728 results match your criteria genotype configuration

Towards fine-scale population stratification modeling based on kernel principal component analysis and random forest.

Genes Genomics 2021 Jun 7. Epub 2021 Jun 7.

School of Computers, Guangdong University of Technology, Guangzhou, China.

Background: Population stratification modeling is essential in Genome-Wide Association Studies.

Objective: In this paper, we aim to build a fine-scale population stratification model to efficiently infer individual genetic ancestry.

Methods: Kernel Principal Component Analysis (PCA) and random forest are adopted to build the population stratification model, together with parameter optimization. Read More

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Allele-dosage genetic polymorphisms of cannabinoid receptor 1 predict attention, but not working memory performance in humans.

Acta Psychol (Amst) 2021 May 31;216:103299. Epub 2021 Mar 31.

Lab. Neurogenómica Cognitiva, Coord. Psicobiología y Neurociencias, Fac. Psicología, Universidad Nacional Autónoma de México (UNAM), Mexico. Electronic address:

Attention and working memory (WM) are under high genetic regulation. Single nucleotide polymorphisms (SNPs) of the CNR1 gene, that encode for CB1R, have previously been shown to be related with individual differences in attentional control and WM. However, it remains unclear whether there is an allele-dosage or a dominant contribution of polymorphisms of CNR1 affecting attention and WM performance. Read More

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Complete sequencing of expanded SAMD12 repeats by long-read sequencing and Cas9-mediated enrichment.

Brain 2021 May;144(4):1103-1117

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

A pentanucleotide TTTCA repeat insertion into a polymorphic TTTTA repeat element in SAMD12 causes benign adult familial myoclonic epilepsy. Although the precise determination of the entire SAMD12 repeat sequence is important for molecular diagnosis and research, obtaining this sequence remains challenging when using conventional genomic/genetic methods, and even short-read and long-read next-generation sequencing technologies have been insufficient. Incomplete information regarding expanded repeat sequences may hamper our understanding of the pathogenic roles played by varying numbers of repeat units, genotype-phenotype correlations, and mutational mechanisms. Read More

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Methylenetetrahydrofolate Reductase Dimer Configuration as a Risk Factor for Maternal Meiosis I-Derived Trisomy 21.

Hum Hered 2020 30;85(2):61-65. Epub 2021 Mar 30.

Department of Biology and Medical Genetics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.

Background: Evidence suggests that the dimer configuration of methylenetetrahydrofolate reductase (MTHFR) enzyme might be destabilized by polymorphisms in monomers at the positions C677T and A1298C. It has been observed that these polymorphisms may lead to stable (CCAA, CCAC, CCCC) and unstable (CTAA, CTAC, TTAA) enzyme dimer configurations.

Objective: The aim of this study was to evaluate the association of the MTHFR enzyme dimer configuration and folate dietary intake with the stage of meiotic nondisjunction in mothers of children with maternally derived trisomy 21. Read More

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Genomic characterization of a novel G3P[10] rotavirus strain from a diarrheic child in Thailand: Evidence for bat-to-human zoonotic transmission.

Infect Genet Evol 2021 01 5;87:104667. Epub 2020 Dec 5.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

An unusual rotavirus strain with the G3P[10] genotype (RVA/Human-wt/THA/MS2015-1-0001/2015/G3P[10]) was identified in a stool sample from a hospitalized child aged 11 months with severe gastroenteritis in Thailand. In the current study, we sequenced and characterized the full genome of strain MS2015-1-0001. On full-genomic analysis, strain MS2015-1-0001 exhibited the following genotype configuration: G3-P[10]-I8-R3-C3-M3-A9-N3-T3-E3-H6, which is identical or closely related to those of bat and bat-like rotavirus strains (MYAS33-like). Read More

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January 2021

Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten.

Sci Rep 2020 10 14;10(1):17227. Epub 2020 Oct 14.

Institute of Genetics and Biophysics, CNR, Naples, Italy.

The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05 and HLA-DQB1*02 predisposing alleles, in trans configuration. The alleles encode the DQ2. Read More

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October 2020

Phylogeographic structure of the dunes sagebrush lizard, an endemic habitat specialist.

PLoS One 2020 16;15(9):e0238194. Epub 2020 Sep 16.

Department of Ecology and Conservation Biology, Biodiversity Research and Teaching Collections, Texas A&M University, College Station, Texas, United States of America.

