Thursday, May 31, 2007

Frequency of XY sperm 10 percent higher among fathers of Klinefelters in 30s, 31 percent highers in 40s, 160 percent higher in fathers in their 50s

Am. J. Hum. Genet., 69:1046-1054, 2001
© 2001 by The American Society of Human Genetics. All rights reserved.


Frequency of XY Sperm Increases with Age in Fathers of Boys with Klinefelter Syndrome
1Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA, and 2School of Public Health, University of California, Berkeley

Received June 18, 2001; accepted for publication August 13, 2001; electronically published October 1, 2001.

With increasing availability of drugs for impotence and advanced reproductive technologies for the treatment of subfertility, more men are fathering children at advanced ages. We conducted a study of the chromosomal content of sperm of healthy men aged 2457 years to (a) determine whether father's age was associated with increasing frequencies of aneuploid sperm including XY, disomy X, disomy Y, disomy 21, and sperm diploidy, and (b) examine the association between the frequencies of disomy 21 and sex-chromosomal aneuploidies. The study group consisted of 38 fathers of boys with Klinefelter syndrome (47, XXY) recruited nationwide, and sperm aneuploidy was assessed using multicolor X-Y-21 sperm FISH (10,000 sperm per donor). Paternal age was significantly correlated with the sex ratio of sperm (Y/X; P = .006) and with the frequency of XY sperm (P = .02), with a clear trend with age by decades (P < .006). Compared with fathers in their 20s (who had an average frequency of 7.5 XY sperm per 10,000), the frequencies of XY sperm were 10% higher among fathers in their 30s, 31% higher among those in their 40s, and 160% higher among those in their 50s (95% CI 69%300%). However, there was no evidence for age effects on frequencies of sperm carrying nullisomy sex; disomies X, Y, or 21; or meiosis I or II diploidies. The frequencies of disomy 21 sperm were significantly associated with sex-chromosomal aneuploidy (P = .04)in particular, with disomy X (P = .004), but disomy 21 sperm did not preferentially carry either sex chromosome. These findings suggest that older fathers produce higher frequencies of XY sperm, which may place them at higher risk of fathering boys with Klinefelter syndrome, and that age effects on sperm aneuploidy are chromosome specific.

* The first two authors contributed equally to this work.
Present affiliation: Department of Psychiatry, California Pacific Medical Center, San Francisco.

Labels: ,

Increased Paternal Age is a Risk Factor For Alzheimer's Disease in the Absence of a Major Gene

Neurogenetics. 1998 Aug;1(4):277-80. Links
Paternal age is a risk factor for Alzheimer disease in the absence of a major gene.Bertram L, Busch R, Spiegl M, Lautenschlager NT, Muller U, Kurz A.
Department of Psychiatry, Technical University Munich, Germany

We compared the parental age at birth of patients with Alzheimer disease (AD) with that of cognitively healthy control subjects. Within 206 carefully diagnosed AD patients, two groups were distinguished according to the likelihood of carrying a major gene for AD (MGAD). This likelihood was calculated by applying a Bayesian approach which incorporates data on aggregation of the disease, age at onset, and "censoring" ages within the family. All AD patients were ranked by MGAD probability. According to the sample's quartiles, two subgroups were defined representing the 52 individuals with the lowest and the 52 with the highest MGAD probability. Age at onset of dementia, education, and apolipoprotein E epsilon4 allele frequencies were not statistically different between the two groups. Fathers of patients with a low MGAD probability were significantly older (35.7+/-8.1 years) than fathers of both other groups (high MGAD probability 31.3+/-6.9 years, P=0.004; controls 32.6+/-6.8 years, P=0.04, n=50). The differences for mothers were less pronounced and not statistically significant. These findings suggest that increased paternal age is a risk factor for AD in the absence of a major gene, whereas increased maternal age and AD are associated only weakly and independently of genetic disposition.

PMID: 10732803 [PubMed - indexed for MEDLINE]

George Bartzokis,M.D.

Visiting Professor

Laboratory of Neuro Imaging,
Department of Neurology, UCLA School of Medicine
635 Charles Young Drive South, Suite 225
Los Angeles, CA 90095-7332


1975-1979, BA Harvard University, Cambridge, MA
1979-1983, MD Yale Medical School, New Haven, CT
1983-1984, Internship, UCLA/WLA VA, Los Angeles, CA
1984-1987, Psychiatry Residency, UCLA NPI, Los Angeles, CA
1987-1990, Schizophrenia Research Fellow, UCLA Dept of Psychology, Los Angeles, CA


Development of brain imaging biomarkers for use in diagnosis of neuropsychiatric disorders and medication development
Assessing brain maturation and degeneration trajectories over the life-span in normal populations and how neuropsychiatric disorders interact with these processes


Myelin breakdown in aging and Alzheimer's disease
In vivo quantification of age-related increases in brain iron levels
Evaluation of brain maturational trajectories in normal adults and patientss with neuropsychiatrc diseases


Quantification of brain iron levels
Quantification of limbic structures volumes
Quantification of brain myelination
Quantification of myelin integrity
Clinical trials
Administration of multidisciplinary teams


U.S. Patent, Method for Quantitatively Measuring Stored Iron in Tissue Using MRI

This quote is not from a published paper.
I had asked Dr. Bartzokis why risk of non-familial autism, schizophrenia, MS, and Alzheimer's risk increases with the age of the father at a person's birth.

"The issue is that the older man will have sperm that has undergone more divisions and therefore had more chances to have mutations.
The COMPLEXITY of the myelination process makes it more vulnerable to mutations. I am not talking of one specific mutation. Many things could MANIFEST in the myelination or myelin breakdown process because it is so vulnerable - something going slightly wrong will impact it while it will not impact bone growth or the heart. A good example is ApoE4 - whatever else it may affect, it manifests in the reduced capacity of myelin repair and earlier onset of AD."


