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Current Protocols in Human Genetics最新文献

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Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients 法布里病患者血浆中溶索- gb3及6种相关类似物的串联质谱测定
Current Protocols in Human Genetics Pub Date : 2016-07-01 DOI: 10.1002/cphg.4
Michel Boutin, Pamela Lavoie, Mona Abaoui, Christiane Auray-Blais
{"title":"Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients","authors":"Michel Boutin,&nbsp;Pamela Lavoie,&nbsp;Mona Abaoui,&nbsp;Christiane Auray-Blais","doi":"10.1002/cphg.4","DOIUrl":"10.1002/cphg.4","url":null,"abstract":"<p>Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in <i>α</i>-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb<sub>3</sub>), globotriaosylceramide (Gb<sub>3</sub>), and galabiosylceramide (Ga<sub>2</sub>) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb<sub>3</sub> analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb<sub>3</sub> with different chemical modifications on the sphingosine chain (−C<sub>2</sub>H<sub>4</sub>, −H<sub>2</sub>, +O, +H<sub>2</sub>O, +H<sub>2</sub>O<sub>2,</sub> and +H<sub>2</sub>O<sub>3</sub>). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the multiplex analysis of lyso-Gb<sub>3</sub> and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed-mode strong cation exchange (MCX) cartridges. An in-house synthesized N-glycinated lyso-Gb<sub>3</sub> derivative was used for the internal standard. The limits of detection (LODs) measured for lyso-Gb<sub>3</sub> and its analogs ranged from 0.06 to 0.29 nM. © 2016 by John Wiley &amp; Sons, Inc.</p>","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34693734","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: 17
Integrative Analysis of Histone ChIP-seq and RNA-seq Data 组蛋白ChIP-seq和RNA-seq数据的整合分析
Current Protocols in Human Genetics Pub Date : 2016-07-01 DOI: 10.1002/cphg.17
Hans-Ulrich Klein, Martin Schäfer
{"title":"Integrative Analysis of Histone ChIP-seq and RNA-seq Data","authors":"Hans-Ulrich Klein,&nbsp;Martin Schäfer","doi":"10.1002/cphg.17","DOIUrl":"10.1002/cphg.17","url":null,"abstract":"<p>The R package epigenomix has been designed to detect differentially transcribed gene isoforms that, in addition, exhibit altered histone modifications at their respective genomic loci. The package provides methods to map histone ChIP-seq profiles to isoforms and estimate their transcript abundances from RNA-seq data. Based on the differences observed between case and control samples in the RNA-seq and ChIP-seq data, a correlation measure is calculated for each isoform. The distribution of this correlation measure is further investigated by a Bayesian mixture model to (i) reveal the relationship between the studied histone modification and transcriptional activity, and (ii) detect specific isoforms with differences in both transcription values and histone modifications. The method is designed for experiments with a few or no replicates, and is superior to separate analyses of both data types in that setting. This unit illustrates the integrative analysis of ChIP-seq and RNA-seq data with epigenomix. © 2016 by John Wiley &amp; Sons, Inc.</p>","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34693736","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
Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells 人多能干细胞高效生成下丘脑神经元
Current Protocols in Human Genetics Pub Date : 2016-07-01 DOI: 10.1002/cphg.3
Liheng Wang, Dieter Egli, Rudolph L. Leibel
{"title":"Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells","authors":"Liheng Wang,&nbsp;Dieter Egli,&nbsp;Rudolph L. Leibel","doi":"10.1002/cphg.3","DOIUrl":"10.1002/cphg.3","url":null,"abstract":"<p>The hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFβ signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2.1+ hypothalamic progenitors. Subsequent incubation with BDNF induces the differentiation and maturation of pro-opiomelanocortin and neuropeptide Y neurons, which are major cell types in the arcuate hypothalamus. These neurons have molecular and cellular characteristics consistent with arcuate neurons. © 2016 by John Wiley &amp; Sons, Inc.</p>","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34693737","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: 21
Quality Control for the Illumina HumanExome BeadChip Illumina HumanExome芯片的质量控制
Current Protocols in Human Genetics Pub Date : 2016-07-01 DOI: 10.1002/cphg.15
Robert P. Igo Jr., Jessica N. Cooke Bailey, Jane Romm, Jonathan L. Haines, Janey L. Wiggs