Phylogeographic divergence and population genetic diversity within species reflect the impacts of habitat connectivity, demographics, and landscape level processes in both the recent and distant past. Characterizing patterns of differentiation across the geographic range of a species provides insight on the roles of organismal and environmental traits in evolutionary divergence and future population persistence. This is particularly true of habitat specialists where habitat availability and resource dependence may result in pronounced genetic structure as well as increased population vulnerability. Read More

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October 2020

Phenotypic noise and the cost of complexity.

Evolution 2020 10 3;74(10):2221-2237. Epub 2020 Sep 3.

Inria, 78150 Rocquencourt, France.

Experimental studies demonstrate the existence of phenotypic diversity despite constant genotype and environment. Theoretical models based on a single phenotypic character predict that during an adaptation event, phenotypic noise should be positively selected far from the fitness optimum because it increases the fitness of the genotype, and then be selected against when the population reaches the optimum. It is suggested that because of this fitness gain, phenotypic noise should promote adaptive evolution. Read More

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October 2020

Improved structural variant interpretation for hereditary cancer susceptibility using long-read sequencing.

Genet Med 2020 11 6;22(11):1892-1897. Epub 2020 Jul 6.

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.

Purpose: Structural variants (SVs) may be an underestimated cause of hereditary cancer syndromes given the current limitations of short-read next-generation sequencing. Here we investigated the utility of long-read sequencing in resolving germline SVs in cancer susceptibility genes detected through short-read genome sequencing.

Methods: Known or suspected deleterious germline SVs were identified using Illumina genome sequencing across a cohort of 669 advanced cancer patients with paired tumor genome and transcriptome sequencing. Read More

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November 2020

Recently Evolved Enhancers Emerge with High Interindividual Variability and Less Frequently Associate with Disease.

Cell Rep 2020 06;31(12):107799

Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, the Netherlands; Erasmus University Medical Center, Department of Developmental Biology, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands. Electronic address:

Mutations in non-coding regulatory DNA such as enhancers underlie a wide variety of diseases including developmental disorders and cancer. As enhancers rapidly evolve, understanding their function and configuration in non-human disease models can have important clinical applications. Here, we analyze enhancer configurations in tissues isolated from the common marmoset, a widely used primate model for human disease. Read More

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First isolation and whole-genome characterization of a G9P[14] rotavirus strain from a diarrheic child in Egypt.

J Gen Virol 2020 09;101(9):896-901

Division of Viral Diseases, Centers for Diseases Control and Prevention, Atlanta, GA 30329, USA.

An unusual group A rotavirus (RVA) strain (RVA/Human-tc/EGY/AS997/2012/G9[14]) was isolated for the first time in a faecal sample from a 6-month-old child who was hospitalized for treatment of acute gastroenteritis in Egypt in 2012. Whole-genome analysis showed that the strain AS997 had a unique genotype constellation: G9-P[14]-I2-R2-C2-M2-A11-N2-T1-E2-H1. Phylogenetic analysis indicated that the strain AS997 had the consensus P[14] genotype constellation with the G9, T1 and H1 reassortment. Read More

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September 2020

Range-wide genetic structure in the thorn-tailed rayadito suggests limited gene flow towards peripheral populations.

Sci Rep 2020 06 10;10(1):9409. Epub 2020 Jun 10.

Instituto de Ecología y Biodiversidad, Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.

Understanding the population genetic consequences of habitat heterogeneity requires assessing whether patterns of gene flow correspond to landscape configuration. Studies of the genetic structure of populations are still scarce for Neotropical forest birds. We assessed range-wide genetic structure and contemporary gene flow in the thorn-tailed rayadito (Aphrastura spinicauda), a passerine bird inhabiting the temperate forests of South America. Read More

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Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method.

Biosci Rep 2020 05;40(5)

Central laboratory, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Mitochondrial 12S rRNA A1555G and C1494T mutations are the major contributors to hearing loss. As patients with these mutations are sensitive to aminoglycosides, mutational screening for 12S rRNA is therefore recommended before the use of aminoglycosides. Most recently, we developed a novel multiplex allele-specific PCR (MAS-PCR) that can be used for detecting A1555G and C1494T mutations. Read More

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Genetic analysis of type 2 tri-allelic pattern at TPOX locus in the Chinese Han population.

