2011/08/30 by Eva Lana‐Elola, Sheona Watson-Scales, Elizabeth Fisher +1 · 148 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Biology #Chromosome #Chromosome 21 #Chromosome engineering #Computational biology #Down syndrome #Down syndrome and intellectual disability research #Gene #Gene dosage #Gene expression #Genetics #Genetics and Neurodevelopmental Disorders #Genomics and Rare Diseases #Human genetics #Identification (biology) #Phenotype #Trisomy
paper · doi:10.1242/dmm.008078
published in Disease Models & Mechanisms 4(5), 586-595 (The Company of Biologists)
openalex publication_date 2011/08/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and results in a large number of phenotypes, including learning difficulties, cardiac defects, distinguishing facial features and leukaemia. These are likely to result from an increased dosage of one or more of the ∼310 genes present on Hsa21. The identification of these dosage-sensitive genes has become a major focus in DS research because it is essential for a full understanding of the molecular mechanisms underlying pathology, and might eventually lead to more effective therapy. The search for these dosage-sensitive genes is being carried out using both human and mouse genetics. Studies of humans with partial trisomy of Hsa21 have identified regions of this chromosome that contribute to different phenotypes. In addition, novel engineered mouse models are being used to map the location of dosage-sensitive genes, which, in a few cases, has led to the identification of individual genes that are causative for certain phenotypes. These studies have revealed a complex genetic interplay, showing that the diverse DS phenotypes are likely to be caused by increased copies of many genes, with individual genes contributing in different proportions to the variance in different aspects of the pathology.