Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells DOI Creative Commons
Karen Grimes, Hyobin Jeong, Amanda Amoah

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(6), P. 1134 - 1146

Published: May 28, 2024

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors increasing age, discovered the heterogeneous mSV landscapes hematopoietic stem progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones our cohort confined to individuals >60. Cells already harboring more likely acquire additional somatic variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive micrococcal nuclease digestion with sequencing reference data, conducted high-resolution cell-typing for eight Clonally disrupt function by dysregulating diverse pathways, enriching myeloid progenitors. Our findings underscore contribution molecular phenotypes associated aging system, establish a foundation deciphering links between mSVs, disease susceptibility tissues.

Language: Английский

The complete sequence of a human Y chromosome DOI
Arang Rhie, Sergey Nurk, Monika Čechová

et al.

Nature, Journal Year: 2023, Volume and Issue: 621(7978), P. 344 - 354

Published: Aug. 23, 2023

Language: Английский

Citations

238
Telomere-to-telomere assembly of diploid chromosomes with Verkko DOI
Mikko Rautiainen, Sergey Nurk, Brian P. Walenz

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(10), P. 1474 - 1482

Published: Feb. 16, 2023

Language: Английский

Citations

220
Chromosomal inversion polymorphisms shape the genomic landscape of deer mice DOI Creative Commons
Olivia S. Harringmeyer, Hopi E. Hoekstra

Nature Ecology & Evolution, Journal Year: 2022, Volume and Issue: 6(12), P. 1965 - 1979

Published: Oct. 17, 2022

Abstract Chromosomal inversions are an important form of structural variation that can affect recombination, chromosome structure and fitness. However, because be challenging to detect, the prevalence hence significance segregating within species remains largely unknown, especially in natural populations mammals. Here, by combining population-genomic long-read sequencing analyses a single, widespread deer mouse ( Peromyscus maniculatus ), we identified 21 polymorphic large (1.5–43.8 Mb) cause near-complete suppression recombination when heterozygous (0–0.03 cM Mb −1 ). We found inversion breakpoints frequently occur centromeric telomeric regions often flanked long inverted repeats (0.5–50 kb), suggesting they probably arose via ectopic recombination. By genotyping across species’ range, do not harbour deleterious mutational loads, many likely maintained as polymorphisms divergent selection. Comparisons forest prairie ecotypes mice revealed 13 contribute differentiation between populations, which five exhibit significant associations with traits implicated local adaptation. Taken together, these results show have impact on genome genetic diversity facilitate adaptation range this species.

Language: Английский

Citations

85
Assembly of 43 human Y chromosomes reveals extensive complexity and variation DOI
Pille Hallast, Peter Ebert, Mark Loftus

et al.

Nature, Journal Year: 2023, Volume and Issue: 621(7978), P. 355 - 364

Published: Aug. 23, 2023

Language: Английский

Citations

66
Structurally divergent and recurrently mutated regions of primate genomes DOI Creative Commons
Yafei Mao, William T. Harvey, David Porubský

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1547 - 1562.e13

Published: Feb. 29, 2024

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, marmoset. identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes 136,932 regulatory elements, including most complete set human-specific differences. estimate that 819.47 Mbp or ∼27% genome has been affected by SVs across primate evolution. identify 1,607 structurally divergent regions wherein recurrent variation contributes to creating SV hotspots where are recurrently lost (e.g., CARD, C4, OLAH gene families) additional generated CKAP2, VPS36, ACBD7, NEK5 paralogs), becoming targets rapid chromosomal diversification positive selection RGPD family). High-fidelity made these dynamic accessible for sequence-level analyses within between species.

Language: Английский

Citations

41
A 25-year odyssey of genomic technology advances and structural variant discovery DOI Creative Commons
David Porubský, Evan E. Eichler

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1024 - 1037

Published: Jan. 29, 2024

Language: Английский

Citations

27
Leveraging a phased pangenome for haplotype design of hybrid potato DOI Creative Commons
Lin Cheng, Nan Wang, Zhigui Bao

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

Citations

5
Structural polymorphism and diversity of human segmental duplications DOI Creative Commons
Hyeonsoo Jeong, Philip C. Dishuck, DongAhn Yoo

et al.

Nature Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 genome assemblies (from 85 samples representing 38 Africans 47 non-Africans) in which majority autosomal are fully resolved using long-read assembly. Excluding acrocentric short arms sex chromosomes, we identify 173.2 Mb duplicated (47.4 not telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. find that intrachromosomal among most variable, with rare events mapping near their progenitor sequences. African genomes harbor more likely recently gene families higher copy numbers than non-African samples. Comparison resource 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding these number SDs.

Language: Английский

Citations

2
Verkko: telomere-to-telomere assembly of diploid chromosomes DOI Open Access
Mikko Rautiainen, Sergey Nurk, Brian P. Walenz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: June 26, 2022

Abstract The Telomere-to-Telomere consortium recently assembled the first truly complete sequence of a human genome. To resolve most complex repeats, this project relied on manual integration ultra-long Oxford Nanopore sequencing reads with high-resolution assembly graph built from long, accurate PacBio HiFi reads. We have improved and automated strategy in Verkko, an iterative, graph-based pipeline for assembling complete, diploid genomes. Verkko begins multiplex de Bruijn progressively simplifies via haplotype-specific markers. result is phased, both haplotypes, many chromosomes automatically telomere to telomere. Running HG002 genome resulted 20 46 without gaps at 99.9997% accuracy. genomes critical step towards construction comprehensive pangenome databases chromosome-scale comparative genomics.

Language: Английский

Citations

42
Gaps and complex structurally variant loci in phased genome assemblies DOI Creative Commons
David Porubský, Mitchell R. Vollger, William T. Harvey

et al.

Genome Research, Journal Year: 2023, Volume and Issue: 33(4), P. 496 - 510

Published: April 1, 2023

There has been tremendous progress in phased genome assembly production by combining long-read data with parental information or linked-read data. Nevertheless, a typical generated trio-hifiasm still generates more than 140 gaps. We perform detailed analysis of gaps, breaks, and misorientations from 182 haploid assemblies obtained diversity panel 77 unique human samples. Although trio-based approaches using HiFi are the current gold standard, chromosome-wide phasing accuracy is comparable when Strand-seq instead Importantly, majority gaps cluster near largest most identical repeats (including segmental duplications [35.4%], satellite DNA [22.3%], regions enriched GA/AT-rich [27.4%]). Consequently, 1513 protein-coding genes overlap at least one haplotype, 231 recurrently disrupted missing five haplotypes. Furthermore, we estimate that 6–7 Mbp misorientated per haplotype irrespective whether trio-free used. Of these misorientations, 81% correspond to bona fide large inversion polymorphisms species, which flanked duplications. also identify large-scale alignment discontinuities consistent 11.9 deletions 161.4 insertions genome. 99% this variation corresponds DNA, 230 euchromatic frequent expansions contractions, nearly half 197 genes. Such variable incompletely assembled important targets for future algorithmic development pangenome representation.

Language: Английский

Citations

31