Scientists To Discus Genetic Coding, Do All These Disorders Increase in Sporadic Cases, in Offspring of Older Fathers?

Local Scientists To Discus Genetic Coding
POSTED: 3:43 pm PDT June 9, 2007
UPDATED: 3:53 pm PDT June 9, 2007


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SAN DIEGO -- Scientists will meet in San Diego next week to compare notes on whether some particular human genes may be responsible for more than one type of disease.


Scientists have known for decades that genetic coding can make some people more likely to come down with particularly diseases, such as Tay-Sachs or sickle-cell anemia. The Federation of Clinical Immunology Societies next week will bring experts together to look into whether the same gene can cause widely differing types of hereditary illness.



Dr. Francis Collins of the National Human Genome Research Institute will present several studies about common gene abnormalities possibly linking inflammatory bowel disease, juvenile arthritis, multiple sclerosis, rheumatoid arthritis, systemic lupus and type 1 diabetes.


The meeting Monday will be at the Sheraton San Diego Resort & Marina.
POSTED: 3:43 pm PDT June 9, 2007
UPDATED: 3:53 pm PDT June 9, 2007

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Sign Up for Breaking News Alerts


SAN DIEGO -- Scientists will meet in San Diego next week to compare notes on whether some particular human genes may be responsible for more than one type of disease.


Scientists have known for decades that genetic coding can make some people more likely to come down with particularly diseases, such as Tay-Sachs or sickle-cell anemia. The Federation of Clinical Immunology Societies next week will bring experts together to look into whether the same gene can cause widely differing types of hereditary illness.



Dr. Francis Collins of the National Human Genome Research Institute will present several studies about common gene abnormalities possibly linking inflammatory bowel disease, juvenile arthritis, multiple sclerosis, rheumatoid arthritis, systemic lupus and type 1 diabetes.


The meeting Monday will be at the Sheraton San Diego Resort & Marina.

TYPE 1 DIABETES IS A RISK FACTOR FOR AUTISM AND ADVANCED PATERNAL AGE IS A RISK FACTOR FOR TYPE 1 DIABETES

Contact: Emma Mason
wordmason@mac.com
44-077-112-96986
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.

STEEP INCREASE IN DIABETES TYPE 1 INCIDENCE IN AUSTRIA SINCE 1999 in a prior study in Austria Fathers of diabetic children were significantly older

1: Eur J Pediatr. 2007 Apr 24; [Epub ahead of print] Links
Steep increase of incidence of childhood diabetes since 1999 in Austria. Time trend analysis 1979-2005. A nationwide study.Schober E, Rami B, Waldhoer T; Austrian Diabetes Incidence Study Group.
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.

In a prospective population-based incidence study all newly diagnosed type 1 diabetic patients 0-<15 years of age were registered by the Austrian Diabetes Incidence Study Group. The nationwide incidence of type 1 diabetes between 2000-2005 was compared with the previously published incidence rates. Long-term trends as well as seasonal trends were estimated by Poisson regression models. A total of 3,599 incident cases (1,908 boys; 1,691 girls) were identified. Case ascertainment was >92%. The overall incidence rate doubled from 7.3 (95% CI; 6.8-7.9)/100,000 in the period 1979-84 to 14.6 (95% CI, 13.7-15.4)/100,000 in the time period 2000-2005. A significant increase during the observation period of 26 years could be demonstrated in all age groups and both sexes (p<0.01), with the steepest increment during the last 5 years. Until 1994 the incidence rate in children 0-<5 years was rather stable, but afterwards increased dramatically with 9.2% (95% CI, 5.2-13.4) annually. Despite this steep increase in time trend, we did not observe a seasonal variation in this age group (0-<5) in contrast to significant seasonal variations in the groups 5-<10 and 10-<15 years of age. Over the past 26 years incidence of type 1 diabetes in childhood increased clearly in Austria. The steepest rise was observed in the last 5 years and in the younger age groups.

PMID: 17453237 [PubMed - as supplied by publisher]

1: Eur J Pediatr. 1999 May;158(5):362-6. Links
Risk factors for type I diabetes mellitus in children in Austria
Rami B, Schneider U, Imhof A, Waldhor T, Schober E.
University Children's Hospital Vienna, Austria.

