Jonathan Sebat Is Sporadic Autism Not Related to Increasing Paternal Age???

Summary for 2007 [at-glance overview of Jonathan Sebat work for the selected year as suggested by data mining algorithms]
This is an Authoratory overview of author Jonathan Sebat. According to available data, in 2007 Jonathan Sebat published at least 4 articles. This work was completed in collaboration with several authors including Geschwind, Daniel H and Ye, Kenny. Many other authors have collaborated with Jonathan Sebat as well. At least 2 different grants are awarded to Jonathan Sebat to support this work. All time total of the grant awards on file exceeds $1,703,066.

Jonathan Sebat has rank 235 when compared to all other authors using the keyword Genome, Human. Analysis of the article abstracts and the titles suggests that Jonathan Sebat professional interests are focused around "de novo copy", "novo copy number" and "theory sporadic inherited". These might also be referred to as "de novo", "major changes" or "copy number". Statistical analysis shows that Jonathan Sebat's writing is likely to contains terms "autism", "genetic", "novo", "de", "risk" and "families".

The majority of Jonathan Sebat articles are affiliated with Cold Spring Harbor Laboratory, One 1 Bungtown Road, Cold Spring Harbor, New York NY 11724, USA. Luckily, one email address is on file.

Researchers find high rates of copy number mutations in non-heritable forms of autism

http://www.the-scientist.com/news/home/52940/



Most of the mutations seen in the autistic children overall were deletions.


who said that human bodies are "less tolerant" of deletions. "When you're down to only your back-up copy for a gene, you're at greater risk for whatever minor defects may exist in that that gene." said Jonathan Sebat


-------------------------------------------------------------------------------------Increased paternal age and deletions are connected in the area of genetics known as point mutations.
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Copy number linked to autismResearchers find high rates of copy number mutations in non-heritable forms of autism

[Published 15th March 2007 06:02 PM GMT]


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Copy number variation could be an important factor in autism, according to a new study published in Science today (March 15).

The largest percentage of copy number mutations occurred in families with one autistic child, the so-called sporadic, or spontaneously occurring cases -- not in families with multiple autistic children, indicating genetic inheritance.

Autism and Paternal Age

Paul Law, Jonathan Sebat, Michael Wigler, Clara Lajonchere, etc. know it is the older father that transmits the muated genes for autism. They will never tell the public the connection.


The full citation of the paper published in the July 31, 2007 print edition of the Proceedings of the National Academy of Sciences is: "A unified theory for sporadic and inherited autism," by Xiaoyue Zhao, Anthony Leotta, Vlad Kustanovich, Clara Lajonchere, Daniel H. Geschwind, Kiely Law, Paul Law, Shanping Qiu, Catherine Lord, Jonathan Sebat, Kenny Ye and Michael Wigler.


Finally, we examined if paternal age was related to the risk for autism in our cohort. We found very strong effects of advancing paternal age on the risk for autism and related pervasive developmental disorders (Reichenberg et al., in press). Compared to the offspring of fathers aged 30 years or younger, the risk was tripled for offspring of fathers in their forties and was increased fivefold when paternal age was >50 years. Together, these studies provide strong and convergent support for the hypothesis that later paternal age can influence neural functioning. The translational animal model offers the opportunity to identify candidate genes and epigenetic mechanisms that may explain the association of cognitive functioning with advancing paternal age.

BACK TO THE SUBJECT OF COPY NUMBER VARIATIONS IN SPORADIC AUTISM IN 10% OF THE OFFSPRING IN SEBAT AND WIGLER'S STUDY? IS IT DAD'S SPERM?

Genomics & Proteomics
Advantage Business Media





We tested the hypothesis that de novo copy number variation (CNV) is associated with autism
spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the
genomic DNA of patients and unaffected subjects to detect copy number variants not present in
their respective parents. Candidate genomic regions were validated by higher-resolution CGH,
paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping.
Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were
identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients
with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs
were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous
and included mutations of single genes. These findings establish de novo germline mutation as a
more significant risk factor for ASD than previously recognized.

Will Researchers Look For Copy Number Variations in the Sperm Making Cells of Fathers of children with CNVs?

The groundbreaking research finding CNVs in some children with sporadic autism has been published. Will the researchers look at the sperm and spermatagonia of the fathers of these children along with all the other fathers and control group?


67.

Vorstman JAS, Staal WG, van DE, van EH, Hochstenbach PFR,
Franke L: Identification of novel autism candidate regions
through analysis of reported cytogenetic abnormalities
associated with autism. Mol Psychiatry 2006, 11:18-28.
This paper summarized chromosome regions known to be associated
with autism phenotype. 15q11.2, 2qter and 22qter represent the most
frequent loci.
68.

Jacquemont M-L, Sanlaville D, Redon R, Raoul O,
Cormier-Daire V, Lyonnet S, Amiel J, Le MM, Heron D,
De Blois M-C et al.: Array- based comparative genomic
hybridization identifies high frequency of cryptic
chromosomal rearrangements in patients with syndromic
autism spectrum disorders. J Med Genet 2006, 43:843-849.
The authors used 1 Mb array CGH to screen 29 patients with autism
spectrum disorders and identified eight clinically relevant genomic rearrangements.
69.

Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T,
Yamrom B, Yamron B, Yoon S, Krasnitz A et al.: Strong
association of de novo copy number mutations with autism.
Science 2007, in press.
The application of a genome-wide array CGH with 85 000 oligonucleotide
probes (ROMA) (see [27]) in 165 families with autism showed a statistically
significant association of de novo CNV.