Browsing by Subject "Bone Development"
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Item Open Access Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation.(BMC Genomics, 2015-01-22) Lock, Eric F; Soldano, Karen L; Garrett, Melanie E; Cope, Heidi; Markunas, Christina A; Fuchs, Herbert; Grant, Gerald; Dunson, David B; Gregory, Simon G; Ashley-Koch, Allison EBACKGROUND: Expression quantitative trait loci (eQTL) play an important role in the regulation of gene expression. Gene expression levels and eQTLs are expected to vary from tissue to tissue, and therefore multi-tissue analyses are necessary to fully understand complex genetic conditions in humans. Dura mater tissue likely interacts with cranial bone growth and thus may play a role in the etiology of Chiari Type I Malformation (CMI) and related conditions, but it is often inaccessible and its gene expression has not been well studied. A genetic basis to CMI has been established; however, the specific genetic risk factors are not well characterized. RESULTS: We present an assessment of eQTLs for whole blood and dura mater tissue from individuals with CMI. A joint-tissue analysis identified 239 eQTLs in either dura or blood, with 79% of these eQTLs shared by both tissues. Several identified eQTLs were novel and these implicate genes involved in bone development (IPO8, XYLT1, and PRKAR1A), and ribosomal pathways related to marrow and bone dysfunction, as potential candidates in the development of CMI. CONCLUSIONS: Despite strong overall heterogeneity in expression levels between blood and dura, the majority of cis-eQTLs are shared by both tissues. The power to detect shared eQTLs was improved by using an integrative statistical approach. The identified tissue-specific and shared eQTLs provide new insight into the genetic basis for CMI and related conditions.Item Open Access The case for thyroid disruption in early life stage exposures to thiram in zebrafish (Danio rerio).(General and comparative endocrinology, 2019-01) Chen, Xing; Fang, Mingliang; Chernick, Melissa; Wang, Feng; Yang, Jingfeng; Yu, Yongli; Zheng, Na; Teraoka, Hiroki; Nanba, Satomi; Hiraga, Takeo; Hinton, David E; Dong, WuThiram, a pesticide in the dithiocarbamate chemical family, is widely used to prevent fungal disease in seeds and crops. Its off-site movement to surface waters occurs and may place aquatic organisms at potential harm. Zebrafish embryos were used for investigation of acute (1 h) thiram exposure (0.001-10 µM) at various developmental stages. Survival decreased at 1 µM and 10 µM and hatching was delayed at 0.1 µM and 1 µM. Notochord curvatures were seen at 0.1 and 1 μM thiram when exposure was initiated at 2 and at 10 hpf. Similar notochord curvatures followed exposure to the known TPO inhibitor, methimazole (MMI). Changes were absent in embryos exposed at later stages, i.e., 12 hpf. In embryos exposed to 0.1 or 1 μM at 10 hpf, levels of the thyroid enzyme, Deiodinase 3, increased by 12 hpf. Thyroid peroxide (TPO), important in T4 synthesis, decreased by 48 hpf in embryos exposed to 1 µM at 10 hpf. Thiram toxicity was stage-dependent and early life stage exposure may be responsible for adverse effects seen later. These effects may be due to impacts on the thyroid via regulation of specific thyroid genes including TPO and Deiodinase 3.