genome wide association studiesgenome wide association studies
What if the Geneticists are Wrong?
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The program is part of an ongoing collaboration between the \u003ca href=\"http://genetics.stanford.edu/\">Stanford Department of Genetics\u003c/a> and \u003ca href=\"http://www.thetech.org/\">The Tech Museum of Innovation\u003c/a>. Together these two partners created the \u003ca href=\"http://www.thetech.org/exhibits/permanent/index.php?sGalKey=gtwt&galKey=lt\">Genetics: Technology with a Twist\u003c/a> exhibition.\r\n\r\nYou can also see \u003ca href=\"https://ww2.kqed.org/science/author/dr-barry-starr/\">additional posts by Barry at KQED Science\u003c/a>, and read his \u003ca href=\"http://science.kqed.org/quest/author/dr-barry-starr/\">previous contributions\u003c/a> to \u003ca href=\"http://science.kqed.org/quest/\">QUEST\u003c/a>, a project dedicated to exploring the Science of Sustainability.","avatar":"https://secure.gravatar.com/avatar/4a5680e4c642ea0f0f3041af16018969?s=600&d=blank&r=g","twitter":"geneticsboy","facebook":null,"instagram":null,"linkedin":null,"sites":[{"site":"science","roles":["author"]},{"site":"quest","roles":["subscriber"]}],"headData":{"title":"Dr. Barry Starr | KQED","description":null,"ogImgSrc":"https://secure.gravatar.com/avatar/4a5680e4c642ea0f0f3041af16018969?s=600&d=blank&r=g","twImgSrc":"https://secure.gravatar.com/avatar/4a5680e4c642ea0f0f3041af16018969?s=600&d=blank&r=g"},"isLoading":false,"link":"/author/dr-barry-starr"}},"breakingNewsReducer":{},"campaignFinanceReducer":{},"firebase":{"requesting":{},"requested":{},"timestamps":{},"data":{},"ordered":{},"auth":{"isLoaded":false,"isEmpty":true},"authError":null,"profile":{"isLoaded":false,"isEmpty":true},"listeners":{"byId":{},"allIds":[]},"isInitializing":false,"errors":[]},"navBarReducer":{"navBarId":"home","fullView":true,"showPlayer":false},"navMenuReducer":{"menus":[{"key":"menu1","items":[{"name":"News","link":"/","type":"title"},{"name":"Politics","link":"/politics"},{"name":"Science","link":"/science"},{"name":"Education","link":"/educationnews"},{"name":"Housing","link":"/housing"},{"name":"Immigration","link":"/immigration"},{"name":"Criminal Justice","link":"/criminaljustice"},{"name":"Silicon Valley","link":"/siliconvalley"},{"name":"Forum","link":"/forum"},{"name":"The California Report","link":"/californiareport"}]},{"key":"menu2","items":[{"name":"Arts & Culture","link":"/arts","type":"title"},{"name":"Critics’ Picks","link":"/thedolist"},{"name":"Cultural Commentary","link":"/artscommentary"},{"name":"Food & Drink","link":"/food"},{"name":"Bay Area Hip-Hop","link":"/bayareahiphop"},{"name":"Rebel Girls","link":"/rebelgirls"},{"name":"Arts Video","link":"/artsvideos"}]},{"key":"menu3","items":[{"name":"Podcasts","link":"/podcasts","type":"title"},{"name":"Bay Curious","link":"/podcasts/baycurious"},{"name":"Rightnowish","link":"/podcasts/rightnowish"},{"name":"The Bay","link":"/podcasts/thebay"},{"name":"On Our Watch","link":"/podcasts/onourwatch"},{"name":"Mindshift","link":"/podcasts/mindshift"},{"name":"Consider This","link":"/podcasts/considerthis"},{"name":"Political Breakdown","link":"/podcasts/politicalbreakdown"}]},{"key":"menu4","items":[{"name":"Live Radio","link":"/radio","type":"title"},{"name":"TV","link":"/tv","type":"title"},{"name":"Events","link":"/events","type":"title"},{"name":"For Educators","link":"/education","type":"title"},{"name":"Support KQED","link":"/support","type":"title"},{"name":"About","link":"/about","type":"title"},{"name":"Help Center","link":"https://kqed-helpcenter.kqed.org/s","type":"title"}]}]},"pagesReducer":{},"postsReducer":{"stream_live":{"type":"live","id":"stream_live","audioUrl":"https://streams.kqed.org/kqedradio","title":"Live Stream","excerpt":"Live Stream information currently unavailable.","link":"/radio","featImg":"","label":{"name":"KQED Live","link":"/"}},"stream_kqedNewscast":{"type":"posts","id":"stream_kqedNewscast","audioUrl":"https://www.kqed.org/.stream/anon/radio/RDnews/newscast.mp3?_=1","title":"KQED Newscast","featImg":"","label":{"name":"88.5 FM","link":"/"}},"quest_5871":{"type":"posts","id":"quest_5871","meta":{"index":"posts_1591205157","site":"quest","id":"5871","score":null,"sort":[1273500009000]},"guestAuthors":[],"slug":"what-if-the-geneticists-are-wrong","title":"What if the Geneticists are Wrong?","publishDate":1273500009,"format":"standard","headTitle":"QUEST | KQED Science","labelTerm":{"site":"quest"},"content":"\u003cp>\u003cspan class=\"left\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/05/gimp_kaleidoscope300.jpg\" alt=\"\">\u003c/a>\u003cem>Genetic disease may be as different as different kaleidoscope pictures. This complicates finding the cause of most genetic disease.