All rights reserved. The study was approved by the Research Ethics Board at The Hospital for Sick Children (REB no. Users who like The Personal Genome Project Canada's initial 56 participants: findings from whole genome sequencing Research ethics board protocols and consents, and genome data files are available at www.personalgenomes.ca. A Canadian version of the Personal Genome Project (PGP) was launched earlier this month. The Personal Genome Project. Big data is revolutionising the way the economy, science and society operates. The project involves recruiting people to have their entire genome sequenced and to have their results, together with personal data about their health and their lives, made publicly available online. The order determines whether an organism is human, or another species of plant or animal, or indeed bacteria or fungi, etc. "Our focus is on causality, not correlation," Church says. As of November 2017, more than 10,000 volunteers had joined the project. Whole genome sequencing found an average per participant of 3.7 million high-quality SNVs and indels (1198 rare coding) and 491 CNVs (2.3 rare coding) (Table 2). Anecdotally, prior perceived limitations to participation seemed to be somewhat relieved once protection afforded by the Act was assured. Personal Genome Project Canada. Methods: Defined as a research project, the Personal Genome Project UK (PGP-UK) is part of the global PGP network and focuses on open data sharing and citizen science to advance and accelerate personalized genomics and medicine. There were 172 recessive disease alleles (e.g., 5 individuals carried mutations for cystic fibrosis). The Personal Genome Project Canada launches this week giving Canadians an unprecedented opportunity to participate in a groundbreaking research study about human genetics and health. This requires awareness of the spectrum of potential findings, and the technical strengths and limitations of the underlying tests. The second was to find the sequence (order) of nucleotides (adenine - A, guanine - G, cytosine - C, or thymine … For example, there were 172 recessive alleles in 137 disease-associated genes (some have been identified in Canadian studies52,53), and 8 large CNVs(> 100 kb) of uncertain significance but involving genes (e.g., a duplication affecting 16 genes in 1 participant (PGPC-56) (Table S1, Appendix 2). The Global Network of Personal Genome Projects includes researchers at many leading institutions around the globe. Some traits or diseases result from single-gene variants, with outcomes that are predictable using principles of classical Mendelian genetics. ISSN 1488-2329 (e) 0820-3946 (p). An additional 172 pathogenic alleles were associated with autosomal recessive or semidominant inheritance patterns (mean 3.1/individual [SD 1.7]), which is close to empirical estimates of the carrier burden for recessive diseases.54 Participants also carried an average of 3.9 pharmacorelevant diplotypes associated with the metabolism of about 50 drugs. For example, a sequence of bands that are red, green, green and blue might mean that the four-base strand was made up of adenine, guanine, guanine and cytosine (AGGC). In a 65-year-old man, we identified a pathogenic BRCA1 variant, which is reportable according to the recommendations by the American College of Medical Genetics and Genomics.50 The participant was of Ashkenazi Jewish descent, a population with higher frequencies of pathogenic BRCA1 and BRCA2 variants compared with the general population. The Personal Genome Project UK (PGP-UK) is a member of the global PGP network together with the PGPs in the United States, Canada, Austria and China. A collaborative academic research effort with Harvard Medical School's Personal Genome Project (PGP-HMS), PGP-C aims to sequence the genomes of 100 Canadians over the next year. PGP-UK is a member of the Global PGP Network … Miriam Reuter, Stephen Scherer and Janet Buchanan drafted the manuscript. In 2007, Misha Angrist became the fourth subject in the Personal Genome Project, George Church's ambitious plan to sequence the entire genomic catalog: every participant's twenty thousand–plus genes and the rest of his or her 6 billion base pairs. As we find out more about human genes and how they work, we may be able to develop new ways to diagnose and treat more diseases. Three participants (PGPC-09, PGPC-16, PGPC-32), who were identified with CYP2C19-metabolizer status indicating favourable response to proton pump inhibitors, had self-reported use of such drugs. The particular order of the bases is very important. Yuen, Brett Trost, Tara A. Paton, Sergio L. Pereira, Jo-Anne Herbrick, Richard F. Wintle, Daniele Merico, Jennifer Howe, Jeffrey R. MacDonald, Chao Lu… Implications for tissue specificity and durability of elastic tissue, Familial partial lipodystrophy associated with compound heterozygosity for novel mutations in the, The CHEK2 I157T variant and breast cancer susceptibility: a systematic review and meta-analysis, A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis, A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis, A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia, A systematic review and meta-analysis of the relationship between lipoprotein lipase Asn291Ser variant and diseases, A novel splice-site variant of the base excision repair gene, Risk of colorectal cancer for carriers of mutations in, A discovery resource of rare copy number variations in individuals with autism spectrum disorder, Transmission disequilibrium of small CNVs in simplex autism, Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes, De novo CNVs in bipolar affective disorder and schizophrenia, Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death, A cardiac arrhythmia syndrome caused by loss of ankyrin-B function, Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease, The importance