Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci

Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1). Through analysis of de novo mutations in autism spectrum disorder (ASD), Sanders et al. find that small deletions, but not large deletions/duplications, contain one critical gene. Combining CNV and sequencing data, they identify 6 loci and 65 genes associated with ASD. © 2015 Elsevier Inc

Direct evidence for partial target specificity in lymphokine-activated killer thymocytes

Thymocytes were removed from mice at different times before and after birth, and their phenotype and killing repertoire were analysed after stimulation with human recombinant interleukin 2 (IL-2). Whereas three different tumour targets were killed by all lymphokine-activated killer (LAK) populations tested. EL4 lymphoma cells were only killed by LAK cells derived from thymocytes after, but not before, birth. Cold-target competition tests showed that LAK thymocytes recognized antigenic structures on EL4 cells that arc different from those on other tumour targets. Analysis of EL4 target killing after removal of different subsets from LAK cells revealed that the major part of this killing is exerted by CD8+ cells. Our findings are additional and more direct evidence for partial target specificity in LAK cells