Developmental problems: Some exist in the genes
Philadelphia, PA, 17 August 2010 - Everyone is special in their own unique way. From a genetic point of view, no two humans are genetically identical. This means that DNA for each individual contains variants that are more or less comm. on in the overall population.
Some gene variations are actually genetic deletions, where sections of DNA ‘code’ are missing entirely. These variants are likely to have important effects on gene function and, therefore, likely to contribute to diseases associated with that gene. But what happens when multiple genes are disrupted in a single family?
A large collaborative study led by scientists based in Oxford, Bologna and Utrecht sheds some light on this complicated situation by describing the genomic characterization of a family with two rare microdeletions, in CNTNAP5 and DOCK4. Multiple members of this family were diagnosed with autism, dyslexia, and/or learning or social difficulties.
The genetic analysis revealed that the CNTNAP5 deletionsegregated with autism. In contrast, the DOCK4 deletion was present in multiple individuals without autism, but this gene microdeletion co-segregated with reading difficulties.
“This report provides further evidence linking CNTNAP geneswith autism, one of the most promising gene families in autism research,” commented Dr. John Krystal, Editor of Biological Psychiatry, where this research is published. “But it also highlights how complex the connection between genes and syndromes can be, supporting the importance of DOCK4 for brain development – particularly in circuits involved in reading- but questioning its role in autism.”
"This is another example of the emerging theme whereby multiple rare genomic variants within a single family might, in combination, lead to the variable phenotypes associated with autism spectrum disorders," said first author Dr. Alistair Pagnamenta.
Interestingly, CNTNAP5 is closely related to other genes that can influence susceptibility to autism, such as CNTNAP2, which was first identified in 2008. DOCK4 is thought to be involved in the growth and development of nerve cells in the brain. Together, these results may open up new lines of research to help understand mechanisms behind neurological disorders and brain development.
The authors have noted that additional studies, which are needed to confirm these associations, are already underway.
Notes for editors
The article is “Characterization of a Family with Rare Deletions in CNTNAP5 and DOCK4 Suggests Novel Risk Loci for Autism and Dyslexia” by Alistair T. Pagnamenta, Elena Bacchelli, Maretha V. de Jonge, Ghazala Mirza, Thomas S. Scerri, Fiorella Minopoli, Andreas Chiocchetti, Kerstin U. Ludwig, Per Hoffmann, Silvia Paracchini, Ernesto Lowy, Denise H. Harold, Jade A. Chapman, Sabine M. Klauck, Fritz Poustka, Renske H. Houben, Wouter G. Staal, Roel A. Ophoff, Michael C. O’Donovan, Julie Williams, Markus M. Nöthen, Gerd Schulte-Körne, Panos Deloukas, Jiannis Ragoussis, Anthony J. Bailey, Elena Maestrini, Anthony P. Monaco, and the International Molecular Genetic Study Of Autism Consortium. The article appears in Biological Psychiatry, Volume 68, Issue 4 (August 15, 2010), published by Elsevier.
The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.
Full text of the article mentioned above is available upon request. Contact Maureen Hunter at email@example.com to obtain a copy or to schedule an interview
About Biological Psychiatry
This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.
Biological Psychiatry is ranked 4th out of 117 Psychiatry titles and 13th out of 230 Neurosciences titles in the 2009 ISI Journal Citations Reports® published by Thomson Reuters. The 2009 Impact Factor score for Biological Psychiatry has increased to 8.926.
Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we’re committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. www.elsevier.com
Strategic Marketing Manager - Elsevier