Unlike most other cell types, red blood cells do not have a nucleus and do not make proteins; they're made to carry as much hemoglobin as possible. But small changes in gene sequences affect the characteristics of red blood cells as well as others like white blood cells that do have DNA and make proteins. Now researchers have performed a large study to investigate how variants in human genes affect physiology, and they have done so by analyzing genetic material from five different populations instead of focusing only on people of European ancestry as many older genomic studies have.
This work, reported in Cell, can help scientists learn more about how small changes in genes impact a person's risk of developing some condition, like platelet counts or hemoglobin production. It included data from almost 750,000 people. Though most - about 560,000 - were of European origin, the remainder were of African, East Asian, South Asian, and Hispanic ancestry. Including more people with diverse backgrounds in genetic studies has become crucial, as there has historically been a bias towards people with European ancestry. Expanding genetic databases to represent all of humanity will only benefit everyone.
"Each human population is subject to different environments," said Université de Montréal professor Guillaume Lettre, a researcher at the Montreal Heart Institute who led an international consortium on this project. "Over thousands of years, these environmental pressures have resulted in the progressive appearance of variations in DNA, called genetic mutations, which can influence our physical characteristics, such as skin size or color, but also our risk of getting certain diseases."
This study focused on 15 features of red blood cells, and assessed 45 million gene variants (or mutations, which are not always deleterious) carried by each person. The team identified over 5,000 variations in the human genome that impact blood cells.
When combined with a study that had included individuals with European ancestry, the work indicated that most gene variants linked to blood cells are carried by all population groups. There were, however, about 100 mutations that only affected certain non-European populations. One of those was in a gene called interleukin-7; the mutation promoted its production, causing an increase in the number of immune cells called lymphocytes.
"Of course, this kind of mutation can affect the health of people of South Asian origin," Lettre said. "It's thought that this mutation could influence their capacity to resist certain infections or develop diseases like blood cancer." He noted, however, that "these are, at present, only hypotheses, as researchers do not have the capacity to test them, given the immense costs and the difficulty of finding participants for this type of study."
The research suggested that there are some genes that seem to affect the overall production of blood cells. This information could help create better ways to predict who is at risk for certain diseases and potentially help prevent or effectively treat them.