{"id":911,"date":"2012-08-03T11:09:56","date_gmt":"2012-08-03T09:09:56","guid":{"rendered":"http:\/\/slanedeti.sk\/cms\/odhalenie-nepredpokladanej-mutacie-2\/201208"},"modified":"2014-01-02T11:55:08","modified_gmt":"2014-01-02T10:55:08","slug":"odhalenie-nepredpokladanej-mutacie-dcnt4","status":"publish","type":"post","link":"https:\/\/slanedeti.sk\/cms\/odhalenie-nepredpokladanej-mutacie-dcnt4\/911","title":{"rendered":"Odhalenie nepredpokladanej mut\u00e1cie DCTN4"},"content":{"rendered":"<p>Porovnanie DNA pacientov s najmiernej\u0161\u00edmi a najz\u00e1va\u017enej\u0161\u00edmi formami ochorenia m\u00f4\u017ee odhali\u0165 g\u00e9ny podmie\u0148uj\u00face odolnos\u0165 a citlivos\u0165 vo\u010di bakteri\u00e1lnym infekci\u00e1m. Tento pr\u00edstup viedol k objavu zriedkavej mut\u00e1cie g\u00e9nu DCTN4 u pacientov najviac n\u00e1chyln\u00fdch na skor\u00fd n\u00e1stup p\u013e\u00facnych infekci\u00ed.<\/p>\n<p>G\u00e9n DCTN4 k\u00f3duje dynactin 4. Tento prote\u00edn je s\u00fa\u010das\u0165ou patog\u00e9ny likviduj\u00faceho molekul\u00e1rneho syst\u00e9mu lyzoz\u00f3mov.<\/p>\n<p>\u0160t\u00fadia veden\u00e1 z University of Washington je s\u00fa\u010das\u0165ou projektu GO Exome Sequencing Project\u00a0 a spolupracuj\u00fa na \u0148om aj National Heart, Lung and Blood Institute a National Institutes of Health.<\/p>\n<p>Strat\u00e9gia \u201ctestovania extr\u00e9mov\u201c bola u\u017e v minulosti vyu\u017eit\u00e1 pri \u0161t\u00fadiu genetick\u00fdch faktorov u roz\u0161\u00edrenej\u0161\u00edch ochoren\u00ed, alebo \u010d\u0155t ako napr\u00edklad v\u00fdskum ochoren\u00ed srdca. V\u00fdsledky tejto \u0161t\u00fadie o bakteri\u00e1lnej citlivosti boli publikovan\u00e9 v Nature Genetics [1].<\/p>\n<p>V\u00fdskum sa vz\u0165ahoval k bakt\u00e9rii Pseudomonas aeruginosa, oportunistickej p\u00f4dnej bakt\u00e9ri\u00ed, ktor\u00e1 be\u017ene infikuje p\u013e\u00faca pacientov s cystickou fibr\u00f3zou a \u010fal\u0161\u00edch ochoreniach, pri ktor\u00fdch doch\u00e1dza k upch\u00e1vaniu p\u013e\u00fac hlienom.<\/p>\n<p>T\u00e1to bakt\u00e9ria zvykne vytv\u00e1ra\u0165 biofilm, \u010do z\u0165a\u017euje d\u00fdchanie, po\u0161kodzuje p\u013e\u00facne tkanivo a ve\u013emi \u0165a\u017eko sa lie\u010di. D\u00f4sledkom chronick\u00fdch pseudomon\u00e1dov\u00fdch infekci\u00ed je zn\u00ed\u017eenie p\u013e\u00facnych funkci\u00ed, skr\u00e1tenie priemernej d\u013a\u017eky \u017eivota CF pacientov. Tieto bakt\u00e9rie nap\u00e1daj\u00fa iba ve\u013emi zriedkavo zdrav\u00e9 p\u013e\u00faca u \u013eud\u00ed so spr\u00e1vne funguj\u00facim imunitn\u00fdm syst\u00e9mom.