{"502281":{"#nid":"502281","#data":{"type":"news","title":"Looking Beyond the Structure","body":[{"value":"\u003Cp class=\u0022p1\u0022\u003EThe last few years have seen a revolution in the way that diagnosticians evaluate the genetic mechanisms that cause debilitating congenital abnormalities, from heart defects to intellectual disability.\u0026nbsp; Whole genome sequencing (WGS) is just around the corner, and in about a third of cases it finds a strong candidate mutation, sometimes suggesting new treatment options, but otherwise bringing understanding to parents. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EBut what about all of the other cases?\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EA study from School of Biology Professor Greg Gibson\u2019s group at the Georgia Institute of Technology, recently published in the \u003Cem\u003EAmerican Journal of Human Genetics\u003C\/em\u003E, argues that we should be looking not just at the structural parts of genes, but also the regulatory regions around them. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe paper, entitled \u201cA Burden of Rare Variants Associated with Extremes of Gene Expression in Human Peripheral Blood,\u201d demonstrates that there is a burden of rare genetic variants in these regions that associates with abnormal gene expression.\u0026nbsp; It does not show that they cause birth defects, but does suggest that they need to be seriously considered as WGS technology develops.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EGibson explains it in the form of a metaphor about building a house. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cThere are two critical components, the bricks and mortar, and the plans for where to put them,\u201d says Gibson, a faculty member of the Petit Institute for Bioengineering and Bioscience. \u201cIf there is a defect in the glass or a crack in a piece of wood, then sooner or later the structure may fall apart. This is what current approaches focus on, the so-called protein coding-regions. But if the architect\u2019s plans call for more windows than the beams can support, or the contractor doesn\u2019t deliver enough concrete, then the consequences can be just as bad.\u201d \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EWe now know that a lot more of the genetic component related to differences in the way we look and behave (or what makes us susceptible to different diseases) is in the planning than the structural components. This insight is based on studies of common polymorphisms, namely the millions of genetic differences that we all share. The new study argues that it will also be true of rare genetic variants, including new mutations that are specific to a single person.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EGraduate student Jing Zhao sequenced the regulatory regions of almost 500 genes from 500 participants in the Georgia Tech-Emory Predictive Health Institute study, and added up the number of rare mutations in people whose expression of those genes was toward the extreme.\u0026nbsp; The result is what she calls a \u201csmile plot,\u201d because the curve has a high number at either end and low number in the middle. It means that the plans can be off in either direction, making too little or too much transcript for each gene. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cIt is as if all the houses with crooked window frames are that way not because of the wood quality, but because each builder made different mistakes when putting the frames in,\u201d Gibson says.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EFurthermore, Gibson says, there seem to be specific subsets of genes where these events are more or less likely to happen. This is important, because it implies that we may be able to develop algorithms that identify the most likely places for regulation to go wrong, based on the evolutionary conservation of different parts of genes.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EProjects such as President Obama\u2019s precision medicine initiative aim to use genomics to help researchers decipher individual causes of disease.\u0026nbsp; In the next few years, Gibson expects that much larger datasets of tens and eventually hundreds of thousands of people, in many different tissues, will appear. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cThe challenges,\u201d Gibson says, \u201care as much in the bioinformatics than the technology. \u201c\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cem\u003EIn addition to Gibson and Zhao, also contributing to the published study were research scientist Dalia Arafat-Gulick (lab manager for the Gibson lab), T.J. Cradick (former director of the Protein Engineering Facility at Georgia Tech, now head of genome editing for CRISPR Therapeutics in Cambridge, Massachusetts), Cirian Lee (former postdoc at Georgia Tech, now at Rice University), Urko Marigorta (postdoc in the School of Biology), Gang Bao (former Georgia Tech professor, now at Rice University), Idowu Akinsanmi (former researcher in Bao\u2019s lab at Georgia Tech) and Samridhi Banskota, an undergraduate student in the Gibson lab.\u003C\/em\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cem\u003ERead the study \u003Ca href=\u0022http:\/\/www.cell.com\/ajhg\/fulltext\/S0002-9297(16)00004-5\u0022\u003E\u003Cstrong\u003Ehere.\u003C\/strong\u003E\u003C\/a\u003E\u003C\/em\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003E\u003Cbr \/\u003E\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003ECONTACT:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Genetics study shows a burden of rare mutations affecting how our genes are used"}],"field_summary":[{"value":"\u003Cp class=\u0022p1\u0022\u003EGenetics study shows a burden of rare mutations affecting how our genes are used\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Genetics study shows a burden of rare mutations affecting how our genes are used"}],"uid":"28153","created_gmt":"2016-02-17 16:59:29","changed_gmt":"2016-10-08 03:20:46","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-02-17T00:00:00-05:00","iso_date":"2016-02-17T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"502661":{"id":"502661","type":"image","title":"Medical Genetics","body":null,"created":"1455904800","gmt_created":"2016-02-19 18:00:00","changed":"1475895263","gmt_changed":"2016-10-08 02:54:23","alt":"Medical Genetics","file":{"fid":"204758","name":"medical_genetics.jpg","image_path":"\/sites\/default\/files\/images\/medical_genetics_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/medical_genetics_0.jpg","mime":"image\/jpeg","size":2181076,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/medical_genetics_0.jpg?itok=PsiwPxf8"}}},"media_ids":["502661"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[],"keywords":[{"id":"146341","name":"go_genomics"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}