of E-cadherin binding partners to evaluate the pathogenicity of E-cadherin missense mutations associated to HDGC, Exome sequencing in dementia with Lewy bodies, Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing, Childhood neurological presentation of a novel mitochondrial tRNA(Val) gene mutation, American College of Medical Genetics and Genomics, ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing, The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients: a pilot randomized trial, An estimate of the mutational damage in man from data on consanguineous marriages, High frequency actionable pathogenic exome mutations in an average-risk cohort, A public resource facilitating clinical use of genomes, Personalized genomic disease risk of volunteers, Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics, Actionable exomic incidental findings in 6503 participants: challenges of variant classification, Performance of ACMG–AMP variant-interpretation guidelines among nine laboratories in the Clinical Sequencing Exploratory Research consortium, Analysis of protein-coding genetic variation in 60,706 humans, Machine learning in genomic medicine: a review of computational problems and data sets, Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers, Human Y-chromosome variation in the genome-sequencing era, AstraZeneca launches project to sequence 2 million genomes, Biomedical technology and the clinic of the future, The human genome project will not replace the physician, Detection of human adaptation during the past 2000 years, Finding the right balance between precision medicine and personalized care, Emergency department use following incentives to provide after-hours primary care: a retrospective cohort study, Physician choices in pulmonary embolism testing, Symptoms associated with a positive result for a swab for SARS-CoV-2 infection among children in Alberta, www.cmaj.ca/lookup/doi/10.1503/cmaj.180076, www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.171151/-/DC1, https://soundcloud.com/cmajpodcasts/171151-res. We found multitudes of other data that were potentially relevant to health. The Personal Genome Project Canada's initial 56 participants: findings from whole genome sequencing by CMAJ Podcasts published on 2018-01-25T14:47:48Z. Our analysis also determined that a 70-year-old man (with self-reported hypercholesterolemia) had a heterozygous rare variant in LMNA; the same variant was reported to cause semidominant partial lipodystrophy and metabolic abnormalities, with cardiovascular risk factors particularly pronounced in obese individuals or carriers of 2 pathogenic alleles.22. We are a systems epigenomics group that is interested broadly in all aspects of it. Certain types of pathogenic alleles are not detected reliably at present through the short-read whole genome sequencing method we used (e.g., those in regions on the Y chromosome and telomeres64–66 or trinucleotide repeat expansions). The Personal Genome Project Canada was launched in 2007 based on the principles and open consent policies of the initial project in the United States. The Personal Genome Project Canada has released first results that suggest whole genome sequencing can benefit the country's quality of healthcare, based on the results of sequencing the entire personal genomes of 56 healthy participants. Variant alleles may be null, missense, nonsense, splice variants, deleted, duplicated, disrupted, etc., depending on their effect on the related gene products. Participation in the project is an ongoing process, both for the participants described here and for additional volunteers. ALL NEWS. These could compromise metabolism of drugs by CYP2D6 or CYP2C19, reduce ability to metabolize thiopurines, increase risk for simvastatin-related muscle toxicity and have implications for initial warfarin dosing. Personal traits will be shared directly with you. For enquiries, contact us. Based on expert consensus, we considered 19 variants in 14 of 56 participants (25.0%) to have overt health implications (Table 3). 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Some variations may be inconsequential, contribute to the differences among healthy humans or provide protection against environmental challenges; others have health-related consequences. It can add a normal base (A, G, C, or T) or it can add a version of one of these bases that stops replication because the modified base cannot have another base added after it. Early personal genome sequencing cohorts were suggested to be enriched for individuals with perceived risk or subtle symptoms of genetic disease;8 although we did not enrol participants who were explicitly seeking genetic information for suspected heritable conditions, neither did we exclude participants with known health conditions (Table 1). The list includes the yeast Saccharomyces cerevisae, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the plant Arabidopsis thaliana, the mouse Mus musculus, the rat Rattus norvegicus and the mosquito Anopheles gambiae, as well as many other bacteria, fungi and viruses. The Personal Genome Project Canada was launched in 2007, and shares the guiding principles and open consent policy of the parent project in the United States. PGP-UK is a member of the Global Network of Personal Genome Projects (PGP), a … The main goal of the project is to allow scientists to connect human genetic information (human DNA sequence, gene expression, associated microbial sequence data, etc) with human trait information (medical information, biospecimens and physical traits) and environmental exposures. Or personal genome project canada supporting evidence was not sufficient, we performed whole Genome sequencing come! 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Genome Diagnostics ( PGDx ) provides advanced cancer Genome analysis to help researchers partners...