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The medical genetics of Jewish people is the study, screening and treatment of genetic disorders that are more common in particular Jewish populations than in the population as a whole.[1] The genetics of Ashkenazi Jews have been particularly well-studied, resulting in the discovery of many genetic disorders that are associated with this ethnic group. In contrast, the medical genetics of Sephardic Jews and Oriental Jews are more complicated, since they are more genetically diverse and there are consequently no genetic disorders that are more common in these groups as a whole; instead they tend to have the genetic diseases that are common in their various countries of origin.[1][2] Several organizations offer screening for Ashkenazi genetic diseases, such as Dor Yeshorim,[3] and these screening programs have had a significant impact, in particular by reducing the number of cases of Tay–Sachs disease.[4]


Genetics of Jewish populations

Different ethnic groups tend to suffer from different rates of hereditary diseases, with some being more common, and some less common. Hereditary diseases, particularly hemophilia were recognized early in Jewish history, even being described in the Talmud.[5] However, the scientific study of hereditary disease in Jewish populations was initially hindered by the shadow of the racist and unscientific ideas of eugenics and "racial hygiene", which tried to describe various ethnic groups as inferior.[6][7]

However, modern studies on the genetics of particular ethnic groups have the tightly-defined purpose of avoiding the birth of children with genetic diseases, or identifying people at particular risk of developing a disease in the future.[8] Consequently, the Jewish community has been very supportive of modern genetic testing programs, although this unusually high degree of cooperation has raised concerns that it might lead to the false perception that Jews are more susceptible to genetic diseases than other groups of people.[5]

However, most populations contain hundreds of alleles that could potentially cause disease and most people are heterozygotes for one or two recessive alleles that would be lethal in a homozygote.[9] Although the overall frequency of disease-causing alleles does not vary much between populations, the practice of consanguineous marriage (marriage between second cousins or closer relatives) is common in some Jewish communities, which produces a small increase in the number of children with congenital defects.[10]

According to Daphna Birenbaum Carmeli at the University of Haifa, Jewish populations have been studied more thoroughly than most other human populations because:

  • Geneticists are intrinsically interested in Jewish populations as a disproportionate percentage of genetics researchers are Jewish. Israel in particular has become an international center of such research.
  • Jewish populations, and particularly the large Ashkenazi Jewish population, are ideal for such research studies, because they exhibit a high degree of endogamy, yet they are sizable.
  • Jewish populations are overwhelmingly urban, and are concentrated near biomedical centers where such research has been carried out. Such research is especially easy to carry out in Israel, where cradle-to-grave medical insurance is available, together with universal screening for genetic disease.
  • Jewish communities are comparatively well informed about genetics research, and have been supportive of community efforts to study and prevent genetic diseases.
  • Participation of Jewish scientists and support from the Jewish community alleviates ethical concerns that sometimes hinder such genetic studies in other ethnic groups.

The result is a form of ascertainment bias. This has sometimes created an impression that Jews are more susceptible to genetic disease than other populations. Carmeli writes, "Jews are over-represented in human genetic literature, particularly in mutation-related contexts."[11] Another factor that may aid genetic research in this community is that Jewish culture results in excellent medical care, which is coupled to a strong interest in the community's history and demography.[12]

This set of advantages have led to Ashkenazi Jews in particular being used in many genetic studies, not just in the study of genetic diseases. For example, a series of publications on Ashkenazi centenarians established that their longevity was strongly inherited and associated with lower rates of age-related diseases.[13] This "healthy aging" phenotype may be due to higher levels of telomerase in these individuals.[14]

Ashkenazi diseases

Although there is no reason to think that the Ashkenazi Jewish population has any more or fewer mutations than other ethnic groups, this group has been particularly intensively-studied, so many mutations have been identified as common in Ashkenazis.[15] Of these diseases, many also occur in other Jewish groups and in non-Jewish populations, although the specific mutation which causes the disease may vary between populations. For example, two different mutations in the glucocerebrosidase gene causes Gaucher's disease in Ashkenazis, which is their most common genetic disease, but only one of these mutations is found in non-Jewish groups.[4] A few diseases are unique to this group: for example familial dysautonomia is almost unknown in other populations.[4]

