Detecting genetic variants that are highly divergent from a reference sequence remains a major challenge in genome sequencing. We introduce de novo assembly algorithms using colored de Bruijn graphs for detecting and genotyping simple and complex genetic variants in an individual or population. We provide an efficient software implementation, Cortex, the first de novo assembler capable of assembling multiple eukaryotic genomes simultaneously. Four applications of Cortex are presented. First, we detect and validate both simple and complex structural variations in a high-coverage human genome. Second, we identify more than 3 Mb of sequence absent from the human reference genome, in pooled low-coverage population sequence data from the 1000 Genomes Project. Third, we show how population information from ten chimpanzees enables accurate variant calls without a reference sequence. Last, we estimate classical human leukocyte antigen (HLA) genotypes at HLA-B, the most variable gene in the human genome.

Original publication

DOI

10.1038/ng.1028

Type

Journal article

Journal

Nat Genet

Publication Date

08/01/2012

Volume

44

Pages

226 - 232

Keywords

Algorithms, Animals, Base Sequence, Chromosome Mapping, Genome, Human, Genotyping Techniques, HLA-B Antigens, Humans, Pan troglodytes, Sequence Analysis, DNA, Software