“Autosomal Allelic Inactivation: Variable Replication and Dosage Sensitivity,” is now available as a reviewed preprint in eLife!
“Autosomal Allelic Inactivation: Variable Replication and Dosage Sensitivity,” is now available as a reviewed preprint in eLife!
In this latest study, the Gilbert lab contributed to a larger effort that explored why some genes are expressed more from one copy of a chromosome than the other.
Typically, you inherit two copies of genes, one from each parent, and both tend to be active to determine hereditary traits. In some cases, however, one copy may be active and the other silent. Based on this, the researchers identified the regions, called Inactivation/Stability Centers (I/SCs), that influence which gene copy is used in a cell and when each copy is duplicated during cell division. The choice of which copy is active appears to be random.
Because different cells may activate different gene copies, tissues can then become a patchwork of cells with slightly different gene activity. While this cellular diversity may be a normal part of development, it can also affect how genetic diseases appear.
If a person carries a harmful mutation in one copy of such a gene, the random silencing of the healthy copy in some cells could reduce the amount of functional gene product below what the body needs. The researchers found that many genes located within these regions are linked to conditions such as Parkinson’s disease, Epilepsy, inherited deafness, and intellectual disabilities.
Overall, this work reveals a previously underappreciated layer of gene regulation in the human genome and suggests that random, cell-to-cell differences in gene activity may play an important role in human development and disease.
Congrats to the Gilbert lab and colleagues for their findings and hard work!