{"title":"Quality Control for the Illumina HumanExome BeadChip","authors":"Robert P. Igo Jr.,&nbsp;Jessica N. Cooke Bailey,&nbsp;Jane Romm,&nbsp;Jonathan L. Haines,&nbsp;Janey L. Wiggs","doi":"10.1002/cphg.15","DOIUrl":"10.1002/cphg.15","url":null,"abstract":"<p>The Illumina HumanExome BeadChip and other exome-based genotyping arrays offer inexpensive genotyping of some 240,000 mostly nonsynonymous coding variants across the human genome. The HumanExome chip, with its highly non-uniform distribution of markers and emphasis on rare coding variants, presents some unique challenges for quality control (QC) and data cleaning. Here, we describe QC procedures for HumanExome data, with examples of challenges specific to exome arrays from our experience cleaning a data set of ∼7,500 samples from the NEIGHBORHOOD Consortium. We focus on standard procedures for QC of genome-wide array data including genotype calling, sex verification, sample identity verification, relationship checking, and population structure that are complicated by the HumanExome panel's enrichment in rare, exonic variation. © 2016 by John Wiley &amp; Sons, Inc.</p>","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34693735","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
Engineering Large Animal Species to Model Human Diseases 工程大型动物物种模拟人类疾病
Current Protocols in Human Genetics Pub Date : 2016-07-01 DOI: 10.1002/cphg.18
Christopher S. Rogers
{"title":"Engineering Large Animal Species to Model Human Diseases","authors":"Christopher S. Rogers","doi":"10.1002/cphg.18","DOIUrl":"10.1002/cphg.18","url":null,"abstract":"<p>Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley &amp; Sons, Inc.</p>","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34530377","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
Reporting of Diagnostic Cytogenetic Results 诊断细胞遗传学结果报告
Current Protocols in Human Genetics Pub Date : 2016-04-01 DOI: 10.1002/0471142905.hg01ds89
A. Giersch, F. Bieber, A. Dubuc, J. Fletcher, A. Ligon, H. Mason-Suares, C. Morton, S. Weremowicz, S. Xiao, P. Cin
{"title":"Reporting of Diagnostic Cytogenetic Results","authors":"A. Giersch, F. Bieber, A. Dubuc, J. Fletcher, A. Ligon, H. Mason-Suares, C. Morton, S. Weremowicz, S. Xiao, P. Cin","doi":"10.1002/0471142905.hg01ds89","DOIUrl":"https://doi.org/10.1002/0471142905.hg01ds89","url":null,"abstract":"This appendix, developed by the staff at the Center for Advanced Molecular Diagnostics in the Department of Pathology at the Brigham and Women's Hospital, includes a comprehensive list of current “macros” or standardized statements used to facilitate reporting of cytogenetic results. These are provided as a useful reference for other laboratories. The statements are organized under the general categories of constitutional or acquired abnormalities and subdivided into analysis type (GTG‐banding, FISH, or chromosomal microarray). Multi‐specimen usage macros are included that can be applied to two or more specimen types. © 2016 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"28 1","pages":"A.1D.1 - A.1D.23"},"PeriodicalIF":0.0,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81036564","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: 0
Overview of Clinical Cytogenetics 临床细胞遗传学综述
Current Protocols in Human Genetics Pub Date : 2016-04-01 DOI: 10.1002/0471142905.hg0801s89
Patrick R. Gonzales, Andrew J. Carroll, Bruce R. Korf
{"title":"Overview of Clinical Cytogenetics","authors":"Patrick R. Gonzales,&nbsp;Andrew J. Carroll,&nbsp;Bruce R. Korf","doi":"10.1002/0471142905.hg0801s89","DOIUrl":"10.1002/0471142905.hg0801s89","url":null,"abstract":"<p>Chromosome analysis is one of the first approaches to genetic testing and remains a key component of genetic analysis of constitutional and somatic genetic disorders. Numerical or unbalanced structural chromosome abnormalities usually lead to multiple congenital anomalies. Sometimes these are compatible with live birth, usually resulting in severe cognitive and physical handicaps; other times they result in miscarriage or stillbirth. Chromosome rearrangements also occur as somatic changes in malignancies. Identification of constitutional chromosomal anomalies (anomalies present in most or all cells of the body and/or the germline) can provide important information for genetic counseling. In this unit, we introduce chromosomal microarray analysis (CMA), which is a relatively recent addition to cytogenetic technologies, and has become the recommended first-tier testing method for patients with developmental delay, intellectual disability, autism, and/or multiple congenital anomalies. We also discuss non-invasive prenatal testing/screening (NIPTS), which uses circulating cell-free fetal DNA (cfDNA) from maternal plasma to rapidly screen for autosomal and sex-chromosome aneuploidies. Cytogenetic analysis of tumors is helpful in diagnosis and in monitoring the effects of treatment. The protocols in this chapter cover the clinical study of chromosomes in nonmalignant tissues. © 2016 by John Wiley &amp; Sons, Inc.</p>","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0471142905.hg0801s89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72733550","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
Using ClinVar as a Resource to Support Variant Interpretation 使用ClinVar作为支持变量解释的资源
Current Protocols in Human Genetics Pub Date : 2016-04-01 DOI: 10.1002/0471142905.hg0816s89
