Mutations common in Ashkenazi Jewish populations

Ashkenazi Jews are descendants of Jewish communities that were established mainly in Eastern Europe along the Rhine River around the 12th century AD. The Ashkenazi Jewish people traditionally married within their community, and genetic mutations that naturally cropped up within the population have been studied extensively. [ref]

Why are Ashkenazi Jews at a higher risk for certain genetic diseases?

People who are of Ashkenazi Jewish ancestry are at a higher risk of certain genetic diseases. This is in part due to historically marrying fairly strictly within their own community. But there is also confirmation bias involved here — a lot of the genetic mutations are known and linked with Ashkenazi ancestry due to more studies being done on the population. Other population groups that didn’t marry much outside of their community also have inherited genetic mutations, but most population groups aren’t as well studied or well known. [ref]

A word of caution:
The genetic data from 23andMe, AncestryDNA, etc. is not guaranteed to be clinically accurate (for the most part). Errors are possible…  When it comes to figuring out whether you should eat more green vegetables or cut down on sugar, the statistical possibility of errors in genetic data are not all that worrisome. For something that is really important, getting a clinical-grade test done before making any medical decisions is recommended.

Also, keep in mind that errors are possible in the genetics research and that there could be a typo on this page (yes, everything was double-checked…). The mutations listed below are currently marked ‘pathogenic’ or ‘likely pathogenic’ in ClinVar.

This compilation of common Ashkenazi Jewish mutations only covers part of the known mutations. Additionally, people who are not of Ashkenazi Jewish ancestry can also carry these mutations (of course!).

The column labeled ‘risk allele’ contains the letter (A, C, G, T) corresponding to the nucleotide base that represents the mutation. For the most part, these are diseases that require two mutations to actually have the disease.  So what you are checking for here is to see if you carry one copy of the mutation and are thus a carrier for the disease. These risk alleles are given in the positive (plus) orientation to match with 23andMe and AncestryDNA data.


List of common Ashkenazi Jewish mutations:

Disease: Gene: RS ID Risk allele: Available in:
Familial adenomatous polyposis 1 risk
(10% lifetime risk of colon cancer)
APC rs1801155 A 23andMe v4, v5; AncestryDNA [ref]
Hyperapobetalipoproteinemia (high lipid levels) LPL rs268 G 23andMe v4, v5;  AncestryDNA [ref]
Spongy degeneration of central nervous system ASPA rs28940574 A 23andMe v4, v5;  AncestryDNA [ref]
Spongy degeneration of central nervous system ASPA rs28940279 C 23andMe v4, v5;  AncestryDNA [ref]
Brugada syndrome SCN5A rs137854603 T  AncestryDNA [ref]
21-hydroxylase deficiency CYP21A2 rs6476 A 23andMe v4;  AncestryDNA [ref]
Deafness GJB2 rs72474224 T 23andMe v4;  AncestryDNA [ref]
Deafness GJB2 rs35887622 C 23andMe v5; [ref]
Deafness GJB2 rs28931594 (i6011365) T 23andMe v4; [ref]
Deafness GJB2 rs104894401 (i5001992) T 23andMe v4;  AncestryDNA [ref]
Deafness LOXHD1 rs75949023 T 23andMe v5;  AncestryDNA [ref]
Dihydropyrimidine dehydrogenase deficiency DPYD rs3918290 T 23andMe v4, v5;  AncestryDNA [ref]
Dyskeratosis congenita WRAP53 rs281865548 T 23andMe v5;  AncestryDNA [ref]
S-cone syndrome; Goldmann-Favre NR2E3 rs28937873 A 23andMe v4, v5;  AncestryDNA [ref]
Factor XI deficiency F11 rs121965064
(i4000399)
C 23andMe v4, v5;  AncestryDNA [ref]
Factor XI deficiency F11 rs121965063
(i4000398)
T 23andMe v4, v5;  AncestryDNA [ref]
Familial dysautonomia IKBKAP rs111033171
(i4000334)
G 23andMe v4, v5;  AncestryDNA [ref]
Familial hyperinsulinemia ABCC8 rs151344623 T 23andMe v4, v5; [ref]
Fructose Intolerance ALDOB rs1800546 G 23andMe v4, v5;  AncestryDNA [ref]
Galactosemia GALT rs111033773 T 23andMe v4, v5;  AncestryDNA [ref]
Glycogen storage disease G6PC rs1801175
(i3002486)
T 23andMe v4;  AncestryDNA [ref]
Homocystinuria CBS rs5742905 G 23andMe v4; [ref]
Apolipoprteinemia MTTP rs146064714 T 23andMe v5;  AncestryDNA [ref]
Butyryl-dehydrogenase deficiency ACADS rs61732144 T 23andMe v4, v5;  AncestryDNA [ref]
Pigmented nodular adrenocortical disease PDE11A rs76308115 A 23andMe v4, v5;  AncestryDNA [ref]
Franconi anemia FANCC rs104886456
(i4000336)
A 23andMe v4, v5;  AncestryDNA [ref]
Hermansky-Pudlak HPS3 rs201227603 A 23andMe v4, v5;  AncestryDNA [ref]
Primary hyperoxaluria HOGA1 rs138207257 T 23andMe  v5;  AncestryDNA [ref]
Gait ataxia DARS2 rs142433332 C 23andMe v4, v5;  AncestryDNA [ref]
Mucolipidosis MCOLN1 rs104886461 G 23andMe v4;  AncestryDNA [ref]
Leber congenital amaurosis LCA5 rs121918165 A  23andMe v4, v5;  AncestryDNA [ref]
Retinitis pigmentosa DHDDS rs147394623 G  23andMe v5;  AncestryDNA [ref]

