Publication Date:
2014-11-11
Description:
The human genome is arguably the most complete mammalian reference assembly, yet more than 160 euchromatic gaps remain and aspects of its structural variation remain poorly understood ten years after its completion. To identify missing sequence and genetic variation, here we sequence and analyse a haploid human genome (CHM1) using single-molecule, real-time DNA sequencing. 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317254/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317254/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaisson, Mark J P -- Huddleston, John -- Dennis, Megan Y -- Sudmant, Peter H -- Malig, Maika -- Hormozdiari, Fereydoun -- Antonacci, Francesca -- Surti, Urvashi -- Sandstrom, Richard -- Boitano, Matthew -- Landolin, Jane M -- Stamatoyannopoulos, John A -- Hunkapiller, Michael W -- Korlach, Jonas -- Eichler, Evan E -- HG002385/HG/NHGRI NIH HHS/ -- HG007497/HG/NHGRI NIH HHS/ -- K99 NS083627/NS/NINDS NIH HHS/ -- K99NS083627/NS/NINDS NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- U41 HG007497/HG/NHGRI NIH HHS/ -- U41 HG007635/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 29;517(7536):608-11. doi: 10.1038/nature13907. Epub 2014 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA. ; 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA. ; Dipartimento di Biologia, Universita degli Studi di Bari 'Aldo Moro', Bari 70125, Italy. ; Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. ; Pacific Biosciences of California, Inc., Menlo Park, California 94025, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383537" target="_blank"〉PubMed〈/a〉
Keywords:
Chromosome Inversion/genetics
;
Chromosomes, Human, Pair 10/genetics
;
Cloning, Molecular
;
GC Rich Sequence/genetics
;
Genetic Variation/*genetics
;
Genome, Human/*genetics
;
*Genomics
;
Haploidy
;
Humans
;
Mutagenesis, Insertional/genetics
;
Reference Standards
;
Sequence Analysis, DNA/*methods
;
Tandem Repeat Sequences/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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