The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P<0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). CONCLUSION: In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.
PMID: 10333115 [PubMed - indexed for MEDLINE]





ENDOCRINOLOGY
B. Rami á U. Schneider á A. Imhof á T. WaldhoÈ r á E. Schob
Risk factors for type I diabetes mellitus
in children in Austria
Received: 5 May 1998 / Accepted in revised form: 27 August 1998
Eur J Pediatr (1999) 158: 362±366



Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015).




Results
Family/social factors
Fathers of type 1 diabetes cases were signi®cantly older
at the time of birth than fathers of control children
(31.7 ‹ 6.7 vs 30.1 ‹ 6.1 years, P = 0.015). Mothers
of children with diabetes did not di€er signi®cantly in
age at the birth of their children from mothers of con-
trols (27.8 ‹ 5.7 vs 26.9 ‹ 5.1 years, P = 0.13).

Discussion
Previous reports have shown that the risk for type 1
diabetes increases with higher maternal age [3, 6, 24, 30,
33, 40, 41]; only one study group from India reported a
higher risk with lower maternal age [31]. Mothers of
Austrian children with diabetes were older, too, but this
was statistically not signi®cant. In those reports, pater-
nal age as a possible risk factor was not investigated as
much, but either no di€erence was found compared to
controls [3, 5], or fathers of diabetic children were even
younger than fathers of control children [40]. These re-
sults thus contradict our ®ndings. As far as birth order
in our cohort families was concerned, again in contrast
to previous studies [30, 40, 41], the highest risk was
observed in second- or third-born children.

IS SEVERE AUTISM RELATED TO EARLY CHILDHOOD SCHIZOPHRENIA?

OBJECTIVE: Individuals with schizophrenia and their relatives tend to have either higher or lower than expected prevalences of autoimmune disorders, especially rheumatoid arthritis, celiac disease, autoimmune thyroid diseases, and type 1 diabetes. The purpose of the study was to estimate the association of schizophrenia with these disorders as well as a range of other autoimmune diseases in a single large epidemiologic study. METHOD: The Danish Psychiatric Register, the National Patient Register, and a register with socioeconomic information were linked to form a data file that included all 7,704 persons in Denmark diagnosed with schizophrenia from 1981 to 1998 and their parents along with a sample of matched comparison subjects and their parents. The data linkage required that the autoimmune disease occur before the diagnosis of schizophrenia. RESULTS: A history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia. Nine autoimmune disorders had higher prevalence rates among patients with schizophrenia than among comparison subjects (crude incidence rate ratios ranging from 1.9 to 12.5), and 12 autoimmune diseases had higher prevalence rates among parents of schizophrenia patients than among parents of comparison subjects (adjusted incidence rate ratios ranging from 1.3 to 3.8). Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren’s syndrome had higher prevalence rates among patients with schizophrenia than among comparison subjects and also among family members of schizophrenia patients than among family members of comparison subjects. CONCLUSIONS: Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.

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

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

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



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

Type 1 Diabetes Risk Rises With Paternal Age

: Eur J Pediatr. 1999 May;158(5):362-6. Links
Risk factors for type I diabetes mellitus in children in Austria.Rami B, Schneider U, Imhof A, Waldhor T, Schober E.
University Children's Hospital Vienna, Austria.

The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P<0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). CONCLUSION: In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.

PMID: 10333115 [PubMed - indexed for MEDLINE]

"Autoimmune" Disorders In Relatives and Autism, Older Fathers in Prior Generations are Implicated

J Child Neurol. 1999 Jun;14(6):388-94. Links
Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism.Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN.
Johns Hopkins Hospital, Division of Pediatric Neurology, Baltimore, MD 21212, USA. acomimd@aol.com
Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism; 46% had two or more members with autoimmune disorders. As the number of family members with autoimmune disorders increased from one to three, the risk of autism was greater, with an odds ratio that increased from 1.9 to 5.5, respectively. In mothers and first-degree relatives of autistic children, there were more autoimmune disorders (16% and 21%) as compared to controls (2% and 4%), with odds ratios of 8.8 and 6.0, respectively. The most common autoimmune disorders in both groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus erythematosus. Forty-six percent of the autism group reported having relatives with rheumatoid diseases, as compared to 26% of the controls. Prenatal maternal urinary tract, upper respiratory, and vaginal infections; asphyxia; prematurity, and seizures were more common in the autistic group, although the differences were not significant. Thirty-nine percent of the controls, but only 11% of the autistic, group, reported allergies. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis.

PMID: 10385847 [PubMed - indexed for MEDLINE