S. Harrison, E. Riggs, D. Maglott, Jennifer M. Lee, Danielle R Azzariti, A. Niehaus, E. Ramos, Christa L. Martin, M. Landrum, H. Rehm
{"title":"Using ClinVar as a Resource to Support Variant Interpretation","authors":"S. Harrison, E. Riggs, D. Maglott, Jennifer M. Lee, Danielle R Azzariti, A. Niehaus, E. Ramos, Christa L. Martin, M. Landrum, H. Rehm","doi":"10.1002/0471142905.hg0816s89","DOIUrl":"https://doi.org/10.1002/0471142905.hg0816s89","url":null,"abstract":"ClinVar is a freely accessible, public archive of reports of the relationships among genomic variants and phenotypes. To facilitate evaluation of the clinical significance of each variant, ClinVar aggregates submissions of the same variant, displays supporting data from each submission, and determines if the submitted clinical interpretations are conflicting or concordant. The unit describes how to (1) identify sequence and structural variants of interest in ClinVar by multiple searching approaches, including Variation Viewer and (2) understand the display of submissions to ClinVar and the evidence supporting each interpretation. By following this protocol, ClinVar users will be able to learn how to incorporate the wealth of resources and knowledge in ClinVar into variant curation and interpretation. © 2016 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"70 1","pages":"8.16.1 - 8.16.23"},"PeriodicalIF":0.0,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83742551","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: 98
Genetic Mapping 基因映射
Current Protocols in Human Genetics Pub Date : 2016-04-01 DOI: 10.1002/0471142905.hg0100s89
Jonathan L. Haines
{"title":"Genetic Mapping","authors":"Jonathan L. Haines","doi":"10.1002/0471142905.hg0100s89","DOIUrl":"10.1002/0471142905.hg0100s89","url":null,"abstract":"T he goal of this chapter is to provide the investigator with sufficient information to undertake the design and perform the initial steps in trait-gene discovery—i.e., in identifying genetic variations that modulate (e.g., increasing or decreasing) the risk of developing a particular human trait or modulate the expression of a particular trait. It covers the stages from initial definition of a trait through identification of the genetic variation that either is the causative, susceptibility, or functional variation, or lies close to it. The approaches presented for ascertainment, and the laboratory procedures presented for genotype generation (also see Chapter 2, “Genotyping”), can be applied to traits with either a simple or a complex genetic etiology. The data analyses presented for the simpler genetic traits provide the basis for understanding approaches to more complex traits. There have been numerous advances in analytical methods for complex genetic traits, but no standard or ubiquitous approach has yet emerged that is successful under all circumstances. This is not surprising, since the underlying genetic architectures of human traits are extremely variable. To understand this chapter, the reader must have a basic understanding of genetics, including meiosis, recombination, and the structure of the genome. A basic understanding of statistics and biostatistics is also recommended for some of the units (see recommended texts in the preface to this manual, and citations below).","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0471142905.hg0100s89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84368363","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: 0
Quantitative Analysis of Total Plasma Homocysteine by LC‐MS/MS LC - MS/MS定量分析血浆总同型半胱氨酸
Current Protocols in Human Genetics Pub Date : 2016-04-01 DOI: 10.1002/0471142905.hg1721s89
Libin Yuan, J. D. Sharer
{"title":"Quantitative Analysis of Total Plasma Homocysteine by LC‐MS/MS","authors":"Libin Yuan, J. D. Sharer","doi":"10.1002/0471142905.hg1721s89","DOIUrl":"https://doi.org/10.1002/0471142905.hg1721s89","url":null,"abstract":"Homocysteine is a nonessential, sulfur‐containing amino acid involved in one‐carbon (folate) metabolism. A number of inherited and acquired conditions cause increased accumulation of this metabolite in blood (homocysteinemia) and other biofluids. Homocysteinemia is a risk factor for cardiovascular disease, including recurrent thrombosis. Accurate measurement of total plasma homocysteine is an important element in the diagnostic evaluation of these disorders. While a number of different methods have been developed for this purpose, the focus of this unit will be on a specific technique utilizing liquid chromatography‐tandem mass spectrometry, which provides several advantages in terms of speed, sensitivity, and specificity. © 2016 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"136 1","pages":"17.21.1 - 17.21.10"},"PeriodicalIF":0.0,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86315586","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: 8
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