CALIFORNIA ENVIRONMENTAL PROTECTION AGENCY

In the summer and fall of 2006, the Department of Pesticide Regulation (DPR) sampled water and sediment from 23 marinas to assess the geographical scope and severity of pollution stemming from the use of antifouling paint (AFP) pesticides in California. Copper, zinc, Irgarol, M1 (the primary breakdown product of Irgarol), and aquatic toxicity were selected as potential indicators of AFP pollution. The highest dissolved copper concentrations were observed in larger salt water marinas along California’s Central and South Coast, the lowest were seen in freshwater lake marinas. Copper and zinc concentrations were almost always higher in the marinas than in the adjacent local reference sites, indicating that significant sources of metals existed in the marinas. Concentrations of zinc never exceeded California’s water quality standards. In contrast, concentrations of dissolved copper in salt and brackish water marinas were frequently above California water quality standards established for the protection of aquatic life. Developmental toxicity tests on the copper-sensitive embryo of the mussel Mytilus galloprovincialis were conducted on 47 marina water samples. Eight of these samples showed a statistically significant toxic response and copper was the likely cause of the toxicity. Several copper toxicity models that account for copper bioavailability to aquatic organisms were used to predict toxicity for the 517 samples for which sitespecifi

Exonic deletions in AUTS2 cause a syndromic form of intellectual disability and suggest a critical role for the C terminus.

Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3'AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future