NPJ Genomic Medicine最新文献_第2页

Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses. 对来自未解决罕见病病例的 ES 数据中的 CNV 进行全面的重新分析，从而得出新的诊断结果。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-10-26 DOI: 10.1038/s41525-024-00436-6

German Demidov, Burcu Yaldiz, José Garcia-Pelaez, Elke de Boer, Nika Schuermans, Liedewei Van de Vondel, Ida Paramonov, Lennart F Johansson, Francesco Musacchia, Elisa Benetti, Gemma Bullich, Karolis Sablauskas, Sergi Beltran, Christian Gilissen, Alexander Hoischen, Stephan Ossowski, Richarda de Voer, Katja Lohmann, Carla Oliveira, Ana Topf, Lisenka E L M Vissers, Steven Laurie

{"title":"Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses.","authors":"German Demidov, Burcu Yaldiz, José Garcia-Pelaez, Elke de Boer, Nika Schuermans, Liedewei Van de Vondel, Ida Paramonov, Lennart F Johansson, Francesco Musacchia, Elisa Benetti, Gemma Bullich, Karolis Sablauskas, Sergi Beltran, Christian Gilissen, Alexander Hoischen, Stephan Ossowski, Richarda de Voer, Katja Lohmann, Carla Oliveira, Ana Topf, Lisenka E L M Vissers, Steven Laurie","doi":"10.1038/s41525-024-00436-6","DOIUrl":"10.1038/s41525-024-00436-6","url":null,"abstract":"We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"49"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biallelic GGGCC repeat expansion leading to NAXE-related mitochondrial encephalopathy. 双倍性 GGGCC 重复扩增导致 NAXE 相关线粒体脑病。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-10-25 DOI: 10.1038/s41525-024-00429-5

Kokoro Ozaki, Yukiko Yatsuka, Yoshinobu Oyazato, Atsushi Nishiyama, Kazuhiro R Nitta, Yoshihito Kishita, Takuya Fushimi, Masaru Shimura, Shohei Noma, Yohei Sugiyama, Michihira Tagami, Moe Fukunaga, Hiroko Kinoshita, Tomoko Hirata, Wataru Suda, Yasuhiro Murakawa, Piero Carninci, Akira Ohtake, Kei Murayama, Yasushi Okazaki

{"title":"Biallelic GGGCC repeat expansion leading to NAXE-related mitochondrial encephalopathy.","authors":"Kokoro Ozaki, Yukiko Yatsuka, Yoshinobu Oyazato, Atsushi Nishiyama, Kazuhiro R Nitta, Yoshihito Kishita, Takuya Fushimi, Masaru Shimura, Shohei Noma, Yohei Sugiyama, Michihira Tagami, Moe Fukunaga, Hiroko Kinoshita, Tomoko Hirata, Wataru Suda, Yasuhiro Murakawa, Piero Carninci, Akira Ohtake, Kei Murayama, Yasushi Okazaki","doi":"10.1038/s41525-024-00429-5","DOIUrl":"https://doi.org/10.1038/s41525-024-00429-5","url":null,"abstract":"Repeat expansions cause at least 50 hereditary disorders, including Friedreich ataxia and other diseases known to cause mitochondrial dysfunction. We identified a patient with NAXE-related mitochondrial encephalopathy and novel biallelic GGGCC repeat expansion as long as ~200 repeats in the NAXE promoter region using long-read sequencing. In addition to a marked reduction in the RNA and protein, we found a marked reduction in nascent RNA in the promoter using native elongating transcript-cap analysis of gene expression (NET-CAGE), suggesting transcriptional suppression. Accordingly, CpG hypermethylation was observed in the repeat region. Genetic analyses determined that homozygosity in the patient was due to maternal chromosome 1 uniparental disomy (UPD). We assessed short variants within NAXE including the repeat region in the undiagnosed mitochondrial encephalopathy cohort of 242 patients. This study identified the GGGCC repeat expansion causing a mitochondrial disease and suggests that UPD could significantly contribute to homozygosity for rare repeat-expanded alleles.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"48"},"PeriodicalIF":4.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic decision frameworks for the socially responsible use of precision medicine. 以对社会负责的方式使用精准医疗的系统决策框架。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-10-05 DOI: 10.1038/s41525-024-00433-9

Ian S Peebles, David B Kinney, Emily Foster-Hanson

引用次数: 0

A genotype imputation reference panel specific for native Southeast Asian populations. 专门针对东南亚本地人群的基因型推算参考面板。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-10-05 DOI: 10.1038/s41525-024-00435-7

Alvin Cengnata, Lian Deng, Wai-Sum Yap, Lay-Hong Renee Lim, Chee-Onn Leong, Shuhua Xu, Boon-Peng Hoh

