Yu, Y EugeneXing, ZhuoDo, CatherinePao, AnnieLee, Eun JoonKrinsky-McHale, SharonSilverman, WayneSchupf, NicoleTycko, Benjamin
Summary
The presence of an extra copy of human chromosome 21 in those with Down syndrome (DS) leads to issues in the brain and immune system. Efforts to understand the molecular mechanisms of these issues could help develop effective therapies, both in DS and in the general population. Researchers highlight the value of combining human studies of DS with mouse models for defining DS critical genes. These studies are starting to uncover fundamental biological mechanisms. Once biological mechanisms are understood, therapies can be developed to intervene.
Abstract
The presence of an extra copy of human chromosome 21 (Hsa21) leads to a constellation of phenotypic manifestations in Down syndrome (DS), including prominent effects on the brain and immune system. Intensive efforts to unravel the molecular mechanisms underlying these phenotypes may help developing effective therapies, both in DS and in the general population. Here we review recent progress in genetic and epigenetic analysis of trisomy 21 (Ts21). New mouse models of DS based on syntenic conservation of segments of the mouse and human chromosomes are starting to clarify the contributions of chromosomal subregions and orthologous genes to specific phenotypes in DS. The expression of genes on Hsa21 is regulated by epigenetic mechanisms, and with recent findings of highly recurrent gene-specific changes in DNA methylation patterns in brain and immune system cells with Ts21, the epigenomics of DS has become an active research area. Here we highlight the value of combining human studies with mouse models for defining DS critical genes and understanding the trans-acting effects of a simple chromosomal aneuploidy on genome-wide epigenetic patterning. These genetic and epigenetic studies are starting to uncover fundamental biological mechanisms, leading to insights that may soon become therapeutically relevant.
Conditions
Aging, Premature, Aneuploidy