\u003c/em>\u003c/span>\u003c/p>\n\u003cp>Scientists have thought that they had a pretty good handle on how genetic diseases work. A certain DNA difference causes a certain gene to work incorrectly leading to a specific genetic disease. And importantly, people with a disease tend to share the same DNA difference.\u003c/p>\n\u003cp>A disease like sickle cell anemia (SCA) is a perfect example. A key DNA difference in the hemoglobin gene causes sickle cell anemia and many people with SCA have the exact same difference.\u003c/p>\n\u003cp>But what if diseases like SCA are the outliers? What if instead most people or families had unique DNA differences that led to their disease? Then scientists have been going about finding the causes of genetic disease in the wrong way.\u003c/p>\n\u003cp>Right now scientists tend to do something called \u003ca href=\"http://www.genome.gov/20019523\">genome wide association studies\u003c/a> (GWAS) to find the causes of genetic diseases. Basically scientists compare the DNA of people with a disease to people without the disease. If they compare enough people, they should be able to pinpoint the differences that matter.\u003c/p>\n\u003cp>[ad fullwidth]\u003c/p>\n\u003cp>This strategy is based on people with the same disease having the same DNA differences. If people have unique differences, then this strategy won’t work. And so far, most GWAS studies have not found a lot.\u003c/p>\n\u003cp>They have tended to find a few DNA differences that can explain a very small part of any disease when they look at related groups like Icelanders or Northern Europeans. And even these small effects sometimes go away when scientists try to apply them to larger, more diverse groups. \u003c/p>\n\u003cp>This is just what you might expect with unique, recent DNA changes causing disease. And if you stop and think about it, the idea of lots of unique DNA changes leading to common diseases makes some sense.\u003c/p>\n\u003cp>Each person in each generation has around 175 new DNA changes that their parents didn’t have. Spread out over the human race over hundreds or thousands of years, that is a lot of relatively recent differences. \u003c/p>\n\u003cp>Any DNA change that has too severe an effect on a person shouldn’t survive long in human DNA. People with the change will be at a disadvantage and so won’t do as well as people without the change. Over time, the change will disappear.\u003c/p>\n\u003cp>The exception to this is if the change can have both good and bad effects. SCA is obviously bad but in areas with a lot of malaria, it is actually helpful. People who carry SCA but do not have the disease are more resistant to malaria and do better. Most bad DNA changes won’t come with benefits though.\u003c/p>\n\u003cp>So instead of a set of static DNA differences that are passed down we might need to think about human DNA as constantly changing. Many DNA differences come and go over time. In this scenario, most human disease is caused by DNA changes in the process of being eliminated. Or they are neutral changes that have turned bad now that we live in a new environment. (Think having lots of food, living longer, having fewer babies, etc.)\u003c/p>\n\u003cp>If this is how things work, then GWAS won’t find much. And as I said before, they really haven’t. But luckily there are other ways to skin a genome.\u003c/p>\n\u003cp>Even if people have unique DNA changes that lead to disease, there will be overlap in the affected genes. One approach is to look at the DNA of people with severe forms of a disease to find the gene involved.\u003c/p>\n\u003cp>Then you’d have to sequence the whole gene and look for changes. The sequencing will be easy…we can sequence a gene in no time these days. The hard part will be figuring out which changes matter. There are bound to be lots of differences in most genes with hardly any of them having any effect. So scientists will need to come up with some way to tell which changes matter.\u003c/p>\n\u003cp>If this is how genetic disease works, more traditional sorts of DNA tests are in real trouble. And we’ve spent an awful lot of time and money heading down blind alleys. But that’s how science works, two steps forward, one step back. \u003c/p>\n\u003cp>A couple of in-depth looks at this problem: \u003c/p>\n\u003cp>\u003ca href=\"http://www.cell.com/abstract/S0092-8674(10)00320-X\">Genetic Heterogeneity in Human Disease\u003c/a> \u003c/p>\n\u003cp>\u003ca href=\"//www.cell.com/trends/genetics/abstract/S0168-9525(09)00266-2\">Beyond genome-wide association studies\u003c/a>\u003c/p>\n\u003cp>\u003c/p>\n\u003cp> 37.7749295 -122.4194155\u003c/p>\n\n","blocks":[],"excerpt":"What if most people or families had unique DNA differences that led to their disease? Then scientists have been going about finding the causes of genetic disease in the wrong way.","status":"publish","parent":0,"modified":1273500009,"stats":{"hasAudio":false,"hasVideo":false,"hasChartOrMap":false,"iframeSrcs":[],"hasGoogleForm":false,"hasGallery":false,"hasHearkenModule":false,"hasPolis":false,"paragraphCount":22,"wordCount":753},"headData":{"title":"What if the Geneticists are Wrong? | KQED","description":"What if most people or families had unique DNA differences that led to their disease? Then scientists have been going about finding the causes of genetic disease in the wrong way.","ogTitle":"","ogDescription":"","ogImgId":"","twTitle":"","twDescription":"","twImgId":"","schema":{"@context":"http://schema.org","@type":"Article","headline":"What if the Geneticists are Wrong?","datePublished":"2010-05-10T14:00:09.000Z","dateModified":"2010-05-10T14:00:09.000Z","image":"https://cdn.kqed.org/wp-content/uploads/2020/02/KQED-OG-Image@1x.png"}},"disqusIdentifier":"5871 http://www.kqed.org/quest/blog/2010/05/10/what-if-the-geneticists-are-wrong/","disqusUrl":"https://ww2.kqed.org/quest/2010/05/10/what-if-the-geneticists-are-wrong/","disqusTitle":"What if the Geneticists are Wrong?","path":"/quest/5871/what-if-the-geneticists-are-wrong","audioTrackLength":null,"parsedContent":[{"type":"contentString","content":"\u003cdiv class=\"post-body\">\u003cp>\u003cp>\u003cspan class=\"left\">\u003ca href=\"http://www.kqed.org/quest\">\u003cimg src=\"http://ww2.kqed.org/quest/wp-content/uploads/sites/39/2010/05/gimp_kaleidoscope300.jpg\" alt=\"\">\u003c/a>\u003cem>Genetic disease may be as different as different kaleidoscope pictures. This complicates finding the cause of most genetic disease.\u003c/em>\u003c/span>\u003c/p>\n\u003cp>Scientists have thought that they had a pretty good handle on how genetic diseases work. A certain DNA difference causes a certain gene to work incorrectly leading to a specific genetic disease. And importantly, people with a disease tend to share the same DNA difference.\u003c/p>\n\u003cp>A disease like sickle cell anemia (SCA) is a perfect example. A key DNA difference in the hemoglobin gene causes sickle cell anemia and many people with SCA have the exact same difference.\u003c/p>\n\u003cp>But what if diseases like SCA are the outliers? What if instead most people or families had unique DNA differences that led to their disease? Then scientists have been going about finding the causes of genetic disease in the wrong way.\u003c/p>\n\u003cp>Right now scientists tend to do something called \u003ca href=\"http://www.genome.gov/20019523\">genome wide association studies\u003c/a> (GWAS) to find the causes of genetic diseases. Basically scientists compare the DNA of people with a disease to people without the disease. If they compare enough people, they should be able to pinpoint the differences that matter.\u003c/p>\n\u003cp>\u003c/p>\u003c/div>","attributes":{"named":{},"numeric":[]}},{"type":"component","content":"","name":"ad","attributes":{"named":{"label":"fullwidth"},"numeric":["fullwidth"]}},{"type":"contentString","content":"\u003cdiv class=\"post-body\">\u003cp>\u003c/p>\n\u003cp>This strategy is based on people with the same disease having the same DNA differences. If people have unique differences, then this strategy won’t work. And so far, most GWAS studies have not found a lot.\u003c/p>\n\u003cp>They have tended to find a few DNA differences that can explain a very small part of any disease when they look at related groups like Icelanders or Northern Europeans. And even these small effects sometimes go away when scientists try to apply them to larger, more diverse groups. \u003c/p>\n\u003cp>This is just what you might expect with unique, recent DNA changes causing disease. And if you stop and think about it, the idea of lots of unique DNA changes leading to common diseases makes some sense.