Cell genomicsPub Date : 2024-08-14Epub Date: 2024-07-30DOI: 10.1016/j.xgen.2024.100625
Yoshihiko Tomofuji, Ryuya Edahiro, Kyuto Sonehara, Yuya Shirai, Kian Hong Kock, Qingbo S Wang, Shinichi Namba, Jonathan Moody, Yoshinari Ando, Akari Suzuki, Tomohiro Yata, Kotaro Ogawa, Tatsuhiko Naito, Ho Namkoong, Quy Xiao Xuan Lin, Eliora Violain Buyamin, Le Min Tan, Radhika Sonthalia, Kyung Yeon Han, Hiromu Tanaka, Ho Lee, Tatsusada Okuno, Boxiang Liu, Koichi Matsuda, Koichi Fukunaga, Hideki Mochizuki, Woong-Yang Park, Kazuhiko Yamamoto, Chung-Chau Hon, Jay W Shin, Shyam Prabhakar, Atsushi Kumanogoh, Yukinori Okada
{"title":"Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues.","authors":"Yoshihiko Tomofuji, Ryuya Edahiro, Kyuto Sonehara, Yuya Shirai, Kian Hong Kock, Qingbo S Wang, Shinichi Namba, Jonathan Moody, Yoshinari Ando, Akari Suzuki, Tomohiro Yata, Kotaro Ogawa, Tatsuhiko Naito, Ho Namkoong, Quy Xiao Xuan Lin, Eliora Violain Buyamin, Le Min Tan, Radhika Sonthalia, Kyung Yeon Han, Hiromu Tanaka, Ho Lee, Tatsusada Okuno, Boxiang Liu, Koichi Matsuda, Koichi Fukunaga, Hideki Mochizuki, Woong-Yang Park, Kazuhiko Yamamoto, Chung-Chau Hon, Jay W Shin, Shyam Prabhakar, Atsushi Kumanogoh, Yukinori Okada","doi":"10.1016/j.xgen.2024.100625","DOIUrl":"10.1016/j.xgen.2024.100625","url":null,"abstract":"<p><p>Several X-linked genes escape from X chromosome inactivation (XCI), while differences in escape across cell types and tissues are still poorly characterized. Here, we developed scLinaX for directly quantifying relative gene expression from the inactivated X chromosome with droplet-based single-cell RNA sequencing (scRNA-seq) data. The scLinaX and differentially expressed gene analyses with large-scale blood scRNA-seq datasets consistently identified the stronger escape in lymphocytes than in myeloid cells. An extension of scLinaX to a 10x multiome dataset (scLinaX-multi) suggested a stronger escape in lymphocytes than in myeloid cells at the chromatin-accessibility level. The scLinaX analysis of human multiple-organ scRNA-seq datasets also identified the relatively strong degree of escape from XCI in lymphoid tissues and lymphocytes. Finally, effect size comparisons of genome-wide association studies between sexes suggested the underlying impact of escape on the genotype-phenotype association. Overall, scLinaX and the quantified escape catalog identified the heterogeneity of escape across cell types and tissues.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-14Epub Date: 2024-07-11DOI: 10.1016/j.xgen.2024.100607
Jiahong Wu, Fujiang Liu, Jie Jiao, Haoran Luo, Shiyu Fan, Jiao Liu, Hongxiang Wang, Ning Cui, Ning Zhao, Qingming Qu, Shigehiro Kuraku, Zhen Huang, Luohao Xu
{"title":"Comparative genomics illuminates karyotype and sex chromosome evolution of sharks.","authors":"Jiahong Wu, Fujiang Liu, Jie Jiao, Haoran Luo, Shiyu Fan, Jiao Liu, Hongxiang Wang, Ning Cui, Ning Zhao, Qingming Qu, Shigehiro Kuraku, Zhen Huang, Luohao Xu","doi":"10.1016/j.xgen.2024.100607","DOIUrl":"10.1016/j.xgen.2024.100607","url":null,"abstract":"<p><p>Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-14Epub Date: 2024-07-24DOI: 10.1016/j.xgen.2024.100610
Yuki Sugiyama, Satoshi Okada, Yasukazu Daigaku, Emiko Kusumoto, Takashi Ito
{"title":"Strategic targeting of Cas9 nickase induces large segmental duplications.","authors":"Yuki Sugiyama, Satoshi Okada, Yasukazu Daigaku, Emiko Kusumoto, Takashi Ito","doi":"10.1016/j.xgen.2024.100610","DOIUrl":"10.1016/j.xgen.2024.100610","url":null,"abstract":"<p><p>Gene/segmental duplications play crucial roles in genome evolution and variation. Here, we introduce paired nicking-induced amplification (PNAmp) for their experimental induction. PNAmp strategically places two Cas9 nickases upstream and downstream of a replication origin on opposite strands. This configuration directs the sister replication forks initiated from the origin to break at the nicks, generating a pair of one-ended