Haplotype-resolved assemblies and variant benchmark of a Chinese Quartet.
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
04 Dec 2023
04 Dec 2023
Historique:
received:
25
08
2023
accepted:
21
11
2023
medline:
6
12
2023
pubmed:
5
12
2023
entrez:
4
12
2023
Statut:
epublish
Résumé
Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology). The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent-child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (< 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity-including those located at long repeat regions, complex structural variants, and de novo mutations-are systematically examined in this study. In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.
Sections du résumé
BACKGROUND
BACKGROUND
Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology).
RESULTS
RESULTS
The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent-child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (< 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity-including those located at long repeat regions, complex structural variants, and de novo mutations-are systematically examined in this study.
CONCLUSIONS
CONCLUSIONS
In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.
Identifiants
pubmed: 38049885
doi: 10.1186/s13059-023-03116-3
pii: 10.1186/s13059-023-03116-3
pmc: PMC10694985
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
277Subventions
Organisme : National Key R&D Program of China
ID : 2022YFC3400300
Organisme : National Natural Science Foundation of China
ID : 32125009
Organisme : National Natural Science Foundation of China
ID : 62172325
Organisme : National Natural Science Foundation of China
ID : 32200510
Organisme : National Natural Science Foundation of China
ID : 62172325
Organisme : Natural Science Basic Research Program of Shaanxi Province
ID : 2021GXLH-Z-098
Organisme : National Key Research and Development Program of China
ID : 2017YFF0204605
Informations de copyright
© 2023. The Author(s).
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