HGG Advances最新文献_第8页

Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment. 在小鼠神经发育过程中，Kcnk9的印记表达先于双拷贝非生产性增强子-启动子相互作用。

IF 4.4

HGG Advances Pub Date : 2024-04-11 Epub Date: 2024-01-30 DOI: 10.1016/j.xhgg.2024.100271

Cecilia Rengifo Rojas, Jil Cercy, Sophie Perillous, Céline Gonthier-Guéret, Bertille Montibus, Stéphanie Maupetit-Méhouas, Astrid Espinadel, Marylou Dupré, Charles C Hong, Kenichiro Hata, Kazuhiko Nakabayashi, Antonius Plagge, Tristan Bouschet, Philippe Arnaud, Isabelle Vaillant, Franck Court

{"title":"Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment.","authors":"Cecilia Rengifo Rojas, Jil Cercy, Sophie Perillous, Céline Gonthier-Guéret, Bertille Montibus, Stéphanie Maupetit-Méhouas, Astrid Espinadel, Marylou Dupré, Charles C Hong, Kenichiro Hata, Kazuhiko Nakabayashi, Antonius Plagge, Tristan Bouschet, Philippe Arnaud, Isabelle Vaillant, Franck Court","doi":"10.1016/j.xhgg.2024.100271","DOIUrl":"10.1016/j.xhgg.2024.100271","url":null,"abstract":"It is only partially understood how constitutive allelic methylation at imprinting control regions (ICRs) interacts with other regulation levels to drive timely parental allele-specific expression along large imprinted domains. The Peg13-Kcnk9 domain is an imprinted domain with important brain functions. To gain insights into its regulation during neural commitment, we performed an integrative analysis of its allele-specific epigenetic, transcriptomic, and cis-spatial organization using a mouse stem cell-based corticogenesis model that recapitulates the control of imprinted gene expression during neurodevelopment. We found that, despite an allelic higher-order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts occurred on both alleles, although they were productive only on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side and suggests a more nuanced role for allelic CTCF binding at some ICRs.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Queering Genomics: How Cisnormativity Undermines Genomic Science. Queering Genomics: How Cisnormativity Undermines Genomic Science.

IF 4.4

HGG Advances Pub Date : 2024-04-01 DOI: 10.1016/j.xhgg.2024.100297

Leila Jamal, Kimberly Zayhowski, Tala Berro, Kellan Baker

引用次数: 0

The severity of MUSK pathogenic variants is predicted by the protein domain they disrupt. MUSK 致病变体的严重程度可通过其破坏的蛋白质结构域来预测。

IF 4.4

HGG Advances Pub Date : 2024-04-01 DOI: 10.1016/j.xhgg.2024.100288

Benjamin T. Cocanougher, Samuel W. Liu, Ludmila Francescatto, Alexander Behura, Mariele Anneling, David G. Jackson, Kristen L. Deak, Chi D. Hornik, Mai K. ElMallah, Carolyn E Pizoli, Edward C. Smith, Khoon Ghee Queenie Tan, Marie T. McDonald

引用次数: 0

MRBEE: A bias-corrected multivariable Mendelian Randomization method. MRBEE：一种偏差校正多变量孟德尔随机方法。

IF 4.4

HGG Advances Pub Date : 2024-04-01 DOI: 10.1016/j.xhgg.2024.100290

Noah Lorincz-Comi, Yihe Yang, Gen Li, Xiaofeng Zhu

引用次数: 0

In vitro data suggest a role for PMS2 Kozak sequence mutations in Lynch Syndrome risk. 体外数据表明，PMS2 Kozak 序列突变在林奇综合征风险中发挥作用。

IF 4.4

HGG Advances Pub Date : 2024-04-01 DOI: 10.1016/j.xhgg.2024.100298

Evanjalina J. Matoy, Jocelyn N. Plowman, Cynthia J. Watson, Michael A. Belshan, Elizabeth E. Blue, Chad D. Huff, Holly A F Stessman