double-strand breaks. If homologous sequences flank the two break sites, then end resection converts them to single-stranded DNAs that readily anneal to drive duplication of the region bounded by the homologous sequences. PNAmp induces duplication of segments as large as ∼1 Mb with efficiencies exceeding 10% in the budding yeast Saccharomyces cerevisiae. Furthermore, appropriate splint DNAs allow PNAmp to duplicate/multiplicate even segments not bounded by homologous sequences. We also provide evidence for PNAmp in mammalian cells. Therefore, PNAmp provides a prototype method to induce structural variations by manipulating replication fork progression.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-14Epub Date: 2024-08-02DOI: 10.1016/j.xgen.2024.100627
Jayne A Barbour, Tong Ou, Haocheng Yang, Hu Fang, Noel C Yue, Xiaoqiang Zhu, Michelle W Wong-Brown, Yuen T Wong, Nikola A Bowden, Song Wu, Jason W H Wong
{"title":"ERCC2 mutations alter the genomic distribution pattern of somatic mutations and are independently prognostic in bladder cancer.","authors":"Jayne A Barbour, Tong Ou, Haocheng Yang, Hu Fang, Noel C Yue, Xiaoqiang Zhu, Michelle W Wong-Brown, Yuen T Wong, Nikola A Bowden, Song Wu, Jason W H Wong","doi":"10.1016/j.xgen.2024.100627","DOIUrl":"10.1016/j.xgen.2024.100627","url":null,"abstract":"<p><p>Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-14Epub Date: 2024-07-16DOI: 10.1016/j.xgen.2024.100609
Taehwan Shin, Janet H T Song, Michael Kosicki, Connor Kenny, Samantha G Beck, Lily Kelley, Irene Antony, Xuyu Qian, Julieta Bonacina, Frances Papandile, Dilenny Gonzalez, Julia Scotellaro, Evan M Bushinsky, Rebecca E Andersen, Eduardo Maury, Len A Pennacchio, Ryan N Doan, Christopher A Walsh
{"title":"Rare variation in non-coding regions with evolutionary signatures contributes to autism spectrum disorder risk.","authors":"Taehwan Shin, Janet H T Song, Michael Kosicki, Connor Kenny, Samantha G Beck, Lily Kelley, Irene Antony, Xuyu Qian, Julieta Bonacina, Frances Papandile, Dilenny Gonzalez, Julia Scotellaro, Evan M Bushinsky, Rebecca E Andersen, Eduardo Maury, Len A Pennacchio, Ryan N Doan, Christopher A Walsh","doi":"10.1016/j.xgen.2024.100609","DOIUrl":"10.1016/j.xgen.2024.100609","url":null,"abstract":"<p><p>Little is known about the role of non-coding regions in the etiology of autism spectrum disorder (ASD). We examined three classes of non-coding regions: human accelerated regions (HARs), which show signatures of positive selection in humans; experimentally validated neural VISTA enhancers (VEs); and conserved regions predicted to act as neural enhancers (CNEs). Targeted and whole-genome analysis of >16,600 samples and >4,900 ASD probands revealed that likely recessive, rare, inherited variants in HARs, VEs, and CNEs substantially contribute to ASD risk in probands whose parents share ancestry, which enriches for recessive contributions, but modestly contribute, if at all, in simplex family structures. We identified multiple patient variants in HARs near IL1RAPL1 and in VEs near OTX1 and SIM1 and showed that they change enhancer activity. Our results implicate both human-evolved and evolutionarily conserved non-coding regions in ASD risk and suggest potential mechanisms of how regulatory changes can modulate social behavior.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-14Epub Date: 2024-07-02DOI: 10.1016/j.xgen.2024.100604
Mireia Ramos-Rodríguez, Marc Subirana-Granés, Richard Norris, Valeria Sordi, Ángel Fernández, Georgina Fuentes-Páez, Beatriz Pérez-González, Clara Berenguer Balaguer, Helena Raurell-Vila, Murad Chowdhury, Raquel Corripio, Stefano Partelli, Núria López-Bigas, Silvia Pellegrini, Eduard Montanya, Montserrat Nacher, Massimo Falconi, Ryan Layer, Meritxell Rovira, Abel González-Pérez, Lorenzo Piemonti, Lorenzo Pasquali
