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Carrier screening for genetic disease in the Ashkenazi Jewish population

Ashley S Roman, MD, MPH
Section Editor
Louise Wilkins-Haug, MD, PhD
Deputy Editor
Vanessa A Barss, MD, FACOG


When a mutant allele is introduced into a community that procreates mostly among themselves, the frequency of the allele will become higher in the community than in the general population. As a result, the community will have a higher incidence of rare genetic disorders associated with the allele, a situation known as the "founder effect." The increased incidence of Tay-Sachs disease and several other disorders (table 1) among descendants of Ashkenazi Jews is an example of this phenomenon. Because these serious disorders are more common among Ashkenazi Jews, genetic carrier screening programs have been successful and have a high acceptance rate in this population [1,2].


Rationale — Ashkenazi Jews are descendants of Jews from Central and Eastern Europe (eg, Germany, France, Poland, Hungary, Russia, Ukraine, Lithuania), while Sephardic Jews are descendants of Jews from Spain, Portugal, and North Africa. Individuals of Ashkenazi Jewish descent are an example of the founder effect. One in four to one in five individuals of Ashkenazi Jewish descent carry a mutation for one of the autosomal recessive disorders included in a group of disorders sometimes called "Jewish genetic disorders" [3]. Some of these disorders have a high incidence, primarily among individuals of Ashkenazi Jewish descent (eg, Tay-Sachs disease); for many of the disorders (eg, familial dysautonomia), the mutation has been identified almost exclusively in these individuals [1]. Some of the disorders (eg, cystic fibrosis) are also common in other high-risk ethnic groups. Although the disorders can also affect Sephardic Jews, non-Jews, and Jews from mixed backgrounds, they are less prevalent in these populations. Most of the disorders are severely disabling, untreatable, and associated with a shortened life expectancy.

Carrier screening in this population is performed to identify asymptomatic individuals who carry genetic mutations causing any of the genetic disorders more common in descendants of Ashkenazi Jews. If both parents are carriers of a mutation causing the same disorder, there is a one in four chance their offspring will inherit two copies of the mutation (one from each parent) and will be susceptible to developing the phenotype. Identification of these couples gives them the opportunity to pursue reproductive options to avoid an affected pregnancy, prepare for the birth of an affected child, or terminate an affected pregnancy. Negative test results relieve some of the anxiety associated with pregnancy. (See 'Post-test management' below.)

What to screen for — Laboratories offer screening panels that test for several disorders as a group in a single multiplex assay. The number of disorders included in panels for individuals of Ashkenazi Jewish descent is variable (eg, 4, 9, 11, or more), based in part on the carrier frequency in this population and the severity of the phenotype. Some panels include disorders that are rare even in this population if only a few mutations account for the majority of disease.

The American College of Medical Genetics and Genomics (ACMG) recommends routinely offering carrier screening for the following nine disorders: Tay-Sachs disease, Canavan disease, cystic fibrosis, familial dysautonomia, mucolipidosis IV, Niemann Pick disease type A, Fanconi anemia group C, Bloom Syndrome, and Gaucher disease, because of carrier detection rates ≥90 percent and population carrier frequency of ≥1 percent (table 1) [3].

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Literature review current through: Nov 2017. | This topic last updated: Apr 14, 2017.
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