引用次数: 0

DNA methylation episignature and comparative epigenomic profiling for Pitt-Hopkins syndrome caused by TCF4 variants. TCF4变体导致的皮特-霍普金斯综合征的DNA甲基化表征和表观基因组比较分析。

IF 4.4

HGG Advances Pub Date : 2024-04-01 DOI: 10.1016/j.xhgg.2024.100289

Liselot van der Laan, Peter Lauffer, Kathleen Rooney, Ananília Silva, Sadegheh Haghshenas, R. Relator, M. Levy, S. Trajkova, Sylvia A Huisman, E. Bijlsma, T. Kleefstra, B. V. van Bon, Özlem Baysal, Christiane Zweier, M. Palomares-Bralo, Jan Fischer, K. Szakszon, Laurence Faivre, Amélie Piton, S. Mesman, Ron Hochstenbach, M. Elting, J. M. van Hagen, Astrid S Plomp, M. Mannens, Marielle Alders, M. M. van Haelst, G. B. Ferrero, Alfredo Brusco, P. Henneman, D. Sweetser, B. Sadikovic, A. Vitobello, L. Menke

引用次数: 0

Mendelian randomization with incomplete measurements on the exposure in the Hispanic Community Health Study/Study of Latinos. 西班牙裔社区健康研究/拉丁裔研究中暴露不完全测量的孟德尔随机化。

IF 4.4

HGG Advances Pub Date : 2024-01-11 Epub Date: 2023-10-28 DOI: 10.1016/j.xhgg.2023.100245

Yilun Li, Kin Yau Wong, Annie Green Howard, Penny Gordon-Larsen, Heather M Highland, Mariaelisa Graff, Kari E North, Carolina G Downie, Christy L Avery, Bing Yu, Kristin L Young, Victoria L Buchanan, Robert Kaplan, Lifang Hou, Brian Thomas Joyce, Qibin Qi, Tamar Sofer, Jee-Young Moon, Dan-Yu Lin

{"title":"Mendelian randomization with incomplete measurements on the exposure in the Hispanic Community Health Study/Study of Latinos.","authors":"Yilun Li, Kin Yau Wong, Annie Green Howard, Penny Gordon-Larsen, Heather M Highland, Mariaelisa Graff, Kari E North, Carolina G Downie, Christy L Avery, Bing Yu, Kristin L Young, Victoria L Buchanan, Robert Kaplan, Lifang Hou, Brian Thomas Joyce, Qibin Qi, Tamar Sofer, Jee-Young Moon, Dan-Yu Lin","doi":"10.1016/j.xhgg.2023.100245","DOIUrl":"10.1016/j.xhgg.2023.100245","url":null,"abstract":"Mendelian randomization has been widely used to assess the causal effect of a heritable exposure variable on an outcome of interest, using genetic variants as instrumental variables. In practice, data on the exposure variable can be incomplete due to high cost of measurement and technical limits of detection. In this paper, we propose a valid and efficient method to handle both unmeasured and undetectable values of the exposure variable in one-sample Mendelian randomization analysis with individual-level data. We estimate the causal effect of the exposure variable on the outcome using maximum likelihood estimation and develop an expectation maximization algorithm for the computation of the estimator. Simulation studies show that the proposed method performs well in making inference on the causal effect. We apply our method to the Hispanic Community Health Study/Study of Latinos, a community-based prospective cohort study, and estimate the causal effect of several metabolites on phenotypes of interest.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conflating race and ancestry: Tracing decision points about population descriptors over the precision medicine research life course. 种族和祖先的冲突：追踪精准医学研究生命过程中关于人口描述符的决策点。

IF 4.4

HGG Advances Pub Date : 2024-01-11 Epub Date: 2023-09-27 DOI: 10.1016/j.xhgg.2023.100243

Michael Bentz, Aliya Saperstein, Stephanie M Fullerton, Janet K Shim, Sandra Soo-Jin Lee

引用次数: 0

CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction. CRISPR/Cas9产生的PTCHD1 2489T>G干细胞在进行神经诱导时重现患者表型。