Mol Genet Genomics 2020 Jul 1;295(4):933-939. Epub 2020 May 1.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

Tri-allelic patterns can occasionally be observed during the profiling of short tandem repeats (STRs) in routine forensic practice. In previous studies, the Type 2 tri-allelic pattern at TPOX has been widely studied in African and Brazilian populations. In this study, we investigated the incidence, rearrangement, and inheritance of the Type 2 tri-allelic pattern at the TPOX locus in a Chinese Han population. Read More

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The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and gene fusion presenting as B-lymphoblastic leukemia.

Cold Spring Harb Mol Case Stud 2020 04 1;6(2). Epub 2020 Apr 1.

Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109-2800, USA.

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. Read More

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Effects of deficiency in the -encoded visual cycle protein CRALBP on visual dysfunction in humans and mice.

J Biol Chem 2020 05 18;295(19):6767-6780. Epub 2020 Mar 18.

Department of Ophthalmology, Columbia University Irving Medical Center, New York, New York 10032

Mutations in (), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11--retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11--retinol oxidation to 11--retinal. CRALBP also maintains the 11- configuration and protects against unwanted retinaldehyde activity. Read More

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Clinical and genetic features of somatic mosaicism in facioscapulohumeral dystrophy.

J Med Genet 2020 11 13;57(11):777-785. Epub 2020 Mar 13.

Department of Neurology, Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China

Purpose: To analyse the clinical spectrum, genetic features, specific D4Z4 hypomethylation status and genotype-phenotype correlations for somatic mosaicism in facioscapulohumeral dystrophy (FSHD).

Methods: This was a prospective, hospital-based, case-control, observational study of 35 participants with FSHD with somatic mosaicism recruited over 10 years, with 17 penetrant patients and 18 non-penetrant mutation carriers. This study also included a univariate comparison of 17 paired mosaic and non-mosaic patients with FSHD. Read More

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November 2020

DEN-IM: dengue virus genotyping from amplicon and shotgun metagenomic sequencing.

Microb Genom 2020 03;6(3)

Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

Dengue virus (DENV) represents a public health threat and economic burden in affected countries. The availability of genomic data is key to understanding viral evolution and dynamics, supporting improved control strategies. Currently, the use of high-throughput sequencing (HTS) technologies, which can be applied both directly to patient samples (shotgun metagenomics) and to PCR-amplified viral sequences (amplicon sequencing), is potentially the most informative approach to monitor viral dissemination and genetic diversity by providing, in a single methodological step, identification and characterization of the whole viral genome at the nucleotide level. Read More

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Prevalence and clinical features of hearing loss caused by EYA4 variants.

Sci Rep 2020 02 27;10(1):3662. Epub 2020 Feb 27.

Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. Read More

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February 2020

Phenotypic Spectrum of the Foveal Configuration and Foveal Avascular Zone in Patients With Alport Syndrome.

Invest Ophthalmol Vis Sci 2020 02;61(2)


Purpose: To investigate characteristics of the foveal pit and the foveal avascular zone (FAZ) in patients with Alport syndrome (AS), a rare monogenetic disease due to mutations in genes encoding for collagen type IV.

Methods: Twenty-eight eyes of nine patients with AS, and five autosomal-recessive carriers and 15 eyes from 15 age-similar healthy control subjects were examined using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Foveal configuration and FAZ measures including the FAZ area, circularity, and vessel density in the central 1° and 3° were correlated. Read More

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February 2020

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration.

J Vis Exp 2020 01 9(155). Epub 2020 Jan 9.

Department of Genetics, University of North Carolina; Neuroscience Center, University of North Carolina;

Genome-wide association studies (GWAS) have successfully identified hundreds of genomic loci that are associated with human traits and disease. However, because the majority of the genome-wide significant (GWS) loci fall onto the non-coding genome, the functional impact of many remain unknown. Three-dimensional chromatin interactions identified by Hi-C or its derivatives can provide useful tools to annotate these loci by linking non-coding variants to their actionable genes. Read More

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January 2020

Genome analysis and knowledge-driven variant interpretation with TGex.

BMC Med Genomics 2019 12 30;12(1):200. Epub 2019 Dec 30.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Background: The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient's phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. Read More

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December 2019

Development of a high throughput human stool specimen processing method for a molecular Helicobacter pylori clarithromycin resistance assay.

PLoS One 2019 16;14(12):e0224356. Epub 2019 Dec 16.

Meridian Bioscience, Inc., Cincinnati, Ohio, United States of America.

