Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study
Conclusions. Our genetic study identified a novel association at NMT2 for CKD and showed for the first time strong associations of the APOL1 variants with ESKD across multi-ethnic populations. Our findings suggest differences in genetic effects across CKD severity and provide information for study design of genetic studies of CKD in diverse populations. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Multifaceted Stoichiometry Control of Bacterial Operons Revealed by Deep Proteome Quantification
In this study, we performed a label-free data-independent acquisition hyper reaction monitoring mass-spectrometry (HRM-MS) experiment to quantify the Escherichia coli proteome in exponential phase and quantified 93.6% of the cytosolic proteins, covering 67.9% and 56.0% of the translating polycistronic operons in BW25113 and MG1655 strains, respectively. We found that the translational regulation seems contributes greatly to the proteome complexity: the shorter operons tend to be more tightly controlled for stoichiometry than longer operons; the operons which mainly code for complexes is more tightly controlled for stoichio...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Whole-Exome Sequencing Enables the Diagnosis of Variant-Type Xeroderma Pigmentosum
Conclusions: A novel XPV pathogenic homozygous nonsense mutation in the POLH gene was identified. Our case proves that next-generation sequencing is an effective method for the rapid diagnosis and determination of XP genetic aetiology. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

LINC00673 rs11655237 C > T Polymorphism Impacts Hepatoblastoma Susceptibility in Chinese Children
In conclusion, we confirmed that the LINC00673 rs11655237 C>T polymorphism may be associated with HB susceptibility. Prospective studies with larger sample sizes and patients of different ethnicities are needed to validate our findings. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Abundance of HPV L1 Intra-Genotype Variants With Capsid Epitopic Modifications Found Within Low- and High-Grade Pap Smears With Potential Implications for Vaccinology
Background: The aim of this study was to explore the Human Papillomavirus (HPV) genotype composition and intra-genotype variants within individual samples of low- and high-grade cervical cytology by deep sequencing. Clinical, cytological, sequencing, and functional/structural data were forged into an integrated variant profiling pipeline for the detection of potentially vaccine-resistant genotypes or variants. Methods: Low- and high-grade intraepithelial lesion (LSIL and HSIL) cytology samples with +HPV were subjected to amplicon (L1 gene fragment) sequencing by dideoxy (Sanger) and deep methods. Taxonomic, abundance, ...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

A Systems Analysis of the Relationships Between Anemia and Ischemic Stroke Rehabilitation Based on RNA-Seq Data
In this study, we choose 28 IS patients, of which 12 were suffering from anemia. Statistical analyses results showed that the outcome of the patients were different when dividing them into two groups characterized by Hb concentration. 2 sex and age matched patients were first chosen to perform RNA-seq analyses twice on different time points, after which the Hb counts were tested at least 24 hours after sequencing. Results showed that the outcome of anemia patients was poor compared with non-anemia patients. Two other patients were then chosen for analyses which excluded the coincidence of other factors. The results showed ...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders
Conclusion: The significantly higher diagnosis rate of Trio-WES accompanied by CNVseq makes this strategy a potential alternative to the most widely used approaches for pediatric children with rare and undiagnosed NDDs. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Dicyemida and Orthonectida: Two Stories of Body Plan Simplification
Two enigmatic groups of morphologically simple parasites of invertebrates, the Dicyemida (syn. Rhombozoa) and the Orthonectida, since the 19th century have been usually considered as two classes of the phylum Mesozoa. Early molecular evidence suggested their relationship within the Spiralia (=Lophotrochozoa), however high rates of dicyemid and orthonectid sequence evolution led to contradicting phylogeny reconstructions. Genomic data for orthonectids revealed that they are highly simplified spiralians and possess a reduced set of genes involved in metazoan development and body patterning. Acquiring genomic data for dicyemi...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Quantification of Facial Traits
Measuring facial traits by quantitative means is a prerequisite to investigate epidemiological, clinical, and forensic questions. This measurement process has received intense attention in recent years. We divided this process into the registration of the face, landmarking, morphometric quantification and dimension reduction. Face registration is the process of standardizing pose and landmarking annotates positions in the face with anatomic description or mathematically defined properties (pseudolandmarks). Morphometric quantification computes pre-specified transformations such as distances. Landmarking We review face ...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Comparative Analysis of the TRB Locus in the Camelus Genus
T cells can be separated into two major subsets based on the heterodimer that forms their T cell receptors. αβ T cells have receptors consisting of α and β chains, while γδ T cells are composed of γ and δ chains. αβ T cells play an essential role within the adaptive immune responses against pathogens. The recent genomic characterization of the Camelus dromedarius T cell receptor β (TRB) locus has allowed us to infer the structure of this locus from the draft genome sequences of its wild and domestic Bactrian congeners, Camelus ferus and Camelus bactrianus. The...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

