Current Protocols in Human Genetics最新文献_第3页

Genotype Imputation in Genome-Wide Association Studies. 全基因组关联研究中的基因型插入。

Current Protocols in Human Genetics Pub Date : 2019-06-01 DOI: 10.1002/cphg.84

Adam C Naj

{"title":"Genotype Imputation in Genome-Wide Association Studies.","authors":"Adam C Naj","doi":"10.1002/cphg.84","DOIUrl":"https://doi.org/10.1002/cphg.84","url":null,"abstract":"Genotype imputation infers missing genotypes in silico using haplotype information from reference samples with genotypes from denser genotyping arrays or sequencing. This approach can confer a number of improvements on genome-wide association studies: it can improve statistical power to detect associations by reducing the number of missing genotypes; it can simplify data harmonization for meta-analyses by improving overlap of genomic variants between differently-genotyped sample sets; and it can increase the overall number and density of genomic variants available for association testing. This article reviews the general concepts behind imputation, describes imputation approaches and methods for various types of genotype data, including family-based data, and identifies web-based resources that can be used in different steps of the imputation process. For practical application, it provides a step-by-step guide to implementation of a two-step imputation process consisting of phasing of the study genotypes and the imputation of reference panel genotypes into the study haplotypes. In addition, this review describes recently developed haplotype reference panel resources and online imputation servers that are capable of remotely and securely implementing an imputation workflow on uploaded genotype array data. © 2019 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"102 1","pages":"e84"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.84","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37084177","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: 14

Issue Information TOC 发布信息TOC

Current Protocols in Human Genetics Pub Date : 2019-06-01 DOI: 10.1002/cphg.77

引用次数: 0

Issue Information TOC 发布信息TOC

Current Protocols in Human Genetics Pub Date : 2019-03-19 DOI: 10.1002/cphg.76

引用次数: 0

Methods for the Analysis and Interpretation for Rare Variants Associated with Complex Traits 复杂性状相关罕见变异的分析与解释方法

Current Protocols in Human Genetics Pub Date : 2019-03-08 DOI: 10.1002/cphg.83

J. Dylan Weissenkampen, Yu Jiang, Scott Eckert, Bibo Jiang, Bingshan Li, Dajiang J. Liu

引用次数: 12

Conducting a Reproducible Mendelian Randomization Analysis Using the R Analytic Statistical Environment 利用R分析统计环境进行可重复的孟德尔随机化分析

Current Protocols in Human Genetics Pub Date : 2019-01-15 DOI: 10.1002/cphg.82

Danielle Rasooly, Chirag J. Patel

引用次数: 34

Simultaneous Targeted Methylation Sequencing (sTM-Seq) 同步靶向甲基化测序(sTM-Seq)

Current Protocols in Human Genetics Pub Date : 2019-01-08 DOI: 10.1002/cphg.81

Natalie Asmus, Ligia A. Papale, Andy Madrid, Reid S. Alisch

{"title":"Simultaneous Targeted Methylation Sequencing (sTM-Seq)","authors":"Natalie Asmus, Ligia A. Papale, Andy Madrid, Reid S. Alisch","doi":"10.1002/cphg.81","DOIUrl":"10.1002/cphg.81","url":null,"abstract":"Mapping patterns of DNA methylation throughout the epigenome are critical to our understanding of several important biological and regulatory functions, such as transcriptional regulation, genomic imprinting, and embryonic development. The development and rapid advancement of next-generation sequencing (NGS) technologies have provided clinicians and researchers with accurate and reliable read-outs of genomic and epigenomic information at the nucleotide level. Such improvements have significantly lowered the cost required for genome-wide sequencing, facilitating the vast acquisition of data that has led to many improvements in patient care. However, the torrid rate of NGS data generation has left targeted validation approaches behind, including the confirmation of epigenetic marks such as DNA methylation. To overcome these shortcomings, we present a rapid and robust protocol for the parallel examination of multiple methylated sequences that we have termed simultaneous targeted methylation sequencing (sTM-Seq). Key features of this technique include the elimination of the need for large amounts of high-molecular weight DNA and the nucleotide specific distinction of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Moreover, sTM-Seq is scalable and can be used to investigate multiple loci in dozens of samples within a single sequencing run. By utilizing freely available web-based software and universal primers for multipurpose barcoding, library preparation, and customized sequencing, sTM-Seq is affordable, efficient, and widely applicable. Together, these features enable sTM-Seq to have wide-reaching clinical applications that will greatly improve turnaround rates for same-day procedures and allow clinicians to collect high-resolution data that can be used in a variety of patient settings. © 2019 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36843310","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: 2

