Genome research最新文献

Closing the gaps, and improving somatic structural variant analysis and benchmarking using CHM13-T2T

IF 7 2区生物学

Genome research Pub Date : 2025-03-17 DOI: 10.1101/gr.279352.124

Luis F. Paulin, Jeremy Fan, Kieran O'Neill, Erin Pleasance, Vanessa L. Porter, Steven J.M. Jones, Fritz J. Sedlazeck

{"title":"Closing the gaps, and improving somatic structural variant analysis and benchmarking using CHM13-T2T","authors":"Luis F. Paulin, Jeremy Fan, Kieran O'Neill, Erin Pleasance, Vanessa L. Porter, Steven J.M. Jones, Fritz J. Sedlazeck","doi":"10.1101/gr.279352.124","DOIUrl":"https://doi.org/10.1101/gr.279352.124","url":null,"abstract":"The complexities of cancer genomes are becoming more easily interpreted due to advancements in sequencing technologies and improved bioinformatic analysis. Structural variants (SVs) represent an important subset of somatic events in tumors. While the detection of SVs has been markedly improved by the development of long-read sequencing, somatic variant identification and annotation remain challenging. We hypothesized that the use of a completed human reference genome (CHM13-T2T) would improve somatic SV calling. Our findings in a tumor–normal matched benchmark sample and three patient samples show that the CHM13-T2T improves SV detection accuracy compared to GRCh38 with a notable reduction in false-positive calls, and thus supports improved prioritization. We also overcame the lack of annotation resources for CHM13-T2T by lifting over CHM13-T2T-aligned reads to the GRCh38 genome, therefore combining both improved alignment and advanced annotations. In this process, we assessed the current SV benchmark set for COLO829/COLO829BL across four replicates sequenced at different centers with different long-read technologies. We discovered instability of this cell line across these replicates; 346 SVs (1.13%) were only discoverable in a single replicate. We identify 54 somatic SVs, which appear to be stable as they are consistently present across the four replicates. As such, we propose this consensus set as an updated benchmark for somatic SV calling and include both GRCh38 and CHM13-T2T coordinates in our benchmark. Our work demonstrates new approaches to optimize somatic SV detection in cancer with potential improvements in other genetic diseases.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"33 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BINDER achieves accurate identification of hierarchical TADs by comprehensively characterizing consensus TAD boundaries

IF 7 2区生物学

Genome research Pub Date : 2025-03-17 DOI: 10.1101/gr.279647.124

Yangyang Liu, Sr., Bingqiang Liu, Sr., Juntao Liu, Sr.

{"title":"BINDER achieves accurate identification of hierarchical TADs by comprehensively characterizing consensus TAD boundaries","authors":"Yangyang Liu, Sr., Bingqiang Liu, Sr., Juntao Liu, Sr.","doi":"10.1101/gr.279647.124","DOIUrl":"https://doi.org/10.1101/gr.279647.124","url":null,"abstract":"As a crucial chromatin structure, hierarchical TADs play important roles in epigenetic organization, transcriptional activity, gene regulation, and cell differentiation. Currently, it remains a highly challenging task to accurately identify hierarchical TADs in a computational manner. The key bottleneck for existing TAD callers lies in the difficulty on prediction of precise TAD boundaries. We solve this problem by introducing a novel algorithm, called BINDER, which conducts a boundary consensus approach, and then precisely locate hierarchical TAD boundaries by developing a multifaceted boundary characterization strategy. After comparison with other leading TAD callers, BINDER shows great improvement in identifying hierarchical TADs and exhibits the strongest robustness with ultrasparse data, which fully indicates the importance of boundary identification in calling hierarchical TADs. Applying BINDER to experimental data and mouse hematopoietic cases, we find that the hierarchical TADs identified by BINDER show strong biological relevance with epigenetic organization, transcriptional activity, DNA motifs, and coregulation during cellular differentiation. BINDER discovers differences in the enrichment of two specific transcription factors, CHD1 and CHD2 at TAD boundaries with different hierarchies. It also observes variations in gene expression of TADs with different hierarchies during cellular differentiation.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"60 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Taurine pangenome uncovers a segmental duplication upstream of KIT associated with depigmentation in white-headed cattle. 牛磺酸泛基因组揭示了与白头牛色素沉着相关的KIT上游片段重复。

