Resolving the complexity of the human genome using single-molecule sequencing.

• Autores: Mark J. P. Chaisson, John Huddleston, Megan Y. Dennis, Peter H. Sudmant, Maika Malig, Fereydoun Hormozdiari
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 517, Nº 7536, 2015, págs. 609-611
• Idioma: inglés
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• Resumen

  • The human genome is arguably the most complete mammalian reference assembly 1-3, yet more than 160 euchromatic gaps remain 4-6 and aspects of its structural variation remain poorly understood ten years after its completion 7-9. To identify missing sequence and genetic variation, here we sequence and analyse a haploid human genome (CHM1) using single-molecule, real-time DNA sequencing 10. We close or extend 55% of the remaining interstitial gaps in the human GRCh37 reference genome-78% of which carried long runs of degenerate short tandem repeats, often several kilobases in length, embedded within (G+C)-rich genomic regions. We resolve the complete sequence of 26,079 euchromatic structural variants at the base-pair level, including inversions, complex insertions and long tracts of tandem repeats. Most have not been previously reported, with the greatest increases in sensitivity occurring for events less than 5 kilobases in size. Compared to the human reference, we find a significant insertional bias (3:1) in regions corresponding to complex insertions and long short tandem repeats. Our results suggest a greater complexity of the human genome in the form of variation of longer and more complex repetitive DNA that can now be largely resolved with the application of this longer-read sequencing technology.