Objectives: This study aimed to identify risk alleles in families with more than one child with ASDs in a sample of Italian families, living in an island in the south of Italy (Sardinia) with high level of genetic homogeneity, by employing a genome-wide association methodology.
Methods: For the present study we selected 8 families, each one with two children affected by idiopatic autism. We realized a genome-wide association study (GWAS) and a copy number variant (CNV) analysis by the means of whole-genome genotyping arrays HumanOmni1-Quad. Specifically, we purified genomic DNA by salting out extraction from blood samples of patients and their parents. Samples concentration was evaluated by absorbance (Nanodrop 1000) and fluorometric reading (Pico-green/Qubit). Each sample was genotyped using commercial chip, that interrogate more than a million points in the genome, including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs).
Results: Our analysis revealed genomic variations at the level of recurrent CNVs. In particular, some do not seem to co-segregate with the trait of interest. On the contrary, a CNV mapping on chromosome 17q12, shows, in approximately 30% of patients analyzed, only one copy of genomic DNA. This is a region extending from 1.5 to 3.3 Mb, in the different patients. The region contains the following genes: TBC1D3B, CCL3L1, TBC1D3C, CCL3L3, CCL4L1, TBC1D3H, TBC1D3C, TBC1D3G. The TBC family of genes encodes for proteins involved in RAB GTPase signaling and vesicle trafficking; the CCL family of genes encodes for cytokines, secreted proteins involved in immunoregulatory and inflammatory.
Conclusions: These preliminary results are suggestive of interesting developments but need to be replicated in a larger sample, in which we would endeavor to confirm the results highlighted by the chip, by real-time PCR. Moreover, it might be of interest to evaluate the possible genotype correlations identified through the present study.
See more of: Genetic Factors in ASD
See more of: Biological Mechanisms