Closing Human Reference Genome Gaps: Identifying and Characterizing Gap-Closing Sequences.

G3 : Genes - Genomes - Genetics
Tingting ZhaoHui Lu

Abstract

Despite continuous updates of the human reference genome, there are still hundreds of unresolved gaps which account for about 5% of the total sequence length. Given the availability of whole genome de novo assemblies, especially those derived from long-read sequencing data, gap-closing sequences can be determined. By comparing 17 de novo long-read sequencing assemblies with the human reference genome, we identified a total of 1,125 gap-closing sequences for 132 (16.9% of 783) gaps and added up to 2.2 Mb novel sequences to the human reference genome. More than 90% of the non-redundant sequences could be verified by unmapped reads from the Simons Genome Diversity Project dataset. In addition, 15.6% of the non-reference sequences were found in at least one of four non-human primate genomes. We further demonstrated that the non-redundant sequences had high content of simple repeats and satellite sequences. Moreover, 43 (32.6%) of the 132 closed gaps were shown to be polymorphic; such sequences may play an important biological role and can be useful in the investigation of human genetic diversity.

References

Feb 22, 2001·Science·J C VenterX Zhu
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Oct 6, 2001·Science·M G SchuelerH F Willard
Jan 16, 2003·Nucleic Acids Research·S Sri KrishnaNick V Grishin
Feb 5, 2004·Genome Biology·Stefan KurtzSteven L Salzberg
Oct 22, 2004·Nature·UNKNOWN International Human Genome Sequencing Consortium
Sep 2, 2005·Nature·UNKNOWN Chimpanzee Sequencing and Analysis Consortium
May 30, 2009·Current Opinion in Genetics & Development·Heather C Mefford, Evan E Eichler
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
May 8, 2010·Science·Richard E GreenSvante Pääbo
May 19, 2010·Nature Reviews. Genetics·Evan E EichlerJoseph H Nadeau
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Mar 9, 2012·Nature·Aylwyn ScallyRichard Durbin
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Jun 23, 2012·Nature·Kay PrüferSvante Pääbo
Oct 13, 2012·Bioinformatics·Limin FuWeizhong Li
Nov 11, 2014·Nature·Mark J P ChaissonEvan E Eichler
May 18, 2016·Nature Reviews. Genetics·Sara GoodwinW Richard McCombie
Jul 1, 2016·Nature Communications·Lingling ShiKai Wang
Oct 6, 2016·Nature·Jeong-Sun SeoChanghoon Kim
Feb 13, 2018·Nature Biotechnology·Miten JainMatthew Loose
Mar 31, 2018·Nature Reviews. Genetics·Fritz J SedlazeckMichael C Schatz
May 12, 2018·Bioinformatics·Heng Li
Jun 29, 2018·Bioinformatics·Alla MikheenkoAlexey Gurevich
Oct 26, 2018·Nucleic Acids Research·Adam FrankishPaul Flicek
Nov 21, 2018·Nature Genetics·Rachel M ShermanSteven L Salzberg
Jan 22, 2019·Cell·Peter A AudanoEvan E Eichler
Feb 9, 2020·Nature Reviews. Genetics·Rachel M Sherman, Steven L Salzberg

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Citations

Mar 7, 2021·International Journal of Molecular Sciences·Thomas Liehr

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Datasets Mentioned

BETA
GM12878
PRJEB9586
ERR1625860

Methods Mentioned

BETA
Human Genome Sequencing

Software Mentioned

CD
blastp
RepeatMasker
minimap2
MUMmer
ORF Finder
CpGProD
HIT
IGV
nucmer

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