IF 6.2 2区生物学

Genome research Pub Date : 2025-03-14 DOI: 10.1101/gr.279064.124

Sotiria Milia, Alexander S Leonard, Xena Marie Mapel, Sandra Milena Bernal Ulloa, Cord Drögemüller, Hubert Pausch

{"title":"Taurine pangenome uncovers a segmental duplication upstream of KIT associated with depigmentation in white-headed cattle.","authors":"Sotiria Milia, Alexander S Leonard, Xena Marie Mapel, Sandra Milena Bernal Ulloa, Cord Drögemüller, Hubert Pausch","doi":"10.1101/gr.279064.124","DOIUrl":"10.1101/gr.279064.124","url":null,"abstract":"Cattle have been selectively bred for coat color, spotting, and depigmentation patterns. The assumed autosomal dominant inherited genetic variants underlying the characteristic white head of Fleckvieh, Simmental, and Hereford cattle have not been identified yet, although the contribution of structural variation upstream of the KIT gene has been proposed. Here, we construct a graph pangenome from 24 haplotype assemblies representing seven taurine cattle breeds to identify and characterize the white-head-associated locus for the first time based on long-read sequencing data and pangenome analyses. We introduce a pangenome-wide association mapping approach that examines assembly path similarities within the graph to reveal an association between two most likely serial alleles of a complex structural variant (SV) 66 kb upstream of KIT and facial depigmentation. The complex SV contains a variable number of tandemly duplicated 14.3 kb repeats, consisting of LTRs, LINEs, and other repetitive elements, leading to misleading alignments of short and long reads when using a linear reference. We align 250 short-read sequencing samples spanning 15 cattle breeds to the pangenome graph, further validating that the alleles of the SV segregate with head depigmentation. We estimate an increased count of repeats in Hereford relative to Simmental and other white-headed cattle breeds from the graph alignment coverage, suggesting a large under-assembly in the current Hereford-based cattle reference genome, which had fewer copies. Our work shows that exploiting assembly path similarities within graph pangenomes can reveal trait-associated complex SVs.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity

IF 7 2区生物学

Genome research Pub Date : 2025-03-14 DOI: 10.1101/gr.279317.124

Mayank Murali, Jamie Saquing, Senbao Lu, Ziyang Gao, Emily F. Watts, Ben Jordan, Zachary Peters Wakefield, Ana Fiszbein, David R. Cooper, Peter J. Castaldi, Dmitry Korkin, Gloria M. Sheynkman

{"title":"Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity","authors":"Mayank Murali, Jamie Saquing, Senbao Lu, Ziyang Gao, Emily F. Watts, Ben Jordan, Zachary Peters Wakefield, Ana Fiszbein, David R. Cooper, Peter J. Castaldi, Dmitry Korkin, Gloria M. Sheynkman","doi":"10.1101/gr.279317.124","DOIUrl":"https://doi.org/10.1101/gr.279317.124","url":null,"abstract":"Long-read RNA-seq has shed light on transcriptomic complexity, but questions remain about the functionality of downstream protein products. We introduce Biosurfer, a computational approach for comparing protein isoforms, while systematically tracking the transcriptional, splicing, and translational variations that underlie differences in the sequences of the protein products. Using Biosurfer, we analyzed the differences in 35,082 pairs of GENCODE annotated protein isoforms, finding a majority (70%) of variable N-termini are due to the alternative transcription start sites, while only 9% arise from 5′ UTR alternative splicing (AS). Biosurfer's detailed tracking of nucleotide-to-residue relationships helps reveal an uncommonly tracked source of single amino acid residue changes arising from the codon splits at junctions. For 17% of internal sequence changes, such split codon patterns lead to single residue differences, termed “ragged codons.” Of variable C-termini, 72% involve splice- or intron retention-induced reading frameshifts. We systematically characterize an unusual pattern of reading frame changes, in which the first frameshift is closely followed by a distinct second frameshift that restores the original frame, which we term a “snapback” frameshift. We analyze the long-read RNA-seq-predicted proteome of a human cell line and find similar trends as compared to our GENCODE analysis, with the exception of a higher proportion of transcripts predicted to undergo nonsense-mediated decay. Biosurfer's comprehensive characterization of long-read RNA-seq data sets should accelerate insights of the functional role of protein isoforms, providing mechanistic explanation of the origins of the proteomic diversity driven by the AS. Biosurfer is available as a Python package.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"32 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution 通过长短线程同源物测序，以批量或单细胞分辨率准确鉴定融合转录本

