Medical genetics of Jewish people

Medical genetics of Jewish people

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, such as Dor Yeshorim,[3] offer screening for Ashkenazi genetic diseases, and these screening programs have had a significant impact, in particular by reducing the number of cases of Tay–Sachs disease.[4]

Contents

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.[6] 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.[8] 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.[9]

According to Daphna Birenbaum Carmeli at the University of Haifa, Jewish populations have been studied more thoroughly than most other human populations because:[10]

  • 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."[10] 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.[11]

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.[12] This "healthy aging" phenotype may be due to higher levels of telomerase in these individuals.[13]

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.[14] 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 dominant LRRK2 1/42[15]
 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,[16] although high levels of the disease are also found in some Pennsylvania Dutch, Southern Louisiana Cajun and Eastern Quebec French Canadian populations.[17] Since the 1970s, however, proactive genetic testing has been quite effective in eliminating Tay–Sachs from the Ashkenazi Jewish population.[18]

Lipid transport diseases

Gaucher's disease, in which lipids accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews;[19] the disease is carried by roughly 1 in every 15 Ashkenazi Jews, compared to 1 in 100 of the general American population.[20] 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.[21] and Niemann–Pick disease, which can prove fatal.[22] 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.[23]

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).[24] 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).[25][26] 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.[27]

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;[28] Ashkenazi Jews are almost 100 times more likely to carry the disease than anyone else.[29]

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, Portugal, Morocco, Tunisia, Algeria, 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 PAH 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.[44] 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.[45]

Prenatal testing for several genetic diseases is offered as commercial panels for Ashkenazi couples by both CIGNA and Quest Diagnostics. The CIGNA panel is available for testing for parental/preconception screening or following chorionic 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.[46]

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.[47] 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. It is not divulged if one member is a carrier, so as to protect the carrier and his or her family from stigmatization.[47] 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 disorders such as Gaucher's disease.[3]

See also

Related:

References

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  41. ^ Glycogen Storage Disease Type Ia Mutation Analysis (Ashkenazi Jewish)"
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Further reading

  • Abel, Ernest L. (2001). Jewish genetic disorders: a layman's guide. Jefferson, N.C: McFarland. ISBN 0-7864-0941-X. 
  • Goodman, Richard M. (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. 

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