{"id":15990,"date":"2025-04-14T16:21:52","date_gmt":"2025-04-14T19:21:52","guid":{"rendered":"https:\/\/www.ufrgs.br\/ppgbm\/?p=15990"},"modified":"2025-04-14T16:21:52","modified_gmt":"2025-04-14T19:21:52","slug":"16-04-seminario-de-dados-mestrado-ingrid-paola-neves-tuchtenhagen","status":"publish","type":"post","link":"https:\/\/www.ufrgs.br\/ppgbm\/16-04-seminario-de-dados-mestrado-ingrid-paola-neves-tuchtenhagen\/","title":{"rendered":"16\/04 &#8211; SEMIN\u00c1RIO DE DADOS (Mestrado) &#8211; INGRID PAOLA NEVES TUCHTENHAGEN"},"content":{"rendered":"<p><strong>\u00a0<\/strong><\/p>\n<p><strong>SEMIN\u00c1RIO\u00a0DE\u00a0DADOS\u00a0(Mestrado)<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><strong>INGRID PAOLA NEVES TUCHTENHAGEN \u00a0<\/strong><\/p>\n<p><strong>Effect of variants in DNA repair genes as modifying factors for age of onset in Machado-Joseph Disease<\/strong><\/p>\n<p>Orientadora: Dra. Laura Bannach Jardim<\/p>\n<p>Avaliadora: Dra. Ursula da Silveira Matte<\/p>\n<p>16 de abril de 2025 (quarta-feira)<\/p>\n<p><strong>12h<\/strong><\/p>\n<p><strong>Presencial:\u00a0<\/strong>Anfiteatro do\u00a0Departamento\u00a0de\u00a0Gen\u00e9tica da UFRGS (Campus do Vale, pr\u00e9dio 43312)<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p>Spinocerebellar Ataxia Type 3 (SCA3\/MJD) is the most common form of hereditary ataxia, caused by a CAG repeat expansion in the\u00a0<em>ATXN3\u00a0<\/em>gene. Although this expansion is strongly associated with age at symptom onset, it accounts for only part of the variability observed among patients. Evidence suggests that variants in DNA repair genes, particularly those in the Mismatch Repair (MMR) pathway, may modulate age at onset by influencing expansion instability. This study investigated the association between variants in seven MMR genes (<em>MLH1, MLH3, MSH2, MSH3, MSH6, PMS1, PMS2<\/em>) and the age at onset of gait ataxia (AOga), also including variants previously implicated in the cohort, such as\u00a0<em>FAN1\u00a0<\/em>and intermediate CAG alleles in\u00a0<em>ATXN2<\/em>. A total of 356 symptomatic individuals from the SCA3\/MJD cohort in Rio Grande do Sul, Brazil, were analyzed, all of whom had available clinical and genetic data and stored DNA samples. Genotyping was performed by real-time PCR using TaqMan assays. Associations between variants and AOga were assessed using Linear Mixed Models, controlling for CAG expansion size and family. Significant associations were found for <em>MLH1 <\/em>(rs1799977), <em>MSH3<\/em> (rs2250063), <em>MSH6<\/em> (rs1042821), and <em>ATXN2<\/em>, all linked to delays in AOga ranging from 1.7 to 7.7 years. Variants in\u00a0<em>MLH3<\/em>,\u00a0<em>MSH2<\/em>,\u00a0<em>PMS1<\/em>, and\u00a0<em>FAN1\u00a0<\/em>showed no association, and the effect of\u00a0<em>PMS2\u00a0<\/em>could not be evaluated due to lack of genotypic variability. These findings reinforce the modulatory role of genetic variants in DNA repair pathways on the onset of symptoms in SCA3\/MJD, contributing to a better understanding of the mechanisms underlying clinical variability in the disease.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u00a0 SEMIN\u00c1RIO\u00a0DE\u00a0DADOS\u00a0(Mestrado) &nbsp; INGRID PAOLA NEVES TUCHTENHAGEN \u00a0 Effect of variants in DNA repair genes as modifying factors for age of onset in Machado-Joseph Disease Orientadora: Dra. Laura Bannach Jardim [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[108],"tags":[],"class_list":["post-15990","post","type-post","status-publish","format-standard","hentry","category-seminarios-e-defesas"],"_links":{"self":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts\/15990","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/comments?post=15990"}],"version-history":[{"count":1,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts\/15990\/revisions"}],"predecessor-version":[{"id":15991,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/posts\/15990\/revisions\/15991"}],"wp:attachment":[{"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/media?parent=15990"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/categories?post=15990"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ufrgs.br\/ppgbm\/wp-json\/wp\/v2\/tags?post=15990"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}