Autism: from genetics to biomarkers.

Abstract

The development of biomarkers for psychiatric disorders is particularly challenging, given the frequent clinical heterogeneity, and the subjective nature of symptoms which requires finely tuned quantification methods for accurate diagnosis. Yet the more clinically heterogeneous a disease, the more valuable becomes an objective measure of disease state or severity. While identifying biological markers for psychiatric disorders has thus far remained out of reach, groundbreaking progress in DNA sequencing technologies and the completed human genome sequence have set the foundation for a novel perspective on clinical care, which also brings promising new approaches for biomarker discovery. The aim of genomic medicine [1] is to take advantage of the wealth of information encoded in an individual’s genome regarding their disease risk and potential responses to therapy. For diseases having significant contribution of genetic factors, the possibility to quantify genetic variation with enough depth is expected to lead to the development of effective markers of disease risk. This special issue of Disease Markers is dedicated to autism spectrum disorders (ASD) and discusses the current understanding of ASD genetics, as well as the possibilities of translating genetic research toward biomarker development in ASD. ASD are a spectrum of neurodevelopmental conditions characterized by language deficits, dysfunctions of social-reciprocal interactions and repetitiverestrictive behaviors. The clinical manifestations of autism are highly variable, both between individuals, and along an individual’s developmental trajectory. Although some individualswith ASD are highly functional, many are severely impaired and require permanent care. The significant level of impairment combined with the fact that no specific therapy is yet available for ASD, make ASD a devastating illness for patients and families, and a heavy financial burden for the healthcare system. The most effective intervention for ASD has proven to be early behavioral therapy [2]. Thus the identification of biological markers for ASD, allowing very early detection, even before the onset of symptoms, would be of tremendous value At the same time, one of the most well established characteristics of ASD is it’s high heritability, and significant research efforts have been geared toward understanding the genetic basis of autism. Thefield ofASD genetic research is still far from fully elucidating the mechanisms that govern ASD heritability, but the last two decades have undoubtedly brought about remarkable progress. Currently it is believed that both common genetic variation and rare DNA sequence variants contribute to the ASD genetic susceptibility [3], and that the relative contribution of common and rare alleles is variable among ASD cases. In the first article of this issue, “Mutant mouse models of autism spectrum disorders”, Yuri Bozzi and colleagues review the phenotypic characteristics of currently available mouse models of ASD as well as the contribution of mouse models toward the development of pharmacological therapy for ASD. Of particular importance for dissecting out the cellular and molecular mechanisms of ASD are several genes that have been identified as causes of genetic syndromes with a high incidence of ASD (FMR1, the gene mutated in fragile X syndrome, TSC1/TSC2, the genes responsible for tuberous sclerosis and NF1, the gene implicated in neurofibromatosis are just a few examples). Despite the