Ph.D. Program in Cellular, Molecular and Industrial Biology (Project n. 1: Physiology and Cellular Biology)
Molecular genetic study of Autism. The aim of this project is to identify and characterize genes involved in autism and other Autism Spectrum Disorders (ASD), a group of conditions characterised by impairments in communication, social deficits and restricted or repetitive behaviours. Twin and family studies have provided convincing evidence for the involvement of genetic factors in the development of ASD, although it is clear that these genetic influences are complex: autism is likely to result from the combined effect of several susceptibility alleles, possibly interacting with environmental factors. The absence of consistent evidence for any specific environmental, biochemical or neuroanatomical cause has led to an increasing number of genetic studies worldwide to determine the basis of this disorder. 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. We have identified a number of chromosomal regions with evidence of linkage, which are currently being further investigated. Our group is focussing on a region on chromosome 2q, using a combination of candidate gene approaches and linkage disequilibrium mapping. This region provided the strongest linkage result in the IMGSAC study, with additional from overlapping linkage findings in independent genome scans. However, the identification of the causative gene still represents a challenging task, as the linkage peak remains very broad, spanning approximately 40 Mb and containing about two hundred known genes. In order to isolate the susceptibility variant(s) at this locus we have carried out systematic screening of several positional candidate genes, having a plausible role in brain development or function. To date, these studies have failed to conclusively identify any etiological variants. Recent technological advances, the availability of millions of SNPs from public databases and the generation of whole genome haplotype maps, are now enabling more systematic investigation of candidate genes through linkage disequilibrium mapping using high-density SNPs. In collaboration with the team lead by Prof AP Monaco at the Wellcome Trust Centre for Human Genetics in Oxford, we are currently carrying out a high-density genotyping and association study of all the ~200 genes localized in the 40Mb region of interest on chromosome 2. This strategy will allow us to comprehensively investigate the large majority of genetic variation existing at these genes in our sample of autism families, in order to identify susceptibility variants.
Research Group
Fiorella Minopoli (PhD student)
Elena Bacchelli (Postdoc)
Paola Poggi (undergraduate student)
Elena Maestrini (Associate professor)