Genetic disorders common in Ashkenazi Jews[1]
Disease Mode of inheritance Gene Carrier frequency
 Bloom syndrome Autosomal recessive BLM 1/100
 Breast cancer and ovarian cancer Autosomal dominant BRCA1 or BRCA2 1/100 and 1/75, respectively
 Canavan disease Autosomal recessive ASPA 1/60
 Congenital deafness Autosomal recessive GJB2 or GJB6 1/25
 Cystic fibrosis Autosomal recessive CFTR 1/25
 Haemophilia C Autosomal recessive F11 1/12
 Familial dysautonomia Autosomal recessive IKBKAP 1/30
 Familial hypercholesterolemia Autosomal dominant LDLR 1/69
 Familial hyperinsulinism Autosomal recessive ABCC8 1/125–1/160
 Fanconi anemia C Autosomal recessive FACC 1/100
 Gaucher disease Autosomal recessive GBA 1/7–1/18
 Glycogen Storage Disease type 1a Autosomal recessive G6PC 1/71
 Mucolipidosis IV Autosomal recessive MCOLN1 1/110
 Niemann–Pick (type A) Autosomal recessive SMPD1 1/90
 Nonclassical 21 OH deficiency Autosomal recessive CPY21 1/6
 Parkinson's disease Autosomal recessive LRRK2 1/42[16]
 Tay–Sachs Autosomal recessive HEXA 1/25–1/30
 Torsion dystonia Autosomal dominant DYT1 1/4000
 Usher syndrome Autosomal recessive PCDH15 1/72

Tay–Sachs disease

Tay–Sachs disease, a fatal illness of children that causes mental deterioration prior to death, was historically more prevalent among Ashkenazi Jews,[17] although high levels of the disease are also found in some Pennsylvania Dutch, Southern Louisiana Cajun and Eastern Quebec French Canadian populations.[18] Since the 1970s, however, proactive genetic testing has been quite effective in eliminating Tay–Sachs from the Ashkenazi Jewish population.[19]

Lipid transport diseases

Gaucher's disease, in which lipids accumulates in inappropriate locations, occurs most frequently among Ashkenazi Jews;[20] the disease is carried by roughly 1 in every 15 Ashkenazi Jews, compared to 1 in 100 of the general American population[21]. Gaucher's disease can cause brain damage and seizures, but these effects are not usually present in the form manifested among Ashkenazi Jews; nevertheless, sufferers still bruise easily, and it can still potentially rupture the spleen, although it generally has only a minor impact on life expectancy.

Ashkenazi Jews are also highly affected by other lysosomal storage diseases, particularly in the form of lipid storage disorders. They more frequently act as carriers of mucolipidosis, than do other ethnic groups.[22] and Niemann–Pick disease, which can prove fatal.[23] The occurrence of several lysosomal storage disorders in the same population suggested the idea that the alleles responsible might have conferred some selective advantage in the past.[24]

This would be similar to the partial immunity to malaria that is conferred by having one copy of the allele that causes sickle-cell disease in people with two copies of the allele (an effect called heterozygote advantage).[25] It has been proposed that some of these disorders became common in this population due to selection for high levels of intelligence (see ashkenazi intelligence).[26][27] However, other research suggests that there is no difference between the frequency of this group of diseases and other genetic diseases in Ashkenazis, which is evidence against this hypothesis.[28]

Familial dysautonomia

Familial dysautonomia (Riley–Day Syndrome), which causes vomiting, speech problems, an inability to cry, and false sensory perception, is almost exclusive to Ashkenazi Jews[29]; Ashkenazi Jews are almost 100 times more likely to carry the disease, than anyone else[30].

Other Ashkenazi diseases and disorders

Diseases that are inherited in an autosomal recessive pattern often occur in endogamous populations. Among Ashkenazi Jews, a higher incidence of specific genetic disorders and hereditary diseases have been verified, including:

Non-Ashkenazi disorders

In contrast to the Ashkenazi population, Sephardic and Oriental Jews are much more divergent groups, with ancestors from Spain, Morocco, Tunisia, Algeria, Spain, Italy, Libya, the Balkans, Iran, Iraq, India and Yemen, with specific genetic disorders that are found in each regional group, or even in specific sub-populations in these regions.[1]