IF 7 2区生物学

Genome research Pub Date : 2025-03-14 DOI: 10.1101/gr.279200.124

Qian Qin, Victoria Popic, Kirsty Wienand, Houlin Yu, Emily White, Akanksha Khorgade, Asa Shin, Christophe Georgescu, Catarina D. Campbell, Arthur Dondi, Niko Beerenwinkel, Francisca Vazquez, Aziz M. Al'Khafaji, Brian J. Haas

{"title":"Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution","authors":"Qian Qin, Victoria Popic, Kirsty Wienand, Houlin Yu, Emily White, Akanksha Khorgade, Asa Shin, Christophe Georgescu, Catarina D. Campbell, Arthur Dondi, Niko Beerenwinkel, Francisca Vazquez, Aziz M. Al'Khafaji, Brian J. Haas","doi":"10.1101/gr.279200.124","DOIUrl":"https://doi.org/10.1101/gr.279200.124","url":null,"abstract":"Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics and prognostics and for guiding therapeutic development. Most currently available methods for fusion transcript detection are compatible with Illumina RNA-seq involving highly accurate short-read sequences. Recent advances in long-read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single-cell samples. Here, we developed a new computational tool, CTAT-LR-Fusion, to detect fusion transcripts from long-read RNA-seq with or without companion short reads, with applications to bulk or single-cell transcriptomes. We demonstrate that CTAT-LR-Fusion exceeds the fusion detection accuracy of alternative methods as benchmarked with simulated and genuine long-read RNA-seq. Using short- and long-read RNA-seq, we further apply CTAT-LR-Fusion to bulk transcriptomes of nine tumor cell lines and to tumor single cells derived from a melanoma sample and three metastatic high-grade serous ovarian carcinoma samples. In both bulk and single-cell RNA-seq, long isoform reads yield higher sensitivity for fusion detection than short reads with notable exceptions. By combining short and long reads in CTAT-LR-Fusion, we are able to further maximize the detection of fusion splicing isoforms and fusion-expressing tumor cells.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"6 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KRAB zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution

IF 7 2区生物学

Genome research Pub Date : 2025-03-12 DOI: 10.1101/gr.279924.124

Kai Otsuka, Akihiko Sakashita, So Maezawa, Richard M. Schultz, Satoshi H. Namekawa

{"title":"KRAB zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution","authors":"Kai Otsuka, Akihiko Sakashita, So Maezawa, Richard M. Schultz, Satoshi H. Namekawa","doi":"10.1101/gr.279924.124","DOIUrl":"https://doi.org/10.1101/gr.279924.124","url":null,"abstract":"As transposable elements (TEs) coevolved with the host genome, the host genome exploited TEs as functional regulatory elements of gene expression. Here we show that a subset of KRAB domain–containing zinc-finger proteins (KZFPs), which are highly expressed in mitotically dividing spermatogonia, repress the enhancer function of endogenous retroviruses (ERVs) and that the release from KZFP-mediated repression allows activation of ERV enhancers upon entry into meiosis. This regulatory feature is observed for independently evolved KZFPs and ERVs in mice and humans, suggesting evolutionary conservation in mammals. Further, we show that KZFP-targeted ERVs are underrepresented on the sex chromosomes in meiosis, suggesting that meiotic sex chromosome inactivation (MSCI) may antagonize the coevolution of KZFPs and ERVs in mammals. Our study uncovers a mechanism by which a subset of KZFPs regulate ERVs to sculpt germline transcriptomes. We propose that epigenetic programming during the transition from mitotic spermatogonia to meiotic spermatocytes facilitates the coevolution of KZFPs and TEs on autosomes and is antagonized by MSCI.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"208 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing DNA methylation detection for primary human tissue using nanopore sequencing