Charles Lee, Ph.D.

This analysis of so-called copy number variation (CNV) has now revealed some startling results.

It would seem the assumption that the DNA of any two humans is 99.9% similar in content and identity no longer holds.

The researchers were astonished to locate 1,447 CNVs in nearly 2,900 genes, the starting "templates" written in the DNA that are used by cells to make the proteins which drive our bodies.

This is a huge, hitherto unrecognised, level of variation between one individual and the next.

"Each one of us has a unique pattern of gains and losses of complete sections of DNA," said Matthew Hurles, of the UK's Wellcome Trust Sanger Institute.

"One of the real surprises of these results was just how much of our DNA varies in copy number. We estimate this to be at least 12% of the genome.

"The copy number variation that researchers had seen before was simply the tip of the iceberg, while the bulk lay submerged, undetected. We now appreciate the immense contribution of this phenomenon to genetic differences between individuals."

Evolving story

The new understanding will change the way in which scientists search for genes involved in disease.

"Many examples of diseases resulting from changes in copy number are emerging," commented Charles Lee, one of the project's leaders from Brigham and Women's Hospital and Harvard Medical School in Boston, US.

"A recent review lists 17 conditions of the nervous system alone - including Parkinson's disease and Alzheimer's disease - that can result from such copy number changes."

Scientists are not sure why the copy variations emerge, but it probably has something to do with the shuffling of genetic material that occurs in the production of eggs and sperm; the process is prone to errors.

As well as aiding the investigation of disease and the development of new drugs, the research will also inform the study of human evolution, which probes genetic variation in modern populations for what it can say about their relationship to ancestral peoples.


285 of the approximately 3,000 CNVs are already known to be
associated with disease, and copy number variations of some of
these genes have been or are now being speculated as risk
factors for ailments such as AIDS, inflammatory bowel disease, lupus, cataracts, arterial disease and

One interesting observation that the researchers made during this study was that many of the CNVs have
population-specific characteristics and frequencies, which could explain increased prevalence of some diseases in
certain populations. For example, previous research found that the deletion of the UGT2B17 gene may lead to an
increased risk of prostate cancer in African American men. As a result of this and other research, the consortium is
expanding their studies to thousands of healthy individuals from populations outside of the HapMap collection.




ADVANCED PATERNAL AGE: How old is too old?
Isabelle Bray, David Gunnel and George Davey Smith
Department of Social Medicine, University of Bristol, UK

Journal of Epidemiology amd Community Health 2006;60:851-853

"Average paternal age in the UK is increasing. The public health implications of this trend have not been widely anticipated or debated. .....Accumulated chromosomal aberrations and mutations occurring during the maturation of the male germ cells are thought to be responsible for the increased risk of certain conditions with older fathers. Growing evidence shows that the offspring of older fathers have reduced fertility and an increased risk of birth defects, some cancers and schizophrenia." ......

Labels: , , , , , , , ,

Tuesday, May 29, 2007

Paternal age and Congenital Malformations increase with age of father

1: Hum Reprod. 2005 Nov;20(11):3173-7. Epub 2005 Jul 8. Links
Paternal age and congenital malformations.Zhu JL, Madsen KM, Vestergaard M, Olesen AV, Basso O, Olsen J.
The Danish Epidemiology Science Centre, University of Aarhus, Denmark.

BACKGROUND: Spontaneous mutations in germ cells increase with male age, but an association between paternal age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association. METHODS: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71937). Diagnoses of congenital malformations in children were obtained by linkage to the nationwide hospital register (1980-1999). RESULTS: Overall, there were no differences in the prevalence of malformations as a function of paternal age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Down's syndrome, increased with increasing paternal age. For example, in comparison with fathers age 20-29 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.81-1.65] for age 35-39 years, 1.33 (95% CI 0.79-2.25) for age 40-44 years, 1.73 (95% CI 0.82-3.65) for age 45-49 years, and 3.20 (95% CI 1.37-7.48) for age > or = 50 years (test for trend P = 0.01). CONCLUSIONS: Our data suggest that advanced paternal age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of the gametes in men induced by biological or environmental factors


Monday, May 28, 2007


You can be too old to be a dad!
By Akintayo Abodunrin

An old couple

It is believed that age has very little effect on men as it pertains to fertility. But it has now been revealed that men who think age has no effect on their fertility need to have a rethink as emerging scientific facts suggest otherwise. Akintayo Abodunrin reports.


Minding Your Mind

New Key to Autism

September 25, 2006

By Michael Craig Miller, M.D.
Harvard Medical School

Convincing Evidence
What Causes These Genetic Errors?
Should Older Men Stop Fathering Babies?
A study published in the September, 2006 issue of the Archives of General Psychiatry may give older prospective fathers pause before plunging into biological parenthood. The authors found a significant increase in the risk of autism and similar disorders as fathers got older.

What Is Autism?
Autism is a profoundly disabling disorder that starts in early childhood. The key features are:

Abnormal social development – little or no eye contact, prefers to be alone
Difficulty communicating – impaired language ability, uses gestures or pointing rather than words
Unusual behavior – spins objects, doesn't like being cuddled
Evidence of strong abilities sometimes in non-verbal areas, such as math or music
Older people with autism may have some ability to interact with people, but about two-thirds are mentally retarded and most cannot live on their own
Unfortunately, the incidence of this illness appears to be on the rise. Some experts think autism is diagnosed more often simply because more people are aware of it. But that's probably not the whole explanation.

Genetic factors almost certainly play a big role. So autism researchers are eager to discover anything that might increase a person's genetic vulnerability, such as delaying parenthood until age 40 or beyond.

The risk was smallest for children of fathers younger than 20 and greatest for children of fathers older than 50. A man in his 40s, for example, was almost 6 times as likely to have an autistic child as a man age 20. This relationship held even after researchers adjusted the results for the year of the person's birth, their socioeconomic status, or the mother’s age.

