The proteins of human chromosome 21

Abstract

Recent genomic sequence annotation suggests that the long arm of human chromosome 21 encodes more than 400 genes. Because there is no evidence to exclude any significant segment of 21 q from containing genes relevant to the Down syndrome (DS) cognitive phenotype, all genes in this entire set must be considered as candidates. Only a subset, however, is likely to make critical contributions. Determining which these are is both a major focus in biology and a critical step in efficient development of therapeutics. The subtle molecular abnormality in DS, the 50% increase in chromosome 21 gene expression, presents significant challenges for researchers in detection and quantitation. Another challenge is the current limitation in understanding gene functions and in interpreting biological characteristics. Here, we review information on chromosome 21-encoded proteins compiled from the literature and from genomics and proteomics databases. For each protein, we summarize their evolutionary conservation, the complexity of their known protein interactions and their level of expression in brain, and discuss the implications and limitations of these data. For a subset, we discuss neurologically relevant phenotypes of mouse models that include knockouts, mutations, or overexpression. Lastly, we highlight a small number of genes for which recent evidence suggests a function in biochemical/cellular pathways that are relevant to cognition. Until knowledge deficits are overcome, we suggest that effective development of gene-phenotype correlations in DS requires a serious and continuous effort to assimilate broad categories of information on chromosome 21 genes, plus the creation of more versatile mouse models.

RETRACTED: Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts

“…Although the phenotypes of DS are complex and variable they include congenital heart defects, craniofacial abnormalities, gastrointestinal anomalies, cognitive impairment, leukemia and Alzheimer's disease [4,5]. Over-expression of the genes on Hsa21 by 50% in many tissues is thought to initiate the DS phenotypes, however, there is currently no explanation for how this relatively small increase in transcript levels results in any specific feature of DS [6,7].…”

Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome

“…Additionally, the presence of SYNJ1 on human chromosome 21 (HSA21) raises the possibility that it may play a role in Down's syndrome (DS). This condition, also known as trisomy 21, is the most common genetic cause of mental retardation and stems from the overexpression of some unknown number of genes present on this chromosome (9)(10)(11). Along with early development of the pathology of Alzheimer's disease and muscle hypotonia, mental retardation occurs in all DS-affected individuals, whereas other phenotypes (e.g., congenital heart defects) occur in a fraction of patients (9,12).…”

Trisomie 21 : 50 ans entre médecine et science

“…Le nombre exact de gènes n'a pas été déterminé avec certitude, l'estimation initiale était de 225 gènes, mais l'étude de la transcription suggère que l'annotation de la séquence est loin d'être complète. L'estimation actuelle est de près de 400 gènes codant pour des protéines [21]. L'annotation génique du 21 s'appuie aussi sur la génomique comparative, par exemple avec la séquence du chr 22 du chimpanzé, qui est homologue du chr 21 humain, ou avec le génome murin.…”