Distilled database identifies genetic links to rare diseases
24 March 2023
Published online 17 September 2015
Sequencing the genomes of a relatively isolated population can provide insights into the biological mechanisms of disease.
An international team, which included an affiliation with Qatar’s Sidra Medical and Research Center, compared information from the genomes of about 6,600 Sardinians with their blood levels of cholesterol, other lipids, and inflammatory markers.
These markers are used by physicians to rule out or detect underlying inflammatory diseases.
The correlation allowed them to identify changes in genetic sequences, known as variants, which were specifically associated with changes in blood lipid and inflammatory marker levels.
For example, the group found that healthy carriers of a common mutation that causes beta thalassaemia — a blood disorder in which haemoglobin production is reduced — exhibited reduced cholesterol levels. The mutation causes increased production of red blood cells to overcome haemoglobin losses. The scientists believe that healthy carriers of the mutation have reduced cholesterol levels because large amounts of cholesterol are required for increased red blood cell production.
“The findings have potential clinical implications since both lipid levels and inflammatory markers may influence risk of heart disease,” says medical geneticist Francesco Cucca from Italy’s National Research Council.
The Sardinian population studied has had very little in-migration for thousands of years, causing certain gene variants to be more common in this population than in others. This enables the scientists to better analyse the effects of these variants on biological processes within the body in a way that is not possible by studying other, much more mixed, populations.
“I believe that similar analyses on various traits of biomedical relevance performed in Middle Eastern populations using the same approach we used in Sardinia can generate very interesting results because they will assess the effects of a thus far largely unexplored portion of human genetic variation,” says Cucca.
Sidore, C. et al. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers. Nat. Genet. http://dx.doi.org/10.1038/ng.3368 (2015).