This is not the first discovery of its type. Healthcare professionals have long known that as parents age, the risk of giving birth to a child with certain illnesses goes up. Older mothers, for example, are more likely to have a child with Down syndrome. In recent years, studies have revealed a link between aging fathers and schizophrenia.

Convincing Evidence

The Archives study took advantage of the extraordinarily complete health records of over 300,000 Israeli men and women who underwent a complete health assessment when they were 17-year olds — draft age. This gave researchers a good way to determine the incidence of autism in the population. The researchers had access to intellectual, medical and psychiatric evaluations of almost all Israeli boys and three-quarters of girls. (Their identities were kept secret, however.) For most individuals, the father’s age at birth was known.


: Mol Psychiatry. 2007 May;12(5):419-421.Paternal age and autism are associated in a family-based sample.Cantor RM, Yoon JL, Furr J, Lajonchere CM.
[1] 1Department of Human Genetics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [2] 2Department of Pediatrics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [3] 3AGRE Consortium, Los Angeles, CA, USA.

PMID: 17453057 [PubMed - as supplied by publisher]

The paternal age distribution of the AGRE fathers, whose first child is autistic differs significantly from that of the 'control' sample (P=0.005). A 2 goodness-of-fit test with 2 degrees of freedom was conducted using percents in the 'control' group age categories to calculate the expected values in the AGRE sample. The shift toward higher paternal ages in those with an affected first-born is seen most dramatically in the group of AGRE fathers who are 30–39 years inclusive, which is 54.7% of the distribution compared with the 41.9 % that is expected. We interpret this shifted age distribution to provide support for the recently reported finding by Reichenberg and co-workers that autism risk is associated with advancing paternal age.
Labels: CM Lajonchere, J Furr, JL Yoon, RM Cantor

Labels: , , ,


We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis.

The latest finding, published last month: Older fathers are more likely to have children with autism. Researchers tracked 387,000 people born in Israel and concluded the odds of fathering an autistic child are about 6 in 1,000 for men under 20. When a man reaches 50, those odds shoot up to about 52 in 1,000.

"The optimal time for a man to father a healthy child is the same as for a woman — 25 or so," says Dolores Malaspina, a psychiatry professor at New York University and coauthor of the study.

Sporadic type 1 diabetes, prostate cancers, Alzheimer's disease, ALL, MS, nervous system cancers,autism, schizophrenia,etc. etc. all rise with the age of the father at conception.

Biological Clock Ticks for Men, Too
Genetic Defects Linked to Sperm of Older Fathers
Paul D. Thacker

lawmummylike Donna Reed, Martha Stewart and Sandra Day O'Connor all rolled into one. Only not on TV. Or on the Supreme Court. Or with cute crinoline dresses... But a mom. And an attorney. And in apparent need of therapy.« Life's Too Short. | Main | For Richer, For Poorer? »

25 May 2007
Don't Get a Dog, Get a Baby Instead.
Ahh, the words of someone clearly ready to be a mother

Lest you think it's some young kid, let me set you straight: those are the words of 60 year old Frieda Birnbaum, a psychologist from Saddle River, New Jersey. She just delivered her fourth and fifth children (twins) in Hackensack this week. That's right, twins, at 60.

She had them deliberately - through in vitro fertilization. Because of her age, no US clinic would agree to treat her, so flying in the face of both medical science and common sense, she went to a clinic in South Africa that will apparently do anything for a dollar.

I've been critical of much older parents like Frieda before - I think it's selfish and unfair to the children - but this time around, I thought I'd make an effort to listen and find out whether there was some reason that Ms. Birnbaum had that would make it all okay. Years of trying to having a baby and couldn't? Previously in a bad relationship? Not financially secure? Nope on all counts. Frieda has a good life, financially, has been married to the same man for more than 30 years and has three other children ranging in age from 6 to 31.

And what do her other children think of this? Her 29 year old daughter is "appalled" and well she should be. Frieda described her relationship with her daughter on CNN as "basically, she thinks I'm crazy." Well, good. That makes two of us.

Her reasons for having these babies this late in life sounded flip and contrite. She cited that holding babies was "peaceful" (um, for about 10 minutes, lady, didn't you do this once or twice before?) and made her feel "whole". She wanted a playmate for her younger son, she said (right, since 6 year olds sooo enjoy sharing 60 year old mom with babies) - apparently the kids at the park must shun her child if she can't find a playmate within her own community.

But my favorite reason for having the babies? "Don't get a dog, get a baby instead." I swear I'm not making this up.


Labels: , , ,

Friday, May 25, 2007

The Paternal-Age effect in Apert Syndrome is due, in part, to the increased frequency of mutations in sperm

J Hum Genet. 2003 Oct;73(4):939-47. Epub 2003 Jul 31. Links
The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm.Glaser RL, Broman KW, Schulman RL, Eskenazi B, Wyrobek AJ, Jabs EW.
Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, Department of Pediatrics, The Johns Hopkins University, Baltimore, MD 21287, USA.

A paternal-age effect and the exclusive paternal origin of mutations have been reported in Apert syndrome (AS). As the incidence of sporadic AS births increases exponentially with paternal age, we hypothesized that the frequency of AS mutations in sperm would also increase. To determine the frequency of two common FGFR2 mutations in AS, we developed allele-specific peptide nucleic acid-PCR assays. Analyzing sperm DNA from 148 men, age 21-80 years, we showed that the number of sperm with mutations increased in the oldest age groups among men who did not have a child with AS. These older men were also more likely to have both mutations in their sperm. However, this age-related increase in mutation frequency was not sufficient to explain the AS-birth frequency. In contrast, the mutation frequency observed in men who were younger and had children with AS was significantly greater. In addition, our data suggest selection for sperm with specific mutations. Therefore, contributing factors to the paternal-age effect may include selection and a higher number of mutant sperm in a subset of men ascertained because they had a child with AS. No age-related increase in the frequency of these mutations was observed in leukocytes. Selection and/or quality-control mechanisms, including DNA repair and apoptosis, may contribute to the cell-type differences in mutation frequency.