It has become critical to detect Helicobacter pylori (H. pylori) infection due to the link to gastric cancer with some strains. These strains are also increasing in resistance to antibiotics with clarithromycin leading the way as the first line treatment. Read More

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Male and female inheritance patterns in tetraploid 'Moncada' mandarin.

Plant Cell Rep 2020 Mar 28;39(3):335-349. Epub 2019 Nov 28.

Centro de Citricultura y Producción Vegetal, Instituto Valenciano de Investigaciones Agrarias (IVIA), Carretera CV-315, km 10.7, Moncada, 46113, Valencia, Spain.

Key Message: Tetraploid `Moncada´ mandarin, used as male and female in interploidy hybridizations, displays mainly tetrasomic inheritance for most LGs, with slight variations according to the direction of the crossing. Triploid-breeding programs in citrus are key tool to develop seedless cultivars. Obtaining triploid citrus hybrids may be achieved through different strategies, such as the exploitation of female unreduced gamete in crosses between diploid parents and diploid by tetraploid sexual hybridizations, in which tetraploid genotypes can be used as male or female parents. Read More

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Linking of genetic risk variants to disease-specific gene expression via multi-omics studies in rheumatoid arthritis.

Semin Arthritis Rheum 2019 12;49(3S):S49-S53

Laboratory for Autoimmune diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown pathologic mechanism. Extensive single-level analyses have been conducted, including genome-wide association studies (GWASs) and genome-wide copy number variation analyses, whole transcriptomics, and epigenetic analyses. These data are analyzed separately to identify RA-associated genetic components. Read More

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December 2019

Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge.

J Exp Med 2020 02;217(2)

Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO.

We previously generated a panel of human monoclonal antibodies (mAbs) against Zika virus (ZIKV) and identified one, ZIKV-116, that shares germline usage with mAbs identified in multiple donors. Here we show that ZIKV-116 interferes with ZIKV infection at a post-cellular attachment step by blocking viral fusion with host membranes. ZIKV-116 recognizes the lateral ridge of envelope protein domain III, with one critical residue varying between the Asian and African strains responsible for differential binding affinity and neutralization potency (E393D). Read More

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February 2020

Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation.

Clin Exp Otorhinolaryngol 2020 May 2;13(2):113-122. Epub 2019 Nov 2.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Objectives: We, herein, report two novel USH2A variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL).

Methods: Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. Read More

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Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1.

Am J Hum Genet 2019 11 17;105(5):894-906. Epub 2019 Oct 17.

Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA. Electronic address:

Hereditary hemorrhagic telangiectasia (HHT) is a Mendelian disease characterized by vascular malformations (VMs) including visceral arteriovenous malformations and mucosal telangiectasia. HHT is caused by loss-of-function (LoF) mutations in one of three genes, ENG, ACVRL1, or SMAD4, and is inherited as an autosomal-dominant condition. Intriguingly, the constitutional mutation causing HHT is present throughout the body, yet the multiple VMs in individuals with HHT occur focally, rather than manifesting as a systemic vascular defect. Read More

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November 2019

A Single Nucleotide C3 Polymorphism Associates With Clinical Outcome After Lung Transplantation.

Front Immunol 2019 26;10:2245. Epub 2019 Sep 26.

Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.

Development of chronic rejection is still a severe problem and causes high mortality rates after lung transplantation (LTx). Complement activation is important in the development of acute rejection (AR) and bronchiolitis obliterans syndrome, with C3 as a key complement factor. We investigated a single nucleotide polymorphism (SNP) in the C3 gene (rs2230199) in relation to long-term outcome after LTx in 144 patient-donor pairs. Read More

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October 2020

Assessing Ploidy Level Analysis and Single Pollen Genotyping of Diploid and Euploid Citrus Genotypes by Fluorescence-Activated Cell Sorting and Whole-Genome Amplification.

Front Plant Sci 2019 24;10:1174. Epub 2019 Sep 24.

Centro de Citricultura y Producción Vegetal, Instituto Valenciano de Investigaciones Agrarias (IVIA), Moncada, Valencia, Spain.

Flow cytometry is widely used to determine genome size and ploidy level in plants. This technique, when coupled with fluorescence-activated cell sorting (FACS), whole genome amplification and genotyping (WGA), opens up new opportunities for genetic studies of individualized nuclei. This strategy was used to analyze the genetic composition of single pollen nuclei of different citrus species. Read More

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September 2019