{"title":"Implications of noncoding regulatory functions in the development of insulinomas.","authors":"Mireia Ramos-Rodríguez, Marc Subirana-Granés, Richard Norris, Valeria Sordi, Ángel Fernández, Georgina Fuentes-Páez, Beatriz Pérez-González, Clara Berenguer Balaguer, Helena Raurell-Vila, Murad Chowdhury, Raquel Corripio, Stefano Partelli, Núria López-Bigas, Silvia Pellegrini, Eduard Montanya, Montserrat Nacher, Massimo Falconi, Ryan Layer, Meritxell Rovira, Abel González-Pérez, Lorenzo Piemonti, Lorenzo Pasquali","doi":"10.1016/j.xgen.2024.100604","DOIUrl":"10.1016/j.xgen.2024.100604","url":null,"abstract":"<p><p>Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in β cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of β cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-09DOI: 10.1016/j.xgen.2024.100630
Anniina Tervi, Markus Ramste, Erik Abner, Paul Cheng, Jacqueline M Lane, Matthew Maher, Jesse Valliere, Vilma Lammi, Satu Strausz, Juha Riikonen, Trieu Nguyen, Gabriella E Martyn, Maya U Sheth, Fan Xia, Mauro Lago Docampo, Wenduo Gu, Tõnu Esko, Richa Saxena, Matti Pirinen, Aarno Palotie, Samuli Ripatti, Nasa Sinnott-Armstrong, Mark Daly, Jesse M Engreitz, Marlene Rabinovitch, Caroline A Heckman, Thomas Quertermous, Samuel E Jones, Hanna M Ollila
{"title":"Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity.","authors":"Anniina Tervi, Markus Ramste, Erik Abner, Paul Cheng, Jacqueline M Lane, Matthew Maher, Jesse Valliere, Vilma Lammi, Satu Strausz, Juha Riikonen, Trieu Nguyen, Gabriella E Martyn, Maya U Sheth, Fan Xia, Mauro Lago Docampo, Wenduo Gu, Tõnu Esko, Richa Saxena, Matti Pirinen, Aarno Palotie, Samuli Ripatti, Nasa Sinnott-Armstrong, Mark Daly, Jesse M Engreitz, Marlene Rabinovitch, Caroline A Heckman, Thomas Quertermous, Samuel E Jones, Hanna M Ollila","doi":"10.1016/j.xgen.2024.100630","DOIUrl":"https://doi.org/10.1016/j.xgen.2024.100630","url":null,"abstract":"<p><p>Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative trait loci (eQTLs), particularly in distal arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci modified gene expression and in situ RNAscope clarified the specificity of ADRA2A in small vessels and IRX1 around small capillaries in the skin. A functional contraction assay in the cold showed lower contraction in ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth muscle cells. Overall, our study highlights the power of genome-wide association testing with functional follow-up as a method to understand complex diseases. The results indicate temperature-dependent adrenergic signaling through ADRA2A, effects at the microvasculature by IRX1, endothelial signaling by NOS3, and immune mechanisms by the HLA locus in Raynaud's syndrome.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-08DOI: 10.1016/j.xgen.2024.100634
Felix Drost, Emilio Dorigatti, Adrian Straub, Philipp Hilgendorf, Karolin I Wagner, Kersten Heyer, Marta López Montes, Bernd Bischl, Dirk H Busch, Kilian Schober, Benjamin Schubert
{"title":"Predicting T cell receptor functionality against mutant epitopes.","authors":"Felix Drost, Emilio Dorigatti, Adrian Straub, Philipp Hilgendorf, Karolin I Wagner, Kersten Heyer, Marta López Montes, Bernd Bischl, Dirk H Busch, Kilian Schober, Benjamin Schubert","doi":"10.1016/j.xgen.2024.100634","DOIUrl":"https://doi.org/10.1016/j.xgen.2024.100634","url":null,"abstract":"<p><p>Cancer cells and pathogens can evade T cell receptors (TCRs) via mutations in immunogenic epitopes. TCR cross-reactivity (i.e., recognition of multiple epitopes with sequence similarities) can counteract such escape but may cause severe side effects in cell-based immunotherapies through targeting self-antigens. To predict the effect of epitope point mutations on T cell functionality, we here present the random forest-based model Predicting T Cell Epitope-Specific Activation against Mutant Versions (P-TEAM). P-TEAM was trained and tested on three datasets with TCR responses to single-amino-acid mutations of the model epitope SIINFEKL, the tumor neo-epitope VPSVWRSSL, and the human cytomegalovirus antigen NLVPMVATV, totaling 9,690 unique TCR-epitope interactions. P-TEAM was able to accurately classify T cell reactivities and quantitatively predict T cell functionalities for unobserved single-point mutations and unseen TCRs. Overall, P-TEAM provides an effective computational tool to study T cell responses against mutated epitopes.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-02DOI: 10.1016/j.xgen.2024.100628