Labels: , , , ,

We conclude that a significant proportion of infertile men have elevated levels of DNA damage in the ejaculated spermatozoa

Andrology, Vol 21, Issue 1 33-44, Copyright © 2000 by The American Society of Andrology



DNA integrity in human spermatozoa: relationships with semen quality
D. S. Irvine, J. P. Twigg, E. L. Gordon, N. Fulton, P. A. Milne and R. J. Aitken
Centre for Reproductive Biology, Edinburgh, Scotland.

The literature contains conflicting evidence regarding the existence of DNA damage in spermatozoa from infertile male patients. To examine this phenomenon, we have studied ejaculated spermatozoa from normozoospermic semen donors and from a group of the unselected male partners of couples attending an infertility clinic for initial investigation. Classical semen analysis according to World Health Organization (WHO) guidelines was undertaken with computer-assisted sperm analysis (CASA). Spermatozoa were prepared by sequential washing and centrifugation and were analyzed for DNA fragmentation using three assays: 1) a single-cell gel electrophoresis (comet) assay, 2) in situ nick translation with prior chemical decondensation (ISNT-decondensed), and 3) in situ nick translation without prior chemical decondensation (ISNT-condensed). In addition, reactive oxygen species (ROS) generation by spermatozoa was measured, and seminal plasma was analyzed for its total reactive antioxidant potential (TRAP). When the donor and patient groups were compared, the latter had lower levels of semen quality and higher levels of DNA damage, which was particularly apparent using the comet assay. Highly significant negative correlations were observed between DNA fragmentation, detected by all three assays, and semen quality, particularly sperm concentration. In addition, multiple regression analysis indicated that other attributes of semen quality, such as sperm movement and ROS generation, were also related to DNA damage. We conclude that a significant proportion of infertile men have elevated levels of DNA damage in their ejaculated spermatozoa.

Also ASRM on Introcytoplasmic Sperm Injection


Scientists shed new light on male infertility
Thu May 31, 2007 10:05AM EDT

HONG KONG (Reuters) - Scientists in Hong Kong and China have identified for the first time a protein in sperm from humans and from mice that could be responsible for many unexplained cases of male infertility.

Defective versions of the protein, called epithelial ion channel, have previously been reported to be responsible for female infertility.

Writing in the latest issue of the Proceedings of National Academy of Sciences journal, the researchers said they detected the protein in sperm samples from mice and human subjects.

"(The protein) is involved in the transport of bicarbonate, which is required for sperm activation in order to fertilize the egg. If you have a defect in this (protein), then fertilization capacity of the sperm will be impaired or reduced," Chan Hsiao Chang, physiology professor at the Chinese University in Hong Kong, said in a telephone interview on Thursday.

Reuters Pictures

Editors Choice: Best pictures
from the last 24 hours.
View Slideshow
Experiments showed that sperm taken from mutant mice with defective versions of the protein had far lower fertility than sperm taken from normal mice, the researchers said.

The discovery would help doctors more accurately diagnose and explain many cases of male infertility that have so far gone unexplained.

"For many people, they are infertile, but they don't know why, so diagnosis would be the immediate advantage," Chan said.

Between 8 percent and 12 percent of couples with women of childbearing age -- or between 50 and 80 million people -- are infertile globally, according to the World Health Organisation.

Half of infertile couples fail to reproduce because of problems with male fertility.


Saturday, May 19, 2007

"SICKO" The people in the movie didn't fall through the cracks, they were thrown overboard"


Many of those in the New York audience, the real life stars of "Sicko," were brought to tears by a film and filmmaker who viewed their lives with a lot more humanity than the insurance companies who had treated them with such calculated disregard. The people, who, as one industry whistleblower says in the film, didn't just "fall through the cracks." They were deliberately thrown overboard. Cast aside by the same insurance giants that far too many ostensible reformers think we should reward for their greed by funneling them hundreds of millions dollars more. "Sicko" is not just an indictment of an indefensible healthcare industry in the U.S. It's a rejoinder for those who think we can fix the soulless monster by tinkering with an unconscionable system that puts us further in thrall to those who created the crisis. Following the screening, Moore put it as simply as possible: the private insurance companies "have to go." Unlike too many of our friends in the progressive community, Moore did not go for the easy way out. There are no calls here for forcing individuals to buy unaffordable, junk insurance. Or handing over ever more tax dollars to those who profit by denying care, and whose biggest accomplishment, says Moore, "is buying our U.S. Congress" to protect their wealth and stranglehold over our health. There are no cynical ad homonyms to not let "the perfect be the enemy of the good" - the last refuge of the politicians desperate to convince us, and perhaps themselves as well, that the Faustian compromises they propose will all be OK. Tell it to the worker in "Sicko" who had to choose between restoring one severed finger for $60,000 or another for $12,000.

Labels: , , , ,


Richard Insel

Robert Wood Johnson IV
Jackson Laboratory researcher receives JDRF's Grodsky award
Dr. David Serreze honored for work in immunology of type 1 diabetes
New York, NY— May 18, 2007 -- The Juvenile Diabetes Research Foundation, the world’s largest charitable funder of type 1 diabetes research, announced today that Dr. David Serreze, senior staff scientist at The Jackson Laboratory in Bar Harbor, Maine, is the recipient of the 2007 Gerold & Kayla Grodsky Basic Research Scientist Award. The award, among JDRF’s most prestigious, will be given to Dr. Serreze at an awards ceremony tonight at the Marriott Financial Center in downtown Manhattan.