IF 7 2区生物学

Genome research Pub Date : 2025-03-07 DOI: 10.1101/gr.279159.124

Rylee Genner, Stuart Akeson, Melissa Meredith, Pilar Alvarez Jerez, Laksh Malik, Breeana Baker, Abigail Miano-Burkhardt, CARD-long-read Team, Benedict Paten, Kimberley J Billingsley, Cornelis Blauwendraat, Miten Jain

{"title":"Assessing DNA methylation detection for primary human tissue using nanopore sequencing","authors":"Rylee Genner, Stuart Akeson, Melissa Meredith, Pilar Alvarez Jerez, Laksh Malik, Breeana Baker, Abigail Miano-Burkhardt, CARD-long-read Team, Benedict Paten, Kimberley J Billingsley, Cornelis Blauwendraat, Miten Jain","doi":"10.1101/gr.279159.124","DOIUrl":"https://doi.org/10.1101/gr.279159.124","url":null,"abstract":"DNA methylation most commonly occurs as 5-methylcytosine (5mC) in the human genome and has been associated with human diseases. Recent developments in single-molecule sequencing technologies (Oxford Nanopore Technologies (ONT) and Pacific Biosciences) have enabled readouts of long, native DNA molecules, including cytosine methylation. ONT recently upgraded their Nanopore sequencing chemistry and kits from the R9 to the R10 version, which yielded increased accuracy and sequencing throughput. However the effects on methylation detection have not yet been documented. Here, we performed a series of computational analyses to characterize differences in Nanopore-based 5mC detection between the ONT R9 and R10 chemistries. We compared 5mC calls in R9 and R10 for three human genome datasets: a cell line, a frontal cortex brain sample, and a blood sample. We performed an in-depth analysis on CpG islands and homopolymer regions, and documented high concordance for methylation detection among sequencing technologies. The strongest correlation was observed between Nanopore R10 and Illumina bisulfite technologies for cell line-derived datasets. Subtle differences in methylation datasets between technologies can impact analysis tools such as differential methylation calling software. Our findings show that comparisons can be drawn between methylation data from different Nanopore chemistries using guided hypotheses. This work will facilitate comparison among Nanopore data cohorts derived using different chemistries from large scale sequencing efforts, such as the NIH CARD Long Read Initiative.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating short-read and long-read single-cell RNA sequencing for comprehensive transcriptome profiling in mouse retina

IF 7 2区生物学

Genome research Pub Date : 2025-03-06 DOI: 10.1101/gr.279167.124

Meng Wang, Yumei Li, Jun Wang, Soo Hwan Oh, Yexuan Cao, Rui Chen

{"title":"Integrating short-read and long-read single-cell RNA sequencing for comprehensive transcriptome profiling in mouse retina","authors":"Meng Wang, Yumei Li, Jun Wang, Soo Hwan Oh, Yexuan Cao, Rui Chen","doi":"10.1101/gr.279167.124","DOIUrl":"https://doi.org/10.1101/gr.279167.124","url":null,"abstract":"The vast majority of protein-coding genes in the human genome produce multiple mRNA isoforms through alternative splicing, significantly enhancing the complexity of the transcriptome and proteome. To establish an efficient method for characterizing transcript isoforms within tissue samples, we conducted a systematic comparison between single-cell long-read and conventional short-read RNA sequencing techniques. The transcriptome of approximately 30,000 mouse retina cells was profiled using 1.54 billion Illumina short reads and 1.40 billion Oxford Nanopore Technologies long reads. Consequently, we identify 44,325 transcript isoforms, with a notable 38% previously uncharacterized and 17% expressed exclusively in distinct cellular subclasses. We observe that long-read sequencing not only matches the gene expression and cell-type annotation performance of short-read sequencing but also excel in the precise identification of transcript isoforms. While transcript isoforms are often shared across various cell types, their relative abundance shows considerable cell type–specific variation. The data generated from our study significantly enhance the existing repertoire of transcript isoforms, thereby establishing a resource for future research into the mechanisms and implications of alternative splicing within retinal biology and its links to related diseases.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"489 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homozygous editing of multiple genes for accelerated generation of xenotransplantation pigs