ANASTASIA: An Automated Metagenomic Analysis Pipeline for Novel Enzyme Discovery Exploiting Next Generation Sequencing Data
Metagenomic analysis of environmental samples provides deep insight into the corresponding niches' enzymatic arsenal, revealing peptide sequences of novel functional properties. Next generation sequencing methodologies have revolutionized the collection of massive (meta)genomic data but simultaneously have also untapped their complexity , concomitantly requesting ever larger computational configurations to ensure efficient bioinformatic analysis and fine annotation. Aiming to tackle the challenges of such an endeavor, we have developed a novel web-based application named ANASTASIA (Automated Nucleotide Aminoacid Sequences ...
Source: Frontiers in Genetics - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Long Noncoding RNA Can Be a Probable Mechanism and a Novel Target for Diagnosis and Therapy in Fragile X Syndrome
Fragile X syndrome(FXS) is most common congenital hereditary disease of low intelligence after Down Syndrome. Its main pathogenic gene is Fragile X mental retardation 1 (FMR1) gene associated with intellectual disability, autism and Fragile X-related primary ovarian insufficiency (FXPOI) and Fragile X-associated tremor/ataxia syndrome (FXTAS). Fmr1 gene transcription leads to the absence of fragile X mental retardation protein (FMRP). How to relieve or cure disorders associated with FXS has also become a clinically disturbing problem. Previous studies have recently shown that Long noncoding RNAs (lncRNA) contribute to the ...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Genome-Wide Analysis of Lung Adenocarcinoma Identifies Novel Prognostic Factors and a Prognostic Score
In this study, we attempted to identify novel genetic and epigenetic modifications and integrate them as a predictor of the prognosis for LUAD, to supplement the TNM stage with additional information. Methods: A dataset of 445 patients with LUAD was obtained from The Cancer Genome Atlas database. Both genetic and epigenetic aberrations were screened for their prognostic impact on overall survival (OS). A prognostic score (PS) integrating all the candidate prognostic factors was then developed and its prognostic value validated. Results: A total of two micro-RNAs, two mRNAs and two DNA methylation sites were identified as...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Unrecognized High Occurrence of Genetically Confirmed Hereditary Carnitine Palmitoyltransferase II Deficiency in an Austrian Family Points to the Ongoing Underdiagnosis of the Disease
Adult muscle carnitine palmitoyltransferase (CPT) II deficiency is a rare autosomal recessive disorder of long-chain fatty acid metabolism. It is typically associated with recurrent episodes of exercise-induced rhabdomyolysis and myoglobinuria, in most cases caused by a c.338C>T mutation in the CPT2 gene. Here we present the pedigree of one of the largest family studies of CPT II deficiency caused by the c.338C>T mutation, documented so far. The pedigree comprises 24 blood relatives of the index patient, a 32 year old female with genetically proven CPT II deficiency. In total, the mutation was detected in 20 family m...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Whole Genome Linkage Disequilibrium and Effective Population Size in a Coho Salmon (Oncorhynchus kisutch) Breeding Population Using a High-Density SNP Array
The estimation of linkage disequilibrium between molecular markers within a population is critical when establishing the minimum number of markers required for association studies, genomic selection and for inferring historical events influencing different populations. This work aimed to evaluate the extent and decay of linkage disequilibrium in a coho salmon breeding population using a high density chip SNP array. Linkage disequilibrium was estimated between a total of 93,502 SNPs found in 64 individuals (33 dams and 31 sires) from the breeding population. The markers encompass all 30 coho salmon chromosomes and comprise...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Genetic Screening of the Usher Syndrome in Cuba
Conclusions: Although the sample size is very small, it is tempting to speculate that the gene frequencies in Cuba are distinct from other populations mainly due to an “island effect” and genetic drift. The two recurrent mutations appear to be of Spanish origin. Further studies with a larger cohort are needed to elucidate the real genetic landscape of Usher syndrome in the Cuban population. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