Genetic disorders common in Sephardic Jews.[1]
Disease Mode of inheritance Gene Carrier frequency Populations
 Oculocutaneous albinism Autosomal recessive TYR 1/30 Morocco
 Ataxia telangiectasia Autosomal recessive ATM 1/80 Morocco, Tunisia
 Creutzfeldt–Jakob disease Autosomal dominant PRNP 1/24,000 Libya
 Cerebrotendinous xanthomatosis Autosomal recessive CYP27A1 1/70 Morocco
 Cystinuria Autosomal recessive SLC7A9 1/25 Libya
 Familial Mediterranean fever Autosomal recessive MEFV 1/5–1/7 Libya, Morocco, Tunisia
 Glycogen storage disease III Autosomal recessive AGL 1/35 Morocco
 Limb girdle muscular dystrophy Autosomal recessive DYSF 1/10 Libya
 Tay–Sachs Autosomal recessive HEXA 1/110 Morocco
 11-β-hydroxylase deficiency Autosomal recessive CYP11B1 1/30–1/128 Morocco
Genetic disorders common in Oriental Jews.[1]
Disease Mode of inheritance Gene Carrier frequency Populations
 Beta-thalassemia Autosomal recessive HBB 1/6 Iran, Iraq, Kurdistan
 Factor VII deficiency Autosomal recessive F7 1/40 Iran
 Familial Mediterranean fever Autosomal recessive MEFV 1/5–1/7 Iraq, Iran, Armenia, North-African Jews, Ashkenazi
 Glucose-6-phosphate dehydrogenase deficiency X-linked G6PD 1/4 Iraq
 Inclusion body myopathy Autosomal recessive GNE 1/12 Iran
 Metachromatic leukodystrophy Autosomal recessive ARSA 1/50 Yemen
 Oculopharyngeal muscular dystrophy Autosomal, recessive or dominant PABPN1 1/7 Bukhara
 Phenylketonuria Autosomal recessive PHA 1/35 Yemen

Genetic testing in Jewish populations

One of the first genetic testing programs to identify heterozygote carriers of a genetic disorder was a program aimed at eliminating Tay–Sachs disease. This program began in 1970 and over one million people have now been screened for the mutation.[43] Identifying carriers and counseling couples on reproductive options have had a large impact on the incidence of the disease, with a decrease from 40–50 per year worldwide to only 4–5 per year.[4] Screening programs now test for several genetic disorders in Jews, although these focus on the Ashkenazi Jews, since other Jewish groups cannot be given a single set of tests for a common set of disorders.[2] In the USA, these screening programs have been widely accepted by the Ashkenazi community, and have greatly reduced the frequency of the disorders.[44]

Prenatal testing for several genetic diseases is offered as commercial panels for Ashkanezi couples by both CIGNA and Quest Diagnostics. The CIGNA panel is available for testing for parental/preconception screening or following chronic villus sampling or amniocentesis and tests for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia, Gaucher disease, mucolipidosis IV, Neimann-Pick disease type A, Tay-Sachs disease and torsion dystonia. The Quest panel is for parental/preconception testing and tests for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Neimann-Pick disease types A & B and Tay-Sachs disease.

The official recommendations of the American College of Obstetricians and Gynecologists is that Ashkenazi individuals be offered screening for Tay Sachs, Canavan, cystic fibrosis and familial dysautonomia as part of routine obstetrical care. [45]

In the orthodox community an organization called Dor Yeshorim carries out anonymous genetic screening of couples before marriage in order to reduce the risk of children with genetic diseases being born.[46] The program educates young people on medical genetics and screens school-aged children for any disease genes. These results are then entered into an anonymous database, identified only by a unique ID number that is given to the person who was tested. If two people are considering getting married, they call the organization and tell them their ID numbers. The organization then tells them if they are genetically compatible. Importantly, if a problem is found, the people involved have no way of knowing who was the carrier, thereby avoiding carriers from being stigmatized.[46] However, this program as been criticized for exerting social pressure on people to be tested, and for screening for a broad range of recessive genes, including mild disorders such as Gaucher's disease.[3]