BRCA1 and BRCA2 mutations and Ashkenazi ancestry.

The BRCA1 and BRCA2 mutations are deliberately not included here. 23andMe does offer information on a few of the BRCA1 and BRCA2 in their health reports, but do be aware that the report doesn’t include all of the possible mutations. If you have a reason to suspect a BRCA1/2 mutation, you should go with a company that offers a complete screening of those genes and talk with a genetic counselor.

What does it mean to be a carrier of a genetic disease?

If you are a carrier of one copy of a mutation of an autosomal recessive genetic disease, you will usually have few, if any,  symptoms of the disease. Autosomal recessive diseases (such as most of those listed above) require two copies of the mutation in order to have the disease.

Interestingly, now that so many people have done genetic testing, researchers are realizing that many genetic diseases that are caused by a single gene mutation can exhibit different phenotypes – or symptoms/traits of the disease. It isn’t quite so cut-and-dried as we learned in high school biology with Punnett squares and Mendel’s peas.

Can carriers of a mutation have symptoms?

For diseases that require two copies of the mutation, people with only one copy of the mutation usually have one functioning copy of the gene. Depending on the disease, some people with one copy of a mutation will have mild symptoms related to the mutation. This article in Nature explains how large genetic studies have shown that there is a range of symptoms for many genetic diseases and that carriers can exhibit mild symptoms.

Another great review of this topic is from the American Journal of Human Genetics. In it, the authors explain how other genes generally modify the effects of genetic disease-causing mutations. This causes a range of phenotypes for almost all genetic diseases (except for albinism).

Take cystic fibrosis for example. A study in JAMA showed that carriers of one cystic fibrosis mutation were much more likely to have chronic rhinosinusitis. Similarly, a study in Nature showed that carriers of one cystic fibrosis mutation can sometimes be diagnosed with mild cystic fibrosis. In fact, over a quarter of mild cystic fibrosis patients only carried one copy of a mutation.


Related Genes and Topics

Familial Mediterranean Fever
Familial Mediterranean fever (FMF) is a genetic condition of inflammatory episodes that cause painful joints, pain in the abdomen, or pain in the chest, and is most often accompanied by a fever. FMF is often misdiagnosed as various pain-related conditions such as fibromyalgia, myofascial pain syndrome, or gouty arthritis.

HIF1A: Cancer and Hypoxia
The hypoxia-inducible factor-1 alpha (HIF1A) gene codes for a transcription factor, which responds to the amount of oxygen available to the cell. This is important in cancer prevention, and several HIF1A genetic variants alter the susceptibility to several types of cancer.