Laura V Blanton, Adrianna K San Roman, Geryl Wood, Ashley Buscetta, Nicole Banks, Helen Skaletsky, Alexander K Godfrey, Thao T Pham, Jennifer F Hughes, Laura G Brown, Paul Kruszka, Angela E Lin, Daniel L Kastner, Maximilian Muenke, David C Page
{"title":"Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses in vivo and in vitro in four human cell types.","authors":"Laura V Blanton, Adrianna K San Roman, Geryl Wood, Ashley Buscetta, Nicole Banks, Helen Skaletsky, Alexander K Godfrey, Thao T Pham, Jennifer F Hughes, Laura G Brown, Paul Kruszka, Angela E Lin, Daniel L Kastner, Maximilian Muenke, David C Page","doi":"10.1016/j.xgen.2024.100628","DOIUrl":"10.1016/j.xgen.2024.100628","url":null,"abstract":"<p><p>Recent in vitro studies of human sex chromosome aneuploidy showed that the Xi (\"inactive\" X) and Y chromosomes broadly modulate autosomal and Xa (\"active\" X) gene expression. We tested these findings in vivo. Linear modeling of CD4<sup>+</sup> T cells and monocytes from individuals with one to three X chromosomes and zero to two Y chromosomes revealed 82 sex-chromosomal and 344 autosomal genes whose expression changed significantly with Xi and/or Y dosage in vivo. Changes in sex-chromosomal expression were remarkably constant in vivo and in vitro; autosomal responses to Xi and/or Y dosage were largely cell-type specific (∼2.6-fold more variation than sex-chromosomal responses). Targets of the sex-chromosomal transcription factors ZFX and ZFY accounted for a significant fraction of these autosomal responses both in vivo and in vitro. We conclude that the human Xi and Y transcriptomes are surprisingly robust and stable, yet they modulate autosomal and Xa genes in a cell-type-specific fashion.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2024-08-02DOI: 10.1016/j.xgen.2024.100629
Daphna Rothschild, Teodorus Theo Susanto, Xin Sui, Jeffrey P Spence, Ramya Rangan, Naomi R Genuth, Nasa Sinnott-Armstrong, Xiao Wang, Jonathan K Pritchard, Maria Barna
{"title":"Diversity of ribosomes at the level of rRNA variation associated with human health and disease.","authors":"Daphna Rothschild, Teodorus Theo Susanto, Xin Sui, Jeffrey P Spence, Ramya Rangan, Naomi R Genuth, Nasa Sinnott-Armstrong, Xiao Wang, Jonathan K Pritchard, Maria Barna","doi":"10.1016/j.xgen.2024.100629","DOIUrl":"10.1016/j.xgen.2024.100629","url":null,"abstract":"<p><p>With hundreds of copies of rDNA, it is unknown whether they possess sequence variations that form different types of ribosomes. Here, we developed an algorithm for long-read variant calling, termed RGA, which revealed that variations in human rDNA loci are predominantly insertion-deletion (indel) variants. We developed full-length rRNA sequencing (RIBO-RT) and in situ sequencing (SWITCH-seq), which showed that translating ribosomes possess variation in rRNA. Over 1,000 variants are lowly expressed. However, tens of variants are abundant and form distinct rRNA subtypes with different structures near indels as revealed by long-read rRNA structure probing coupled to dimethyl sulfate sequencing. rRNA subtypes show differential expression in endoderm/ectoderm-derived tissues, and in cancer, low-abundance rRNA variants can become highly expressed. Together, this study identifies the diversity of ribosomes at the level of rRNA variants, their chromosomal location, and unique structure as well as the association of ribosome variation with tissue-specific biology and cancer.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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