A New Method of RNA Secondary Structure Prediction Based on Convolutional Neural Network and Dynamic Programming
In recent years, obtaining RNA secondary structure information has been playing important role in RNA and gene function research. Although some RNA secondary structures can be gained experimentally, in most cases efficient and accurate computational methods are still needed to predict RNA secondary structure. Current RNA secondary structure prediction methods are mainly based on the minimum free energy algorithm, which finds the optimal folding state of RNA in vivo by the iterative method to meet the minimum energy or other constraints. However, due to the complexity of biotic environment, true RNA structure always keeps t...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Coding or Noncoding, the Converging Concepts of RNAs
Technological advances over the past decade have unraveled the remarkable complexity of RNA. The identification of small peptides encoded by long non-coding RNAs (lncRNAs) as well as regulatory functions mediated by non-coding regions of mRNAs have further complicated our understanding of the multifaceted functions of RNA. In this review, we summarize current evidence pointing to dual roles of RNA molecules defined by their coding and non-coding potentials. We also discuss how the emerging roles of RNA transform our understanding of gene expression and evolution. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Identification of Breast Cancer Stem Cell Related Genes Using Functional Cellular Assays Combined With Single-Cell RNA Sequencing in MDA-MB-231 Cells
Breast cancer tumors display different cellular phenotypes. A growing body of evidence points towards a population of cancer stem cells that is important for metastasis and treatment resistance, although the characteristics of these cells are incomplete. We used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of cancer stem cell properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing. We clustered the cells based on their gene expression profiles and identified three subpopulations, including a cancer ste...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Genetic Differentiation of Eastern Honey Bee (Apis cerana) Populations Across Qinghai-Tibet Plateau-Valley Landforms
This study contributes significantly to the current understanding of the mechanism underlying population genetic differentiation and highlights the potential effects of utilizing genetic resources that are subject to the ecological conditions of the long and narrow geographic distributions of plateau-valley landforms. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Quantitative PCR Measurement of miR-371a-3p and miR-372-p Is Influenced by Hemolysis
Cell-free microRNAs have been reported as biomarkers for several diseases. For testicular germ cell tumors (GCT), circulating microRNAs 371a-3p and 372-3p in serum and plasma have been proposed as biomarkers for diagnostic and disease monitoring purposes. The most widely used method for quantification of specific microRNAs in serum and plasma is reverse transcriptase real-time quantitative PCR (RT-qPCR) by the comparative Ct-method. In this method one or several reference genes or reference microRNAs are needed in order to normalize and calculate the relative microRNA levels across samples. One of the pitfalls in analysis ...
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids
This report provides diverse neuroimaging and clinical characteristics of a novel CSF1R mutation with different disease penetrance. The large clinical heterogeneity in the same family who all had the same mutation indicates that modifying genes and environmental factors may play a role in the pathogenesis of HDLS. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Genetic Influences on Behavioral Outcomes After Childhood TBI: A Novel Systems Biology-Informed Approach
Conclusions: Findings demonstrate the promise of applying a genomics approach, informed by systems biology, to understanding behavioral recovery after pediatric TBI. A mixture of biologic pathways and processes are associated with behavioral recovery, specifically genes associated with cell death, inflammatory response, neurotransmitter signaling, and brain development. These results provide insights into the complex biology of TBI recovery. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

A First Y-Chromosomal Haplotype Network to Investigate Male-Driven Population Dynamics in Domestic and Wild Bactrian Camels
Polymorphic markers on the male-specific part of the Y chromosome (MSY) provide useful information for tracking male genealogies. While maternal lineages are well studied in Old World camelids using mitochondrial DNA, the lack of Y-chromosomal references hampers the analysis of male-driven demographics. Recently, a shotgun assembly of the horse MSY was generated based on short read next generation sequencing data. The haplotype network resulting from single copy MSY variants using the assembly as a reference revealed sufficient resolution to trace individual male lines in this species. In a similar approach we generated a ...
Source: Frontiers in Genetics - May 21, 2019 Category: Genetics & Stem Cells Source Type: research

