A5031267363- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Peroxisome Proliferator-Activated Receptors
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Genetic Mapping and Diversity in Plants and Animals
- Fungal and yeast genetics research
- Gene expression and cancer classification
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Chromatin Dynamics
- Nuclear Receptors and Signaling
- Metabolism and Genetic Disorders
- Bioinformatics and Genomic Networks
- Genetic factors in colorectal cancer
- Chromosomal and Genetic Variations
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Vitamin K Research Studies
- Asthma and respiratory diseases
- Immunodeficiency and Autoimmune Disorders
- Congenital heart defects research
British Columbia Children's Hospital
2018-2025
University of British Columbia
2018-2024
University of Colorado Boulder
2014-2020
University of Colorado System
2014
Abstract JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release JASPAR, the CORE collection has been expanded with 245 new PFMs (169 vertebrates, 42 plants, 17 nematodes, 10 insects, and 7 fungi), 156 were updated (125 28 plants 3 insects). These represent 18% expansion compared to previous...
Abstract Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat remain to be discovered. Existing methods detecting in short-read sequencing data require predefined catalogs. Recent discoveries emphasize the need that do not pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method genome-wide expansion detection. Analysis of real simulated shows our can identify large 41 out...
STAT6 (signal transducer and activator of transcription 6) is a factor that plays central role in the pathophysiology allergic inflammation. We have identified 16 patients from 10 families spanning three continents with profound phenotype early-life onset immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, anaphylaxis. The cases were either sporadic (seven...
Less than half of individuals with a suspected Mendelian condition receive precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest using long-read sequencing (LRS) to streamline genomic testing, but the absence control datasets for variant filtering prioritization has made tertiary analysis LRS challenging. To address this, 1000 Genomes Project ONT Sequencing Consortium aims generate from at least 800 samples....
Fewer than half of individuals with a suspected Mendelian or monogenic condition receive precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest using long-read sequencing (LRS) to streamline genomic testing, but the absence control datasets for variant filtering prioritization has made tertiary analysis LRS challenging. To address this, 1000 Genomes Project ONT Sequencing Consortium aims generate from at least...
We report an inborn error of metabolism caused by expansion a GCA-repeat tract in the 5' untranslated region gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The observed three unrelated patients who presented early-onset delay overall development, progressive ataxia, elevated levels glutamine. In addition to one patient also showed cerebellar atrophy. associated relative deficiency GLS messenger...
Abstract Background Mammalian X and Y chromosomes share a common evolutionary origin retain regions of high sequence similarity. Similar content can confound the mapping short next-generation sequencing reads to reference genome. It is therefore possible that presence both sex in genome cause technical artifacts genomic data affect downstream analyses applications. Understanding this problem critical for medical genomics population inference. Results Here, we characterize how homology on...
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal cancer cells. However, the exact regulatory mechanisms action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic transcriptome changes response HDACI largazole a transformed non-transformed cell line. Exposure low nanomolar concentrations (<GI50) predominantly resulted upregulation transcripts whereas higher doses (≥GI50)...
Abstract Background Expansions of short tandem repeats are the cause many neurogenetic disorders including familial amyotrophic lateral sclerosis, Huntington disease, and others. Multiple methods have been recently developed that can identify repeat expansions in whole genome or exome sequencing data. Despite widely recognized need for visual assessment variant calls clinical settings, current computational tools lack ability to produce such visualizations expansions. Expanded difficult...
Polyploidization events have occurred during the evolution of many fungi, plant, and animal species are thought to contribute speciation tumorigenesis, however little is known about how ploidy level contributes adaptation at molecular level. Here we integrate whole genome sequencing, RNA expression analysis, relative fitness ∼100 evolved clones three levels. Independent haploid, diploid, tetraploid populations were grown in a low carbon environment for 250 generations. We demonstrate that...
Abstract Background Trinucleotide repeat expansions are an emerging class of genetic variants associated with various movement disorders. Unbiased genome‐wide analyses can reveal novel genotype–phenotype associations and provide a diagnosis for patients families. Objective The aim was to identify the cause severe progressive disorder phenotype in 2 affected brothers. Methods A family brothers unaffected parents had extensive phenotyping since birth. Whole‐genome long‐read sequencing methods...
Genome-wide sequencing (GWS) is a standard of care for diagnosis suspected genetic disorders, but the proportion patients found to have pathogenic or likely variants ranges from less than 30% more 60% in reported studies. It has been suggested that diagnostic rate can be improved by interpreting genomic context each affected individual's full clinical picture and regular follow-up reinterpretation GWS laboratory results. Trio exome was performed 415 families trio genome 85 CAUSES study. The...
X-linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with highly complex clinical presentation. ALD caused by mutations in the ABCD1 gene, and characterized accumulation of very long-chain fatty acids plasma tissues. Disease-causing are 'loss function' mutations, no prognostic value respect to outcome an individual. All male patients develop spinal cord disease peripheral neuropathy adulthood, although age onset variable. However, lifetime prevalence progressive white...
Many inborn errors of metabolism (IEMs) are amenable to treatment, therefore early diagnosis is imperative. Whole-exome sequencing (WES) variant prioritization coupled with phenotype-guided clinical and bioinformatics expertise typically used identify disease-causing variants; however, it can be challenging the causal candidate gene when a large number rare potentially pathogenic variants detected. Here, we present network-based approach, metPropagate, that uses untargeted metabolomics (UM)...
Abstract Interpreting the functional impact of noncoding variants is an ongoing challenge in field genome analysis. With most associated with complex traits and disease residing regulatory regions, altered transcription factor (TF) binding has been proposed as a mechanism action. It therefore imperative to develop methods that predict at TF sites (TFBSs). Here, we describe update our MANTA database stores: 1) TFBS predictions human genome, 2) potential on for all possible single nucleotide...
Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring importance defining mechanisms underlying differences in regulation gene expression between individuals. We discovered a pair co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed one strain Saccharomyces cerevisiae, ∑1278b, but not another, S288c. By combining classical genetics techniques high-throughput sequencing, we identified trans-acting single...
Background We previously reported that acute functional tolerance (AFT) to the hypnotic effects of alcohol was significantly correlated with drinking in dark (DID) LXS recombinant inbred panel, but only mice had been pretreated alcohol. Here, we have conducted quantitative trait locus (QTL) mapping for AFT. DNA sequencing progenitor ILS and ISS strains microarray analyses were also identify candidate genes correlates. Methods given either saline or (5 g/kg) on day 1 then tested loss righting...
Abstract Mammalian X and Y chromosomes share a common evolutionary origin retain regions of high sequence similarity. This homology can cause the mismapping short sequencing reads derived from sex affect variant calling other downstream analyses. Understanding correcting this problem is critical for medical genomics population genomic inference. Here, we characterize how analyses on present XYalign, new tool that: (1) facilitates inference chromosome complement next-generation data; (2)...
The Inbred Long- and Short-Sleep (ILS, ISS) mouse lines were selected for differences in acute ethanol sensitivity using the loss of righting response (LORR) as selection trait. show an over tenfold difference LORR and, along with a recombinant inbred panel derived from them (the LXS), have been widely used to dissect genetic underpinnings sensitivity. Here we sequenced genomes ILS ISS investigate DNA variants that contribute their difference. We identified ~2.7 million high-confidence SNPs...
Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification multiple loci via linkage analyses, no specific genes have identified from these studies. The current study based on seven-generation family isolated inherited an autosomal dominant manner. A total 13 individuals ancestor included for analysis. Among these, nine are affected and four unaffected. single signal at 8.5...