Autism is a neurodevelopmental disorder showing a striking sex bias with a male:female ratio of 4:1. Despite some genetic variants have been identified as responsible for autism in about 17% of cases, its etiology is still largely unknown. Increasing evidences highlight the possible role of environmental factors, such as infections, xenobiotics and drugs in enhancing autism genetic susceptibility. Among genetic variants, we focused on the X-linked neuroligin genes NLGN-3 and NLGN-4X that are involved in synaptic plasticity, are mutated in a few number of autistic patients, and because males are hemizygous for the X-chromosome. Here we analyzed NLGN-3 and NLGN-4X in 52 Italian autistic cases (male:female=4,6:1) and in 31 healthy siblings (male:female=1:1,1) by Sanger sequencing. Among the other variants, we found that 3 SNPS give 2 different haplotypes, one of which already described in a non specific mental retardation Chinese group, in the 3'UTR of NLGN-4X. Both haplotypes have statistical significance in autistics comparing to the minor allele frequencies (MAF) from the 1000 Genomes Project CEU. Interestingly, healthy siblings, half of which were female, have a middle statistical significance between autistics and MAF-CEU. In NLGN-3, we found 3 already described intronic SNPS giving an halplotype, correlated with autism. As these SNPs map to non-coding regions, they could be involved in the genetic susceptibility to trigging environmental factors (lacking in the siblings), and, being located on X-chromosome, could explain the male prevalence of autism. AKNOWLEDGEMENTS: Italian Ministry of Health "GR-2009-1570296", Italian Ministry of Education, University and Research "InterOmics" Flagship projects.
Three SNP aplotypes in neuroligins may correlate to autism susceptibility
Landini M;Mezzelani A;Merelli I;Milanesi L
2014
Abstract
Autism is a neurodevelopmental disorder showing a striking sex bias with a male:female ratio of 4:1. Despite some genetic variants have been identified as responsible for autism in about 17% of cases, its etiology is still largely unknown. Increasing evidences highlight the possible role of environmental factors, such as infections, xenobiotics and drugs in enhancing autism genetic susceptibility. Among genetic variants, we focused on the X-linked neuroligin genes NLGN-3 and NLGN-4X that are involved in synaptic plasticity, are mutated in a few number of autistic patients, and because males are hemizygous for the X-chromosome. Here we analyzed NLGN-3 and NLGN-4X in 52 Italian autistic cases (male:female=4,6:1) and in 31 healthy siblings (male:female=1:1,1) by Sanger sequencing. Among the other variants, we found that 3 SNPS give 2 different haplotypes, one of which already described in a non specific mental retardation Chinese group, in the 3'UTR of NLGN-4X. Both haplotypes have statistical significance in autistics comparing to the minor allele frequencies (MAF) from the 1000 Genomes Project CEU. Interestingly, healthy siblings, half of which were female, have a middle statistical significance between autistics and MAF-CEU. In NLGN-3, we found 3 already described intronic SNPS giving an halplotype, correlated with autism. As these SNPs map to non-coding regions, they could be involved in the genetic susceptibility to trigging environmental factors (lacking in the siblings), and, being located on X-chromosome, could explain the male prevalence of autism. AKNOWLEDGEMENTS: Italian Ministry of Health "GR-2009-1570296", Italian Ministry of Education, University and Research "InterOmics" Flagship projects.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
