Current Protocols in Human Genetics最新文献_第6页

Genome-Scale Sequencing to Identify Genes Involved in Mendelian Disorders 基因组级测序鉴定孟德尔疾病相关基因

Current Protocols in Human Genetics Pub Date : 2018-02-16 DOI: 10.1002/0471142905.hg0613s79

Thomas C. Markello, David R. Adams

{"title":"Genome-Scale Sequencing to Identify Genes Involved in Mendelian Disorders","authors":"Thomas C. Markello, David R. Adams","doi":"10.1002/0471142905.hg0613s79","DOIUrl":"10.1002/0471142905.hg0613s79","url":null,"abstract":"The analysis of genome-scale sequence data can be defined as the interrogation of a complete set of genetic instructions in a search for individual loci that produce or contribute to a pathological state. Bioinformatic analysis of sequence data requires sufficient discriminant power to find this needle in a haystack. Current approaches make choices about selectivity and specificity thresholds, and the quality, quantity, and completeness of the data in these analyses. There are many software tools available for individual, analytic component-tasks, including commercial and open-source options. Three major types of techniques have been included in most published exome projects to date: frequency/population genetic analysis, inheritance state consistency, and predictions of deleteriousness. The required infrastructure and use of each technique during analysis of genomic sequence data for clinical and research applications are discussed. Future developments will alter the strategies and sequence of using these tools and are also discussed. Curr. Protoc. Hum. Genet. 79:6.13.1-6.13.19. © 2013 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0471142905.hg0613s79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32101513","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}

引用次数: 4

Diagnosing Lysosomal Storage Disorders: Mucopolysaccharidosis Type II 诊断溶酶体贮积障碍:粘多糖病II型

Current Protocols in Human Genetics Pub Date : 2018-02-16 DOI: 10.1002/0471142905.hg1714s79

Britt A. Johnson, Otto P. van Diggelen, Angela Dajnoki, Olaf A. Bodamer

{"title":"Diagnosing Lysosomal Storage Disorders: Mucopolysaccharidosis Type II","authors":"Britt A. Johnson, Otto P. van Diggelen, Angela Dajnoki, Olaf A. Bodamer","doi":"10.1002/0471142905.hg1714s79","DOIUrl":"10.1002/0471142905.hg1714s79","url":null,"abstract":"Mucopolysaccharidosis type II (MPS II) is an X-linked lysosomal storage disorder caused by a deficiency of iduronate 2-sulfatase (IDS). Progressive, intralysosomal accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate in almost all tissues leads to multi-organ involvement in affected males but to virtual absence of symptoms in heterozygote female carriers due to preferential inactivation of the mutant allele. Diagnosis of MPS II in males is based on IDS analysis in leukocytes, fibroblasts, plasma, or dried blood spots (DBS), whereas IDS activities may be within the normal range in heterozygote females. The advent of fluorometric and mass spectrometry methods for enzyme analysis in DBS has simplified the diagnostic approach for MPS II males. Molecular analysis of the IDS gene confirms the diagnosis of MPS II in males and is the only diagnostic test to confirm carrier status in females. This unit provides detailed analytical protocols for measurement of IDS activity in DBS and plasma using a fluorometric assay. Curr. Protoc. Hum. Genet. 79:17.14.1-17.14.9. © 2013 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0471142905.hg1714s79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10482438","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}

引用次数: 6

Analysis and Annotation of Whole-Genome or Whole-Exome Sequencing–Derived Variants for Clinical Diagnosis 用于临床诊断的全基因组或全外显子组测序衍生变异的分析和注释

Current Protocols in Human Genetics Pub Date : 2018-02-16 DOI: 10.1002/0471142905.hg0924s79

Elizabeth A. Worthey

{"title":"Analysis and Annotation of Whole-Genome or Whole-Exome Sequencing–Derived Variants for Clinical Diagnosis","authors":"Elizabeth A. Worthey","doi":"10.1002/0471142905.hg0924s79","DOIUrl":"10.1002/0471142905.hg0924s79","url":null,"abstract":"Over the last several years, next-generation sequencing (NGS) has transformed genomic research through substantial advances in technology and reduction in the cost of sequencing, and also in the systems required for analysis of these large volumes of data. This technology is now being used as a standard molecular diagnostic test under particular circumstances in some clinical settings. The advances in sequencing have come so rapidly that the major bottleneck in identification of causal variants is no longer the sequencing but rather the analysis and interpretation. Interpretation of genetic findings in a clinical setting is scarcely a new challenge, but the task is increasingly complex in clinical genome-wide sequencing given the dramatic increase in dataset size and complexity. This increase requires the development of novel or repositioned analysis tools, methodologies, and processes. This unit provides an overview of these items. Specific challenges related to implementation in a clinical setting are discussed. Curr. Protoc. Hum. Genet. 79:9.24.1-9.24.24. © 2013 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0471142905.hg0924s79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473565","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}

