Conversion - Anusim - Genetic basis?

Smithsonian Magazine: [referred by Jersey Girl]
One september day in 2001, Teresa Castellano, Lisa Mullineaux, Jeffrey Shaw and Lisen Axell were having lunch in Denver. Genetic counselors from nearby hospitals and specialists in inherited cancers, the four would get together periodically to talk shop. That day they surprised one another: they'd each documented a case or two of Hispanic women with aggressive breast cancer linked to a particular genetic mutation. The women had roots in southern Colorado, near the New Mexico border. "I said, 'I have a patient with the mutation, and she's only in her 40s,'" Castellano recalls. "Then Lisa said that she had seen a couple of cases like that. And Jeff and Lisen had one or two also. We realized that this could be something really interesting."

Curiously, the genetic mutation that caused the virulent breast cancer had previously been found primarily in Jewish people whose ancestral home was Central or Eastern Europe. Yet all of these new patients were Hispanic Catholics.

Mullineaux contacted Ruth Oratz, a New York City-based oncologist then working in Denver. "Those people are Jewish," Oratz told her. "I'm sure of it."

Pooling their information, the counselors published a report in a medical journal about finding the gene mutation in six "non-Jewish Americans of Spanish ancestry." The researchers were cautious about some of the implications because the breast cancer patients themselves, as the paper put it, "denied Jewish ancestry."

The finding raised some awkward questions. What did the presence of the genetic mutation say about the Catholics who carried it? How did they happen to inherit it? Would they have to rethink who they were—their very identity—because of a tiny change in the three billion "letters" of their DNA? More important, how would it affect their health, and their children's health, in the future?

Some people in the valley were reluctant to confront such questions, at least initially, and a handful even rejected the overtures of physicians, scientists and historians who were suddenly interested in their family histories. But rumors of secret Spanish Jewry had floated around northern New Mexico and the San Luis Valley for years, and now the cold hard facts of DNA appeared to support them. As a result, families in this remote high-desert community have had to come to grips with a kind of knowledge that more and more of us are likely to face. For the story of this wayward gene is the story of modern genetics, a science that increasingly has the power both to predict the future and to illuminate the past in unsettling ways.

Expanding the DNA analysis, Sharon Graw, a University of Denver geneticist, confirmed that the mutation in the Hispanic patients from San Luis Valley exactly matched one previously found in Ashkenazi Jews from Central and Eastern Europe. The mutation, 185delAG, is a variant of a gene called BRCA1. When normal and healthy, BRCA1 helps to protect breast and ovarian cells from cancer. An extremely long gene, it has thousands of DNA letters, each corresponding to one of four chemical compounds that make up the genetic code and run down either strand of the DNA double helix; a "misspelling"—a mutation—can occur at virtually any letter. Some are of no consequence, but the deletion of the chemicals adenine (A) and guanine (G) at a site 185 rungs into the DNA ladder—hence the name 185delAG—will prevent the gene from functioning. Then the cell becomes vulnerable to a malignancy. To be sure, most breast and ovarian cancers do not run in families. The cases owing to BRCA1 and a similar gene, BRCA2, make up less than 10 percent of cases overall.

By comparing DNA samples from Jews around the world, scientists have pieced together the origins of the 185delAG mutation. It is ancient. More than 2,000 years ago, among the Hebrew tribes of Palestine, someone's DNA dropped the AG letters at the 185 site. The glitch spread and multiplied in succeeding generations, even as Jews migrated from Palestine to Europe. Ethnic groups tend to have their own distinctive genetic disorders, such as harmful variations of the BRCA1 gene, but because Jews throughout history have often married within their religion, the 185delAG mutation gained a strong foothold in that population. Today, roughly one in 100 Jews carries the harmful form of the gene variant.

Meanwhile, some of the Colorado patients began to look into their own heritage. With the zeal of an investigative reporter, Beatrice Wright searched for both cancer and Jewish ancestry in her family tree. Her maiden name is Martinez. She lives in a town north of Denver and has dozens of Martinez relatives in the San Luis Valley and northern New Mexico. In fact, her mother's maiden name was Martinez also. Wright had been diagnosed with breast cancer in 2000, when she was 45. Her right breast was removed and she was treated with chemotherapy. Later, her left breast, uterus, fallopian tubes and ovaries were removed as a precaution. She had vaguely known that the women on her father's side were susceptible to the disease. "With so much cancer on Dad's side of the family," she said, "my cancer doctor thought it might be hereditary." Advised by Lisa Mullineaux about BRCA testing, she provided a blood sample that came back positive for 185delAG.

When Wright was told that the mutation was characteristic of Jewish people, she recalled a magazine article about the secret Jews of New Mexico. It was well known that during the late Middle Ages the Jews of Spain were forced to convert to Catholicism. According to a considerable body of scholarship, some of the conversos maintained their faith in secret. After Judaism was outlawed in Spain in 1492 and Jews were expelled, some of those who stayed took their beliefs further underground. The exiles went as far as the New World. [...]