{"id":18269,"date":"2020-02-04T10:11:57","date_gmt":"2020-02-04T09:11:57","guid":{"rendered":"https:\/\/news.embl.de\/?p=18269"},"modified":"2024-03-22T11:21:25","modified_gmt":"2024-03-22T10:21:25","slug":"pinpointing-rare-disease-mutations","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/pinpointing-rare-disease-mutations\/","title":{"rendered":"Pinpointing rare disease mutations"},"content":{"rendered":"\n<p>Researchers at EMBL\u2019s European Bioinformatics Institute (EMBL-EBI) and Queen Mary University of London have led a study to categorise which genes are essential for supporting life. The results from this study could be a useful new resource to help researchers identify mutations responsible for rare childhood diseases.<\/p>\n\n\n\n<p>Identifying which genes are linked to a rare disease is one of the most difficult challenges geneticists face. The low prevalence of these diseases within the population makes it difficult to research and fully understand their causes. However, huge advances in the diagnosis of rare diseases are now being made thanks to innovations in sequencing technology.<\/p>\n\n\n\n<p>This research, published in <a href=\"https:\/\/www.nature.com\/articles\/s41467-020-14284-2\"><em>Nature Communications<\/em><\/a>, compares knockout mice viability and phenotyping data from the <a href=\"https:\/\/www.mousephenotype.org\/\">International Mouse Phenotyping Consortium (IMPC)<\/a> with human cell lines provided by <a href=\"https:\/\/depmap.org\/portal\/achilles\/\">the Broad Institute\u2019s Project Achilles<\/a> to create categories indicating how crucial a gene is to producing viable life.<\/p>\n\n\n\n<p>The researchers also identified new mutations likely responsible for rare childhood diseases by comparing their data with unsolved cases of genetic disorders identified in the <a href=\"https:\/\/www.genomicsengland.co.uk\/about-genomics-england\/the-100000-genomes-project\/\">100,000 Genomes Project<\/a> and the <a href=\"https:\/\/www.ddduk.org\/\">Deciphering Developmental Disorders (DDD)<\/a> datasets.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Defining genes essential for life<\/h2>\n\n\n\n<p>&#8220;Loss of gene function is often referred to as a binary concept; lethal or viable,&#8221; says <a href=\"https:\/\/www.ebi.ac.uk\/about\/people\/violeta-munoz-fuentes\">Violeta Mu\u00f1oz-Fuentes, Biologist, Mouse Informatics at EMBL-EBI<\/a>. &#8220;In this study we show that gene essentiality is more of a spectrum ranging from cellular lethal, developmental lethal, subviable, viable with a visible phenotype, and viable without a visible phenotype.&#8221;<\/p>\n\n\n\n<p>The scientists define these categories for 3819 genes to create an open access database that benefits other researchers and provide insight for clinical applications.<\/p>\n\n\n\n<p>\u201cWhen you sequence a person\u2019s genome it\u2019s not always one mutation that stands out as altering a gene\u2019s function,\u201d says <a href=\"https:\/\/www.ebi.ac.uk\/about\/people\/terry-meehan\">Terry Meehan, Coordinator of Mouse Informatics at EMBL-EBI<\/a>. \u201cWe currently don\u2019t have a handle on which genes are important for development and which have a minor impact.\u201d<\/p>\n\n\n\n<div\n  class=\"vf-box vf-box--factoid\">\n\n  <h3 class=\"vf-box__heading\">Loss of function gene categories<\/h3>\n  <p class=\"vf-box__text\"><strong> Cellular lethal:<\/strong> genes essential for cell viability<br \/><strong> Developmental lethal:<\/strong> genes essential for organism development<br \/><strong> Viable:<\/strong> organisms fully develop<br \/><strong> Subviable:<\/strong> organism survival is less than expected <\/p>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\">Diagnosing rare disorders<\/h2>\n\n\n\n<p>Advances in whole genome sequencing (WGS) are changing the way we research and diagnose rare genetic diseases. However, the majority of rare disease patients remain undiagnosed due to a lack of detection or because a previously unknown gene is disrupted. This study furthers our understanding of rare disease genes by providing clinicians and researchers with an open access resource, which identifies high-quality candidates for rare disease mutations.<\/p>\n\n\n\n<p>\u201cOf particular interest for application to healthcare, we demonstrate that the set of genes that are essential for organism development is particularly associated with known human developmental disorders,\u201d says <a href=\"https:\/\/www.qmul.ac.uk\/whri\/people\/academic-staff\/items\/smedleydamian.html\">Damian Smedley, Reader in Computational Genomics at Queen Mary University of London<\/a>. \u201cThis provides candidates for undiscovered causative genes for these conditions.\u201d<\/p>\n\n\n\n<p>Several high-scoring candidates from this study have been added to the open access resource <a href=\"https:\/\/genematcher.org\/\">GeneMatcher<\/a>, used by researchers and clinicians all over the globe to share gene information. You can also freely access the study data in <a href=\"https:\/\/www.ebi.ac.uk\/biostudies\/studies\/S-BSST293\">EMBL-EBI\u2019s Biostudies<\/a> and at the <a href=\"https:\/\/www.mousephenotype.org\/\">International Mouse Phenotyping Consortium.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>New resource that categorises genes essential for supporting life could be used to identify rare disease mutations<\/p>\n","protected":false},"author":77,"featured_media":18272,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[782,55,36,41,32,5686],"embl_taxonomy":[5140],"class_list":["post-18269","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-database","tag-development","tag-embl-ebi","tag-genetics","tag-health","tag-rare-disease","embl_taxonomy-developmental-biology"],"acf":{"article_intro":"<p>New resource that categorises genes essential for supporting life could be used to identify rare disease mutations<\/p>\n","related_links":[{"link_description":"Melting reveals drug targets","link_url":"https:\/\/news.embl.de\/science\/melting-reveals-drug-targets\/"},{"link_description":"Faster, cheaper and more detailed","link_url":"https:\/\/news.embl.de\/science\/new-method-cancer-diagnosis\/"},{"link_description":"Study identifies new diabetes genes","link_url":"https:\/\/news.embl.de\/science\/mouse-study-identifies-new-diabetes-genes\/"}],"article_sources":[{"source_description":"<p>Cacheiro, et al. Nature Communications, (published online) 31 January 2020,\u00a0DOI: 10.1038\/s41467-020-14284-2<\/p>\n","source_link_url":"https:\/\/www.nature.com\/articles\/s41467-020-14284-2"}],"vf_locked":false,"featured":false,"color":"#007B53","link_color":"#fff","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"None","embl_taxonomy_term_who":false,"embl_taxonomy_term_what":false,"embl_taxonomy_term_where":false},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"7ca3ce91-dc32-47ea-8d4b-7a53c3a3a9fd\";i:2;s:36:\"6a2f2be6-8bb7-4425-b318-5ed992f715cc\";}","parents":[],"name":["Developmental Biology"],"slug":"developmental-biology","description":"What &gt; Research Units &gt; Developmental Biology"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Pinpointing rare disease 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