PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.

Summary: PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers.

Genomic atlas of the human plasma proteome.

Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins.

PhenoScanner: a database of human genotype-phenotype associations.

Unlabelled: PhenoScanner is a curated database of publicly available results from large-scale genetic association studies. This tool aims to facilitate 'phenome scans', the cross-referencing of genetic variants with many phenotypes, to help aid understanding of disease pathways and biology. The database currently contains over 350 million association results and over 10 million unique genetic variants, mostly single nucleotide polymorphisms.

A Role for Non-B DNA Forming Sequences in Mediating Microlesions Causing Human Inherited Disease.

Missense/nonsense mutations and microdeletions/microinsertions (<21 bp) represent ∼ 76% of all mutations causing human inherited disease, and their occurrence has been associated with sequence motifs (direct, inverted, and mirror repeats; G-quartets) capable of adopting non-B DNA structures. We found that a significant proportion (∼ 21%) of both microdeletions and microinsertions occur within direct repeats, and are explicable by slipped misalignment. A novel mutational mechanism, DNA triplex formation followed by DNA repair, may explain ∼ 5% of microdeletions and microinsertions at mirror repeats.

Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD.

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation.