Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Reliability Properties of Solderable Conductive Adhesives with Low-Melting-Point Alloy Fillers

A solderable conductive adhesive (SCA) using low-melting-point alloy (LMPA) filler was developed to overcome the limitations of conventional electrically conductive adhesives (ECAs), which include their low electrical conductivity, increased contact resistance, and low joint strength. The SCA formed good metallurgical conduction path between the corresponding electrodes due to the rheology-coalescence-wetting behaviors of molten LMPA fillers in SCA. This study examined the reliability of SCA assembly through the thermal shock test (218 to 398K, 1000 cycles) and the high temperature and high humidity test (358K/85%RH, 1000 h). The electrical resistance of the SCA assembly with metallurgical interconnections was much more stable than those with conventional ICAs. Before the reliability tests, a scallop-type Cu6Sn5 (©-phase) intermetallic compound (IMC) layer was formed on the Sn-plated Cu lead/LMPA and LMPA/Cu metallization interface based on the results of interfacial microstructure observations of quad flat packages (QFPs) that were assembled with SCA. After the reliability tests, the thickness of IMC layer increased with time, and Cu6Sn5 (©-phase) and Cu3Sn (-phase) were formed. In addition, the fracture surface exhibited a cleavage fracture mode with the fracture propagating along the CuSn IMC/SnBi interface. These results demonstrate that SCA assembly with metallurgical interconnection has stable electrical and mechanical bonding characteristics. [doi:10.2320/matertrans.MB201207

Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism