg A. et al. Arch. Gen. Psychiatry 63, 1026-1032 (2006) PubMed ↩
Croen L. et al. Arch. Pediatr. Adolesc. Med. 161, 334-340 (2007) PubMed ↩
Sebat J. et al. Science 316, 445-449 (2007) PubMed ↩