Genes driving age-related blood cell mutations uncovered

 New research identifies a larger pool of genes involved in clonal haematopoiesis than previously thought, and their implications for disease and diagnostic tests.

Scientists have discovered 17 additional genes that drive the abnormal overgrowth of mutated blood cells as we age. The findings, published in Nature Genetics, provide a more complete view of the genetic factors behind clonal haematopoiesis -- a process associated with aging and linked to increased risks of blood cancers.

Researchers from the Wellcome Sanger Institute, Calico Life Sciences, California, and the University of Cambridge analysed sequencing data from over 200,000 individuals in the UK Biobank cohort. They searched for genes showing signals of "positive selection" -- where mutations allow mutant cell populations to greatly expand over time.

The 17 newly discovered genes were found to have similar disease associations as previously known clonal haematopoiesis mutations, highlighting their clinical significance in driving the accumulation of mutant blood cell clones.

By uncovering these previously unrecognised genetic drivers, the research opens new avenues for studying the molecular mechanisms underlying clonal haematopoiesis and its role in disease development, leading to new ways to promote healthier aging. Additionally, it could lead to better genetic tests that help identify the risks of blood cancers and cardiovascular diseases.

As we age, our cells accumulate random genetic mutations. Some of these mutations can provide a competitive growth advantage, allowing mutant cells to multiply and outnumber the healthy cells, forming large 'clones' or populations of identical mutant cells. When this positive selection happens in blood stem cells, it is called clonal haematopoiesis. This process is associated with blood cancers, cardiovascular disease and other age-related diseases.

While previous studies have identified around 70 genes linked to clonal haematopoiesis, most cases observed recently have not involved mutations in any of these known driver genes. This suggests the involvement of additional genetic factors.

Source: ScienceDaily