<\/p>\n<p>V tejto \u0161t\u00fadii sa DCTN4 mut\u00e1cie u pacientov najviac odoln\u00fdch vo\u010di pseudomon\u00e1dov\u00fdm infekci\u00e1m nevyskytovali. Pacienti n\u00e1chyln\u00ed vo\u010di skor\u00e9mu n\u00e1stupu chronick\u00fdch infekci\u00ed mali aspo\u0148 jeden variant DCTN4 mut\u00e1cie so zmenou zmyslu. Mut\u00e1cie so zmenou zmyslu spravidla ved\u00fa k strate funk\u010dnosti prote\u00ednu.<br \/>\nVed\u00facou autorkou spr\u00e1vy publikovanej 8. j\u00fala v Nature Genetics je Mary J. Emond, profesorka bio\u0161tatistiky na University of Washington School of Public Health v Seatli. Spoluautorom je aj uzn\u00e1van\u00fd medic\u00ednsky genetik Michael Bamshad, profesor pediatrie na Oddelen\u00ed genetickej medic\u00edny na University of Washington.<\/p>\n<p>Autori na z\u00e1klade svojich sk\u00fasenost\u00ed predpokladaj\u00fa, \u017ee m\u00f4\u017ee \u00eds\u0165 o prv\u00fd pr\u00edpad ke\u010f boli genetick\u00e9 odli\u0161nosti podmie\u0148uj\u00face komplexn\u00e9 \u010drty objaven\u00e9 sekvenovan\u00edm prote\u00edn k\u00f3duj\u00facich \u010dast\u00ed gen\u00f3mov \u013eud\u00ed s krajn\u00fdmi formami sk\u00faman\u00e9ho ochoren\u00eda.<\/p>\n<p>\u201cPri tejto \u0161t\u00fadii sme nemali kandid\u00e1tsky g\u00e9n\u201c hovori Emondov\u00e1. \u0160tatistick\u00e1 anal\u00fdza DNA 91 pacientov priviedla v\u00fdskumn\u00fd t\u00fdm ku konkr\u00e9tnemu g\u00e9nu. V p\u00f4vodnej \u0161tudovanej skupine bolo 43 det\u00ed so skor\u00fdm n\u00e1stupom chronickej pseudomon\u00e1dovej p\u013e\u00facnej infekcie a 48 dospel\u00fdch pacientov, ktor\u00ed zatia\u013e nemali chronick\u00fa infekciu. Pacienti, ktor\u00fdch vzorky boli sekvenovan\u00e9 boli vybran\u00ed z observa\u010dnej \u0161t\u00fadie Early Pseudomonas Control (EPIC), projektu Children`s Research Instittute v Seatli a North American Cystic Fibrosis Genetic Modifiers Study. Ex\u00f3mov\u00e9 sekvenovanie uskuto\u010dnili v\u00fdskumn\u00edci University of Washington v laborat\u00f3riu pod veden\u00edm profesorky genetiky Deborah Nickerson.<\/p>\n<p>Porovnanie prote\u00edn k\u00f3duj\u00facich \u00fasekov DNA pacientov upriamilo pozornos\u0165 vedcov na zmysel meniacu mut\u00e1ciu DCTN4 g\u00e9nu. Vedci za\u010dali so skr\u00edningom \u010fal\u0161ej 1322 \u010dlennej skupiny \u0161t\u00fadie EPIC pre \u010fal\u0161\u00ed v\u00fdskum a potvrdenie svojich zisten\u00ed.<\/p>\n<p>Vedci z Exome Sequencing Project vyu\u017e\u00edvaj\u00fa podobn\u00fd pr\u00edstup ako v tejto \u0161t\u00fadii na v\u00fdskum faktorov podmie\u0148uj\u00facich \u010fal\u0161ie chronick\u00e9 ochorenia ako hypertenzia, obezita, ateroskler\u00f3za. H\u013eadaj\u00fa pritom vari\u00e1cie v g\u00e9noch v spojen\u00ed so srdcovo-cievnymi ochoreniami, napr\u00edklad vytvoren\u00edm DNA m\u00e1p \u013eud\u00ed s ide\u00e1lnou hladinou cholesterolu v porovnan\u00ed s t\u00fdmi \u010do maj\u00fa \u00farove\u0148 cholesterolu patologicky zmenen\u00fa.