Institute de Cardiologie de Montr\u00e9al La g\u00e9n\u00e9tique des maladies cardiovasculaires<\/strong><\/p>\n Les maladies cardiovasculaires (MCVs) sont la cause principale de mortalit\u00e9 dans le monde occidental. Au Canada, les MCVs affectent 1.3 million de personnes et co\u00fbtent $22 milliards (frais directs et indirects) \u00e0 l\u2019\u00e9conomie canadienne. Au-del\u00e0 des facteurs de risque traditionnels (ex. lipides, hypertension, ob\u00e9sit\u00e9), l\u2019histoire familiale (g\u00e9n\u00e9tique) permet \u00e9galement de pr\u00e9dire les futurs \u00e9v\u00e8nements cardiovasculaires. Le laboratoire du Dr Lettre\u00a0utilise des approches de g\u00e9notypage et de s\u00e9quen\u00e7age de l\u2019ADN \u00e0 haut-d\u00e9bit pour identifier et caract\u00e9riser des nouveaux g\u00e8nes impliqu\u00e9s dans l\u2019ath\u00e9roscl\u00e9rose et les autres MCVs. Notre focus porte sur la g\u00e9n\u00e9tique de la maladie coronarienne ainsi que des biomarqueurs pertinents (ex. efflux des particules de HDL) en utilisant la Biobanque de l\u2019ICM (N>17 000) et CARTaG\u00c8NE (N>40 000). Gr\u00e2ce \u00e0 plusieurs collaborations internationales, nous avons acc\u00e8s \u00e0 plusieurs autres larges cohortes (ex. UK Biobank, \u00c9tude longitudinale canadienne du vieillissement, \u00ab\u00a0Exome Sequence Project\u00a0\u00bb, \u00ab\u00a0TOPMed\u00a0\u00bb).<\/p>\n \u00c9tude de la production des cellules sanguines (h\u00e9matopo\u00ef\u00e8se)<\/strong><\/p>\n Le sang est surtout compos\u00e9 de plasma et de cellules sanguines, et joue un r\u00f4le important dans la physiologie humaine : il transporte l’oxyg\u00e8ne, les nutriments et les hormones dans les tissus , \u00e9limine les d\u00e9chets , exerce des fonctions immunologiques et contribue \u00e0 la r\u00e9paration des tissus. Les trois principaux types de cellules sanguines effectuent la plupart de ces activit\u00e9s : les globules rouges transportent l’oxyg\u00e8ne, les globules blancs coordonnent certaines des r\u00e9ponses immunitaires, et les plaquettes sont les briques qui forment des caillots de sang afin de pr\u00e9venir les saignements excessifs. Tous ces types de cellules sont cr\u00e9\u00e9s par la prolif\u00e9ration et la diff\u00e9renciation des cellules souches h\u00e9matopo\u00ef\u00e9tiques. L\u2019anormalit\u00e9 (en terme de nombre, contenu, ou forme) de ces cellules sanguines caract\u00e9risent un grand nombre de maladies humaines (ex. cancer, an\u00e9mie, paludisme\/malaria, VIH). Chez les individus en bonne sant\u00e9, le nombre et les autres propri\u00e9t\u00e9s des cellules sanguines sont en partie contr\u00f4l\u00e9s par la g\u00e9n\u00e9tique. Nous avons cr\u00e9\u00e9 le \u00ab\u00a0Blood-Cell Consortium\u00a0\u00bb pour \u00e9tudier chez 1 million de participants les facteurs g\u00e9n\u00e9tiques qui contr\u00f4lent l\u2019h\u00e9matopo\u00ef\u00e8se humaine. Nous combinons nos analyses g\u00e9n\u00e9tiques avec des approches g\u00e9nomiques (ex. \u00ab\u00a0expression quantitative trait loci\u00a0(eQTL)\u00a0\u00bb) et de \u00ab\u00a0genome editing\u00a0\u00bb (CRISPR\/Cas9) pour identifier de nouveaux g\u00e8nes qui r\u00e9gulent les param\u00e8tres sanguins. De plus, nous \u00e9tudions si ces marqueurs sanguins pourraient \u00eatre utilis\u00e9s comme biomarqueurs pr\u00e9dictifs des maladies h\u00e9matologiques et cardiovasculaires.<\/p>\n<\/div>\n The genetics of cardiovascular diseases<\/strong><\/p>\n Cardiovascular diseases (CVDs) are the main cause of death in the Western world. In Canada, CVDs affect 1.3 million individuals and cost nearly $22 billions (direct and indirect costs) to the Canadian economy. Beyond the traditional risk factors (e.g. lipids, hypertension, obesity), familial history (genetics) is also predictive of an individual\u2019s risk to develop CVDs. My laboratory uses high-throughput DNA genotyping and sequencing to identify and characterize new genes involved in atherosclerosis and other CVDs. We focus on the genetics of atherosclerosis-related complications (e.g. myocardial infarction) and relevant biomarkers (e.g. HDL-cholesterol efflux) using the large Biobank from the Montreal Heart Institute (N>17,000) and CARTaG\u00c8NE (N>40,000). Through collaborations, my lab also has access to additional large datasets (UK Biobank, Canadian Longitudinal Study of Aging, NHLBI Exome Sequence Project and TOPMed).<\/p>\n Blood-cell production and differentiation (hematopoiesis)<\/strong><\/p>\n Blood is mostly composed of plasma and blood cells and plays a major role in a variety of functions involved in general human homeostasis: it transports oxygen, nutrients and hormones to tissues, removes waste, performs immunological functions and contributes tissue damage repair through coagulation. The main three blood cell types carry out most of these activities: red blood cells transport oxygen, white blood cells coordinate some of the immune responses, and platelets are the bricks that form blood clots to prevent excessive bleeding. All of these cell types originate through proliferation and differentiation from common precursors (hematopoietic stem cells). An aberrant number, size or feature of the three main blood cell types characterizes multiple human diseases (e.g. cancer, anemia, malaria, HIV). It is also known that blood-cell phenotypes vary between healthy individuals, and that some of this inter-individual variation is controlled by genetics. We created the international Blood-Cell Consortium to study in 1 million participants the genetic factors that control human hematopoiesis. We combine our genetic analyses with genomic (e.g. expression quantitative trait loci (eQTL)) and genome editing (e.g. CRISPR\/Cas9) approaches to identify genes that regulate blood-cell parameters. Furthermore, we are also interested in exploring whether blood-cell phenotypes can be used as predictive biomarkers of hematological and cardiovascular diseases.<\/p>\n<\/div>\n
\n5000, rue B\u00e9langer
\nMontr\u00e9al, Qu\u00e9bec, H1T 1C8
\nguillaume.lettre@umontreal.ca<\/a>
\nhttp:\/\/www.mhi-humangenetics.org\/<\/a><\/p>\nAxes de recherche<\/h2>\n
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