A5012921319- Lipoproteins and Cardiovascular Health
- Genetic factors in colorectal cancer
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Health and Medical Research Impacts
- Genomic variations and chromosomal abnormalities
- Cancer, Lipids, and Metabolism
- Aortic Thrombus and Embolism
- RNA modifications and cancer
- Lipid metabolism and disorders
- Cancer Genomics and Diagnostics
- Cholesterol and Lipid Metabolism
- RNA Research and Splicing
- Liver Disease Diagnosis and Treatment
- Primary Care and Health Outcomes
- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- RNA regulation and disease
- Cardiomyopathy and Myosin Studies
- BRCA gene mutations in cancer
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Interprofessional Education and Collaboration
Ontario Genomics
2023
Stanford University
2020-2022
Hospital for Sick Children
2021
Western University
2017-2020
Robarts Clinical Trials
2018
•Severe hypertriglyceridemia has a strong genetic basis.•Almost all of those with genetically identified factors had polygenic hypertriglyceridemia.•Biallelic (ie, homozygous or compound heterozygous) variants were infrequent.•The accumulation common was the most predominant determinant. BackgroundHypertriglyceridemia (HTG) is complex trait defined by elevated plasma triglyceride levels. Genetic determinants HTG have so far been examined in piecemeal manner; understanding its molecular...
Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine improved patient care. An essential requirement achieving standardized reliable interpretation data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) an exemplar the utility such resource: it has high incidence, favorable prognosis with early intervention treatment, cascade screening can be offered to...
Abstract Background Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome interpreting variants to inform healthcare management have lacking. Results Here we present ClinGen Variant Curation Interface (VCI), a global open-source variant...
Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the receptor gene (LDLR). In providing molecular diagnosis for FH, current procedure often includes targeted next-generation sequencing (NGS) panels detection small-scale DNA variants, followed multiplex ligation-dependent probe amplification (MLPA) LDLR whole-exon copy number variants (CNVs). The latter essential because ∼10% FH cases...
Abstract Background In 2013, our laboratory designed a targeted sequencing panel, “LipidSeq”, to study the genetic determinants of dyslipidemia and metabolic disorders. Over last 6 years, we have analyzed 3262 patient samples obtained from own Lipid Genetics Clinic international colleagues. Here, highlight findings discuss research benefits clinical implications panel. Methods LipidSeq targets 69 genes 185 single-nucleotide polymorphisms (SNPs) either causally related or associated with This...
BackgroundFamilial hypercholesterolemia (FH) is a common genetic disorder of severely elevated low-density lipoprotein (LDL) cholesterol, characterized by premature atherosclerotic cardiovascular disease. Although copy number variations (CNVs) are large-scale mutation-type capable explaining FH cases, they have been, to date, assessed only in the LDLR gene. Here, we performed novel CNV screening additional FH-associated genes using next-generation sequencing–based approach.MethodsIn 704...
Abstract Accurately modeling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation the formulation of tailored therapeutics. We describe foundation model biology, “BigRNA”, which was trained on thousands genome-matched datasets to predict tissue-specific expression, splicing, microRNA sites, binding protein specificity from DNA sequence. Unlike approaches that are restricted missense variants, BigRNA can identify...
Copy-number variations (CNVs) have been studied in the context of familial hypercholesterolemia but not yet evaluated patients with extreme levels HDL cholesterol. We targeted, next-generation sequencing data from very low cholesterol (i.e., hypoalphalipoproteinemia) VarSeq-CNV® caller algorithm to screen for CNVs that disrupted ABCA1, LCAT, or APOA1 genes. In four individuals, we found three unique deletions ABCA1: a heterozygous deletion exon 4, spanned exons 8 31, and entire ABCA1 gene....
Abstract Polygenic risk scores (PRS), often aggregating the results from genome-wide association studies, can bridge gap between initial variant discovery efforts and disease estimation for clinical applications. However, there is remarkable heterogeneity in reporting of these due to a lack adherence standards no accepted suited current state PRS development application. This best practices hinders translation into care. The ClinGen Complex Disease Working Group, collaboration with Score...
BackgroundFamilial hypercholesterolemia (FH) is an inherited condition of elevated serum low-density lipoprotein (LDL) cholesterol leading to premature coronary heart disease. We evaluated whether FH mutations are independently associated with the development myocardial infarction (MI), after adjusting for LDL level and clinical risk factors.MethodsIn 182 unrelated patients from different families referred clinically suspected FH, targeted next-generation DNA sequencing was performed on 73...
Inhibitors of proprotein convertase subtilisin kexin 9 are indicated in Canada for treatment patients with familial hypercholesterolemia (FH). Classically, FH is considered to be a monogenic condition caused by rare pathogenic mutations; however, some have on polygenic basis. Whether the effect inhibitor differs between and unclear.We performed retrospective chart reviews treated evolocumab 140 mg subcutaneously biweekly from Lipid Genetics Clinic, London Health Sciences Centre....
ABSTRACT Purpose In 2015, the American College of Medical Genetics and Genomics (ACMG) Association for Molecular Pathology (AMP) published consensus standardized guidelines variant classification in Mendelian disorders. To increase accuracy consistency, Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia (FH) Variant Curation Expert Panel (VCEP) was tasked with optimizing existing ACMG/AMP framework disease-specific FH. Here, we provide recommendations most common FH-causing...
Abstract Background Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome interpreting variants to inform healthcare management have lacking. Results Here we present ClinGen Variant Curation Interface (VCI), a global open-source variant...
<title>Abstract</title> Accurately modeling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation the formulation of tailored therapeutics. We describe foundation model biology, “BigRNA”, which was trained on thousands genome-matched datasets to predict tissue-specific expression, splicing, microRNA sites, binding protein specificity from DNA sequence. Unlike approaches that are restricted missense variants,...