Learning Causal Biological Networks With the Principle of Mendelian Randomization
Although large amounts of genomic data are available, it remains a challenge to reliably infer causal (i.e., regulatory) relationships among molecular phenotypes (such as gene expression), especially when multiple phenotypes are involved. We extend the interpretation of the Principle of Mendelian randomization (PMR) and present MRPC, a novel machine learning algorithm that incorporates the PMR in the PC algorithm, a classical algorithm for learning causal graphs in computer science. MRPC learns a causal biological network efficiently and robustly from integrating individual-level genotype and molecular phenotype data, in w...
Source: Frontiers in Genetics - May 21, 2019 Category: Genetics & Stem Cells Source Type: research

Serial Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer to Predict the Therapeutic Response
Early biomarkers of therapeutic responses can help optimize the treatment of metastatic colorectal cancers (mCRC). In this prospective exploratory study, we examined serial changes of plasma-circulating tumor DNA (ctDNA) in 41 mCRC patients receiving first-line chemotherapies and tested its association with treatment outcomes according to radiological assessments. Using next-generation sequencing technologies, we profiled somatic mutations in 50 cancer-related genes in ctDNA before each of the first four treatment cycles. We observed mutations in 95.7% of pre-treatment ctDNA samples. Using mutations of the maximal frequenc...
Source: Frontiers in Genetics - May 21, 2019 Category: Genetics & Stem Cells Source Type: research

Gene Expression Noise Produces Cell-to-Cell Heterogeneity in Eukaryotic Homologous Recombination Rate
Variation in gene expression among genetically identical individual cells (called gene expression noise) directly contributes to phenotypic diversity. Whether such variation can impact genome stability and lead to variation in genotype remains poorly explored. We addressed this question by investigating whether noise in the expression of genes affecting homologous recombination (HR) activity either directly (RAD52) or indirectly (RAD27) confers cell-to-cell heterogeneity in HR rate in Saccharomyces cerevisiae. Using cell sorting to isolate subpopulations with various expression levels, we show that spontaneous HR rate is h...
Source: Frontiers in Genetics - May 21, 2019 Category: Genetics & Stem Cells Source Type: research

An Effective Method to Measure Disease Similarity Using Gene and Phenotype Associations
Motivation: In order to create controlled vocabularies for shared use in different biomedical domains, a large number of biomedical ontologies such as Disease Ontology (DO) and Human Phenotype Ontology (HPO), etc., are created in the bioinformatics community. Quantitative measures of the associations among diseases could help researchers gain a deep insight of human diseases, since similar diseases are usually caused by similar molecular origins or have similar phenotypes, which is beneficial to reveal the common attributes of diseases and improve the corresponding diagnoses and treatment plans. Some previous are proposed ...
Source: Frontiers in Genetics - May 21, 2019 Category: Genetics & Stem Cells Source Type: research

Evaluation of Intestinal Permeability and Liver Bacterial Translocation in Two Modern Broilers and Their Jungle Fowl Ancestor
The objective of this study was to evaluate the of intestinal permeability and liver bacterial translocation (BT) across a modern commercial broiler, a commercial broiler of 1995 genetics, and an unselected Jungle Fowl line. Modern 2015 (MB2015) broiler chicken, random bred line initiated from 1995 (RB1995), and the Giant Jungle fowl (JF). Chickens were randomly allocated to four different dietary treatments. Dietary treatments were 1) a control corn-based diet throughout the trial (corn-corn [C-C]); 2) an early phase malnutrition diet where chicks received a rye-based diet for 10 days, and then switched to the control die...
Source: Frontiers in Genetics - May 21, 2019 Category: Genetics & Stem Cells Source Type: research

Gene Co-expression Network and Copy Number Variation Analyses Identify Transcription Factors Associated With Multiple Myeloma Progression
Multiple myeloma (MM) has two clinical precursor stages of disease: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the mechanism of progression is not well understood. Because gene co-expression network analysis is a well-known method for discovering new gene functions and regulatory relationships, we utilized this framework to conduct differential co-expression analysis to identify interesting transcription factors in two publicly available datasets. We then used copy number variation data from a third public dataset to validate these transcription factors. First,...
Source: Frontiers in Genetics - May 17, 2019 Category: Genetics & Stem Cells Source Type: research

Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites
The human microbiome has been associated with health status, and risk of disease development. While the etiology of microbiome-mediated disease remains to be fully elucidated, one mechanism may be through microbial metabolism. Metabolites produced by commensal organisms, including in response to host diet, may affect host metabolic processes, with potentially protective or pathogenic consequences. We conducted multi-omic phenotyping of healthy subjects (N=136), in order to investigate the interaction between diet, the microbiome, and the metabolome in a cross-sectional sample. We analyzed the nutrient composition of self-r...
Source: Frontiers in Genetics - May 17, 2019 Category: Genetics & Stem Cells Source Type: research

DprA Is Essential for Natural Competence in Riemerella anatipestifer and Has a Conserved Evolutionary Mechanism
Riemerella anatipestifer ATCC11845 (RA ATCC11845) is naturally competent. However, the genes involved in natural transformation in this species remain largely unknown. Bioinformatic analysis predicts that DprA of RA (DprARa) has three domains: a sterile alpha motif (SAM), a Rossmann fold (RF) domain and a Z-DNA-binding domain (Zα). Inactivation of dprA abrogated natural transformation in RA ATCC11845, and this effect was restored by the expression of dprA in trans. The dprA with SAM and RF domains of Streptococcus pneumoniae and the dprA with RF and Zα domains of Helicobacter pylori was able to restore natural ...
Source: Frontiers in Genetics - May 17, 2019 Category: Genetics & Stem Cells Source Type: research

Functional Characterization of Argininosuccinate Lyase Gene Variants by Mini-Gene Splicing Assay
Conclusion: Two new pathogenic mutations of ASL gene, C.208-15 T>A and C.281G>T, were found in an ASA family, which enriches the mutational profile of the ASL gene and provides a basis for genetic diagnosis of ASA. In addition to the mutation in the exon region, the base change in the intron may cause aberrant splicing of mRNA and lead to abnormal structure and function of the protein. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 17, 2019 Category: Genetics & Stem Cells Source Type: research

Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
While substantial progress has been made in finding genetic variants associated with nicotine dependence (ND), a large proportion of the genetic variants remain undiscovered. The current research focuses have shifted toward uncovering rare variants, gene-gene/gene-environment interactions, and structural variations predisposing to ND, the impact of genetic heterogeneity in ND has been nevertheless paid less attention. The study of genetic heterogeneity in ND not only could enhance the power of detecting genetic variants with heterogeneous effects in the population but also improve our understanding of genetic etiology of N...
Source: Frontiers in Genetics - May 17, 2019 Category: Genetics & Stem Cells Source Type: research

Systematic Review and Meta-Analysis to Establish the Association of Common Genetic Variations in Vitamin D Binding Protein With Chronic Obstructive Pulmonary Disease
Conclusion: GC1F and GC1F/1F impose significant genetic risk for COPD, among Asians. Considerable differenced in allele frequencies and LD structure in GC locus may impose population specific risk. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 16, 2019 Category: Genetics & Stem Cells Source Type: research

Large-Scale Automatic Feature Selection for Biomarker Discovery in High-Dimensional OMICs Data
The identification of biomarker signatures in omics molecular profiling is usually performed to predict outcomes in a precision medicine context, such as patient disease susceptibility, diagnosis, prognosis and treatment response. To identify these signatures, we have developed a biomarker discovery tool, called BioDiscML. From a collection of samples and their associated characteristics, i.e. the biomarkers (e.g. gene expression, protein levels, clinico-pathological data), BioDiscML exploits various feature selection procedures to produce signatures associated to machine learning models that will predict efficiently a spe...
Source: Frontiers in Genetics - May 16, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical-Pharmacogenetic Predictive Models for Time to Occurrence of Levodopa Related Motor Complications in Parkinson ’s Disease
The response to dopaminergic treatments in Parkinson's disease depends on many clinical and genetic factors. The very common motor fluctuations and dyskinesia affect approximately half of patients after five years of treatment with levodopa. We did an evaluation of a combined effect of 16 clinical parameters and 34 single nucleotide polymorphisms to build clinical and clinical-pharmacogenetic models for prediction of time of occurrence of motor complications and to compare their predictive abilities. In total, 220 Parkinson's disease patients were included in the analysis. Their demographic, clinical, and genotype data wer...
Source: Frontiers in Genetics - May 16, 2019 Category: Genetics & Stem Cells Source Type: research