IF 7 2区生物学

Genome research Pub Date : 2025-03-05 DOI: 10.1101/gr.279709.124

Xiaoyue Duan, Chaolei Chen, Chang Du, Liang Guo, Jun Liu, Naipeng Hou, Pan Li, Xiaolan Qi, Fei Gao, Xuguang Du, Jiangping Song, Sen Wu

{"title":"Homozygous editing of multiple genes for accelerated generation of xenotransplantation pigs","authors":"Xiaoyue Duan, Chaolei Chen, Chang Du, Liang Guo, Jun Liu, Naipeng Hou, Pan Li, Xiaolan Qi, Fei Gao, Xuguang Du, Jiangping Song, Sen Wu","doi":"10.1101/gr.279709.124","DOIUrl":"https://doi.org/10.1101/gr.279709.124","url":null,"abstract":"Although CRISPR-Cas based genome editing has made significant strides over the past decade, achieving simultaneous homozygous gene editing of multiple targets in primary cells remains a significant challenge. In this study, we optimized a coselection strategy to enhance homozygous gene editing rates in the genomes of primary porcine fetal fibroblasts (PFFs). The strategy utilizes the expression of a surrogate reporter (eGFP) to select for cells with the highest reporter expression, thereby improving editing efficiency. When applied to simultaneous multigene editing, we targeted the most challenging site for selection, while other target sites did not require selection. Using this approach, we successfully obtained single-cell PFF clones (3/10) with seven or more homozygously edited genes, including GGTA1, CMAH, B4GALNT2, CD46, CD47, THBD, and GHR. Importantly, cells edited using this strategy were efficiently used for somatic cell nuclear transfer (SCNT) to generate healthy xenotransplantation pigs in less than five months, a process that previously required years of breeding or multiple rounds of SCNT.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"2 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of the male-specific region on the guppy Y Chromosome from a haplotype-resolved assembly

IF 7 2区生物学

Genome research Pub Date : 2025-03-05 DOI: 10.1101/gr.279582.124

Kang Du, Oliver Deusch, Ilja Bezrukov, Christa Lanz, Yann Guiguen, Margarete Hoffmann, Anette Habring, Detlef Weigel, Manfred Schartl, Christine Dreyer

{"title":"Identification of the male-specific region on the guppy Y Chromosome from a haplotype-resolved assembly","authors":"Kang Du, Oliver Deusch, Ilja Bezrukov, Christa Lanz, Yann Guiguen, Margarete Hoffmann, Anette Habring, Detlef Weigel, Manfred Schartl, Christine Dreyer","doi":"10.1101/gr.279582.124","DOIUrl":"https://doi.org/10.1101/gr.279582.124","url":null,"abstract":"The guppy Y Chromosome has been a paradigmatic model for studying the genetics of sex-linked traits and Y Chromosome–driven evolution for more than a century. Despite strong efforts, knowledge on genomic organization and molecular differentiation of the sex chromosome pair remains unsatisfactory and partly contradictory with respect to regions of reduced recombination. Especially the border between pseudoautosomal and male-specific regions of the Y has not been defined so far. To circumvent the problems in assigning the repeat-rich differentiated hemizygous or heterozygous sequences of the sex chromosome pair, we sequenced a YY male generated by a cross of a sex-reversed Maculatus strain XY female to a normal XY male from the inbred Guanapo population. High-molecular-weight genomic DNA from the YY male was sequenced on the Pacific Biosciences platform, and both Y haplotypes were reconstructed by Trio binning. By mapping of male specific SNPs and RADseq sequences, we identify a single male specific-region of ∼5 Mb length at the distal end of the Y (MSY). Sequence divergence between X and Y in the segment is on average five times higher than in the proximal part in agreement with reduced recombination. The MSY is enriched for repeats and transposons but does not differ in the content of coding genes from the X, indicating that genic degeneration has not progressed to a measurable degree.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"2 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0