Researchers have developed a molecular workflow that may pinpoint specific patient gene mutations, according to a study published in the journal Nature.
The research team sequenced the genomes of cells from 225 children with the blood disease severe congenital neutropenia, a condition that causes individuals to be prone to recurrent infections, and found new alterations in the GFI1 gene that currently do not have known clinical significance.
They created two genetic models to determine if the newly discovered DNA sequence changes in GFI1 led to neutropenia, the presence of abnormally few white blood cells.
In human cells and mice with mutant GFI1, the mutation triggered a cascade of molecular dysfunction that blocked the development of immature white blood cells called neutrophils. This confirmed the disease causing effect of the GFI1 gene DNA sequence alterations.
The new data allowed researchers to genetically repair neutrophil specification, which controls the number of neutrophils. But repairing neutrophil specification did not automatically repair neutrophil commitment, the development stage where the neutrophils’ nonspecific defense mechanism are programmed.
Future work now focuses on understanding the steps of neutrophil commitment, and how developing neutrophils become programmed at the genetic level to fight bacterial and fungal infections.