Isolated communities are more at risk of rare genetic diseases

ISLAND LIFE is famously idyllic, but it has long been known that islanders often suffer disproportionately high rates of rare, genetically transmitted diseases. For example, residents of the Faroe Islands, who live on an archipelago in the North Atlantic Ocean, have a much higher-than-average incidence of carnitine transporter deficiency (CTD), a condition that prevents the body from using certain fats for energy. Residents of Gran Canaria, an island off the northwest coast of Africa, have a much higher than average risk of familial hypercholesterolemia, a condition in which the liver cannot process cholesterol effectively.

A new article in Nature Communications provides another example. Jim Flett Wilson of the University of Edinburgh, who led the study, reports that people living on the Shetland Islands in northern Scotland have a one in 41 chance of being carriers of the gene variant that causes Batten disease, a life-limiting neurodegenerative disease. The comparable figure elsewhere in Britain is one in 300, says Dr Wilson.

Such an increased risk is likely due to genetic isolation. When members of a small population reproduce overwhelmingly with their peers, the likelihood that children will inherit disease-causing mutations (also called variants) from their parents increases over time. This happens because of a process known as random genetic drift, says Dr. Wilson, in which some genetic variants become more common and others are lost. “This effect is amplified in small populations with little or no influx of new people to replenish the genetic stock,” he says.

Such insulation does not have to be solely the product of surrounding water. The new study by Dr. Wilson also found “genetic islands” on the British mainland. In Lancashire, for example, researchers found that locals were more likely to have 10 disease-causing variants, including one linked to Zellweger syndrome, a disease that affects the brain, liver and kidneys and can be fatal in the first year of life. Those from the area were 73 times more likely to have the variant. In South Wales, one variant responsible for a hereditary predisposition to developing kidney stones later in life was 44 times more common, while in Nottinghamshire a variant causing a serious skin condition with blisters was 65 times more common than elsewhere.

Such genetic islands can arise from geography and culture, Dr. Wilson says, including a widely shared preference for individuals to choose spouses from the same community in which they grew up. Some such islands are already being monitored by health authorities. For example, the NHS runs screening programs for people of Ashkenazi Jewish descent, as around one in forty Ashkenazi Jewish people carry harmful variants of the BRCA gene, which puts them at greater risk of breast or ovarian cancer. This compares to around one in 260 people in the general UK population.

The incidence of Batten disease carriers among Shetland Islanders is similar to that of the BRCA variant among Jews, says Dr Wilson, and yet there are no plans for a screening program there. He says reliance on the 'cascade' model, where people are only offered testing after a family member has been diagnosed, is only half as reliable in picking up cases as universal on-demand testing. Until such screening programs are introduced, islanders are at risk of becoming doubly isolated.