EFFECTS OF HSA21 GENE EXPRESSION ON EARLY VERTEBRATE DEVELOPMENT

Zebrafish;human chromosome 21;gene expression;Human Genetics and Molecular Biology

Edie, Sarah McGuireLeach, Steven D. ;

Johns Hopkins University

关键词: Zebrafish;    human chromosome 21;    gene expression;    Human Genetics and Molecular Biology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39300/EDIE-DISSERTATION-2014.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Trisomy for human chromosome 21 (Hsa21) results in Down Syndrome (DS), one of the most genetically complex conditions that is compatible with human survival. Up to half of DS conceptions do not survive to term. Effects of over-expression of individual Hsa21 genes that occur during embryogenesis are difficult to study in mammals. We created a gene expression set of 171 Hsa21 cDNAs. RNA was transcribed from cDNA and injected into 1-2 cell zebrafish embryos which were screened at 5 days post-fertilization for gross morphological effects.Twenty-three genes gave an initial phenotype and ten of those genes robustly recapitulated the phenotype in subsequent experiments.Seven of these gave a phenotype consistent with down regulation of the sonic hedgehog (Shh) pathway, two showed a phenotype that indicated involvement of neural crest cells, and one showed pericardial edema.We performed combinatorial injections with multiple Hsa21 genes and found both additive and compensatory effects. This system and gene set supports many types of examination of multiple gene effects on early vertebrate development that are relevant to DS.