Browsing by Subject "SCA"
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Item Murine models of spinocerebellar ataxia type 5(2009-06) Armbrust, Karen RoseSpinocerebellar ataxia type 5 (SCA5) is a slowly progressive neurodegenerative disease of the cerebellum caused by mutations in the SPTBN2 gene, which encodes the protein β-III spectrin. To characterize how β-III spectrin with the American SCA5 mutation causes Purkinje cell degeneration and cerebellar dysfunction, I developed the first transgenic murine models of SCA5 and identified brain proteins that potentially interact with the region of β-III spectrin where the American SCA5 mutation occurs. Behavioral studies with a conditional model that drives expression of untagged β-III spectrin and a second 3xFLAG-tagged SCA5 model show that overexpressing mutant β- III spectrin in murine cerebellar Purkinje cells causes cerebellar dysfunction. Further studies with the conditional tet-regulated mice show that untagged mutant β-III spectrin alters the localization of the glutamate transporter EAAT4 and the metabotropic glutamate receptor mGluR1α and produces a concomitant deficit in mGluR1 function. Histologic analysis of the 3xFLAG-tagged SCA5 murine model shows that the American SCA5 mutation also alters the Purkinje cell distribution of the mutant β-III spectrin protein itself. Additionally, I identified a number of brain proteins that are novel β-III spectrin interaction candidates, including the dynactin subunit p150Glued. I show that the American and French SCA5 mutations alter the interaction strength of β-III spectrin with p150Glued and α-II spectrin respectively.Item A Novel Mating Design to Optimize Genomic Selection Efficiency for Commercial Corn Breeding(2022-03) Sweet, PatrickIn many commercial corn (Zea. mays L.) breeding programs, lines are selected based only on general combining ability (GCA) during first-year trials. Selection for specific combining ability (SCA) is delayed until later trials, resulting in many unevaluated hybrid combinations. My objective was to determine whether a reciprocal testcross mating design enables simultaneous selection for GCA and SCA, while maintaining the same resources typical in first-year trials. Suppose B1 and B2 are Iowa Stiff Stalk Synthetic (BSSS) lines, whereas N1 and N2 are non-BSSS lines. In a reciprocal testcross design, progeny of B1 × B2 are testcrossed with N1 and N2, and progeny of N1 × N2 are testcrossed with B1 and B2. In 2019, grain yield and moisture of 1,642 hybrids from 10 BSSS and non-BSSS populations were measured at a median of three locations per hybrid across the upper Midwest. In 2020, a validation set consisting of 146 hybrids that were not tested in 2019 were evaluated at a median of five locations per hybrid. The GCA and SCA values were estimated using genomewide prediction with 11,000 SNP markers and the level of dominance was estimated using a subset of these markers. The sizes of training populations were kept constant, and the cross-year predictive ability of the reciprocal testcross design was compared with that of a standard, nonreciprocal design. Including SCA in the models marginally increased predictive abilities for reciprocal designs and the reciprocal designs produced higher predictive abilities than the nonreciprocal designs. The median level of dominance for grain yield was 1.08 indicating complete dominance. The results indicated that the reciprocal testcross mating design combined with genomic prediction could efficiently enable simultaneous selection for GCA and SCA earlier in a breeding pipeline.