引用次数: 11

Induced Pluripotent Stem Cells from Ovarian Tissue 卵巢组织诱导多能干细胞

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.47

Sophia Salas, Nicholas Ng, Behzad Gerami-Naini, Raymond M. Anchan

{"title":"Induced Pluripotent Stem Cells from Ovarian Tissue","authors":"Sophia Salas, Nicholas Ng, Behzad Gerami-Naini, Raymond M. Anchan","doi":"10.1002/cphg.47","DOIUrl":"10.1002/cphg.47","url":null,"abstract":"Yamanaka and colleagues revolutionized stem cell biology and regenerative medicine by observing that somatic cells can be reprogrammed into pluripotent stem cells. Evidence indicates that induced pluripotent stem (iPS) cells retain epigenetic memories that bias their spontaneous differentiation into the originating somatic cell type, therefore epigenetic memory may be exploited to improve tissue specific regeneration. We recently showed that iPS cells reprogrammed from ovarian granulosa cells using mouse and human tissue overwhelmingly differentiate homotypically into ovarian steroidogenic and primordial germ cells. Herein we detail a protocol for the culture of human ovarian granulosa cells. We review approaches for reprogramming human ovarian granulosa cells into iPS cells. Standard methods to induce pluripotency are outlined, concentrating on integrative retroviruses. Additionally, alternative protocols for lentivirus and Sendai virus are provided. Each approach has inherent limitations, such as reprogramming efficiency, insertional mutagenesis, and partial reprogramming. Major advances continue to be made in somatic cell reprogramming to identify an optimal approach and utilization in cell-based therapies. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35461916","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}

引用次数: 5

Analysis and Annotation of Whole-Genome or Whole-Exome Sequencing Derived Variants for Clinical Diagnosis 全基因组或全外显子组测序衍生变异的分析和注释用于临床诊断

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.49

Elizabeth A. Worthey

{"title":"Analysis and Annotation of Whole-Genome or Whole-Exome Sequencing Derived Variants for Clinical Diagnosis","authors":"Elizabeth A. Worthey","doi":"10.1002/cphg.49","DOIUrl":"10.1002/cphg.49","url":null,"abstract":"Over the last 10 years, next-generation sequencing (NGS) has transformed genomic research through substantial advances in technology and reduction in the cost of sequencing, and also in the systems required for analysis of these large volumes of data. This technology is now being used as a standard molecular diagnostic test in some clinical settings. The advances in sequencing have come so rapidly that the major bottleneck in identification of causal variants is no longer the sequencing or analysis (given access to appropriate tools), but rather clinical interpretation. Interpretation of genetic findings in a complex and ever changing clinical setting is scarcely a new challenge, but the task is increasingly complex in clinical genome-wide sequencing given the dramatic increase in dataset size and complexity. This increase requires application of appropriate interpretation tools, as well as development and application of appropriate methodologies and standard procedures. This unit provides an overview of these items. Specific challenges related to implementation of genome-wide sequencing in a clinical setting are discussed. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.49","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35461914","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}

引用次数: 25

High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3) in Urine Collected on Filter Paper 法布里病的高危筛查:用串联质谱法分析滤纸尿液中Globotriaosylceramide (Gb3)

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.34

Christiane Auray-Blais, Pamela Lavoie, Michel Boutin, Mona Abaoui

{"title":"High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3) in Urine Collected on Filter Paper","authors":"Christiane Auray-Blais, Pamela Lavoie, Michel Boutin, Mona Abaoui","doi":"10.1002/cphg.34","DOIUrl":"10.1002/cphg.34","url":null,"abstract":"Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the high-risk screening of patients who might have Fabry disease using a simple, rapid, non-invasive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb3) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for high-risk screening of patients with ophthalmologic manifestations and in an on-going study for high-risk screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34892127","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}

