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Fully understanding the genetic factors involved in Autism Spectrum Disorder (ASD) requires whole-genome sequencing (WGS), which theoretically allows the detection of all types of genetic variants. With the aim of generating an unprecedented resource for resolving the genomic architecture underlying ASD, we analyzed genome sequences and phenotypic data from 5,100 individuals with ASD and 6,212 additional parents and siblings (total n=11,312) in the Autism Speaks MSSNG Project, as well as additional individuals from other WGS cohorts. WGS data and autism phenotyping were based on high-quality short-read sequencing (>30x coverage) and clinically accepted diagnostic measures for ASD, respectively. For initial discovery of ASD-associated genes, we used exonic sequence-level variants from MSSNG as well as whole-exome sequencing-based ASD data from SPARK and the Autism Sequencing Consortium (>18,000 trios plus additional cases and controls), identifying 135 ASD-associated protein-coding genes with false discovery rate SCN2A and a nuclear mitochondrial insertion impacting SYNGAP1. Polygenic risk scores did not differ between children with ASD in multiplex families versus simplex, and rare, damaging recessive events were significantly depleted in multiplex families, collectively suggesting that rare, dominant variation plays a predominant role in multiplex ASD. Our study provides a guidebook for exploring genotype-phenotype correlations in the 15-20% of ASD families who carry ASD-associated rare variants, as well as an entry point to the larger and more diverse studies that will be required to dissect the etiology in the >80% of the ASD population that remains idiopathic. All data resulting from this study are available to the medical genomics research community in an open but protected manner.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

The tremendous impact that Serge Diaghilev's Ballets Russes made on twentieth-century western arts has been well documented by scholars. Rarely has a theatre art made such an impact on society. And this influence spread beyond theatre directors, composers, costume designers, artists and performers to literature. Diaghilev caught the attention of such writers as Marcel Proust, James Joyce, Jean Cocteau, the Sitwells, Leonard Woolf, indeed, the Bloomsbury group in general, T. S. Eliot, Rupert Brooke, E. M. Forster, and, of course, D. H. Lawrence, too. While this has all been noted in biographies and memoirs, few scholars have considered the possible reasons behind the company's creation. Why would a man who had aligned himself with sumptuous and highly successful art exhibitions and demonstrated such strong passion for opera turn to ballet? Any attempt to answer such a question requires an exploration of the events in Diaghilev's life from his St. Petersburg years to the Paris years and early seasons of the Ballets Russes (1895–1913). Two names recur throughout these years: Oscar Wilde and Aubrey Beardsley – in person, in writing, and in spirit. A review of Diaghilev's career between 1895 and 1913 together with a textual study of some early ballets suggest that Wilde and Beardsley may have had a stronger influence on Diaghilev and the creation of the Ballets Russes than has previously been noticed.

In the course of his career, James Macdonald has directed a vast array of plays and operas in London, New York, Vienna, and Berlin, but he is perhaps best known for the premiere productions of Sarah Kane's Blasted, Cleansed, and 4.48 Psychosis at the Royal Court Theatre, where he was an Associate Director from 1992 to 2006. His most recent work includes Peter Handke's The Hour We Knew Nothing of Each Other at the National Theatre and the Broadway revival of Caryl Churchill's Top Girls. Macdonald met with R. Darren Gobert in London on 23 January 2006 to discuss the challenges of working with spare, difficult plays such as Kane's, Churchill's A Number, and Martin Crimp's Fewer Emergencies. R. Darren Gobert wishes to thank Annabel Rutherford for transcribing the conversation and, for their funding, the Faculty of Arts Committee on Research, Grants, and Scholarships at York University.