GORpipe: a query tool for working with sequence data based on a Genomic Ordered Relational (GOR) architecture.

MOTIVATION: Our aim was to create a general-purpose relational data format and analysis tools to provide an efficient and coherent framework for working with large volumes of DNA sequence data. RESULTS: For this purpose we developed the GORpipe software system. It is based on a genomic ordered architecture and uses a declarative query language that combines features from SQL and shell pipe syntax in a novel manner. The system can for instance be used to annotate sequence variants, find genomic spatial overlap between various types of genomic features, filter and aggregate them in various ways. AVAILABILITY AND IMPLEMENTATION: The GORpipe software is freely available for non-commercial academic usage and can be downloaded from www.nextcode.com/gorpipe CONTACT: hakon@wuxinextcode.comSupplementary information: Supplementary data are available at Bioinformatics online.

Large-scale whole-genome sequencing of the Icelandic population.

Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20×. We found 20 million SNPs and 1.5 million insertions-deletions (indels). We describe the density and frequency spectra of sequence variants in relation to their functional annotation, gene position, pathway and conservation score. We demonstrate an excess of homozygosity and rare protein-coding variants in Iceland. We imputed these variants into 104,220 individuals down to a minor allele frequency of 0.1% and found a recessive frameshift mutation in MYL4 that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and an intronic variant in GNAS associating with increased thyroid-stimulating hormone levels when maternally inherited. These data provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.