Sunday, December 21, 2014

Brief Report: Phenotypic Differences and their Relationship to Paternal Age and Gender in Autism Spectrum Disorder.

J Autism Dev Disord. 2014 Dec 20. [Epub ahead of print]
Brief Report: Phenotypic Differences and their Relationship to Paternal Age and Gender in Autism Spectrum Disorder.
Author information


Two modes of inheritance have been proposed in autism spectrum disorder, transmission though pre-existing variants and de novo mutations. Different modes may lead to different symptom expressions in affected individuals. De novo mutations become more likely with advancing paternal age suggesting that paternal age may predict phenotypic differences. To test this possibility we measured IQ, adaptive behavior, and autistic symptoms in 830 probands from simplex families. We conducted multiple linear regression analysis to estimate the predictive value of paternal age, maternal age, and gender on behavioral measures and IQ. We found a differential effect of parental age and sex on repetitive and restricted behaviors. Findings suggest effects of paternal age on phenotypic differences in simplex families with ASD.

Friday, November 07, 2014

[Mutagenic effect of advanced paternal age in neurocardiofaciocutaneous syndrome].

s Lek Cesk. 2014 Fall;153(5):242-5.
[Article in Czech]

Background. Increased frequency of chromosomal aberration in children of mothers aged 35 years and older is very well known and since 1973 it is an indication to investigate the foetal karyotype in cells obtained by invasive method (amniocentesis), because the genetic risk of severe affection is higher than the risk of necessary invasive method. Mutagenic effect of advanced paternal age is known only among geneticists (1-4). The reason is not only low absolute risk of new mutation but particularly a high number of involved genes and last not least the limited spectrum of autosomal dominant disorders without abiotrofic character. Therefore the preventive methods for elimination of this risk are very limited. Only a few of them could be recognized prenatally by noninvasive methods of prenatal diagnostics.Methods. Genealogical, anamnestic and clinical data of 83 patients were studied with clinical suspection on neurocardiofaciocutaneous syndrome (NCFCs) (5-7). The diagnosis has not been confirmed in 29 patients, no mutation was detected in 8 investigated genes (PTPN11, SOS1, HRAS, BRAF, RAF1, MEK1, KRAS, NRAS). In 54 patients with autosomal dominant inherited Noonan syndrome, Costello syndrome and cardiofaciocutaneous syndrome the diagnosis was confirmed on DNA level and the biological fitness was estimated for each disorder. Paternal age at conception was compared in the group of patients with familial and sporadic occurrence of Noonan and NCFC syndromes. The clinical prognosis of this disorder is represented by biological fitness of patients. Coefficient of selection is 0,6 in Noonan and LEOPARD syndromes (29 from 48). All 6 patients with Costello and cardiofaciocutaneous syndromes developed due to a new mutation.Conclusion. Paternal age at birth was studied in 83 children patients with autosomal dominant Neurocardiofaciocutaneous syndrome (Noonan, LEOPARD, Costello, CFC) with a high population incidence and decreased biological fitness. Due to severe congenital heart defects, failure to thrive in infancy, increased risk for malignancy and further health problems the clinical prognosis of patients in the past was not good. Therefore high mutation rate is expected until now. Identification of genes responsible for manifestation of this disorder, enables to confirm the diagnosis and to recognize inherited and de novo mutations. Genealogy and DNA analysis of PTPN11, SOS1, HRAS, BRAF, RAF1, MEK1, KRAS and NRAS were obtained in cohort of 54 patients with NCFC syndromes and their parents. There were 48 patients with Noonan and LEOPARD syndromes, in 29 cases due to mutation de novo, 19 patients inherited the mutation from one of parents. All 6 patients with Costello syndrome and CFC syndrome were affected due to new mutation. DNA analysis revealed 32 mutations in PTPN11 gene, mutation in SOS1 gene was found in 10 patients, RAF1 mutation was present in 3 patients; mutation in MEK1, KRAS and NRAS genes was present in one patient each. In Costello syndrome and CFC syndrome mutations in HRAS (4 patients) and BRAF (2 patients) genes were detected. Genealogic data allow analysing parental age in the group of patients with new mutation and inherited mutation. Paternal age at conception of patients with Noonan syndrome due to new mutation was significantly increased in comparison to the group of fathers of Noonan patients with inherited mutation - 38,4 years and 29,6 years, resp., range 28 to 55 years and 25 to 35 years, resp. Maternal age was slightly increased too, -30,9 and 27,7, resp. and range 24 to 42 years and 21 to 36 years, resp. but not significantly. The results support the mutagenic effect of paternal age, espec. autosomal dominant mutations.

Tuesday, August 05, 2014

Molecular Psychiatry , (5 August 2014) | doi:10.1038/mp.2014.84

Original Article

Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression
M H Milekic, Y Xin, A O’Donnell, K K Kumar, M Bradley-Moore, D Malaspina, H Moore, D Brunner, Y Ge, J Edwards, S Paul, F G Haghighi and J A Gingrich

Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations. Here we test the hypothesis that the integrity of germline DNA methylation is compromised during the aging process. A genome-wide DNA methylation screen comparing sperm from young and old mice revealed a significant loss of methylation in the older mice in regions associated with transcriptional regulation. The offspring of older fathers had reduced exploratory and startle behaviors and exhibited similar brain DNA methylation abnormalities as observed in the paternal sperm. Offspring from old fathers also had transcriptional dysregulation of developmental genes implicated in autism and schizophrenia. Our findings demonstrate that DNA methylation abnormalities arising in the sperm of old fathers are a plausible mechanism to explain some of the risks that APA poses to resulting offspring.

Tuesday, July 22, 2014

[Genetic, environmental, and epigenetic contribution to the susceptibility to autism spectrum disorders].

Rev Neurol. 2013 Dec 16;57(12):556-68.
[Genetic, environmental, and epigenetic contribution to the susceptibility to autism spectrum disorders].
[Article in Spanish]
Author information

Abstractin English, Spanish
Autism spectrum disorders (ASD) are common and complex neuropsychiatric disorders in which multiple factors may contribute to the phenotype.
To review current knowledge about possible risk factors for ASD.
Medline, OMIM and Ensembl databases were searched for possible risk factors, disease and gene information.
There is genetic heterogeneity and probably different modes of transmission in ASD. In addition, many cases are related with non-inherited de novo mutations or uncommon alleles with a large effect. The general heritability in these disorders may be lower than previously reported. Some fraction of it may be explained by relatively common alleles that tend to have a small effect. To some extent, susceptibility alleles may have a different influence on the phenotype depending on other genetic or non-genetic factors. Non-genetic factors in the perinatal and postnatal period, including epigenetics, the age of the father and possibly the age of grandparents at conception may be relevant for ASD. The mechanisms involved in the etiology of ASD may be related with synaptic development and connectivity, neurotransmission, signaling, neuroplasticity, and gene expression. Different methods have contributed to understand the etiology of ASD. Linkage and association studies are not appropriate for ASD cases with de novo mutations with a strong effect. The observed increase in ASD prevalence may be related not only with more awareness, changing diagnostic criteria, and environmental exposures, but also with epigenetic changes, and an increasing number of de novo mutations.
PMID: 24288105 [PubMed - indexed for MEDLINE]

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Saturday, June 14, 2014

Strong male bias drives germline mutation in chimpanzees.

Science. 2014 Jun 13;344(6189):1272-1275. Epub 2014 Jun 12.
Strong male bias drives germline mutation in chimpanzees.
Author information

Germline mutation determines rates of molecular evolution, genetic diversity, and fitness load. In humans, the average point mutation rate is 1.2 × 10-8 per base pair per generation, with every additional year of father's age contributing two mutations across the genome and males contributing three to four times as many mutations as females. To assess whether such patterns are shared with our closest living relatives, we sequenced the genomes of a nine-member pedigree of Western chimpanzees, Pan troglodytes verus. Our results indicate a mutation rate of 1.2 × 10-8 per base pair per generation, but a male contribution seven to eight times that of females and a paternal age effect of three mutations per year of father's age. Thus, mutation rates and patterns differ between closely related species.

Copyright © 2014, American Association for the Advancement of Science.

Thursday, May 22, 2014

Paternal age a determinant of birth success rates with stimulated IUI - Medical News Today

Paternal age a determinant of birth success rates with stimulated IUI - Medical News Today

Wednesday, May 21, 2014

Photographic Proof That Cavities Heal

Photographic Proof That Cavities HealPhotographic Proof That Cavities Heal


The compelling article written by Dr. Judene Smith DDS recently about how cavities heal really brought out the conventional dentists in droves! It has been awhile since I had to delete so many nasty, insulting, even threatening comments from a single blog post!
A sad testament indeed to how closed-minded and condescending a large portion of the dental community can be even toward one of its own.
The truth is that cavities can heal and the vehement denial by conventional dentists who react in a defensive manner (as if they have all the answers) does not change this fact one iota.
To drive another nail in the coffin of the notion that cavities must be filled and can’t remineralize and heal on their own, I am presenting a series of photographs sent to me by Rami Nagel, author of the paradigm shattering book Cure Tooth Decay.
The photos are of an 18 month old child from Baton Rouge, Louisiana.  Rikki, the boy’s mother, took these photos as her son’s cavities remineralized over a period of 8 weeks after commencing a dietary program which included supplementing with fermented cod liver oil and high vitamin butter oil.  It is important to note that regular cod liver oil will not produce the same spectacular results you see in these photos.
The sad truth is that when a parent brings in a child with significant tooth decay, toxic, IQ lowering fluoride treatments, drilling/filling or even crowns and root canals are recommended on baby teeth!  These treatments which can be incredibly expensive are not necessary as in a majority of cases, children’s teeth will quickly remineralize with dietary intervention. Adult teeth with cavities will heal in similar fashion as long as they have never been drilled or compromised by dental treatments in the past.
What Did This Child Eat That Caused These Cavities?
Possibly the most shocking thing about this story is that this toddler was not eating a junk food diet when these cavities formed.  He was still breastfeeding and eating an all-organic diet.  His favorite foods consisted of graham crackers and flaxseed bread.  He also was fond of organic granola bars which he ate regularly.
The problem with store bought whole grain products is that they are high in anti-nutrients like phytic acid that block mineral absorption. These foods are not a good choice for regular consumption by growing children.
Rikki’s son also ate fruits and vegetables and organic eggs although his mother avoided butter and milk thinking they were bad for him. After reading Cure Tooth Decay, she realized that butter and milk from grassfed cows are very healing and strengthening for teeth and bones. Grassfed dairy also counteracts some (but not all) of the negative effects of the toxins and anti-nutrients in processed grain products from the store.
Foods That Healed this Child’s Teeth
Rikki implemented 4 major changes to her son’s diet in order to achieve the results you see below.
  1. She cut out grains and sugars. This reduced the mineral depletion from the commercial grains and sugar.
  2. She started giving him Green Pasture’s Royal Blend (a combination product of blended fermented cod liver oil and butter oil) which gave her son the needed fat-soluble vitamins to remineralize his teeth.
  3. Her son now gets raw milk and raw milk cheese regularly along with fermented vegetables like pickles.
  4. Their family now uses butter liberally, and Rikki makes homemade broths and soups from pasture raised chicken.
Unfortunately, the earliest picture is of the teeth after 1 week on the new dietary protocol described in Cure Tooth Decay.  There wasn’t a control picture available of what the cavities looked like before any changes were made. Even still, the visual healing that takes place is compelling and should give every parent hope that cavity problems can be dealt with at home with simple dietary changes in the majority of cases.
Will these dietary interventions be easy? Most definitely not if a conventional diet is being followed. For those already eating a whole foods based diet in their home, the changes are much easier to accomplish. Far and away the most difficult change to implement for cavity prone children especially if they attend school is eliminating the processed grain based foods.
What do you think of these photos?  Do they finally put to bed the repeated denials from conventional dentists that cavities don’t heal and must be filled?
*These photographs were used with Mr. Nagel’s permission (source).

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Turns Out Coconut Oil Has A Major Dark Side

Turns Out Coconut Oil Has A Major Dark Side