Issue Information TOC 发布信息TOC

Current Protocols in Human Genetics Pub Date : 2019-01-03 DOI: 10.1002/cphg.74

引用次数: 0

Using Electronic Health Records To Generate Phenotypes For Research 使用电子健康记录为研究生成表型

Current Protocols in Human Genetics Pub Date : 2018-12-05 DOI: 10.1002/cphg.80

Sarah A. Pendergrass, Dana C. Crawford

引用次数: 45

Strategies for Pathway Analysis Using GWAS and WGS Data 利用GWAS和WGS数据进行通路分析的策略

Current Protocols in Human Genetics Pub Date : 2018-11-02 DOI: 10.1002/cphg.79

Marquitta J. White, Brian L. Yaspan, Olivia J. Veatch, Pagé Goddard, Oona S. Risse-Adams, Maria G. Contreras

{"title":"Strategies for Pathway Analysis Using GWAS and WGS Data","authors":"Marquitta J. White, Brian L. Yaspan, Olivia J. Veatch, Pagé Goddard, Oona S. Risse-Adams, Maria G. Contreras","doi":"10.1002/cphg.79","DOIUrl":"10.1002/cphg.79","url":null,"abstract":"Single-allele study designs, commonly used in genome-wide association studies (GWAS) as well as the more recently developed whole genome sequencing (WGS) studies, are a standard approach for investigating the relationship of common variation within the human genome to a given phenotype of interest. However, single-allele association results published for many GWAS studies represent only the tip of the iceberg for the information that can be extracted from these datasets. The primary analysis strategy for GWAS entails association analysis in which only the single nucleotide polymorphisms (SNPs) with the strongest p-values are declared statistically significant due to issues arising from multiple testing and type I errors. Factors such as locus heterogeneity, epistasis, and multiple genes conferring small effects contribute to the complexity of the genetic models underlying phenotype expression. Thus, many biologically meaningful associations having lower effect sizes at individual genes are overlooked, making it difficult to separate true associations from a sea of false-positive associations. Organizing these individual SNPs into biologically meaningful groups to look at the overall effects of minor perturbations to genes and pathways is desirable. This pathway-based approach provides researchers with insight into the functional foundations of the phenotype being studied and allows testing of various genetic scenarios. © 2018 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36629806","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: 24

Obtaining a Genetic Family History Using Computer-Based Tools 使用基于计算机的工具获取遗传家族史

Current Protocols in Human Genetics Pub Date : 2018-10-18 DOI: 10.1002/cphg.72

Weilong Li, Michael F. Murray, Monica A. Giovanni

{"title":"Obtaining a Genetic Family History Using Computer-Based Tools","authors":"Weilong Li, Michael F. Murray, Monica A. Giovanni","doi":"10.1002/cphg.72","DOIUrl":"10.1002/cphg.72","url":null,"abstract":"Family health history has long been known to be a powerful predictor of individual disease risk. It can be obtained prior to DNA sequencing in order to examine inheritance patterns, to be used as a proxy for genetic information, or as a tool to guide decision-making on the utility of diagnostic genetic testing. Increasingly, it is also being obtained retrospectively from sequenced individuals to examine familial disease penetrance and to identify at-risk relatives for cascade testing. The collection of adequate family history information to screen patients for disease risk and guide decision-making is a time-consuming process that is difficult to accomplish exclusively through discussion between patients and their providers. Engaging individuals and families in data collection and data entry has the potential to improve data accuracy through re-iterative review with family members and health care providers, and to empower patients in their healthcare. In addition, electronic datasets can be shared amongst relatives and stored in electronic health records or personal files, enabling portability of family history information. The U.S. Surgeon General, the Centers for Disease Control and Prevention (CDC), and others have developed tools for electronic family history collection to help families and providers obtain this useful information in an efficient manner. This unit describes the utility of the web-based My Family Health Portrait (https://familyhistory.hhs.gov) as the prototype for patient-entered family history. © 2018 by John Wiley & Sons, Inc.","PeriodicalId":40007,"journal":{"name":"Current Protocols in Human Genetics","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cphg.72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36639028","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