Current Protocols in Human Genetics 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Resolving Breakpoints of Chromosomal Rearrangements at the Nucleotide Level Using Sanger Sequencing.
Authors: Nalbandian K, Piña-Aguilar RE, Morton CC
Abstract
Novel cytogenetic tools are increasingly based on genome sequencing for detecting chromosomal abnormalities. Different sequence-based techniques optimized for diagnosis of structural variants can be useful for narrowing down the localization of breakpoints of chromosomal abnormalities, but do not offer nucleotide resolution of breakpoints for proper interpretation of gene disruption. This protocol presents the characterization of structural variants at nucleotide resolution using Sanger sequencing after low-pass large-insert genome sequencing or o...
Source: Current Protocols in Human Genetics - December 30, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Informed Consent for Genetic and Genomic Research.
This article addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. © 2020 Wiley Periodicals LLC.
PMID: 33202103 [PubMed - as supplied by publisher] (Source: Current Protocols in Human Genetics)
Source: Current Protocols in Human Genetics - November 18, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
A Guide to Using ClinTAD for Interpretation of DNA Copy Number Variants in the Context of Topologically Associated Domains.
Authors: Spector JD, Wiita AP
Abstract
DNA copy number variants (CNVs) are routinely evaluated as part of clinical diagnosis in both the prenatal and postnatal genetic settings. Current guidelines for interpreting the potential clinical significance of these CNVs, typically identified by chromosomal microarray, focus entirely on genes localized within the CNV region. However, recent work has suggested that some CNVs can actually produce clinical impacts by influencing transcription of genes outside the CNV region. These alterations of transcription appear to occur by disrupting the composition of DNA topol...
Source: Current Protocols in Human Genetics - November 11, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
The AD Knowledge Portal: A Repository for Multi-Omic Data on Alzheimer's Disease and Aging.
We present two primary ways to download data-using a web interface, and using a programmatic method that provides access using the command line. Finally, we show how to merge separate sources of metadata into a comprehensive file that contains factors and covariates necessary in downstream analyses. © 2020 The Authors. Basic Protocol 1: Find and download files associated with a selected study Basic Protocol 2: Download files in bulk using the command line client Basic Protocol 3: Working with file annotations and metadata.
PMID: 33085189 [PubMed - in process] (Source: Current Protocols in Human Genetics)
Source: Current Protocols in Human Genetics - October 22, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
A Practical Guide for Structural Variation Detection in the Human Genome.
Authors: Yang L
Abstract
Profiling genetic variants-including single nucleotide variants, small insertions and deletions, copy number variations, and structural variations (SVs)-from both healthy individuals and individuals with disease is a key component of genetic and biomedical research. SVs are large-scale changes in the genome and involve breakage and rejoining of DNA fragments. They may affect thousands to millions of nucleotides and can lead to loss, gain, and reshuffling of genes and regulatory elements. SVs are known to impact gene expression and potentially result in altered phenotypes and diseas...
Source: Current Protocols in Human Genetics - August 20, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Identification and Genotyping of Transposable Element Insertions From Genome Sequencing Data.
Authors: Chu C, Zhao B, Park PJ, Lee EA
Abstract
Transposable element (TE) mobilization is a significant source of genomic variation and has been associated with various human diseases. The exponential growth of population-scale whole-genome sequencing and rapid innovations in long-read sequencing technologies provide unprecedented opportunities to study TE insertions and their functional impact in human health and disease. Identifying TE insertions, however, is challenging due to the repetitive nature of the TE sequences. Here, we review computational approaches to detecting and genotyping TE insertions u...
Source: Current Protocols in Human Genetics - July 16, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Analytical Approaches for ATAC-seq Data Analysis.
Authors: Smith JP, Sheffield NC
Abstract
ATAC-seq, the assay for transposase-accessible chromatin using sequencing, is a quick and efficient approach to investigating the chromatin accessibility landscape. Investigating chromatin accessibility has broad utility for answering many biological questions, such as mapping nucleosomes, identifying transcription factor binding sites, and measuring differential activity of DNA regulatory elements. Because the ATAC-seq protocol is both simple and relatively inexpensive, there has been a rapid increase in the availability of chromatin accessibility data. Furthermore...
Source: Current Protocols in Human Genetics - June 17, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Introducing an Expanded Trinucleotide Repeat Tract into the Human Genome for Huntington's Disease Modeling In Vitro.
Authors: Malankhanova T, Sorokin M, Medvedev S, Zakian S, Malakhova A
Abstract
In neurodegeneration studies, researchers are faced with problems such as limited material availability and late disease manifestation. Cell models provide the opportunity to investigate molecular mechanisms of pathogenesis. Moreover, genome editing technologies enable generation of isogenic cell models of hereditary diseases. Our protocol outlines an approach for introducing an expanded CAG repeat tract into the first exon of the HTT gene, the Huntington's disease causing mutation. The protocol allows modeling the disease at va...
