Gaucher Disease

Ashkenazi Jewish S c re e n i n g i n th e Tw e n t y - f i r s t C e n t u r y
Susan Klugman,
KEYWORDS  Ashkenazi Jewish genetic screening  Carrier screening  Jewish genetic disorders
MD
a,b,

*, Susan J. Gross,

MD

a,c

Ashkenazi Jewish (AJ) genetic screening has expanded significantly in the past 4 decades. Individuals of eastern European (Ashkenazi) Jewish descent are atincreased risk of having offspring with particular genetic diseases that have significant morbidity and mortality. In addition, there are some disorders, such as cystic fibrosis (CF), for which northern European Caucasians are at comparable risk with those of an AJ background. Carrier screening for many of these Jewish genetic disorders has become standard of care. As technology advances, so does thenumber of disorders for which screening is available. Thus, we need to continue to be cognizant of informed consent, test sensitivity, confidentiality, prenatal diagnosis, preimplantation genetic screening, and public health concerns regarding testing.
HISTORY OF JEWISH POPULATIONS AND GENETIC EFFECTS

The Jewish people have a history spanning more than 2000 years.1 They are a migratory peopleand have established communities throughout the world. Three groups of Jews have been defined by their location of origin: Sephardic Jews (initially from Spain and later predominately northern Africa, the Balkans, Turkey, Lebanon, and Syria), Middle Eastern Jews (from Israel, Iraq, and environs) and Ashkenazi Jews (primarily of eastern European origin). Jews consider themselves a people because oftheir common religion, dialect, customs, and marriage within the community. Thus, they have maintained a group identity as well as a genetic identity.2 Many studies have shown that contemporary Jews share several chromosome markers and polymorphisms as well as genetic mutations.3–5 However, there is no such thing as a Jewish
Obstetrics and Gynecology and Women’s Health, Albert Einstein, Collegeof Medicine, Bronx, NY, USA b Reproductive Genetics, Montefiore Medical Center, 1695 Eastchester Road, Suite 301, Bronx, NY 10461, USA c Obstetrics and Gynecology, North Bronx Healthcare Network, Bronx, NY, USA * Corresponding author. Reproductive Genetics, 1695 Eastchester Road, Suite 301, Bronx, NY 10461. E-mail address: sklugman@montefiore.org Obstet Gynecol Clin N Am 37 (2010) 37–46doi:10.1016/j.ogc.2010.01.001 obgyn.theclinics.com 0889-8545/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.
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genome and Jews are more likely to share sequences with fellow non-Jews than with each other.2 Current estimates of the world’s Jewish population total 13 million, with the overwhelming majority in the United States and Israel. Most individuals ofJewish ancestry in North America are of Ashkenazi origin.6 Although there are disorders of significance in the non-AJ Jewish population, they are beyond the scope of this article. Testing in the non-AJ community remains limited at this time in the United States but for more information, the reader is directed to the review by Zlotogora and colleagues,7 which provides information and links to relevantdatabases.
Founder Effects and Historical Origins

Many of the disorders in the AJ population can be attributed to mutations presumed to have each arisen in a single individual many centuries ago. This phenomenon had been coined the ‘‘founder effect’’8 or ‘‘genetic drift.’’ This phenomenon can occur when an individual with a relatively rare mutation moves with a small group to a new locationand subsequently proceeds to undergo a significant population expansion. The once rare mutation will now be quite common in this new well-defined population group. The same effect can be seen if an individual with a relatively rare mutation is part of a group that is reduced from a once large population to a small group because of loss of members. Again, a once rare mutation will no longer be rare...