PMC:4786408 / 2755-4819
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4786408","sourcedb":"PMC","sourceid":"4786408","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4786408","text":"Introduction\nMacroautophagy, referred to hereafter as autophagy, is a cellular process by which proteins and organelles are degraded and recycled through sequestration within autophagosomes and delivery to lysosomes (Levine and Klionsky, 2004). The autophagy pathway is highly conserved and required for organismal development and function. Defects in autophagy are associated with diseases including cancer, metabolic disruption, and neurodegenerative disorder (Choi et al., 2013; Cuervo and Wong, 2014; Frake et al., 2015). Patients with mutations in any of the non-redundant core autophagy-related (ATG) genes have not previously been reported.\nAtaxia is a neurodegenerative disease caused by disruption of the cerebellum and Purkinje cells, which results in the lack of coordinated muscle movements. Large phenotype diversity is present in individuals with ataxia, including age of onset, rate of progression, and other accompanying neurological and non-neurological features (Jayadev and Bird, 2013), with corresponding genotypic heterogeneity (Sandford and Burmeister, 2014). Even within the more defined phenotype of childhood ataxia with developmental delay, there are a large number of associated genes, such that similar phenotypic features alone are often insufficient information for an accurate diagnosis (Burns et al., 2014; De Michele and Filla, 2012; Jayadev and Bird, 2013). Identification of genetic causes of childhood ataxia is important for understanding disease pathogenesis and for possible future treatment development.\nWhole exome sequencing has been successfully utilized to identify known and novel genetic mutations responsible for ataxia (Burns et al., 2014; Fogel et al., 2014). Identification of candidate genes can be further verified through additional molecular analysis and utilization of specific and general animal models. Here we identified a novel mutation in a core autophagy gene, ATG5, in two children with ataxia, and demonstrate a reduction in autophagic response, also reproducing the phenotype in yeast and fly models.","divisions":[{"label":"Title","span":{"begin":0,"end":12}}],"tracks":[{"project":"2_test","denotations":[{"id":"26812546-15068787-26883459","span":{"begin":238,"end":242},"obj":"15068787"},{"id":"26812546-23406030-26883460","span":{"begin":476,"end":480},"obj":"23406030"},{"id":"26812546-24281265-26883461","span":{"begin":499,"end":503},"obj":"24281265"},{"id":"26812546-25654552-26883462","span":{"begin":519,"end":523},"obj":"25654552"},{"id":"26812546-23538602-26883463","span":{"begin":999,"end":1003},"obj":"23538602"},{"id":"26812546-25055202-26883464","span":{"begin":1075,"end":1079},"obj":"25055202"},{"id":"26812546-25361784-26883465","span":{"begin":1333,"end":1337},"obj":"25361784"},{"id":"26812546-21827899-26883466","span":{"begin":1361,"end":1365},"obj":"21827899"},{"id":"26812546-23538602-26883467","span":{"begin":1385,"end":1389},"obj":"23538602"},{"id":"26812546-25361784-26883468","span":{"begin":1682,"end":1686},"obj":"25361784"},{"id":"26812546-25133958-26883469","span":{"begin":1702,"end":1706},"obj":"25133958"}],"attributes":[{"subj":"26812546-15068787-26883459","pred":"source","obj":"2_test"},{"subj":"26812546-23406030-26883460","pred":"source","obj":"2_test"},{"subj":"26812546-24281265-26883461","pred":"source","obj":"2_test"},{"subj":"26812546-25654552-26883462","pred":"source","obj":"2_test"},{"subj":"26812546-23538602-26883463","pred":"source","obj":"2_test"},{"subj":"26812546-25055202-26883464","pred":"source","obj":"2_test"},{"subj":"26812546-25361784-26883465","pred":"source","obj":"2_test"},{"subj":"26812546-21827899-26883466","pred":"source","obj":"2_test"},{"subj":"26812546-23538602-26883467","pred":"source","obj":"2_test"},{"subj":"26812546-25361784-26883468","pred":"source","obj":"2_test"},{"subj":"26812546-25133958-26883469","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"26812546-15068787-26883459","span":{"begin":238,"end":242},"obj":"15068787"},{"id":"26812546-23406030-26883460","span":{"begin":476,"end":480},"obj":"23406030"},{"id":"26812546-24281265-26883461","span":{"begin":499,"end":503},"obj":"24281265"},{"id":"26812546-25654552-26883462","span":{"begin":519,"end":523},"obj":"25654552"},{"id":"26812546-23538602-26883463","span":{"begin":999,"end":1003},"obj":"23538602"},{"id":"26812546-25055202-26883464","span":{"begin":1075,"end":1079},"obj":"25055202"},{"id":"26812546-25361784-26883465","span":{"begin":1333,"end":1337},"obj":"25361784"},{"id":"26812546-21827899-26883466","span":{"begin":1361,"end":1365},"obj":"21827899"},{"id":"26812546-23538602-26883467","span":{"begin":1385,"end":1389},"obj":"23538602"},{"id":"26812546-25361784-26883468","span":{"begin":1682,"end":1686},"obj":"25361784"},{"id":"26812546-25133958-26883469","span":{"begin":1702,"end":1706},"obj":"25133958"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"26812546-15068787-26883459","pred":"source","obj":"MyTest"},{"subj":"26812546-23406030-26883460","pred":"source","obj":"MyTest"},{"subj":"26812546-24281265-26883461","pred":"source","obj":"MyTest"},{"subj":"26812546-25654552-26883462","pred":"source","obj":"MyTest"},{"subj":"26812546-23538602-26883463","pred":"source","obj":"MyTest"},{"subj":"26812546-25055202-26883464","pred":"source","obj":"MyTest"},{"subj":"26812546-25361784-26883465","pred":"source","obj":"MyTest"},{"subj":"26812546-21827899-26883466","pred":"source","obj":"MyTest"},{"subj":"26812546-23538602-26883467","pred":"source","obj":"MyTest"},{"subj":"26812546-25361784-26883468","pred":"source","obj":"MyTest"},{"subj":"26812546-25133958-26883469","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ecec","default":true},{"id":"MyTest","color":"#ecd293"}]}]}}