Genome to Phenome: Improving Animal Health, Production, and Well-Being – A New USDA Blueprint for Animal Genome Research 2018–2027
In 2008, a consortium led by the Agricultural Research Service (ARS) and the National Institute for Food and Agriculture (NIFA) published the “Blueprint for USDA Efforts in Agricultural Animal Genomics 2008–2017”, which served as a guiding document for research and funding in animal genomics. In the decade that followed, many of the goals set forth in the blueprint were accomplished. However, several other goals require further research. In addition, new topics not covered in the original blueprint, which are the result of emerging technologies, require exploration. To develop a new, updated blueprint, AR...
Source: Frontiers in Genetics - May 16, 2019 Category: Genetics & Stem Cells Source Type: research

A Distance-Based Kernel Association Test Based on the Generalized Linear Mixed Model for Correlated Microbiome Studies
Researchers have increasingly employed family-based or longitudinal study designs to survey the roles of the human microbiota on diverse host traits of interest (e.g., health/disease status, medical intervention, behavioral/environmental factor). Such study designs are useful to properly control for potential confounders or the sensitive changes in microbial composition and host traits. However, downstream data analysis is challenging because the measurements within clusters (e.g., families, subjects including repeated measures) tend to be correlated so that statistical methods based on the independence assumption cannot b...
Source: Frontiers in Genetics - May 16, 2019 Category: Genetics & Stem Cells Source Type: research

The Potential for microRNA Therapeutics and Clinical Research
As FDA approved small RNA drugs start to enter clinical medicine, ongoing studies for the microRNA (miRNA) class of small RNAs expand its preclinical and clinical research applications. A growing number of reports suggest a significant utility of miRNAs as biomarkers for pathogenic conditions, modulators of drug resistance, and/or as drugs for medical intervention in almost all human health conditions. The pleiotropic nature of this class of non protein-coding RNAs make them particularly attractive drug targets for diseases with a multifactorial origin and no current effective treatments. As candidate miRNAs begin to proce...
Source: Frontiers in Genetics - May 16, 2019 Category: Genetics & Stem Cells Source Type: research

