In a study published , scientists at deCODE Genetics demonstrate for the first time how long-read DNA sequencing can be applied at population scale to unravel large structural variants that associate with human disease and other traits.

In a paper published in Nature genetics, scientists at deCODE genetics, a subsidiary of the pharmaceutical company Amgen, have shown that long-read DNA sequencing can be applied at population scale to unravel large structural variants that associate with human disease and other traits. Up until now DNA sequence analysis has been performed using short-read sequencing, where the sequence examined is broken up into fragments that are no more than 151 base pairs.  Using short-read sequencing scientists have been able to discern most small variations in the genome and population studies have allowed them to determine how they associate with diseases and other traits. However of 133,886 reliably genotyped structural variants detected with long-read sequencing only 60% can be detected with short-reads.

Using PromethION sequencers from Oxford Nanopore Technologies, researchers at deCODE genetics whole genome sequenced 3,622 Icelanders.  DNA base pairs in the genome were sequenced on average at least 10 times, allowing for accurate characterization of all genomic variation within the individual.  These variants were then imputed into a larger set of participants in various disease studies at deCODE genetics and associated with phenotypes. This has led to the discovery of several hitherto unknown associations of structural variants with diseases and other traits.

"This technology and algorithms we developed enable us to characterize almost all structural variants reliably and consistently on a population scale," says Bjarni V. Halldórsson, head of Sequence analysis, deCODE genetics.

The problem with short-read sequencing is that larger structural variants are difficult to discern directly.  This is a major stumbling block in the attempt to fully understand the relationship between variation in the sequence of the human genome and human diversity. Due to their size, these large structural variants usually have greater impact than the smaller variants most commonly considered. Large structural variants frequently delete or insert whole genes or large parts of genes, making them particularly harmful.

"We are confident that the long-read sequencing applied at population level is going to help us to find much of the missing sequence diversity that we must have to fully understand how diversity in the sequence of the genome accounts for human diversity," says Kari Stefansson CEO and founder of deCODE genetics.

Based in Reykjavik, Iceland, deCODE is a global leader in analyzing and understanding the human genome. Using its unique expertise and population resources, deCODE has discovered genetic risk factors for dozens of common diseases. The purpose of understanding the genetics of disease is to use that information to create new means of diagnosing, treating and preventing disease. deCODE is a wholly-owned subsidiary of Amgen (NASDAQ: AMGN).