京都大学 / 新制・論文博士 / 博士(医学) / 乙第13442号 / 論医博第2241号 / 新制||医||1054(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 藤田 恭之, 教授 伊藤 貴浩 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Chenopodium quinoa, a South American pseudocereal, has valuable agricultural traits such as salt tolerance and drought tolerance, and it has beneficial nutritional properties such as high protein content and a complete amino acid profile. However, problems including disease susceptibility, low harvest index, lodging, seed shattering, low heat tolerance, and saponin content plague quinoa. Genetic resources for quinoa are needed to fix these problems and make quinoa more available throughout the world. We used ethyl methanesulfonate (EMS) to create a mutant population of QQ74 quinoa (USDA GRIN PI 614886) of 5,030 mutant families. We did whole exome sequencing (WES) on 44 mutant families. Using the recently published quinoa reference genome and MAPS, a mutation detection pipeline, we found a mutation rate of 11.35 mutations/Mb in these families. We also used whole genome sequencing (WGS) to calculate a mutation rate of 21.67 mutations/Mb in an additional nine mutant families. To demonstrate the utility of this population as a genetic resource, we found an EMS-induced nonsense mutation in the betalain synthesis pathway that prevents red betacyanins from accumulating in the hypocotyl of quinoa. With the mutation rates in our population, we calculate that analysis of 300 mutant families will yield 3-7 mutations in any gene of interest, which will facilitate forward and reverse genetic studies in quinoa.

No description available.

The congenital myasthenic syndromes (CMS) are a group of rare genetic diseases affecting the neuromuscular junction (NMJ). These syndromes affect signal transmission and result in fatigable muscle weakness. In this study we performed exome analysis of 2 CMS patient cohorts and identified SYT11, a synaptotagmin inhibitor of clathrin mediated endocytosis (CME), and MGAT5B, a glycosylation protein, as potential novel CMS genes using bioinformatic analysis on the RD-Connect Genome Phenome Analysis Platform (GPAP). To validate them, we utilized morpholino knockdown models of zebrafish orthologues syt11a, syt11b, and mgat5b and conducted functional assays measuring chorion activity and escape response. Our results show that co-knockdown of syt11a/b or syt11b alone (and not mgat5b) results in a substantial neuromuscular deficit, with ablation of chorion activity and severely reduced escape response. Immunofluorescent studies showed both motor neuron growth and NMJ formation was inhibited by syt11a/b knockdown. In conclusion, syt11b causes a severe neuromuscular phenotype in zebrafish which supports SYT11 as a novel CMS-causing gene.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12920号 / 論医博第2095号 / 新制||医||1010(附属図書館) / 32130 / (主査)教授 髙橋 良輔, 教授 松田 文彦, 教授 瀬原 淳子 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20789号 / 医博第4289号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 亮, 教授 大森 孝一, 教授 高田 穣 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第24314号 / 医博第4908号 / 新制||医||1062(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小林 恭, 教授 松田 文彦, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM