Division of Bone Biology, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, Sydney, NSW, 2010, Australia.
Division of Bone Biology, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, Sydney, NSW, 2010, Australia; University of Notre Dame Australia, Sydney, NSW, 2010, Australia.
Bone. 2019 Sep;126:27-36. doi: 10.1016/j.bone.2019.02.015. Epub 2019 Feb 15.
Technological advances have enabled the study of the human genome in incredible detail with relative ease. However, our ability to interpret the functional significance of the millions of genetic variants present within each individual is limited. As a result, the confident assignment of disease-causing variant calls remains a significant challenge. Here we explore how mouse genetics can help address this deficit in functional genomic understanding. Underpinned by marked genetic correspondence, skeletal biology shows inter-species similarities which provide important opportunities to use data from mouse models to direct research into the genetic basis of skeletal pathophysiology. In this article we outline critical resources that may be used to establish genotype/phenotype relationships in skeletal tissue, identify genes with established skeletal effects and define the transcriptome of critical skeletal cell types. Finally, we outline how these mouse resources might be utilized to progress from a list of human sequence variants toward plausible gene candidates that contribute to skeletal disease.
技术进步使得研究人类基因组变得相对容易，并且能够以难以置信的细节进行研究。然而，我们解读每个人体内存在的数百万个遗传变异的功能意义的能力是有限的。因此，有把握地确定致病变异的调用仍然是一个重大挑战。在这里，我们探讨了小鼠遗传学如何有助于解决功能基因组理解方面的这一不足。骨骼生物学以明显的遗传对应为基础，显示出种间相似性，这为利用来自小鼠模型的数据来指导骨骼病理生理学遗传基础的研究提供了重要机会。在本文中，我们概述了可用于在骨骼组织中建立基因型/表型关系、确定具有既定骨骼效应的基因以及定义关键骨骼细胞类型的转录组的关键资源。最后，我们概述了如何利用这些小鼠资源，从人类序列变异列表推进到可能导致骨骼疾病的基因候选物。