IF 4.4

HGG Advances Pub Date : 2024-01-11 Epub Date: 2023-11-24 DOI: 10.1016/j.xhgg.2023.100257

Kathryn O Farley, Catherine A Forbes, Nicole C Shaw, Emma Kuzminski, Michelle Ward, Gareth Baynam, Timo Lassmann, Vanessa S Fear

{"title":"CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction.","authors":"Kathryn O Farley, Catherine A Forbes, Nicole C Shaw, Emma Kuzminski, Michelle Ward, Gareth Baynam, Timo Lassmann, Vanessa S Fear","doi":"10.1016/j.xhgg.2023.100257","DOIUrl":"10.1016/j.xhgg.2023.100257","url":null,"abstract":"An estimated 3.5%-5.9% of the global population live with rare diseases, and approximately 80% of these diseases have a genetic cause. Rare genetic diseases are difficult to diagnose, with some affected individuals experiencing diagnostic delays of 5-30 years. Next-generation sequencing has improved clinical diagnostic rates to 33%-48%. In a majority of cases, novel variants potentially causing the disease are discovered. These variants require functional validation in specialist laboratories, resulting in a diagnostic delay. In the interim, the finding is classified as a genetic variant of uncertain significance (VUS) and the affected individual remains undiagnosed. A VUS (PTCHD1 c. 2489T>G) was identified in a child with autistic behavior, global developmental delay, and hypotonia. Loss of function mutations in PTCHD1 are associated with autism spectrum disorder and intellectual disability; however, the molecular function of PTCHD1 and its role in neurodevelopmental disease is unknown. Here, we apply CRISPR gene editing and induced pluripotent stem cell (iPSC) neural disease modeling to assess the variant. During differentiation from iPSCs to neural progenitors, we detect subtle but significant gene signatures in synaptic transmission and muscle contraction pathways. Our work supports the causal link between the genetic variant and the child's phenotype, providing evidence for the variant to be considered a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. In addition, our study provides molecular data on the role of PTCHD1 in the context of other neurodevelopmental disorders.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility. 多种TP53 p.R337H单倍型及其对肿瘤易感性的影响。

IF 4.4

HGG Advances Pub Date : 2024-01-11 Epub Date: 2023-10-04 DOI: 10.1016/j.xhgg.2023.100244

Emilia M Pinto, Cintia Fridman, Bonald C Figueiredo, Hector Salvador, Manuel R Teixeira, Carla Pinto, Manuela Pinheiro, Christian P Kratz, Cinzia Lavarino, Edith A M F Legal, Anh Le, Gregory Kelly, Erika Koeppe, Elena M Stoffel, Kelsey Breen, Stefanie Hahner, Britta Heinze, Piti Techavichit, Amanda Krause, Tsutomu Ogata, Yasuko Fujisawa, Michael F Walsh, Huma Q Rana, Kara N Maxwell, Judy E Garber, Carlos Rodriguez-Galindo, Raul C Ribeiro, Gerard P Zambetti

{"title":"Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility.","authors":"Emilia M Pinto, Cintia Fridman, Bonald C Figueiredo, Hector Salvador, Manuel R Teixeira, Carla Pinto, Manuela Pinheiro, Christian P Kratz, Cinzia Lavarino, Edith A M F Legal, Anh Le, Gregory Kelly, Erika Koeppe, Elena M Stoffel, Kelsey Breen, Stefanie Hahner, Britta Heinze, Piti Techavichit, Amanda Krause, Tsutomu Ogata, Yasuko Fujisawa, Michael F Walsh, Huma Q Rana, Kara N Maxwell, Judy E Garber, Carlos Rodriguez-Galindo, Raul C Ribeiro, Gerard P Zambetti","doi":"10.1016/j.xhgg.2023.100244","DOIUrl":"10.1016/j.xhgg.2023.100244","url":null,"abstract":"The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134∗ variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplotype as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can influence the cancer phenotype.","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10597792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0