The Genomic Landscape of Crossover Interference in the Desert Tree Populus euphratica
Crossover (CO) interference is a universal phenomenon by which the occurrence of one CO event inhibits the simultaneous occurrence of other COs along a chromosome. Because of its critical role in the evolution of genome structure and organization, the cytological and molecular mechanisms underlying CO interference have been extensively investigated. However, the genome-wide distribution of CO interference and its interplay with sex-, stress-, and age-induced differentiation remain poorly understood. Multi-point linkage analysis has proven to be a powerful tool for landscaping CO interference, especially within species for ...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Deleterious Impact of a Novel CFH Splice Site Variant in Atypical Hemolytic Uremic Syndrome
In conclusion, genetic investigation for pathogenic variants and evaluation of their functional impact, in particular in the case of splice site variants, is clinically relevant and enables not only better molecular understanding but helps to guide therapy with complement inhibitors. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential
The well-known signal mediator and small GTPase family member, RHOA, has now been associated with the progression of specific malignancies. In this review, we appraise the biomedical literature regarding the role of this enzyme in gastric cancer (GC) signaling, suggesting potential clinical significance. To that end, we examined RHOA activity, with regard to second-generation hallmarks of cancer, finding particular association with the hallmark “activation of invasion and metastasis”. Moreover, an abundance of studies show RHOA association with Lauren classification diffuse subtype, in addition to poorly differ...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China
Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disease caused by a defect of mitochondrial acetoacetyl-CoA thiolase. Beginning in 2014, we carried out newborn screening by tandem mass spectrometry MS/MS followed by next-generation sequencing (NGS) and identified two infants with BKTD from among 203,750 newborns born in Jiangsu Province, China. Both infants showed the characteristic chemical abnormalities of BKTD. We used NGS to confirm variants in the ACAT1. Patient 1 had the compound heterozygous variants c.721dupA and c.928G>C. Patient 2 had compound heterozygosity for the c.238+1G>A and c.1163G>T...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Whole-Exome Sequencing Identifies Somatic Mutations Associated With Mortality in Metastatic Clear Cell Kidney Carcinoma
Clear cell renal cell carcinoma (ccRCC) is among the most aggressive histologic subtypes of kidney cancer, representing about 3% of all human cancers. Patients at stage IV have nearly 60% of mortality in 2–3 years after diagnosis. To date, most ccRCC studies have used DNA microarrays and targeted sequencing of a small set of well-established, commonly altered genes. An exception is the large multi-omics study of The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), which identified new ccRCC genes based on whole exome-sequencing (WES) data, and molecular prognostic signatures based on transcriptomics...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Personalized Interpretation and Clinical Translation of Genetic Variants Associated With Cardiomyopathies
Cardiomyopathies are a heterogeneous group of inherited cardiac diseases characterized by progressive myocardium abnormalities associated with mechanical and/or electrical dysfunction. Massive genetic sequencing technologies allow a comprehensive genetic analysis to unravel the cause of disease. However, most identified genetic variants remain of unknown clinical significance due to incomplete penetrance and variable expressivity. Therefore, genetic interpretation of variants and translation into clinical practice remain a current challenge. We performed retrospective comprehensive clinical assessment and genetic analysis ...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Transcriptome Analysis of the Breast Muscle of Xichuan Black-Bone Chickens Under Tyrosine Supplementation Revealed the Mechanism of Tyrosine-Induced Melanin Deposition
The Xichuan black-bone chicken, which is a rare local chicken species in China, is an important genetic resource of black-bone chickens. Tyrosine can affect melanin production, but the molecular mechanism underlying tyrosine-induced melanin deposition in Xichuan black-bone chickens is poorly understood. Here, the blackness degree and melanin content of the breast muscle of Xichuan black-bone chickens fed a basic diet with five levels of added tyrosine (i.e., 0.2%, 0.4%, 0.6%, 0.8% and 1.0%; these groups were denoted test groups I-V, respectively) were assessed, and the results showed that 0.8% tyrosine was the optimal leve...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Identification of Cancer Dysfunctional Subpathways by Integrating DNA Methylation, Copy Number Variation, and Gene-Expression Data
A subpathway is defined as the local region of a biological pathway with specific biological functions. With the generation of large-scale sequencing data, there are more opportunities to study the molecular mechanisms of cancer development. It is necessary to investigate the potential impact of DNA methylation, copy number variation (CNV), and gene-expression changes in the molecular states of oncogenic dysfunctional subpathways. We propose a novel method, Identification of Cancer Dysfunctional Subpathways (ICDS), by integrating multi-omics data and pathway topological information to identify dysfunctional subpathways. We...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

rSeqTU —A Machine-Learning Based R Package for Prediction of Bacterial Transcription Units
A transcription unit (TU) is composed of one or multiple adjacent genes on the same strand that are co-transcribed in mostly prokaryotes. Accurate identification of TUs is a crucial first step to delineate the transcriptional regulatory networks and elucidate the dynamic regulatory mechanisms encoded in various prokaryotic genomes. Many genomic features, e.g., gene intergenic distance, and transcriptomic features including continuous and stable RNA-seq reads count signals, have been collected from a large amount of experimental data and integrated into classification techniques to computationally predict genome-wide TUs. A...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Molecular Organization and Chromosomal Localization Analysis of 5S rDNA Clusters in Autotetraploids Derived From Carassius auratus Red Var. ( ♀) × Megalobrama amblycephala (♂)
The autotetraploid fish (4n = 200, RRRR) (abbreviated as 4nRR) resulted from the whole genome duplication of red crucian carp (Carassius auratus red var., 2n = 100, RR) (abbreviated as RCC). During investigation of the influence of polyploidization on organization and evolution of the multigene family of 5S rDNA, molecular organization and chromosomal localization of the 5S rDNA were characterized in autotetraploid fish. By sequence analysis of the coding region (5S) and adjacent non-transcribed spacer (NTS), three distinct 5S rDNA units (type I: 203 bp; type II: 340 bp; and type III: 477bp) were identi...
Source: Frontiers in Genetics - May 15, 2019 Category: Genetics & Stem Cells Source Type: research