<\/p>\n<p>V\u00fdskumn\u00edci poznamen\u00e1vaj\u00fa, \u017ee pre prisp\u00f4sobenie tejto strat\u00e9gie pre ur\u010denie g\u00e9nov podmie\u0148uj\u00facich komplexn\u00e9 zdravotn\u00e9 stavy u \u013eud\u00ed m\u00f4\u017ee by\u0165 potrebn\u00e1 ove\u013ea v\u00e4\u010d\u0161ia vzorka pacientov.<br \/>\n\u201cKe\u010f\u017ee n\u00e1klady na ex\u00f3mov\u00e9 sekvenovanie r\u00fdchlo klesaj\u00fa a s\u00fa teraz k dispoz\u00edcii efekt\u00edvnej\u0161ie analytick\u00e9 \u0161tatistick\u00e9 n\u00e1stroje, predpoklad\u00e1me, \u017ee tento pr\u00edstup nada\u013eej zostane v ob\u013eube v\u00fdskumn\u00edkov\u201c, predpoklad\u00e1 Bamshad.<\/p>\n<p><em>Zdroj: Medical News Today, 10. j\u00fala 2012<br \/>\n<\/em><\/p>\n<p><em>[1] Emond et al.; Exome sequencing of exreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis; Nature Genetics (2012); published online 08 July 2012 (<\/em><a href=\"http:\/\/www.nature.com\/ng\/journal\/vaop\/ncurrent\/full\/ng.2344.html\"><em>http:\/\/www.nature.com\/ng\/journal\/vaop\/ncurrent\/full\/ng.2344.html<\/em><\/a><em>)<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Porovnanie DNA pacientov s najmiernej&scaron;&iacute;mi a najz&aacute;va&#382;nej&scaron;&iacute;mi formami ochorenia m&ocirc;&#382;e odhali&#357; g&eacute;ny podmie&#328;uj&uacute;ce odolnos&#357; a citlivos&#357; vo&#269;i bakteri&aacute;lnym infekci&aacute;m. Tento pr&iacute;stup viedol k objavu zriedkavej mut&aacute;cie g&eacute;nu DCTN4 u pacientov najviac n&aacute;chyln&yacute;ch na skor&yacute; n&aacute;stup p&#318;&uacute;cnych infekci&iacute;. G&eacute;n DCTN4 k&oacute;duje &hellip; <a href=\"https:\/\/slanedeti.sk\/cms\/odhalenie-nepredpokladanej-mutacie-dcnt4\/911\">Continued<\/a><\/p>\n","protected":false},"author":7,"featured_media":1600,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"kt_blocks_editor_width":"","footnotes":""},"categories":[2],"tags":[225],"class_list":["post-911","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-informacie","tag-dctn4"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Odhalenie nepredpokladanej mut\u00e1cie DCTN4 - Slan\u00e9 deti<\/title>\n<meta name=\"description\" content=\"Porovnanie DNA pacientov s najmiernej\u0161\u00edmi a najz\u00e1va\u017enej\u0161\u00edmi formami ochorenia viedol k objavu zriedkavej mut\u00e1cie g\u00e9nu DCTN4 u pacientov n\u00e1chyln\u00fdch na p\u013e\u00facne infekcie.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/slanedeti.sk\/cms\/odhalenie-nepredpokladanej-mutacie-dcnt4\/911\" \/>\n<meta property=\"og:locale\" content=\"sk_SK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Odhalenie nepredpokladanej mut\u00e1cie DCTN4 - 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