{"id":63901,"date":"2012-02-21T21:58:18","date_gmt":"2012-02-22T05:58:18","guid":{"rendered":"http:\/\/blogs.discovermagazine.com\/gnxp\/?p=15832"},"modified":"2012-02-21T21:58:18","modified_gmt":"2012-02-22T05:58:18","slug":"loss-of-function-variation-in-load","status":"publish","type":"post","link":"https:\/\/www.razib.com\/wordpress\/2012\/02\/21\/loss-of-function-variation-in-load\/","title":{"rendered":"Loss-of-function &amp; variation in load"},"content":{"rendered":"<p><a href=\"http:\/\/westhunt.wordpress.com\/\">Greg Cochran<\/a> pointed out something that I&#8217;d been considering about the <a href=\"http:\/\/blogs.discovermagazine.com\/gnxp\/2012\/02\/extraordinary-mutations-require-extraordinary-evidence\/\">MacArthur et al. paper<\/a>:<strong> if the <em>average<\/em>\u00a0human (OK, non-African human) has ~100 loss-of-function variants, then the standard deviation should be ~10<\/strong>. That&#8217;s because the distribution is presumably <a href=\"http:\/\/en.wikipedia.org\/wiki\/Poisson_distribution\">poisson<\/a>, and variance = mean, and the square root of the of the variance (~100) is the standard deviation (~10). In plainer English there should be a substantial variation in the number of loss-of-function variants within a population, and across siblings. Though by definition these loss-of-function variants don&#8217;t kill you, in general there is the assumption that this class of mutants does exhibit some fitness drag (e.g., the fitness of a heterozygote for a variant which is lethal as a homozygote genotype may be ~0.90). A quick back of the envelope calculation implies to me that there is a 1 out of several hundreds of thousands probability that two siblings may exhibit a range of 60 loss-function-variants. But a 40 unit gap is more like a 1 out of one thousand chance.<\/p>\n<p>This variance in mutational load has been the hobby-horse of intellectuals for a while now. <a href=\"http:\/\/en.wikipedia.org\/wiki\/Armand_Marie_Leroi\">Armand Leroi<\/a> suggested that it correlated with beauty.<a href=\"http:\/\/en.wikipedia.org\/wiki\/Geoffrey_Miller_(psychologist)\"> Geoffrey Miller<\/a> with intelligence. In the near future presumably we&#8217;ll get to see if there&#8217;s anything real in this. And obviously we don&#8217;t need to leave it to scientists. We&#8217;ll all know the summary statistics about own genomes, and probably be able to intuit rough patterns&#8230;if they exist.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/feeds.feedburner.com\/~r\/GeneExpressionBlog\/~4\/DcqlC9zZzNM\" height=\"1\" width=\"1\"\/><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Greg Cochran pointed out something that I&#8217;d been considering about the MacArthur et al. paper: if the average\u00a0human (OK, non-African human) has ~100 loss-of-function variants, then the standard deviation should be ~10. That&#8217;s because the distribution is presumably poisson, and variance = mean, and the square root of the of the variance (~100) is the [&#8230;]<\/p>\n","protected":false},"author":12,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,82,481,525,360],"tags":[],"class_list":["post-63901","post","type-post","status-publish","format-standard","hentry","category-genetics","category-genomics","category-human-genetics","category-human-genomics","category-personal-genomics"],"_links":{"self":[{"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/posts\/63901","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/comments?post=63901"}],"version-history":[{"count":6,"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/posts\/63901\/revisions"}],"predecessor-version":[{"id":64187,"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/posts\/63901\/revisions\/64187"}],"wp:attachment":[{"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/media?parent=63901"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/categories?post=63901"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.razib.com\/wordpress\/wp-json\/wp\/v2\/tags?post=63901"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}