Diversity in human genomes

Diversity in human genomes

Clinical use of human genome sequencing requires suitable quality standards with respect to coverage and accuracy. To evaluate the quality of current whole genome sequencing methods, researchers sequenced more than 10,000 human genomes at 30×–40× mean coverage using a state-of- the-art sequencing platform.

Based on the reproducibility of a reference genome, the authors determined that 84% of the human genome could be sequenced at high confidence, including more than 90% of exons and more than 95% of known pathogenic variant sites.

Sequencing revealed more than 150 million single nucleotide variations, 82 million of which had not been previously reported. Most of these variations occurred with less than 1% frequency.

On average, each additional genome sequenced contributed more than 8,500 novel variations. From the distribution of variations, the authors identified certain sites, such as splice sites, which were particularly intolerant of variation.

These variation-intolerant sites were associated with high frequencies of known pathogenic variants, suggesting that these sites might be essential for health. According to the authors, the results suggest that current sequencing platforms provide genome coverage sufficient for clinical purposes.