PDF(Pubmed)
Abstract：
Genetic diseases affecting the skeletal system present with a wide range of symptoms that make diagnosis and treatment difficult. Genome-wide association and sequencing studies have identified genes linked to human skeletal diseases. Gene editing of zebrafish models allows researchers to further examine the link between genotype and phenotype, with the long-term goal of improving diagnosis and treatment. While current automated tools enable rapid and in-depth phenotyping of the axial skeleton, characterizing the effects of mutations on the craniofacial skeleton has been more challenging. The objective of this study was to evaluate a semi-automated screening tool can be used to quantify craniofacial variations in zebrafish models using four genes that have been associated with human skeletal diseases (meox1, plod2, sost, and wnt16) as test cases. We used traditional landmarks to ground truth our dataset and pseudolandmarks to quantify variation across the 3D cranial skeleton between the groups (somatic crispant, germline mutant, and control fish). The proposed pipeline identified variation between the crispant or mutant fish and control fish for four genes. Variation in phenotypes parallel human craniofacial symptoms for two of the four genes tested. This study demonstrates the potential as well as the limitations of our pipeline as a screening tool to examine multi-dimensional phenotypes associated with the zebrafish craniofacial skeleton.
摘要：
影响骨骼系统的遗传性疾病具有广泛的症状，使诊断和治疗变得困难。全基因组关联和测序研究已经确定了与人类骨骼疾病相关的基因。斑马鱼模型的基因编辑使研究人员能够进一步检查基因型和表型之间的联系，长期目标是改善诊断和治疗。虽然目前的自动化工具能够快速和深入地对轴向骨骼进行表型分析，表征突变对颅面骨骼的影响更具挑战性。本研究的目的是评估一种半自动筛查工具，该工具可用于使用与人类骨骼疾病相关的四个基因（meox1，plod2，sost，和wnt16)作为测试用例。我们使用传统的地标来证实我们的数据集和伪地标来量化各组之间3D颅骨的变化(体细胞脆皮，种系突变体,和控制鱼)。拟议的管道确定了四个基因的脆皮或突变鱼与对照鱼之间的变异。对于所测试的四个基因中的两个，表型的变化与人类颅面症状平行。这项研究证明了我们的管道作为检查与斑马鱼颅面骨骼相关的多维表型的筛选工具的潜力和局限性。
