For the Jewish community, perhaps the biggest success story in genetic testing is Tay-Sachs: The disease is carried by one in 27 Ashkenazi Jews (who come from Eastern Europe), and nearly always has been fatal. Today, among Ashkenazi Jewish populations, it has been almost entirely eradicated. Most of the diseases that have become household names—like Tay-Sachs—affect Ashkenazi Jews. But while Sephardi and Mizrahi Jews are also at risk for a host of genetic diseases, the research hasn’t kept up.
Take Wolman disease, which is “kind of like the Tay-Sachs version for the Iranian Jewish population,” says Gidon Akler, cofounder of the Sephardic Health Organization for Referral & Education. A fat storage disorder, it is carried by about one in 27 Iranian Jews. Other diseases are even more common: Familial Mediterranean Fever, which causes episodes of fever and abdominal inflammation, is carried by one in three to one in seven North African, Iraqi, Armenian and Turkish Jews. And G6PD Deficiency, which can cause anemia, is carried by one in two Kurdish Jews and one in four Iraqi Jews.
Yet these diseases get much less attention than their Ashkenazi counterparts. Why the difference? Part of the problem has to do with population size: In countries like the United States, where awareness is becoming widespread, Ashkenazi populations are significantly larger than Sephardi populations, says Akler. More Ashkenazi Jews means more people develop Ashkenazi genetic diseases. As a result, researchers focused more heavily on these diseases, and organizations dedicated to specific Ashkenazi diseases proliferated.
Researchers have known for a while, for instance, that mutations of the BRCA genes—which increase a person’s risk of several cancers—are more common in Ashkenazi Jews than in the general population. But non-Ashkenazi Jews can also carry separate BRCA mutations, says Tamar Peretz, head of the Sharett Institute of Oncology at Hadassah Medical Center in Israel. Peretz’s team studied mutations among non-Ashkenazi populations, eventually developing a panel of 11 different BRCA mutations—which includes three mutations specific to Sephardi populations. And there is still much more to learn: Although we know that 2.5 percent of Ashkenazi Jews carry BRCA mutations, we don’t yet know how frequently they show up in Sephardi Jews.
The Israel Cancer Research Fund (ICRF) is supporting a project to help overcome these challenges. “There’s a real gap of knowledge for women who are not Ashkenazi,” says Ephrat Levy-Lahad, director of the Medical Genetics Institute at Shaare Zedek Medical Center (pictured above). But Levy-Lahad and Mary-Claire King, the University of Washington researcher who first identified the BRCA gene, hope to change that. Using funding from ICRF, they’re studying inherited breast and ovarian cancer among non-Ashkenazi women in Israel. The project will ultimately survey thousands of women. And while it will directly benefit non-Ashkenazi women, it will also benefit other understudied, genetically diverse groups, says Levy-Lahad. “We’re doing this as a model of what you can do in any population.”
Compared to Ashkenazi Jews, Sephardi and Mizrahi Jews are a disparate group, tracing their origins to the Iberian Peninsula, the Balkans, North Africa and the Middle East. As a result, determining their risk for genetic diseases is much more complicated. “For each subpopulation within the Sephardi and Mizrahi Jews, there are diseases that are more prevalent than in the other populations,” says Akler. “It wasn’t that easy to create such a comprehensive test for such a heterogeneous population.”
Several years ago, at New York’s Mount Sinai, Akler helped develop the first comprehensive genetic testing panel for Sephardi and Mizrahi Jews, which became available for clinical use in 2015. Before that, some panels tested for a handful of diseases based on patients’ ethnic backgrounds, says Akler, but they were narrower in scope. Now, “everyone does the same test, and it screens for all of these diseases—so that way nothing is missed.” The Mount Sinai panel includes 38 diseases specific to Sephardi and Mizrahi Jews and 48 diseases specific to Ashkenazi Jews, as well as 10 diseases that occur in both groups. This third group, Akler adds, is important to stress: If a Sephardi Jew and an Ashkenazi Jew have children, it’s still possible to pass down a disease.
Across all Jewish populations, most genetic diseases proliferate for the same reasons: Historically, Jews tend to marry within their communities. “That causes something called the founder effect,” says Rebecca Wang, a genetic counselor at the Norton & Elaine Sarnoff Center for Jewish Genetics. “Certain mutations stayed in the population due to the population growing from a very small number of founders.”
Most genetic diseases are passed down when a child inherits two copies of a particular recessive gene, while those with only one copy are considered carriers. If a child’s parents are both carriers, she or he has a 25 percent chance of inheriting both copies of the recessive gene. Carriers will not develop the disease—so without genetic testing, they won’t know if their future children are at risk. “Often, with these recessive conditions, people don’t know that they might be a carrier,” says Wang. “You wouldn’t expect to see a family history if people are just carriers.”
Still, within some Sephardi and Mizrahi populations in the United States, there’s a stigma attached to being a carrier. There is “a reluctance to talk about the issue out of fear that their family—their children—will be isolated from the rest of the community,” says Akler. But times are changing, and these days Akler sees couples wanting to get tested on a regular basis. Sephardi and Mizrahi leaders are also speaking out: Earlier this year, Sephardi Chief Rabbi of Israel Yitzchak Yosef called on Sephardic Jews to get tested before holding a “vort (engagement) to avoid any problems, chas v’shalom (God forbid).”
In Israel, around half of Jews are Sephardi. And generally, among all populations, genetic testing is more accepted there compared to the United States. “There is no stigma,” says Peretz. “Especially the younger generations are open to any testing.” Testing is also more streamlined: On its website, Israel’s Ministry of Health lists a number of genetic diseases based on ethnic background. Once a healthy woman is identified as a BRCA carrier, says Peretz, her breast MRIs are covered after age 25. Still, “the Ministry of Health encourages testing even though they don’t completely cover the costs for the more comprehensive testing that includes all Jewish diseases,” Akler adds, “so it is still a problem.”
Now, particularly in the United States, the goal is to teach Sephardi and Mizrahi Jews more about these diseases. Akler hopes to work with American rabbis in Sephardi and Mizrahi communities who can encourage engaged couples to undergo genetic testing—which is more accessible than ever. “We’re all carriers of something,” says Akler. “Everyone who wants to have children should be tested.”