RU Human molecular genetics

Unit of Human molecular genetics

Lab of Genetica molecolare

tel. +0512094178

fax +0512094286

Group Leader: Elena Maestrini

E-mail : elena.maestrini@unibo.it

RU maestrini

Research in progress :

- The aim of this project is to identify and characterise genes involved in autism, a severe neuropsychiatric disorder with a strong genetic component, affecting about 0.1-0.3% of the population. Our research group is part of an international consortium (IMGSAC), which collected a large sample of multiplex autism families, and performed genome-wide linkage studies to map autism susceptibility loci, identifying the two best-replicated linkage loci on chromosomes 2q and 7q (AUTS5 and AUTS1). Recently, we have performed a high-density association and Copy-Number Variants (CNVs) analysis in these two linkage loci, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region. This study highlighted two promising candidate genes which may increase risk to autism spectrum disorders (Maestrini et al, 2009). Current research involves the analysis of these candidate genes, in order to explore their potential role in autism susceptibility. We are also investigating the role of rare microdeletion/microduplications identified in individuals with autism through our study, as well as through genome-wide studies currently in progress, such as the Autism Genome Project (AGP). As the neurobiological basis of autism is largely still unknown, the identification of autism susceptibility genes represents an important step towards a better understanding of the disease process, and possibly in defining enviromental influences and gene-enviroment interactions. This will provide new insights for diagnostic and therapeutic approaches.

Funding :

- Telethon- Italy (GGP030227) 2003- 2005 project title: Identification of an autism susceptibility locus on chromosome 2q.

- Italian Ministry of Health March 2001- March 2004 Neurobiological basis of autism, new methods for diagnosis and pharmacological treatment.

- EU FP6. October 2005- Oct 2008. Using European and International populations to identify autism susceptibility loci

- The Simons Foundation and The Nancy Lurie Marks (NLM) Family Foundation. October 2006-March 2010. Identifying and Understanding the Actions of Autism Susceptibility Genes.

Patents :

Selected Publications :

- Maestrini E, Pagnamenta AT, Lamb JA, Bacchelli E, Sykes NH, Sousa I, Toma C, Barnby G, Butler H, Winchester L, Scerri TS, Minopoli F, Reichert J, Cai G, Buxbaum JD, Korvatska O, Schellenberg GD, Dawson G, Bildt AD, Minderaa RB, Mulder EJ, Morris AP, Baile 2009 High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility Mol Psychiatry Epub ahead of print

- Dianne F Newbury, Pamela C Warburton, Natalie Wilson,Elena Bacchelli, Simona Carone, IMGSAC, Janine A Lamb, Elena Maestrini, Emanuela V Volpi, Shehla Mohammed,Gillian Baird & Anthony P Monaco 2009 Mapping of partially overlapping autism susceptibility region individuals affected by developmental communication impairment. Am J Med Genet 149A 588-97

- Asher JE, Lamb JA, Brocklebank D, Cazier JB, Maestrini E, Addis L, Sen M, Baron-Cohen S, Monaco AP. 2009 A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals evidence of linkage to chromosomes 2q24, 5q33, 6p12, and 12p12 Am J Hum Genet 84 279-85

- Ines Sousa, Taane G Clark, Claudio Toma, Kazuhiro Kobayashi, Maja Choma, Richard Holt, Nuala H Sykes, Janine A Lamb, Anthony J Bailey, Agatino Battaglia, Elena Maestrini, Anthony P Monaco, IMGSAC 2008 MET and autism susceptibility: family and case-control studies. Eur J Hum Genet (Epub ahead of print)

- Gong X, Bacchelli E, Blasi F, Toma C, Betancur C, Chaste P, Delorme R, Durand CM, Fauchereau F, Botros HG, Leboyer M, Mouren-Simeoni MC, Nygren G, Anckarsaeter H, Rastam M, Gillberg IC, Gillberg C, Moreno-De-Luca D, Carone S, Nummela I, Rossi M, Battaglia 2008 Analysis of X chromosome inactivation in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet. 5: 830-5.

- Toma C, Rossi M, Sousa I, Blasi F, Bacchelli E, Alen R, Vanhala R, Monaco AP, Jarvela I, Maestrini 2007 Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations. Mol Psychiatry 12:977-9.

- The Autism Genome Project Consortium 2007 Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39:319-28.

- Blasi F, Bacchelli E, Pesaresi G, Carone S, Bailey AJ, Maestrini E., and IMGSAC 2006 Absence of coding mutations in the X-linked genes Neuroligin 3 and Neuroligin 4 in individuals with autism from the IMGSAC collection. Am J Med Genet B, Neuropsychiatr Genet. 141:220-221.

- Bacchelli E, Maestrini E. Autism spectrum disorders: molecular genetic advances. 2006 Autism spectrum disorders: molecular genetic advances. Am. J. Med. Genet. C Semin. Med. Genet. 142(1):13-23.

- Blasi F, Bacchelli E, Carone S, Toma C, Monaco AP, Bailey AJ, Maestrini E and IMGSAC 2006 Association study of SLC25A12 and CMYA3 in autism. Eur J Hum Genet 14: 123-126

- Lamb JA, Barnby G, Bonora E, Sykes N, Bacchelli E, Blasi F, Maestrini E, Broxholme J, Tzenova J, Weeks D, Bailey AJ, Monaco AP; IMGSAC. 2005 Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects. J. Med. Genet. Feb; 42(2):132-7.

- D'Adamo P, Bacchelli E, Blasi F, Lipp HP, Toniolo D, Maestrini E. 2004 DNA variants in the human RAB3A gene are not associated with autism. Genes Brain Behav. 3:123-124

- Bacchelli E, Blasi F, Biondolillo M, Lamb JA, Bonora E, Barnby G, Parr J, Beyer KS, Klauck SM, Poustka A, Bailey AJ, Monaco AP, Maestrini E et al. 2003 Screening of nine candidate genes for autism on chromosome 2q reveals rare non-synonymous variants in the cAMP-GEFII gene. Mol. Psychiatry 8:916-924

RU Maestrini Lab