Assessment of de novo copy-number variations in Italian patients with schizophrenia: Detection of putative mutations involving regulatory enhancer elements

The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry
Giulio PilusoItalian Network for Research on Psychoses

Abstract

Variants appearing de novo in genes regulating key neurodevelopmental processes and/or in non-coding cis-regulatory elements (CREs), as enhancers, may increase the risk for schizophrenia. However, CREs involvement in schizophrenia needs to be explored more deeply. We investigated de novo copy-number variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of schizophrenia probands by using the Enhancer Chip, a customised array CGH able to investigate the whole genome with a 300-kb resolution, specific disease loci at a ten-fold higher resolution, and which was highly enriched in probes in more than 1,250 enhancer elements selected from Vista Enhancer Browser. In seven patients, we found de novo CNVs, two of which overlapped VISTA enhancer elements. De novo CNVs encompass genes (CNTNAP2, MAGI1, TSPAN7 and MET) involved in brain development, while that involving the enhancer element hs1043, also includes ZIC1, which plays a role in neural development and is responsible of behavioural abnormalities in Zic mutant mice. These findings provide further evidence for the involvement of de novo CNVs in the pathogenesis of schizophrenia and suggest that CNVs affecting regulatory enhancer elements could contribute to the ge...Continue Reading

References

Jan 1, 1987·Schizophrenia Bulletin·S R KayL A Opler
Aug 1, 1995·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A C LahtiC A Tamminga
Dec 31, 1997·The Journal of Biological Chemistry·M CostacheR Mollicone
Jul 8, 1999·Experimental and Clinical Immunogenetics·S YazawaN Kochibe
Oct 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alessandro IeraciCarola Ponzetto
Sep 5, 2003·The Journal of Pharmacology and Experimental Therapeutics·Yoshihiro TaharaHirohito Tsubouchi
Oct 18, 2003·Science·Marcelo A NobregaEdward M Rubin
Dec 19, 2003·Nucleic Acids Research·Axel ViselGregor Eichele
Dec 20, 2003·Nature Reviews. Molecular Cell Biology·Carmen BirchmeierGeorge F Vande Woude
May 8, 2004·Science·Gill BejeranoDavid Haussler
Jun 23, 2004·Molecular and Cellular Neurosciences·Jun Aruga
Sep 24, 2004·Physiological Reviews·Alex W CohenMichael P Lisanti
Nov 24, 2004·Molecular and Cellular Neurosciences·Junko IidaYutaka Hata
Jun 29, 2005·The International Journal of Neuropsychopharmacology·Albert ChetcutiPeter R Schofield
Mar 31, 2006·The New England Journal of Medicine·Kevin A StraussD Holmes Morton
Nov 7, 2006·Nature·Len A PennacchioEdward M Rubin
Nov 30, 2006·Nucleic Acids Research·Axel ViselLen A Pennacchio
Jul 25, 2007·Molecular Psychiatry·J I FriedmanJ A Veltman
Jan 4, 2008·The American Journal of Psychiatry·Robert S KernStephen R Marder
Jan 4, 2008·The American Journal of Psychiatry·Keith H NuechterleinStephen R Marder
Jan 9, 2008·American Journal of Human Genetics·Maricela AlarcónDaniel H Geschwind
Aug 1, 2008·Nature·UNKNOWN International Schizophrenia Consortium
Aug 7, 2008·Journal of Neuroscience Research·Sujatha NarayanElizabeth A Thomas
Dec 26, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ido HorreshElior Peles
Jan 19, 2010·The American Journal of Psychiatry·Katherine E BurdickAnil K Malhotra
Aug 10, 2010·American Journal of Human Genetics·Jennifer Gladys MulleStephen T Warren
Jan 5, 2011·PloS One·Brian P HeadHemal H Patel
Jan 21, 2011·PloS One·Dandan ZhangChunyu Liu
Apr 19, 2011·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Chan-Ying ZhengRonald S Petralia
Jul 12, 2011·Nature Genetics·Simon L GirardGuy A Rouleau
Aug 9, 2011·Nature Genetics·Bin XuMaria Karayiorgou
Aug 16, 2011·Nature Genetics·Gregory M CooperEvan E Eichler
Dec 27, 2011·Neuron·Dheeraj MalhotraJonathan Sebat
Mar 3, 2012·Biological Psychiatry·Robert KarlssonSilvia Paddock

❮ Previous
Next ❯

Citations

Mar 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kerri D PryceArin Bhattacharjee
Aug 17, 2019·Frontiers in Cellular Neuroscience·Elena PerenthalerTahsin Stefan Barakat
Jun 20, 2019·Frontiers in Molecular Neuroscience·Liang QuYuan Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.