"JDRF is in the business of finding a cure for type 1 diabetes. As such, we work with world-class researchers who share our mission and are making significant progress towards that goal," said Dr. Richard Insel, Executive Vice President of Research at JDRF. "After careful consideration of many excellent candidates, we are thrilled to acknowledge Dr. Serreze for his outstanding work in accelerating the pace of diabetes research."

The Gerold & Kayla Grodsky Award is presented annually to a basic research scientist who has made outstanding contributions to diabetes research. JDRF established the award in 1993 to honor the contributions of Dr. Grodsky’s diabetes research at UCSF over four decades. A gift to JDRF from the Grodskys has made it possible for a monetary award to be presented each year to a Ph.D. researcher who has made an outstanding contribution to the study of diabetes.

Through this year’s award, JDRF recognizes Dr. Serreze’s leadership and innovation in the emerging field of diabetic immunology. The award also reflects his expert advice and service on the JDRF Medical Science Review Committee.

"I’m honored and humbled to receive the Grodsky award from the JDRF," said Dr. Serreze. "Type 1 diabetes is a terrible disease, but with the support of the JDRF family, I hope that work from my laboratory may play some small part in leading to cures for type 1 diabetes."

Dr. Serreze has been with the Jackson Laboratory since 1991. He is also adjunct research professor of medicine at the University of Massachusetts Medical Center, Worcester. A two-time recipient of JDRF’s Mary Jane Kugal Research Award, Dr. Serreze is the author or coauthor of more than 100 research papers. He earned his undergraduate and graduate degrees at the University of Maine.

Labels: , , ,




NIH Awards Emory $3.6 Million for Schizophrenia Gene Research

The National Institute of Mental Health of the National Institutes of Health has awarded Emory University School of Medicine a $3.6 million research grant to test schizophrenic patients for a recently discovered variation in the human genome. The project is led by Stephen T. Warren, PhD, Timmie Professor and chair of the Department of Human Genetics.

Recently, scientists have discovered an entirely new and previously unknown form of variation in the human genome, called "copy number variation," or CNV. This variation includes deletions and duplications of segments of DNA previously unrecognized in the general population.

Using cutting-edge technology available to only a few major research centers, the Emory project will screen a collection of 500 schizophrenic patients and 500 controls (individuals without schizophrenia) for CNV throughout the entire human genome...........


Labels: , ,

Thursday, May 17, 2007


From an article in Salon May 9, 2007

Bionic parents and techno-children
Author Liza Mundy talks about "designer babies," the "epidemic" of twins, and why assisted reproduction is the world's biggest social experiment.

By Lynn Harris

Here in the U.S., fertility is estimated to be a $3 billion industry. Nearly 50,000 U.S. children were born via IVF in 2003, a 128 percent increase since 1996; 30,000 had donor sperm for dads. Donor eggs or embryos, gestational carriers (surrogates), screening of embryos for serious disease: Taken all together, the techniques of advanced reproductive technology (ART) add up to more than private discussions between doctors and would-be parents, more than individual stories of heartbreak and bliss. And according to journalist and author Liza Mundy, ART is not just changing "how we think" about parenting and procreation. In her exhaustively reported and tenaciously argued new book, "Everything Conceivable: How Assisted Reproduction Is Changing Men, Women and the World," Mundy observes that virtually every trend documented in the most recent National Vital Statistics Report is related to fertility technology. ART is changing us all: our very society, our very cells.

Labels: ,

Wednesday, May 16, 2007

Does increasing paternal age put a child at any greater risk of antisocial juvenile behavior? I don't know?

Newborns At Risk for Special Ed-Fathers 40 or More at birth

1: Eur J Paediatr Neurol. 2007 Mar 6; [Epub ahead of print]Newborns at risk for special education placement: A population-based study.Mannerkoski MK, Aberg LE, Autti TH, Hoikkala M, Sarna S, Heiskala HJ.
Department of Child Neurology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland.

OBJECTIVES: To establish the contributions of birth weight (BW), gender, socioeconomic status (SES), and parental age on risks for special education (SE) placements in school-age children. METHODS: A population-based sample of 900 school-age children attending the following full-time SE groups: at level 1, children had isolated neurodevelopmental, physical, or other impairments; at level 2, borderline to mild intellectual disability (ID); and at level 3, moderate to severe ID. Three hundred and one children enrolled in mainstream education formed the control group (level 0). For all children with siblings, we defined familiar forms of learning disorders as having a sibling in one of the SE groupings. We performed our analysis for the entire cohort as well as comparing risk factors within the familial and non-familial types of SE groupings. RESULTS: In multinomial logistic regression analysis, age of father 40 years, low BW (<2500g or <-2 SD), male sex, and parent's lower SES, all increased the probability of SE placement. In the familial forms of levels 2 and 3, the parental SES was lower and, in addition, in the level 2, the family size was bigger. Furthermore, in the non-familial form of level 2, both the low and the high (4000g) BW were more common. CONCLUSIONS: Among the known risk factors for learning disabilities (LD), our study highlighted the importance of a higher paternal age and a lower SES especially in the familial forms of LD.

PMID: 17346999 [PubMed - as supplied by publisher]

Neuropsychiatric and experiential correlates of violent juvenile delinquency
Journal Neuropsychology Review
Publisher Springer Netherlands
ISSN 1040-7308 (Print) 1573-6660 (Online)
Issue Volume 1, Number 2 / June, 1990
DOI 10.1007/BF01108714
Pages 125-136
Subject Collection Behavioral Science
SpringerLink Date Monday, February 07, 2005

Neuropsychiatric and experiential correlates of violent juvenile delinquency
Dorothy Otnow Lewis1

(1) Department of Psychiatry, New York University School of Medicine, 10016 New York, New York

Abstract This article reviews evidence regarding contributions of neuropsychiatric and psychological vulnerabilities to violent delinquency, and the interaction between intrinsic vulnerabilities and experiential factors in the genesis of antisocial juvenile behavior. Consideration is given to biochemical and physiological factors, genetics, medical status, and neurological, psychiatric, and neuropsychological factors. Implications for treatment are discussed.
Key words juvenile delinquency - violent behavior - neuropsychology

1: J Am Acad Psychiatry Law. 2001;29(4):420-6. Links
Juvenile and young adult mentally disordered offenders: the role of child neuropsychiatric disorders.Siponmaa L, Kristiansson M, Jonson C, Nyden A, Gillberg C.
Department of Forensic Psychiatry, Karolinska Institute, Huddinge, Sweden.

