All Creatures Great and Small: New Approaches for Understanding Down Syndrome Genetics. Issue 5 (May 2021)

• Record Type: Journal Article
• Authors: Moyer, Anna J.; Gardiner, Katheleen; Reeves, Roger H.
• Is Part Of: Trends in genetics. Volume 37:Issue 5(2021)
• Page Start: 444
• Page End: 459
• Publication Date: 2021-05
• Subjects: Down syndrome -- aneuploidy -- trisomy 21 -- disease models -- model organisms -- complex disease; Genetics -- Periodicals; 576.5
• DOI: 10.1016/j.tig.2020.09.017
• Languages: English
• ISSNs: 0168-9525

Abstract

Abstract : Human chromosome 21 (Hsa21) contains more than 500 genes, making trisomy 21 one of the most complex genetic perturbations compatible with life. The ultimate goal of Down syndrome (DS) research is to design therapies that improve quality of life for individuals with DS by understanding which subsets of Hsa21 genes contribute to DS-associated phenotypes throughout the lifetime. However, the complexity of DS pathogenesis has made developing appropriate animal models an ongoing challenge. Here, we examine lessons learned from a variety of model systems, including yeast, nematode, fruit fly, and zebrafish, and discuss emerging methods for creating murine models that better reflect the genetic basis of trisomy 21. Highlights: Down syndrome (DS) is caused by an extra copy of ~500 genes. Understanding how human chromosome 21 (Hsa21) genes contribute to DS phenotypes is essential for developing effective treatment strategies. Many Hsa21 genes functionally interact, and overexpression of these genes perturbs expression of genes throughout the genome. DS research has focused on only a few Hsa21 genes. Diverse model organisms from yeast to mice are being used to study the effects of aneuploidy, to annotate functions of Hsa21 orthologs, and to model aspects of DS pathology.