Current Protocols in Human Genetics 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.

COSMIC: High-Resolution Cancer Genetics Using the Catalogue of Somatic Mutations in Cancer.
Authors: Forbes SA, Beare D, Bindal N, Bamford S, Ward S, Cole CG, Jia M, Kok C, Boutselakis H, De T, Sondka Z, Ponting L, Stefancsik R, Harsha B, Tate J, Dawson E, Thompson S, Jubb H, Campbell PJ 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 me...
Source: Current Protocols in Human Genetics - October 13, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Analysis of Heritability Using Genome-Wide Data.
Authors: Hall JB, Bush WS Abstract Most analyses of genome-wide association data consider each variant independently without considering or adjusting for the genetic background present in the rest of the genome. New approaches to genome analysis use representations of genomic sharing to better account for confounding factors like population stratification or to directly approximate heritability through the estimated sharing of individuals in a dataset. These approaches use mixed linear models, which relate genotypic sharing to phenotypic sharing, and rely on the efficient computation of genetic sharing amo...
Source: Current Protocols in Human Genetics - October 13, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Genetic Risk Scores.
Authors: Cooke Bailey JN, Igo RP Abstract The generation of genome-wide variation data has 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 measure of disease susceptib...
Source: Current Protocols in Human Genetics - October 13, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Engineering Large Animal Species to Model Human Diseases.
Authors: Rogers CS Abstract 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 h...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Fabry Disease Biomarkers: Analysis of Urinary Lyso-Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry.
Authors: Lavoie P, Boutin M, Abaoui M, Auray-Blais C Abstract Fabry disease is an X-linked lysosomal storage disorder caused by the absence or reduction of the enzyme α-galactosidase A activity. Currently, globotriaosylsphingosine (lyso-Gb3 ) and globotriaosylceramide (Gb3 ) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations. This unit describes a multiplex methodology targeting the analysis of urinary lyso-Gb3 a...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.
Authors: Boutin M, Lavoie P, Abaoui M, Auray-Blais C Abstract Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in α-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, an...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Quality Control for the Illumina HumanExome BeadChip.
Authors: Igo RP, Cooke Bailey JN, Romm J, Haines JL, Wiggs JL Abstract 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 ...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Integrative Analysis of Histone ChIP-seq and RNA-seq Data.
Authors: Klein HU, Schäfer M Abstract 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 ...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells.
Authors: Wang L, Egli D, Leibel RL Abstract 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, ...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Sequence Variant Descriptions: HGVS Nomenclature and Mutalyzer.
Authors: den Dunnen JT Abstract Consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome, in particular in DNA diagnostics. The HGVS nomenclature-recommendations for the description of sequence variants as originally proposed by the Human Genome Variation Society-has gradually been accepted as the international standard for variant description. In this unit, we describe the current recommendations (HGVS version 15.11) regarding how to describe variants at the DNA, RNA, and protein level. We explain the rationale and give example...
Source: Current Protocols in Human Genetics - July 2, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Genetic Mapping.
Authors: Haines JL PMID: 27037485 [PubMed - as supplied by publisher] (Source: Current Protocols in Human Genetics)
Source: Current Protocols in Human Genetics - April 3, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

An Overview of Biochemical Genetics.
Authors: Sharer JD Abstract Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of inherited metabolic disorders. While individually rare, the combined incidence of these diseases makes them a significant source of morbidity and mortality, particularly among infants and young children, and new conditions continue to be identified. Inherited metabolic disorders may present as an acute, life-threatening illness or with more chronic, progressive symptoms. Population-scale newborn screening allows for early detection and treatment for >40 different metabolic disorders. This introdu...
Source: Current Protocols in Human Genetics - April 3, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Quantitative Analysis of Total Plasma Homocysteine by LC-MS/MS.
Authors: Yuan L, Sharer JD 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 spec...
Source: Current Protocols in Human Genetics - April 3, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Overview of Clinical Cytogenetics.
Authors: Gonzales PR, Carroll AJ, Korf BR Abstract 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 anomal...
Source: Current Protocols in Human Genetics - April 3, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research

Using ClinVar as a Resource to Support Variant Interpretation.
Authors: Harrison SM, Riggs ER, Maglott DR, Lee JM, Azzariti DR, Niehaus A, Ramos EM, Martin CL, Landrum MJ, Rehm HL 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 sear...
Source: Current Protocols in Human Genetics - April 3, 2016 Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research