{"title":"A genotype imputation reference panel specific for native Southeast Asian populations.","authors":"Alvin Cengnata, Lian Deng, Wai-Sum Yap, Lay-Hong Renee Lim, Chee-Onn Leong, Shuhua Xu, Boon-Peng Hoh","doi":"10.1038/s41525-024-00435-7","DOIUrl":"10.1038/s41525-024-00435-7","url":null,"abstract":"We report the development of a \"Southeast Asian Specific (SEA-specific) Reference Panel\" through a \"Cross-panel Imputation\" approach, consisting of 2550 samples derived from the GA100K, SG10K, and the Peninsular Malaysia Orang Asli (OA) datasets, covering 113,851,450 variants. The SEA-specific panel produced more high confidence variants than 1000 Genomes Project (1KGP) when imputing the OA (8.9 million SEA-specific vs 8.1 million 1KGP) and the Singapore Genome Variation Project (SGVP) (12.5 million SEA-specific vs 11.8 million 1KGP) genotyping datasets. Further, the SEA-specific panel imputed SNPs with better estimated quality scores (INFO, DR2 and R2) on the OA genotyping dataset when comparing with TOPMED and the Human Genome Diversity Project, but performed similarly on SGVP dataset. This panel also exhibited higher recall and non-reference disconcordance rates, indicating the influence of ancestry closeness of the reference panel. However, we note that the imputation accuracy may be compromised by the size of the reference panel.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"47"},"PeriodicalIF":4.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease. 太空和微重力对镰状细胞病红细胞的基因环境影响

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-09-30 DOI: 10.1038/s41525-024-00427-7

Norris E Igbineweka, Jack J W A van Loon

{"title":"Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease.","authors":"Norris E Igbineweka, Jack J W A van Loon","doi":"10.1038/s41525-024-00427-7","DOIUrl":"10.1038/s41525-024-00427-7","url":null,"abstract":"A fundamental question in human biology and for hematological disease is how do complex gene-environment interactions lead to individual disease outcome? This is no less the case for sickle cell disease (SCD), a monogenic disorder of Mendelian inheritance, both clinical course, severity, and treatment response, is variable amongst affected individuals. New insight and discovery often lie between the intersection of seemingly disparate disciplines. Recently, opportunities for space medicine have flourished and have offered a new paradigm for study. Two recent Nature papers have shown that hemolysis and oxidative stress play key mechanistic roles in erythrocyte pathogenesis during spaceflight. This paper reviews existing genetic and environmental modifiers of the sickle cell disease phenotype. It reviews evidence for erythrocyte pathology in microgravity environments and demonstrates why this may be relevant for the unique gene-environment interaction of the SCD phenotype. It also introduces the hematology and scientific community to methodological tools for evaluation in space and microgravity research. The increasing understanding of space biology may yield insight into gene-environment influences and new treatment paradigms in SCD and other hematological disease phenotypes.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"44"},"PeriodicalIF":4.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Native Hawaiian and Pacific Islander populations in genomic research. 基因组研究中的夏威夷原住民和太平洋岛民。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-09-30 DOI: 10.1038/s41525-024-00428-6

Edra K Ha, Daniel Shriner, Shawneequa L Callier, Lorinda Riley, Adebowale A Adeyemo, Charles N Rotimi, Amy R Bentley

引用次数: 0

Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank. 英国生物库中神经发育拷贝数变异携带者认知结果的多基因分层。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-09-28 DOI: 10.1038/s41525-024-00426-8

Thomas J Dinneen, Fiana Ní Ghrálaigh, Cathal Ormond, Elizabeth A Heron, George Kirov, Lorna M Lopez, Louise Gallagher

{"title":"Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank.","authors":"Thomas J Dinneen, Fiana Ní Ghrálaigh, Cathal Ormond, Elizabeth A Heron, George Kirov, Lorna M Lopez, Louise Gallagher","doi":"10.1038/s41525-024-00426-8","DOIUrl":"https://doi.org/10.1038/s41525-024-00426-8","url":null,"abstract":"Rare copy-number variants associated with neurodevelopmental conditions (ND-CNVs) exhibit variable expressivity of clinical, physical, behavioural outcomes. Findings from clinically ascertained cohorts suggest this variability may be partly due to additional genetic variation. Here, we assessed the impact of polygenic scores (PGS) and rare variants on ND-CNV carrier fluid intelligence (FI) scores in the UK Biobank. Greater PGS for cognition (PSCog) and educational attainment (PSEA) is associated with increased FI scores in all ND-CNVs (n = 1317), 15q11.2 del. (n = 543), and 16p13.11 dup. carriers (n = 275). No association of rare variants associated with intellectual disability, autism, or putatively loss-of-function, brain-expressed genes was found. Positive predictive values in the first deciles of PScog and PSEA showed a two- to five-fold increase in the rate of low FI scores compared to baseline rates. These findings demonstrate that PGS can stratify ND-CNV carrier cognitive outcomes in a population-based cohort.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"43"},"PeriodicalIF":4.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CDK4 is co-amplified with either TP53 promoter gene fusions or MDM2 through distinct mechanisms in osteosarcoma. 在骨肉瘤中，CDK4通过不同的机制与TP53启动子基因融合或MDM2共同扩增。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-09-25 DOI: 10.1038/s41525-024-00430-y

