{"id":3010,"date":"2013-08-28T18:30:00","date_gmt":"2013-08-28T22:30:00","guid":{"rendered":"https:\/\/www.med.unc.edu\/neuroscience\/researchers-discover-a-potential-cause-of-autism\/"},"modified":"2018-07-05T14:53:45","modified_gmt":"2018-07-05T18:53:45","slug":"researchers-discover-a-potential-cause-of-autism","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/neuroscience\/researchers-discover-a-potential-cause-of-autism\/","title":{"rendered":"Researchers discover a potential cause for autism"},"content":{"rendered":"
\n

<\/p>\n

In a paper published in Nature, a team led by Mark Zylka found that key enzymes have a \u2018profound effect\u2019 across dozens of genes linked to autism. The insight could help illuminate environmental factors behind autism spectrum disorder and contribute to a unified theory of how the disorder develops.<\/p>\n

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\nclick to enlarge<\/a><\/span>\"Researchers
\n Topoisomerase inhibitors reduce the expression of long genes in neurons, including a remarkable number of genes implicated in Autism Spectrum Disorders \u2013 200 kb is four times longer than the average gene. Concept: Mark Zylka. Illustration: Janet Iwasa. <\/span> <\/span><\/div>\n

Media contact: <\/b> Tom Hughes, 919-966-6047, tahughes@unch.unc.edu<\/a><\/p>\n

Wednesday, August 28, 2013<\/p>\n

CHAPEL HILL, N.C. \u2013 Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), according to research announced today in the journal Nature<\/i>. Scientists at the University of North Carolina School of Medicine have described a finding that represents a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder\u2019s genetic causes.<\/p>\n

\u201cOur study shows the magnitude of what can happen if topoisomerases are impaired,\u201d said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC. \u201cInhibiting these enzymes has the potential to profoundly affect neurodevelopment \u2014 perhaps even more so than having a mutation in any one of the genes that have been linked to autism.\u201d<\/p>\n

The study could have important implications for ASD detection and prevention.<\/p>\n

\u201cThis could point to an environmental component to autism,\u201d said Zylka. \u201cA temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development. \u201d<\/p>\n

This study could also explain why some people with mutations in topoisomerases develop autism and other neurodevelopmental disorders.<\/p>\n

Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes overwound, a common occurrence that can interfere with key biological processes.<\/p>\n

Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells. \u201cIf there are additional compounds like this in the environment, then it becomes important to identify them,\u201d said Zylka. \u201cThat\u2019s really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects \u2014 so that pregnant women can avoid being exposed to these compounds.\u201d<\/p>\n

Zylka and his colleagues stumbled upon the discovery quite by accident while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy. Investigating the drug\u2019s effects in mouse and human-derived nerve cells, they noticed that the drug tended to interfere with the proper functioning of genes that were exceptionally long \u2014 composed of many DNA base pairs. The group then made the serendipitous connection that many autism-linked genes are extremely long.<\/p>\n

\u201cThat\u2019s when we had the \u2018Eureka moment,\u2019\u201d said Zylka. \u201cWe realized that a lot of the genes that were suppressed were incredibly long autism genes.\u201d<\/p>\n

Of the more than 300 genes that are linked to autism, nearly 50 were suppressed by topotecan. Suppressing that many genes across the board \u2014 even to a small extent \u2014 means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene.<\/p>\n

The study\u2019s findings could also help lead to a unified theory of how autism-linked genes work. About 20 percent of such genes are connected to synapses \u2014 the connections between brain cells. Another 20 percent are related to gene transcription \u2014 the process of translating genetic information into biological functions. Zylka said this study bridges those two groups, because it shows that having problems transcribing long synapse genes could impair a person\u2019s ability to construct synapses.<\/p>\n

\u201cOur discovery has the potential to unite these two classes of genes \u2014 synaptic genes and transcriptional regulators,\u201d said Zylka. \u201cIt could ultimately explain the biological mechanisms behind a large number of autism cases.\u201d<\/p>\n

The study\u2019s coauthors include Benjamin Philpot (co-senior author), Terry Magnuson, Ian King, Chandri Yandava, Angela Mabb, Hsien-Sung Huang, Brandon Pearson, J. Mauro Calabrese, Joshua Starmer and Joel Parker from UNC and Jack S. Hsiao and Stormy Chamberlain of the University of Connecticut Health Center. Full Nature<\/i><\/b> article<\/a><\/p>\n

Drs. Philpot and Zylka discuss the findings in these videos<\/a>.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

<\/p>\n

In a paper published in Nature, a team led by Mark Zylka found that key enzymes have a \u2018profound effect\u2019 across dozens of genes linked to autism. The insight could help illuminate environmental factors behind autism spectrum disorder and contribute to a unified theory of how the disorder develops.<\/p>\n","protected":false},"author":80868,"featured_media":3011,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[],"class_list":["post-3010","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","odd"],"acf":[],"yoast_head":"\nResearchers discover a potential cause for autism | UNC Neuroscience Center<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/neuroscience\/researchers-discover-a-potential-cause-of-autism\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Researchers discover a potential cause for autism | UNC Neuroscience Center\" \/>\n<meta property=\"og:description\" content=\"In a paper published in Nature, a team led by Mark Zylka found that key enzymes have a \u2018profound effect\u2019 across dozens of genes linked to autism. 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