A retrospective study of the prevalence of child neuropsychiatric disorders was done involving pervasive developmental disorder (PDD), attention-deficit/hyperactivity disorder (ADHD), and Tourette syndrome in young offenders (15-22 years, n = 126) consecutively referred for presentencing forensic psychiatric investigation (FPI) in Stockholm, Sweden. Most offenders were referred for FPI because of serious offenses. Case report sheets were prepared, and retrospective neuropsychiatric DSM IV diagnoses were made by the first two authors. For best-estimated diagnoses, the case report sheets were then submitted to the fifth author, a child neuropsychiatrist with expertise in this area. Fifteen percent of the subjects had a definite diagnosis of ADHD, and another 15 percent had PDD, including 12 percent PDD not otherwise specified (NOS) and 3 percent Asperger syndrome. Autistic disorder was not found in any case. Tourette syndrome occurred in two percent of the cases. The rate of PDD is particularly striking. Neuropsychiatric diagnoses had been determined in the FPI in only a few cases. The contribution of constitutional problems to later criminal development may have been underestimated.
PMID: 11785613 [PubMed - indexed for MEDLINE]


Saturday, May 12, 2007

In the mild form of retinitis pigmetosa a significant increase of mean paternal age 38.8 years which is suggestive of new mutations

Josseline Kaplan1 , Dominique Bonneau1, Jean Frézal1, Arnold Munnich1 and Jean-Louis Dufier2

(1) Clinique de Génétique Médicale, Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U.12, Hôpital des Enfants-Malades, 149, Rue de Sèvres, 15 Paris Cedex, France
(2) Consultation d'Ophtalmologie, Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U.12, Hôpital des Enfants-Malades, 149, Rue de Sèvres, 15 Paris Cedex, France

Received: 12 December 1989 Revised: 14 March 1990

Summary The clinical course of defective vision and blindness has been investigated in relation to different modes of genetic transmission in a large series of 93 families with retinitis pigmentosa (RP). For autosomal dominant RP, two clinical subtypes could be distinguished according to the delay in macular involvement. In the severe form, macular involvement occurred within 10 years, while in the mild form, macular involvement occurred after 20 years. Interestingly, a significant increase of mean paternal age (38.8 years, mean controls in France = 29.1 years, P < 0.001) was found in this form of RP, a feature which is suggestive of new mutations. For autosomal recessive RP, four significantly different clinical subtypes could be recognized, according to both age of onset and the pattern of development (P < 0.001), namely cone-rod dystrophy and early-onset severe forms on the one hand (mean age of onset = 7.6 years), late-onset mild forms and senile forms on the other. Similarly, two significantly different clinical subtypes could be recognized in X-linked RP, according to both mode and age of onset, which were either myopia (mean age = 3.5±0.5 years) or night blindness (mean age = 10.6±4.1 years, P < 0.001). By contrast, no difference was noted regarding the clinical course of the disease, which was remarkably severe whatever the clinical subtype (blindness before 25 years). In addition, all obligate carriers in our series were found to have either severe myopia or pigment deposits in their peripheral retina. Finally, sporadic RP represented the majority of cases in our series (42%). There was a considerable heterogeneity in this group, and at least three clinical forms could be recognized, namely cone-rod dystrophy, early onset-severe forms and late onset moderate forms. At the beginning of the disease, the hereditary nature of the sporadic forms was very difficult to ascertain (especially between 7–10 years) and only the clinical course could possibly provide information regarding the mode of inheritance. However, the high level of consanguinity, and the high sex ratio in early onset and severe sporadic forms (including cone-rod dystrophy), was suggestive of an autosomal or X-linked recessive inheritance, while increased paternal age in late onset forms was suggestive of autosomal dominant mutations.


References secured to subscribers.


Hum Genet. 2005 Jul;117(2-3):288-90.

Parents of children with autosomal recessive diseases are not always carriers of the respective mutant alleles.

Zlotogora J.

Department of Community Genetics, Public Health Services, Ministry of Health, Tel Aviv, Israel.

Classically, each parent of a child with an autosomal recessive disease has been considered to carry at least one copy of the abnormal allele. However, with the increasing ability to characterise the molecular basis of genetic diseases, several exceptions have been reported. The most frequent situation is that only one parent is a carrier of the mutation that is present in the patient in two copies either because of uniparental disomy or because of a de-novo mutation on the gene transmitted by the non-carrier parent. In order to give accurate genetic counselling, in particular when prenatal diagnosis is envisaged, molecular analysis of each of the parents of a child affected with an autosomal recessive disease must be routinely performed.

Publication Types:

Labels: ,

Friday, May 11, 2007

Cytogenetic Analysis and genetic counseling would be helpful in infertile males to assess genetic risks to offspring

1: Arch Androl. 2006 Jul-Aug;52(4):263-7. Links
Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia.Samli H, Samli MM, Solak M, Imirzalioglu N.
Afyon Kocatepe University, School of Medicine, Department of Medical Genetics, Afyon, Turkey.