引用次数: 10

Analysis of Gene-Gene Interactions 基因-基因相互作用分析

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.45

Brian S. Cole, Molly A. Hall, Ryan J. Urbanowicz, Diane Gilbert-Diamond, Jason H. Moore

引用次数: 29

Population Stratification in Genetic Association Studies 遗传关联研究中的群体分层。

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.48

Jacklyn N. Hellwege, Jacob M. Keaton, Ayush Giri, Xiaoyi Gao, Digna R. Velez Edwards, Todd L. Edwards

引用次数: 119

COSMIC: High-Resolution Cancer Genetics Using the Catalogue of Somatic Mutations in Cancer COSMIC:利用癌症体细胞突变目录的高分辨率癌症遗传学

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.21

S.A. Forbes, D. Beare, N. Bindal, S. Bamford, S. Ward, C.G. Cole, M. Jia, C. Kok, H. Boutselakis, T. De, Z. Sondka, L. Ponting, R. Stefancsik, B. Harsha, J. Tate, E. Dawson, S. Thompson, H. Jubb, P.J. Campbell

{"title":"COSMIC: High-Resolution Cancer Genetics Using the Catalogue of Somatic Mutations in Cancer","authors":"S.A. Forbes, D. Beare, N. Bindal, S. Bamford, S. Ward, C.G. Cole, M. Jia, C. Kok, H. Boutselakis, T. De, Z. Sondka, L. Ponting, R. Stefancsik, B. Harsha, J. Tate, E. Dawson, S. Thompson, H. Jubb, P.J. Campbell","doi":"10.1002/cphg.21","DOIUrl":"10.1002/cphg.21","url":null,"abstract":"COSMIC (http://cancer.sanger.ac.uk) is an expert-curated database of somatic mutations in human cancer. Broad and comprehensive in scope, recent releases in 2016 describe over 4 million coding mutations across all human cancer disease types. Mutations are annotated across the entire genome, but expert curation is focused on over 400 key cancer genes. Now encompassing the majority of molecular mutation mechanisms in oncogenetics, COSMIC additionally describes 10 million non-coding mutations, 1 million copy-number aberrations, 9 million gene-expression variants, and almost 8 million differentially methylated CpGs. This information combines a consistent interpretation of the data from the major cancer genome consortia and cancer genome literature with exhaustive hand curation of over 22,000 gene-specific literature publications. This unit describes the graphical Web site in detail; alternative protocols overview other ways the entire database can be accessed, analyzed, and downloaded. © 2016 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86522106","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}

引用次数: 142

Matchmaker Exchange 媒人交换

Current Protocols in Human Genetics Pub Date : 2018-02-13 DOI: 10.1002/cphg.50

Nara L. M. Sobreira, Harindra Arachchi, Orion J. Buske, Jessica X. Chong, Ben Hutton, Julia Foreman, François Schiettecatte, Tudor Groza, Julius O.B. Jacobsen, Melissa A. Haendel, Kym M. Boycott, Ada Hamosh, Heidi L. Rehm, on behalf of the Matchmaker Exchange Consortium

{"title":"Matchmaker Exchange","authors":"Nara L. M. Sobreira, Harindra Arachchi, Orion J. Buske, Jessica X. Chong, Ben Hutton, Julia Foreman, François Schiettecatte, Tudor Groza, Julius O.B. Jacobsen, Melissa A. Haendel, Kym M. Boycott, Ada Hamosh, Heidi L. Rehm, on behalf of the Matchmaker Exchange Consortium","doi":"10.1002/cphg.50","DOIUrl":"10.1002/cphg.50","url":null,"abstract":"In well over half of the individuals with rare disease who undergo clinical or research next-generation sequencing, the responsible gene cannot be determined. Some reasons for this relatively low yield include unappreciated phenotypic heterogeneity; locus heterogeneity; somatic and germline mosaicism; variants of uncertain functional significance; technically inaccessible areas of the genome; incorrect mode of inheritance investigated; and inadequate communication between clinicians and basic scientists with knowledge of particular genes, proteins, or biological systems. To facilitate such communication and improve the search for patients or model organisms with similar phenotypes and variants in specific candidate genes, we have developed the Matchmaker Exchange (MME). MME was created to establish a federated network connecting databases of genomic and phenotypic data using a common application programming interface (API). To date, seven databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching). This article guides usage of the MME for rare disease gene discovery. © 2017 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35525269","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}

引用次数: 58