Genetic Variation and Disease
Among groups of people worldwide, genetic variation plays a key role in the prevalence of certain genetic diseases like Gaucher disease. Genetic diseases can affect anyone, but in some groups, certain diseases are more common compared to others. This can be attributed to genetic drift, or how frequently various genotypes (genetic makeups) appear in populations of individuals.
Outside factors are capable of influencing genetic drift, which causes genetic diseases to appear more frequently among specific groups of people. One such factor, called the Founder Effect, has been the subject of extensive research among people of Jewish descent.
We already know that Jewish people are more likely than the general population to carry genetic mutations that result in specific genetic diseases, including Gaucher disease. In fact, Gaucher disease is the most common genetic disease affecting Ashkenazi Jews. But why is the Jewish population more likely to carry these mutations?
What is the Founder Effect?
Over the course of time, countless individuals have gone out on their own, leaving their communities behind and forming new societies with other like-minded people. While this certainly occurs as a result of choice, it has historically, on occasion, occurred forcibly. Either way, the isolation of a newly formed society causes genetic variability among small groups of people to decline.
This is the Founder Effect. Put simply, the Founder Effect begins with a mutation or change in a gene in one person in a small community. “A new geographically or socially isolated population starts from a small number of people, called founders,” explains Karen Arnovitz Grinzaid, Executive Director of the JScreen program. “One of these founders may have a mutation in a gene, like the mutation causing Gaucher disease, and is considered a carrier of that genetic disease. As carriers of this disease have children and the new population starts to grow, the mutated gene becomes more prevalent.”
Today, the general perception is that most Jewish people descended from a few thousand founders living hundreds of years ago in Eastern Europe. Several times during the course of history, Jewish populations abruptly became smaller through events like the Holocaust. Jewish people became isolated in small communities, which eventually expanded as more children were born.
As communities grew, any genetic mutations existing within the community founders were passed on to descendants. Over time, the prevalence of these mutations increased as more children were born, either as carriers of the mutation or as people living with a genetic disease. This is especially important to remember when considering Gaucher disease because the condition is inherited in an autosomal recessive pattern. In autosomal recessive inheritance, each child of two carrier parents is at 25% risk for the disease.
“Due to the Founder Effect, people within small populations had an increased chance of inheriting mutations in certain disease genes. Each child of a carrier parent has a 50% chance of being a carrier as well,” says Grinzaid. “As the population grew in size, the number of carriers in the group increased. If two carriers reproduce, their children are at increased risk for the disease itself.”
About 1 in 10 Ashkenazi Jews are carriers of a genetic mutation causing Gaucher disease. This is dramatically higher than non-Jews, where about 1 in 100 people is a carrier. Many of the genetic diseases so prevalent among Jews, such as Gaucher disease, Tay-Sachs, and familial dysautonomia, started with an original founder who went on to have multiple descendants.
Is There Benefit to the Founder Effect?
The Founder Effect occurs in groups of people around the world. Certain genetic diseases are observed more frequently in some ethnic groups compared to others. For example, sickle cell disease is more common in people of African descent, while thalassemia is prevalent in people from certain Mediterranean, African, or Asian countries.
But it isn’t clear what, if any, evolutionary advantages were offered by specific genetic mutations appearing frequently as a result of the Founder Effect. Some theorize there was some kind of selective advantage to being a carrier. “With sickle cell disease, some research suggests it offered protection against malaria. If you were in an area where malaria was a risk, being a sickle cell carrier could make it easier for you to survive, which is certainly an evolutionary advantage,” says Grinzaid.
Among Jews, some scientists believe being a Tay-Sachs carrier offered some protection against tuberculosis. But it’s not clear what, if any, evolutionary advantages Gaucher carriers benefited from.
Talking with Your Doctor
Knowing about your ancestry and your family health history can open the doors to understanding whether you or your children may be at increased risk of developing certain genetic diseases. Talk with your doctor or a genetic counselor if you have symptoms of a genetic disease or if your ancestry puts you at increased risk.
“If you are planning to have a family, having information about your ancestry is important. You can have genetic testing performed to find out if you’re a carrier for a genetic disease like Gaucher, or other diseases common in people with your ethnic background,” says Grinzaid. Carrier testing for a broader range of genetic diseases is also important, as you may be a carrier of a disease that is not specific to your ethnic group. “Information about your background can also help doctors pinpoint a diagnosis, especially if you’re Jewish and are having symptoms suggestive of a genetic disease like Gaucher disease. In this way, knowing about the Founder Effect is important, both for a person’s individual health and for their future families.”