Genetic factors have a major importance in male infertility etiology. Numerical and structural chromosomal abnormalities seem to be frequent inoligospermia and azoospermia cases with unknown etiology. In this study, 819 patients with azoospermia (383) and oligospermia (436) who attended the infertility department between 1995-2005 were evaluated. Spermogram and basic hormone proties (FSH-testosterone) were studied two times in a one month interval from each patient, and all the cases were evaluated cytogenetically. The 47 (12%) of 383 azoospermia patients and the 20 (4%) of 436 oligospermia patients were found to have chromosomal abnormalities. The 9 (19%) of the chromosomal abnormalities found in azoospermia patients were autosomal and the 38 (80%) were gonosomal. In oligospermia cases, the 8 (40%) of the chromosomal abnormalities were autosomal and 12 (60%) were gonosomal. Cytogenetic analysis and genetic counseling would be helpful in infertile males with azoospermia and oligospermia by determining the genetic factors causing infertility and by assessing the genetic risks of the offsprigs provided by assisted reproductive techniques.

PMID: 16728341 [PubMed - indexed for MEDLINE

Labels: , ,


1: Hinyokika Kiyo. 2007 Feb;53(2):87-91. Links
[Clinical investigation of infertile males with chromosomal anomalies][Article in Japanese]
Yumura Y, Saito K, Ogawa T, Suzuki K, Sato K, Kubota Y, Iwasaki A.

The Department of Urology, Yokohama City University, School of Medicine.

A chromosomal survey using the G-banding technique was performed on 87 subfertile male whose semen analysis demonstrated severe oligospermia and azoospermia at Yokohama City University Hospital between January 1990 and October 2002. Fourteen of these subjects demonstrated major chromosomal anomalies (16.1%). Semen analysis in these cases demonstrated azoospermia, except in one case of autosomal abnormality. Twelve patients showed sex chromosomal abnormalities including 8 Klinefelter syndrome (47XXY) and 2 XX males (46XX) and two patients had autosomal abnormalities. The follicle-stimulating hormone (FSH) value in these patients, except for the two cases of autosomal abnormality and one case of 46XYq-, was much higher than normal. Histological examination was performed in 7 cases. In these cases, intratesticular spermatozoa were seen in only two cases (Klinefelter syndrome case and ring chromosome 21 case). Chromosome studies are important in the evaluation of subfertile patients with azoospermia and severe oligospermia. Because the abnormal genotype could be transferred to the next generation, the importance of chromosome studies before ICSI should be emphasized.

PMID: 17352156 [PubMed - indexed for MEDLINE]


Thursday, May 10, 2007

The Genetics of male Infertility and Age Related Male Infertility

Today at Cornell

Center established to focus on genetics of infertility, combining strengths of Cornell's Ithaca campus with Weill medical college
Cornell University has established the Center for Reproductive Genomics, which will combine basic and clinical research in reproductive sciences on Cornell's Ithaca campus and at Weill Cornell Medical College (WCMC) in New York City, which has one of the country's leading fertility clinics. Infertility affects 10 to 15 percent of couples of childbearing age.
The collaborative center will focus on the genetics of infertility, with specific emphasis on meiosis, the specialized cell division that results in recombination of genetic material and the production of sperm in the male throughout life and eggs in the female fetus, which then develop over 20-plus years.


Genetics of male infertility

It is clear that a significant proportion of infertile male with azoospermia and severe oligospermia have a genetic etiology for reproductive failure. While recent advances in assisted reproductive technologies make possible and practical for many infertile men with severe male factor infertility to father children, they also raised concerns about passing on genetic abnormalities to the offspring of these men. Intracytoplasmic sperm injection (ICSI) is the most invasive technique for assisted reproduction. ICSI bypasses all the physiological mechanisms related to fertilization as well as all protective barriers against sperm with genetic defects and allow even altered spermatozoon to fertilize an oocyte. Since infertile patients with non-obstructive azoospermia are able to achieve pregnancy with surgically retrieved testicular sperm, ICSI carries risk of transmitting both genetically determined diseases and genetically determined infertility. It is imperative for the clinicians involved in the treatment of these couples to initiate genetic evaluation and counseling prior to any therapeutic procedures.


Age Raises Infertility Risk in Men, Too
Risks associated with men's biological clocks may be similar to women's.

By Elizabeth Heubeck, MA
WebMD Feature

Reviewed By Brunilda Nazario, MD

On playgrounds across the country, it's getting tougher to tell who's watching the kids -- dad or granddad. Experts predict the trend of older fathers will continue creeping upward. Why the rise and, more importantly, at what cost?

"The women set the baby-making agenda," says Harry Fisch, MD, director of the Male Reproductive Center at Columbia-Presbyterian Medical Center in New York and author of The Male Biological Clock: the Startling News about Aging and Fertility in Men. As more and more women wait to have children, their spouses are forced to postpone parenthood, too. Back in 1970, less than 15% of all men fathering children were over 35. Today, that percentage has risen to almost one-quarter. Even among men in the 50 to 54 age group, there's been a notable increase in fatherhood.

While it has become more socially acceptable to put off fatherhood, experts caution that the decision is not without risks.

"The role of the male in infertility has been grossly overlooked by lay and professionals alike," says Peter Schlegel, MD, urologist-in-chief at New York-Presbyterian Hospital/ Weill Cornell Medical Center, and president of the Society for Male Reproduction and Urology.

Effects of Age on Male Fertility

Whereas most women realize that their biological clock ticks as they age, the same cannot be said for men. "Not only are men not aware of the impact their age has on infertility, they deny it. They walk around like they're 18 years old," Fisch tells WebMD. It's no wonder.

Until recently, popular belief held that men could father children as easily at 78 as they could at 18. But a mounting body of evidence is showing otherwise.

In one study of couples undergoing high-tech infertility treatments, researchers concluded that a man's chances of fathering a child decrease with each passing year. In the study, the odds of a successful pregnancy fell by 11% every year; their chances for obtaining a successful live birth declined even farther. The study was reported in a 2004 issue of the American Journal of Gynecology.

As sure as men age, so too do their sperm. German researchers compiling the most recent data on aging sperm reported that the volume, motility (ability to move toward its destination, an awaiting egg), and structure of sperm all decline with age. They published this update in a 2004 issue of Human Reproduction Update.

