Abstract
BackgroundIndividuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated.ResultsWe genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies.ConclusionsThese findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.
Highlights
Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities
Williams syndrome represents a paradigmatic neurogenetic condition for such analyses, as it is caused by hemizygous deletion of about 25 genes at 7q11.23, and its social cognitive-behavioral profile has been thoroughly characterized as involving hypersociality and low social anxiety with high, nonselective friendliness, expressive language relatively well-developed but social-communication skills reduced overall, high levels of non-social anxiety, and notably-reduced visual-spatial abilities [1,2,3,4,5,6,7]
* Correspondence: crespi@sfu.ca 1Department of Biology, Simon Fraser University, 8888 University Drive, Burnaby V5A 1S6, BC, Canada Full list of author information is available at the end of the article. In contrast to these effects of gene deletion in Williams syndrome, duplication of the same set of genes has been associated with a directly-contrasting cognitive-behavioral profile of selectively-underdeveloped expressive language and high levels of separation anxiety [8,9,10]. These findings suggest the presence of dosage-sensitive genes in the Williams-syndrome region that affect anxiety, language and social behavior in two opposite directions, in individuals with this syndrome as well as in healthy populations
Summary
Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Williams syndrome represents a paradigmatic neurogenetic condition for such analyses, as it is caused by hemizygous deletion (loss of one copy, from the normal diploid complement of two copies) of about 25 genes at 7q11.23, and its social cognitive-behavioral profile has been thoroughly characterized as involving hypersociality and low social anxiety with high, nonselective friendliness, expressive language relatively well-developed but social-communication skills reduced overall, high levels of non-social anxiety, and notably-reduced visual-spatial abilities [1,2,3,4,5,6,7] In contrast to these effects of gene deletion in Williams syndrome, duplication of the same set of genes has been associated with a directly-contrasting cognitive-behavioral profile of selectively-underdeveloped expressive language and high levels of separation anxiety [8,9,10]. Variable-sized deletions have been generated in mouse models, which have implicated the region including GTF2I, GTF2IRD1, LIMK1, and intervening genes, in sociality and anxiety phenotypes [16]
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