See also



  1. ^ a b c d e f Rosner G, Rosner S, Orr-Urtreger A (2009). "Genetic testing in Israel: an overview". Annu Rev Genomics Hum Genet 10: 175–92. doi:10.1146/annurev.genom.030308.111406. PMID 19453249. 
  2. ^ a b Talia Bloch Sephardi Jews lack screening programs for their genetic diseases Haaretz 21/08/2009
  3. ^ a b Gina Kolata Nightmare or the Dream Of a New Era in Genetics? New York Times Tuesday, December 7, 1993
  4. ^ a b c d Ostrer H (November 2001). "A genetic profile of contemporary Jewish populations". Nat. Rev. Genet. 2 (11): 891–8. doi:10.1038/35098506. PMID 11715044. 
  5. ^ a b Levin M (1999). "Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses". Genet. Test. 3 (2): 207–13. PMID 10464669. 
  6. ^ Abel 2001, p. 7
  7. ^ Bachrach S (July 2004). "In the name of public health—Nazi racial hygiene". N. Engl. J. Med. 351 (5): 417–20. doi:10.1056/NEJMp048136. PMID 15282346. 
  8. ^ Abel 2001, p. 7
  9. ^ Modell B, Darr A (March 2002). "Science and society: genetic counselling and customary consanguineous marriage". Nat. Rev. Genet. 3 (3): 225–9. doi:10.1038/nrg754. PMID 11972160. 
  10. ^ Paul DB, Spencer HG (December 2008). ""It's ok, we're not cousins by blood": the cousin marriage controversy in historical perspective". PLoS Biol. 6 (12): 2627–30. doi:10.1371/journal.pbio.0060320. PMID 19108607. 
  11. ^ Carmeli, Daphna Birenbaum (2004). "Prevalence of Jews as subjects in genetic research: Figures, explanation, and potential implications". American Journal of Medical Genetics 130a (1): 76–83. doi:10.1002/ajmg.a.20291. 
  12. ^ Motulsky AG (February 1995). "Jewish diseases and origins". Nat. Genet. 9 (2): 99–101. doi:10.1038/ng0295-99. PMID 7719352. 
  13. ^ Atzmon G, Schechter C, Greiner W, Davidson D, Rennert G, Barzilai N (February 2004). "Clinical phenotype of families with longevity". J Am Geriatr Soc 52 (2): 274–7. PMID 14728640. 
  14. ^ Atzmon G, Cho M, Cawthon RM, et al. (November 2009). "Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians". Proc. Natl. Acad. Sci. U.S.A.. doi:10.1073/pnas.0906191106. PMID 19915151. 
  15. ^ Nicholas Wade Diseases Common in Ashkenazim May Be Random New York Times March 4, 2003
  16. ^ Orr-Urtreger A, Shifrin C, Rozovski U, et al. (October 2007). "The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect?". Neurology 69 (16): 1595–602. doi:10.1212/01.wnl.0000277637.33328.d8. PMID 17938369. 
  17. ^ "Tay–Sachs Disease Information Page". National Institute of Neurological Disorders and Stroke. February 14, 2007. Retrieved May 25, 2008. 
  18. ^ Sutton VR (June 2002). "Tay–Sachs disease screening and counseling families at risk for metabolic disease". Obstet. Gynecol. Clin. North Am. 29 (2): 287–96. PMID 12108829. 
  19. ^ Buckles, Julie (August 20, 2001). "The Success Story of Gene Tests". Genome News Network, J. Craig Venter Institute. Retrieved April 14, 2008. 
  20. ^ Diaz GA, Gelb BD, Risch N, et al. (2000). "Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations". Am. J. Hum. Genet. 66 (6): 1821–32. doi:10.1086/302946. PMID 10777718. '
  21. ^ "National Gaucher Foundation". Retrieved May 30, 2007. 
  22. ^ "Mount Sinai – Center for Jewish Genetic Diseases – Department of Human Genetics". 
  23. ^ Ashkenazi Disorders: Mendelian – Niemann–Pick disease: from The Chicago Center for Jewish Genetic Disorders
  24. ^ Boas FE (August 2000). "Linkage to Gaucher mutations in the Ashkenazi population: effect of drift on decay of linkage disequilibrium and evidence for heterozygote selection". Blood Cells Mol. Dis. 26 (4): 348–59. doi:10.1006/bcmd.2000.0314. PMID 11042036. 
  25. ^ Harpending H, Cochran G (March 2006). "Genetic diversity and genetic burden in humans". Infect. Genet. Evol. 6 (2): 154–62. doi:10.1016/j.meegid.2005.04.002. PMID 16246638. 