\u003c/p>\n\u003cp>Each person in each generation has around 175 new DNA changes that their parents didn’t have. Spread out over the human race over hundreds or thousands of years, that is a lot of relatively recent differences. \u003c/p>\n\u003cp>Any DNA change that has too severe an effect on a person shouldn’t survive long in human DNA. People with the change will be at a disadvantage and so won’t do as well as people without the change. Over time, the change will disappear.\u003c/p>\n\u003cp>The exception to this is if the change can have both good and bad effects. SCA is obviously bad but in areas with a lot of malaria, it is actually helpful. People who carry SCA but do not have the disease are more resistant to malaria and do better. Most bad DNA changes won’t come with benefits though.\u003c/p>\n\u003cp>So instead of a set of static DNA differences that are passed down we might need to think about human DNA as constantly changing. Many DNA differences come and go over time. In this scenario, most human disease is caused by DNA changes in the process of being eliminated. Or they are neutral changes that have turned bad now that we live in a new environment. (Think having lots of food, living longer, having fewer babies, etc.)\u003c/p>\n\u003cp>If this is how things work, then GWAS won’t find much. And as I said before, they really haven’t. But luckily there are other ways to skin a genome.\u003c/p>\n\u003cp>Even if people have unique DNA changes that lead to disease, there will be overlap in the affected genes. One approach is to look at the DNA of people with severe forms of a disease to find the gene involved.\u003c/p>\n\u003cp>Then you’d have to sequence the whole gene and look for changes. The sequencing will be easy…we can sequence a gene in no time these days. The hard part will be figuring out which changes matter. There are bound to be lots of differences in most genes with hardly any of them having any effect. So scientists will need to come up with some way to tell which changes matter.\u003c/p>\n\u003cp>If this is how genetic disease works, more traditional sorts of DNA tests are in real trouble. And we’ve spent an awful lot of time and money heading down blind alleys. But that’s how science works, two steps forward, one step back. \u003c/p>\n\u003cp>A couple of in-depth looks at this problem: \u003c/p>\n\u003cp>\u003ca href=\"http://www.cell.com/abstract/S0092-8674(10)00320-X\">Genetic Heterogeneity in Human Disease\u003c/a> \u003c/p>\n\u003cp>\u003ca href=\"//www.cell.com/trends/genetics/abstract/S0168-9525(09)00266-2\">Beyond genome-wide association studies\u003c/a>\u003c/p>\n\u003cp>\u003c/p>\n\u003cp> 37.7749295 -122.4194155\u003c/p>\n\n\u003c/div>\u003c/p>","attributes":{"named":{},"numeric":[]}}],"link":"/quest/5871/what-if-the-geneticists-are-wrong","authors":["6177"],"categories":["quest_12"],"tags":["quest_848","quest_1188","quest_1193","quest_1199","quest_2628"],"label":"quest"}},"programsReducer":{"possible":{"id":"possible","title":"Possible","info":"Possible is hosted by entrepreneur Reid Hoffman and writer Aria Finger. Together in Possible, Hoffman and Finger lead enlightening discussions about building a brighter collective future. 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You can also visit the MindShift website for episodes and supplemental blog posts or tweet us \u003ca href=\"https://twitter.com/MindShiftKQED\">@MindShiftKQED\u003c/a> or visit us at \u003ca href=\"/mindshift\">MindShift.KQED.org\u003c/a>","imageSrc":"https://cdn.kqed.org/wp-content/uploads/2024/04/Mindshift-Podcast-Tile-703x703-1.jpg","imageAlt":"KQED MindShift: How We Will Learn","officialWebsiteLink":"/mindshift/","meta":{"site":"news","source":"kqed","order":"2"},"link":"/podcasts/mindshift","subscribe":{"apple":"https://podcasts.apple.com/us/podcast/mindshift-podcast/id1078765985","google":"https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy5tZWdhcGhvbmUuZm0vS1FJTkM1NzY0NjAwNDI5","npr":"https://www.npr.org/podcasts/464615685/mind-shift-podcast","stitcher":"https://www.stitcher.com/podcast/kqed/stories-teachers-share","spotify":"https://open.spotify.com/show/0MxSpNYZKNprFLCl7eEtyx"}},"morning-edition":{"id":"morning-edition","title":"Morning Edition","info":"\u003cem>Morning Edition\u003c/em> takes listeners around the country and the world with multi-faceted stories and commentaries every weekday. 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On Our Watch brings listeners into the rooms where officers are questioned and witnesses are interrogated to find out who this system is really protecting. 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