Source: Current Protocols in Human Genetics - May 31, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Clinical Interpretation of Sequence Variants.
Authors: Zhang J, Yao Y, He H, Shen J
Abstract
Clinical interpretation of DNA sequence variants is a critical step in reporting clinical genetic testing results. Application of next-generation sequencing technology in molecular genetic testing has facilitated diagnoses of genetic disorders in clinical practice. However, the large number of DNA sequence variants detected in clinical specimens, many of which have never been seen before, make clinical interpretation challenging. Recommendations by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) have...
Source: Current Protocols in Human Genetics - March 18, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Quantitative Assessment of Parental Somatic Mosaicism for Copy-Number Variant (CNV) Deletions.
Authors: Liu Q, Grochowski CM, Bi W, Lupski JR, Stankiewicz P
Abstract
As genome sequencing methodologies have become more sensitive in detecting low-frequency rare-variant events, the link between post-zygotic mutagenesis and somatic mosaicism in the etiology of several human genetic conditions other than cancers has become more clear. Given that current clinical-genomics diagnostic methods have limited detection sensitivity for mosaic events, a copy-number variant (CNV) deletion inherited from a parent with low-level (<10%) mosaicism can be erroneously interpreted in the proband to represent a de novo...
Source: Current Protocols in Human Genetics - March 18, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
An Overview of Molecular Genetic Diagnosis Techniques.
Authors: Goswami RS, Harada S
Abstract
Our understanding of genetic disease(s) has increased exponentially since the completion of human genome sequencing and the development of numerous techniques to detect genetic variants. These techniques have not only allowed us to diagnose genetic disease, but in so doing, also provide increased understanding of the pathogenesis of these diseases to aid in developing appropriate therapeutic options. Additionally, the advent of next-generation or massively parallel sequencing (NGS/MPS) is increasingly being used in the clinical setting, as it can detect a number of ab...
Source: Current Protocols in Human Genetics - February 28, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Validation of Fluorescence In Situ Hybridization (FISH) for Chromosome 5 Monosomy and Deletion.
Authors: Zneimer SM
Abstract
In order to comply with regulations set by established local, state, and federal agencies and other regulatory organizations, such as the College of American Pathologists and the International Organization for Standardization, a clinical laboratory needs to develop procedures for the processes of validating laboratory-developed tests (LDTs) and establishing performance specifications for these assays prior to use in clinical testing. This is applicable to all fluorescence in situ hybridization (FISH) assays. Even Food and Drug Administration-approved FISH assays must undergo so...
Source: Current Protocols in Human Genetics - January 12, 2020 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Genetic Risk Scores.
Authors: Igo RP, Kinzy TG, Cooke Bailey JN
Abstract
Genome-wide variation data with millions of genetic markers have become commonplace. However, the potential for interpretation and application of these data for clinical assessment of outcomes of interest, and prediction of disease risk, is currently not fully realized. Many common complex diseases now have numerous, well-established risk loci and likely harbor many genetic determinants with effects too small to be detected at genome-wide levels of statistical significance. A simple and intuitive approach for converting genetic data to a predictive measur...
Source: Current Protocols in Human Genetics - November 26, 2019 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Approaches to Whole Mitochondrial Genome Sequencing on the Oxford Nanopore MinION.
This article describes three approaches to extract, prepare, and sequence mitochondrial DNA on the Oxford Nanopore MinION device. Two of the workflows include enrichment of mitochondrial DNA prior to sequencing, whereas the other relies on direct sequencing of native genomic DNA to allow for simultaneous assessment of the nuclear and mitochondrial genomes. © 2019 by John Wiley & Sons, Inc. Basic Protocol: Enrichment-free mitochondrial DNA sequencing Alternate Protocol 1: Mitochondrial DNA sequencing following enrichment with polymerase chain reaction (PCR) Alternate Protocol 2: Mitochondrial DNA sequencing following e...
Source: Current Protocols in Human Genetics - November 20, 2019 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
Overview of Specifications to the ACMG/AMP Variant Interpretation Guidelines.
This article summarizes the approaches to, and rationale for, specifying three evidence categories (population frequency data, variant type and location, and case-level data), including available resources and a quantitative framework that can inform the specification process. © 2019 by John Wiley & Sons, Inc.
PMID: 31479589 [PubMed - in process] (Source: Current Protocols in Human Genetics)
Source: Current Protocols in Human Genetics - September 4, 2019 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research