  26. ^ Wade, Nicholas. Researchers Say Intelligence and Diseases May Be Linked in Ashkenazic Genes, The New York Times, June 3, 2005. Retrieved February 12, 2007.
  27. ^ Cochran G, Hardy J, Harpending H (September 2006). "Natural history of Ashkenazi intelligence". J Biosoc Sci 38 (5): 659–93. doi:10.1017/S0021932005027069. PMID 16867211. 
  28. ^ Risch N, Tang H, Katzenstein H, Ekstein J (April 2003). "Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection". Am. J. Hum. Genet. 72 (4): 812–22. doi:10.1086/373882. PMID 12612865. 
  29. ^ Ashkenazi Disorders: Mendelian – Familial dysautonomia: from The Chicago Center for Jewish Genetic Disorders
  30. ^ about 1 in 30 Ashkenazi Jews carry the disease, compared to 1 in 3000 of the general population
  31. ^ Ashkenazi Jews and Colorectal Cancer: from The Chicago Center for Jewish Genetic Disorders
  32. ^ Ashkenazi Disorders: Mendelian – Non-Classical Adrenal Hyperplasia
  33. ^ Congenital insensitivity to pain with anhydrosis in a Malaysian family: a genetic analysis, Journal of Orthopedic Surgery 2007;15(3):357-60, "Type III is familial dysautonomia or Riley–Day syndrome. It is multisystemic and affects mainly Ashkenazi Jews."
  34. ^ "Large multicenter study suggests new genetic markers for Crohn's disease: Results shed light on special genetic vulnerabilities of Ashkenazi Jews"
  35. ^ "Epidemiological study of classic Kaposi's sarcoma: a retrospective review of 125 cases from Northern Israel"
  36. ^ Ashkenazi Jewish Diseases: Tufts Medical Center
  37. ^ Ashkenazi Disorders: Mendelian – Mucolipidosis IV: from The Chicago Center for Jewish Genetic Disorders
  38. ^ Ashkenazi Disorders: Mendelian – Nonsyndromic Hearing Loss and Deafness, DFNB1 (Connexin 26): from The Chicago Center for Jewish Genetic Disorders
  39. ^ Ozelius et al. 2006, G2019S as a cause of Parkinson's disease in Ashkenazi Jews
  40. ^ Klein J, Sato A (September 2000). "The HLA system. Second of two parts". N. Engl. J. Med. 343 (11): 782–6. doi:10.1056/NEJM200009143431106. PMID 10984567. 
  41. ^ Glycogen Storage Disease Type Ia Mutation Analysis (Ashkenazi Jewish)"
  42. ^ "A new autosomal recessive syndrome with Zellweger-like manifestations" – "A son and daughter of consanguineous Ashkenazi Jewish parents presented with phenotypic features that are typically seen in Zellweger syndrome..."
  43. ^ Kaback MM (December 2000). "Population-based genetic screening for reproductive counseling: the Tay–Sachs disease model". Eur. J. Pediatr. 159 Suppl 3: S192–5. PMID 11216898. 
  44. ^ Kronn D, Jansen V, Ostrer H (April 1998). "Carrier screening for cystic fibrosis, Gaucher disease, and Tay–Sachs disease in the Ashkenazi Jewish population: the first 1000 cases at New York University Medical Center, New York, NY". Arch. Intern. Med. 158 (7): 777–81. PMID 9554684. 
  45. ^ ACOG committee on genetics (October 2009). "ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent.". Obstet. Gynecol. 114 (4): 950-3. PMID 19888064. 
  46. ^ a b Ekstein J, Katzenstein H (2001). "The Dor Yeshorim story: community-based carrier screening for Tay-Sachs disease". Adv. Genet. 44: 297–310. PMID 11596991. 

Further reading

  • Abel, Ernest L. (2001). Jewish genetic disorders: a layman's guide. Jefferson, N.C: McFarland. ISBN 0-7864-0941-X. 
  • Goodman, Richard Alan (1979). Genetic disorders among the Jewish people. Baltimore: Johns Hopkins University Press. ISBN 0-8018-2120-7. 
  • Goldstein, David I. (2009). Jacob's Legacy: A Genetic View of Jewish History. New Haven, Conn: Yale University Press. ISBN 0-300-15128-4. 

External links


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