Rise of Other Reproductive Risks

For aging men, the risks extend beyond reduced fertility. "The original view that men's contribution to normal reproduction stopped at fertilization needs to be completely revamped," Schlegel tells WebMD. A broader and more accurate view would acknowledge the significant impact of aging sperm on birth outcomes.

We know that once women reach their mid-30s, their risk of having a child with a genetic abnormalities increases sharply. Now we know that the age of fathers can also contribute to that risk. In the most revealing study on this topic to date, Fisch and his colleagues evaluated more than 3,400 cases of Down syndrome. They found the father's age played a significant role when both parents were over 35 at the time of conception. The effect was most pronounced when the woman was over 40. In those cases, says Fisch, "We found the incidence of Down syndrome is related to sperm approximately 50% of the time." These findings appeared in the June 2003 issue of The Journal of Urology.

Children born to older men also run a higher risk of developing schizophrenia, a devastating mental disorder. In one study on the subject, researchers discovered that men between the ages of 45 to 49 were twice as likely to have children with schizophrenia as were men 25 and younger. That risk tripled for men over the age of 50. Investigators, reporting in a 2001 issue of the Archives of General Psychiatry, drew their results from a sample of more than 85,000 people.

Labels: ,

Wednesday, May 02, 2007

Type 1 Diabetes is also a Risk Factor For Autism and Advancing Paternal Age is a Risk Factor For Type 1 and Maybe Type 2 Diabetes


Contact: Emma Mason
European Society for Human Reproduction and Embryology

First research to show that diabetes damages DNA in men's sperm and may affect fertility
Scientists have found that sperm from diabetic men have greater levels of DNA damage than sperm from men who do not have the disease. They warn that such DNA damage might affect a man’s fertility.

In the first study [1] to compare the quality of DNA in sperm from diabetic and non-diabetic men, the researchers from Belfast, Northern Ireland showed that the DNA in the nuclei of the sperm cells had greater levels of fragmentation in diabetic men (52%, versus 32% in non-diabetic men), and that there were more deletions of DNA in the tiny, energy-generating structures in the cells called mitochondria (4 versus 3).

Dr Ishola Agbaje, who undertook the research published online today (Thursday 3 May) in the journal Human Reproduction, said: "As far as we know, this is the first report of the quality of DNA in the nucleus and mitochondria of sperm in diabetes. Our study identifies important evidence of increased DNA fragmentation of nuclear DNA and mitochondrial DNA deletions in sperm from diabetic men. These findings cause concern, as they may have implications for fertility."

The incidence of type 1 and type 2 diabetes is increasing rapidly worldwide. While diet and obesity are known to be key factors in the increase of type 2 (or late onset) diabetes, type 1 diabetes which is usually diagnosed in childhood or adolescence, is increasing by three per cent a year in European children, although the reason for this is not entirely clear. Genetic factors that make people more susceptible, or environmental factors such as viruses that may trigger the onset of type 1 diabetes, could play a role.

Dr Agbaje, a research fellow in the Reproductive Medicine Research Group at Queen’s University, Belfast, said: "If the increasing trend in the incidence of type I diabetes continues, this will result in a 50% increase over the next ten years. As a consequence, diabetes will affect many more men prior to and during their reproductive years. Infertility is already a major health problem in both the developed and developing world, with up to one in six couples requiring specialist investigation or treatment in order to conceive. Moreover, the last 50 years have seen an apparent decline in semen quality. Sperm disorders are thought to cause or contribute to infertility in 40-50% of infertile couples. The increasing incidence of systemic diseases such as diabetes may further exacerbate this decline in male fertility. However, it is not clear to what extent clinics consider information about the diabetic status of their patients when investigating fertility problems." [2]

Dr Agbaje and his colleagues examined sperm from 27 diabetic men, with an average age of 34, and 29 non-diabetic men with an average age of 33. They found that although semen volume was significantly less in diabetic men (2.6 versus 3.3 ml), there were no significant differences in sperm concentration, total sperm output, form and structure of the sperm or their ability to move. When they measured DNA damage they found that the percentage of fragmented nuclear DNA was significantly higher in sperm from the diabetic men and that the number of deletions in mitochondrial DNA was also higher – the number of deletions ranged from three to six (average four) in the diabetic men and from one to four (average three) in the non-diabetic men.

Professor Sheena Lewis, scientific director of the Reproductive Medicine Research Group, said: "Our study shows increased levels of sperm DNA damage in diabetic men. From a clinical perspective this is important, particularly given the overwhelming evidence that sperm DNA damage impairs male fertility and reproductive health. Other studies have already shown that, while the female egg has a limited ability to repair damaged sperm DNA, fragmentation beyond this threshold may result in increased rates of embryonic failure and pregnancy loss. In the context of spontaneous conception, sperm DNA quality has been found to be poorer in couples with a history of miscarriages."

However, Prof Lewis said that it was not possible to say from this current study whether the DNA damage caused by diabetes would have the same effect on men’s fertility and the health of future children as DNA damage caused by other factors such as smoking.

"This is just one, relatively small study that highlights a possible concern. Further studies need to be carried out in order to understand the precise nature of the diabetes-related damage, the causal mechanisms and the clinical significance. Given the global rise in the prevalence of diabetes, it is also vital to examine the reproductive outcomes of pregnancies fathered by diabetic men, and the prevalence of diabetes amongst men attending for infertility treatment," she concluded.

[1] Insulin dependent diabetes mellitus: implications for male reproductive function. Human Reproduction. doi:10.1093/humrep/dem077.

[2] Studies have estimated the prevalence of diabetes in sub-fertile men as 1% – three times more than expected (0.3%), given the prevalence of diabetes and male infertility in the general population. This suggests that diabetes is having a significant impact on male fertility.

Labels: ,

Photarium blog directory Blog Directory - photarium Outpost