Some genetic variants are much more common in Jewish populations than elsewhere — BRCA1 and BRCA2 variants linked to breast and ovarian cancer, the variants behind Tay-Sachs and Gaucher disease, and others. Understandably, people who find one in their results wonder whether it means Jewish ancestry.
Usually it doesn't, and the reasons are worth understanding.
One variant proves very little
Most Jews carry none of these variants. Plenty of non-Jews carry some of them. The variant behind Familial Mediterranean Fever (MEFV), for example, is shared with Armenians, Turks and Arabs. A single carrier result, on its own, is close to useless for ancestry.
Not carrying anything is even less informative. The absence of a variant that most Jews don't have tells you nothing at all.
What does work: many variants together
The useful question is not "do I carry variant X?" It is "across a whole panel of independent variants, how much more likely is my pattern if I have Sephardic ancestry than if I don't?" Each variant adds a small amount of evidence, and those amounts multiply. Carrying two or more from a set enriched in a particular community starts to shift the odds. Carrying one barely does.
The variant worth knowing: BRCA1 185delAG
BRCA1 185delAG is roughly 2,500 years old. That is old enough to predate the separation of the Jewish communities we now call Ashkenazi and Sephardic — and it is found in both, and in Iraqi Jews as well. It is one of the few variants that marks Jewish ancestry broadly rather than Ashkenazi ancestry in particular.
It is also, as the San Luis Valley studies showed, carried by Hispanic Catholic families in Colorado and New Mexico on the Jewish founder background — a converso signal preserved in a cancer gene.
Most panels are really Ashkenazi panels
Tay-Sachs is the contrast. The classic Jewish Tay-Sachs variants are much younger and essentially Ashkenazi. They mark Ashkenazi ancestry, not Jewish ancestry in general.
And there's a twist for readers with French-Canadian roots. Eastern Quebec has its own Tay-Sachs variant, a different mutation in the same gene, which spread through the French-Canadian founder population. A Quebec family carrying Tay-Sachs is far more likely to carry the French-Canadian form than an Ashkenazi one. Same disease, different ancestors.
This is the general problem with "Jewish founder panels": they were built largely from Ashkenazi clinical genetics. Moroccan, Iraqi, Iranian, Libyan and Bukharan Jewish communities each have their own, much less studied sets. A generic panel will tend to find Ashkenazi ancestry and miss Sephardic.
Two rules
- Never run it backwards. Ancestry never tells you whether you carry a disease variant. Only a proper clinical test does.
- This is health information. If you find a BRCA1 or BRCA2 variant, or any carrier result, talk to a doctor or a genetic counsellor. What it means for your health matters far more than what it hints about your ancestry.
Sources
- Studies of BRCA1 185delAG age and distribution in Ashkenazi, Sephardic and Iraqi Jewish populations
- San Luis Valley / New Mexico BRCA1 185delAG founder-haplotype studies
- Studies of the French-Canadian HEXA (Tay-Sachs) founder variant