Karim H Saba, Valeria Difilippo, Emelie Styring, Jenny Nilsson, Linda Magnusson, Hilda van den Bos, René Wardenaar, Diana C J Spierings, Floris Foijer, Michaela Nathrath, Felix Haglund de Flon, Daniel Baumhoer, Karolin H Nord

{"title":"CDK4 is co-amplified with either TP53 promoter gene fusions or MDM2 through distinct mechanisms in osteosarcoma.","authors":"Karim H Saba, Valeria Difilippo, Emelie Styring, Jenny Nilsson, Linda Magnusson, Hilda van den Bos, René Wardenaar, Diana C J Spierings, Floris Foijer, Michaela Nathrath, Felix Haglund de Flon, Daniel Baumhoer, Karolin H Nord","doi":"10.1038/s41525-024-00430-y","DOIUrl":"https://doi.org/10.1038/s41525-024-00430-y","url":null,"abstract":"Amplification of the MDM2 and CDK4 genes on chromosome 12 is commonly associated with low-grade osteosarcomas. In this study, we conducted high-resolution genomic and transcriptomic analyses on 33 samples from 25 osteosarcomas, encompassing both high- and low-grade cases with MDM2 and/or CDK4 amplification. We discerned four major subgroups, ranging from nearly intact genomes to heavily rearranged ones, each harbouring CDK4 and MDM2 amplification or CDK4 amplification with TP53 structural alterations. While amplicons involving MDM2 exhibited signs of an initial chromothripsis event, no evidence of chromothripsis was found in TP53-rearranged cases. Instead, the initial disruption of the TP53 locus led to co-amplification of the CDK4 locus. Additionally, we observed recurring promoter swapping events involving the regulatory regions of the FRS2, PLEKHA5, and TP53 genes. These events resulted in ectopic expression of partner genes, with the ELF1 gene being upregulated by the FRS2 and TP53 promoter regions in two distinct cases.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"42"},"PeriodicalIF":4.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics. 1 型神经纤维瘤病的产前诊断和种系杂交的陷阱。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-09-08 DOI: 10.1038/s41525-024-00425-9

Laurence Pacot, Dominique Vidaud, Manuela Ye, Albain Chansavang, Audrey Coustier, Theodora Maillard, Cécile Barbance, Ingrid Laurendeau, Bérénice Hébrard, Ariane Lunati-Rozie, Benoît Funalot, Pierre Wolkenstein, Michel Vidaud, Alice Goldenberg, Fanny Morice-Picard, Djihad Hadjadj, Béatrice Parfait, Eric Pasmant

{"title":"Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics.","authors":"Laurence Pacot, Dominique Vidaud, Manuela Ye, Albain Chansavang, Audrey Coustier, Theodora Maillard, Cécile Barbance, Ingrid Laurendeau, Bérénice Hébrard, Ariane Lunati-Rozie, Benoît Funalot, Pierre Wolkenstein, Michel Vidaud, Alice Goldenberg, Fanny Morice-Picard, Djihad Hadjadj, Béatrice Parfait, Eric Pasmant","doi":"10.1038/s41525-024-00425-9","DOIUrl":"10.1038/s41525-024-00425-9","url":null,"abstract":"We report our 5-year experience in neurofibromatosis type 1 prenatal diagnosis (PND): 205 PNDs in 146 women (chorionic villus biopsies, 88% or amniocentesis, 12%). The NF1 variant was present in 85 (41%) and absent in 122 (59%) fetuses. Among 205 pregnancies (207 fetuses), 135 were carried to term (119 unaffected and 16 NF1 affected children), 69 pregnancy terminations (affected fetuses), 2 miscarriages, and 1 in utero death. The majority of PND requests came from parents with sporadic NF1. We describe two PNDs in women with mosaic NF1. In both families, direct PND showed the absence of the maternal NF1 variant in the fetus. However, microsatellite markers analysis showed that the risk haplotype had been transmitted. These rare cases of germline mosaicism illustrate the pitfall of indirect PND. Our study illustrates the crucial consequences of PND for medical and genetic counseling decisions. We also point to the challenges of germline mosaics.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"41"},"PeriodicalIF":4.7,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MiRNA expression as outcome predictor in pediatric AML: systematic evaluation of a new model. 作为小儿急性髓细胞白血病预后预测因子的 MiRNA 表达：对一种新模型的系统评估。

IF 4.7 2区医学

NPJ Genomic Medicine Pub Date : 2024-08-06 DOI: 10.1038/s41525-024-00424-w

Ivan Ellson, Jordi Martorell-Marugán, Pedro Carmona-Sáez, Verónica Ramos-Mejia

引用次数: 0