The hominoid-specific gene DSCR4 is involved in regulation of human leukocyte migration

Abstract

DSCR4 (Down syndrome critical region 4) is an orphan retrotransposon-derived de-novo originated protein coding gene present only in hominoids (humans and great apes). Despite being located on the medically critical genomic region and abundance of evidences indicating its functionality, the role of this gene in human cells was utterly unknown. Due to absence of any prior knowledge regarding the function of DSCR4, for the first time here we used a gene-overexpression approach to discover biological importance and cellular roles of this gene. Our analysis strongly indicates DSCR4 to be mainly involved in regulation of the interconnected biological pathways related to cell migration, coagulation and immune system. We also showed that the predicted biological functions are consistent with tissue-specific expression of DSCR4 in migratory immune system leukocyte cells and neural crest cells that shape facial morphology of human embryo. Immune system and neural crest cells are also shown to be affected in Down syndrome patients who suffer from the same type of DSCR4 misregulation as in our study which further support our findings.Providing evidence for the critical roles of DSCR4 in human cells, our findings establish the basis for further investigations on the roles of DSCR4 in etiology of Down syndrome and unique characteristics of hominoids.

Gene Expression Studies in Down Syndrome: What Do They Tell Us about Disease Phenotypes?

“…The DSCR, a segment on chromosome 21, contains genes responsible for various features of DS, including craniofacial dysmorphology [ 5 ]. A study by Saber et al, focused on DSCR4, highlighted that overexpression of DSCR4 in the neural crest cells, which account for over 90% of craniofacial development, specifically alters facial morphology in DS [ 42 ]. The DSCR1 gene on chromosome 21 is a developmental regulator and plays a role in neurogenesis.…”