Many internal organs in the vertebrate body are asymmetrically oriented along the left-right (L-R) body axis. Organ asymmetry and some components of the molecular signaling pathways that direct L-R development are highly conserved among vertebrate species. Although individuals with full reversal of organ L-R asymmetry (situs inversus totalis) are healthy, significant morbidity and mortality is associated with perturbations in laterality that result in discordant orientation of organ systems and complex congenital heart defects. In humans and other vertebrates, genetic alterations of L-R signaling pathways can result in a wide spectrum of laterality defects. In this review we categorize laterality defects in humans, mice, and zebrafish into specific classes based on altered patterns of asymmetric gene expression, organ situs defects, and midline phenotypes. We suggest that this classification system provides a conceptual framework to help consolidate the disparate laterality phenotypes reported in humans and vertebrate model organisms, thereby refining our understanding of the genetics of L-R development. This approach helps suggest candidate genes and genetic pathways that might be perturbed in human laterality disorders and improves diagnostic criteria.

中文翻译：

---

人类侧面性疾病的遗传学：来自脊椎动物模型系统的见解。

脊椎动物体内的许多内部器官沿左右（LR）体轴不对称地定向。在脊椎动物中，器官不对称性和指导LR发育的分子信号传导途径的某些组成部分高度保守。尽管完全逆转了器官LR不对称性的个体（原位反位）是健康的，但明显的发病率和死亡率与侧向扰动有关，导致器官系统方向不一致和复杂的先天性心脏缺陷。在人类和其他脊椎动物中，LR信号通路的遗传改变可导致广泛的侧向缺陷。在这篇综述中，我们根据不对称基因表达，器官位置缺陷，改变的模式，将人，小鼠和斑马鱼的侧向性缺陷分类为特定类别。和中线表型。我们建议该分类系统提供一个概念框架，以帮助巩固在人类和脊椎动物模型生物中报告的不同的横向表型，从而加深我们对LR发育遗传学的理解。这种方法有助于建议可能在人类偏侧性疾病中受到干扰的候选基因和遗传途径，并改善诊断标准。