The medical genetics of Jews have been studied to identify and prevent some rare genetic diseases that, while still rare, are more common than average among people of Jewish descent. There are several autosomal recessive genetic disorders that are more common than average in ethnically Jewish populations, particularly Ashkenazi Jews, because of relatively recent population bottlenecks and because of consanguineous marriage (marriage of second cousins or closer). These two phenomena reduce genetic diversity and raise the chance that two parents will carry a mutation in the same gene and pass on both mutations to a child.
The genetics of Ashkenazi Jews have been particularly well studied because the phenomenon affects them the most. This has resulted in the discovery of many genetic disorders associated with this ethnic group. The medical genetics of Sephardic Jews and Mizrahi Jews are more complicated because they are genetically more diverse, and therefore no genetic disorders are more common in these groups as a whole; instead, they tend to have the genetic diseases common in their various countries of origin.
Several organizations offer screening for Ashkenazi genetic diseases, and these programs have done much, particularly by reducing the incidence of Tay–Sachs disease.
History and purpose Different ethnic groups tend to have 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. Jewish people started to see massive population reductions as they were isolated so much that in the end, Jewish people started to develop characteristics that would be passed down for centuries. This also limited genetic diversity between Jewish populations and created higher chances of certain inherited diseases. However, the scientific study of hereditary disease in Jewish populations was initially hindered by scientific racism, which was based on racial supremacism.
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. Consequently, some members of the Jewish community have been very supportive of modern genetic testing programs; this high level of cooperation has raised concerns that conclusions may lead to stigmatization of the Jewish community.
Genetics of Jewish populations
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. 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) has been common in some Jewish communities, which produces a small increase in the number of children with congenital defects.
According to Daphna Birenbaum Carmeli at the University of Haifa, Jewish populations have been studied thoroughly because: Jewish populations, and particularly the large Ashkenazi Jewish population, are ideal for such research studies, because they exhibit a high degree of endogamy, and at the same time are a large group. Jewish populations are overwhelmingly urban and are concentrated near biomedical centers where such research has been carried out.
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."
This set of advantages has 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 their longevity was strongly inherited and associated with lower rates of age-related diseases. This "healthy aging" phenotype may be due to higher levels of telomerase in these individuals.
Ashkenazi diseases Because of centuries of endogamy, today's ten million Ashkenazi Jews descend from a population of 350 who lived about 600–800 years ago. That population derived from both Europe and the Middle East. Some evidence shows that the population bottleneck may have allowed deleterious alleles to increase in the population by genetic drift.
This group has therefore been particularly intensively studied, and many mutations are common in Ashkenazim. Of these diseases, many also occur in other Jewish groups and non-Jewish populations, although the specific mutation that causes the disease may vary among populations. For example, two mutations in the glucocerebrosidase gene each cause Gaucher's disease in Ashkenazim, which is that group's most common genetic disease, but only one of these mutations is found in non-Jewish groups. A few diseases are unique to this group; familial dysautonomia, for example, is almost unknown in other peoples.
+ Genetic disorders common in Ashkenazi JewsDiseaseSubspecialtyMode of inheritanceGeneCarrier frequencyFavismMedical geneticsX-linkedG6PDBloom syndromeMedical geneticsAutosomal recessiveBLM1/100Breast cancer and ovarian cancerOncologyAutosomal dominantBRCA1 or BRCA21/100 and 1/75, respectivelyCanavan diseaseEndocrinology, neurologyAutosomal recessiveASPA1/60Congenital deafnessNeurology, otorhinolaryngology, audiologyAutosomal recessiveGJB2 or GJB61/25Cystic fibrosisPulmonology, hepatologyAutosomal recessiveCFTR1/25Haemophilia CHematologyAutosomal recessiveF111/12Familial dysautonomiaNeurologyAutosomal recessiveIKBKAP1/30Familial hypercholesterolemiaEndocrinology, chemical pathologyAutosomal dominantLDLR1/69Familial hyperinsulinismGastroenterology, endocrinology, pediatricsAutosomal recessiveABCC81/125–1/160Fanconi anemia CHematologyAutosomal recessiveFACC1/100Gaucher diseaseEndocrinology, neurologyAutosomal recessiveGBA1/7–1/18Glycogen Storage Disease type 1aEndocrinology, hematology, immunologyAutosomal recessiveG6PC1/71Mucolipidosis IV EndocrinologyAutosomal recessiveMCOLN11/110Niemann–Pick (type A)Medical geneticsAutosomal recessiveSMPD11/90Nonclassical 21 OHase deficiencyEndocrinologyAutosomal recessiveCPY211/6Parkinson's diseaseNeurologyAutosomal dominantLRRK21/42Tay–SachsMedical geneticsAutosomal recessiveHEXA1/25–1/30Torsion dystoniaNeurologyAutosomal dominantDYT11/4000Usher syndromeOphthalmologyAutosomal recessivePCDH151/72Warsaw breakage syndromeMedical genetics, pediatricsAutosomal recessiveDDX111/68
Tay–Sachs disease Tay–Sachs disease, which can present as a fatal illness of children that causes mental deterioration prior to death, was historically extremely common among Ashkenazi Jews, with lower levels of the disease in some Pennsylvania Dutch, Italian, Irish Catholic, and French Canadian descent, especially those living in the Cajun community of Louisiana and the southeastern Quebec. Since the 1970s, however, proactive genetic testing has been quite effective in eliminating Tay–Sachs from the Ashkenazi Jewish population. The first mass Tay-Sachs screening program for Ashkenazi Jews occurred in May of 1971 at Congregation Beth El, a Conservative Shul in Bethesda, Maryland.
Lipid transport diseases
Gaucher's disease, in which lipids accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews;' the mutation is carried by roughly one in every 15 Ashkenazi Jews, compared to one in 100 of the general American population. Gaucher's disease can cause brain damage and seizures, but these effects are not usually present in the form manifested among Ashkenazi Jews; while those affected still bruise easily, and it can still potentially rupture the spleen, 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. Compared to other ethnic groups, they more frequently act as carriers of mucolipidosis and Niemann–Pick disease, the latter of which can prove fatal.
The occurrence of several lysosomal storage disorders in the same population suggests the alleles responsible might have conferred some selective advantage in the past. This would be similar to the hemoglobin allele which is responsible for sickle-cell disease, but solely in people with two copies; those with just one copy of the allele have a sickle cell trait and gain partial immunity to malaria as a result. This effect is called heterozygote advantage.
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; Ashkenazi Jews are almost 100 times more likely to carry the disease than anyone else: about one in 30 Ashkenazi Jews carries the disease, compared to 1 in 3000 of the general population.
Other Ashkenazi diseases and disorders Diseases inherited in an autosomal recessive pattern often occur in endogamous populations. Among Ashkenazi Jews, a higher incidence of specific genetic disorders and hereditary diseases has been verified, including: Alport syndrome Colorectal cancer due to hereditary nonpolyposis colorectal cancer Congenital adrenal hyperplasia (nonclassical form) Congenital insensitivity to pain with anhidrosis Crohn's disease (the NOD2/CARD15 locus appears to be implicated) Joubert syndrome type 2 is disproportionately frequent among people of Jewish descent; this has been attributed to the resistance to intermarriage of this population. Kaposi's sarcoma Maple syrup urine disease Mucolipidosis IV Myeloproliferative neoplasms including polycythemia vera and essential thrombocythemia Nonsyndromic hearing loss and deafness, DFNB1 (connexin 26) Parkinson's disease (G2019S/LRRK2 mutation; The LRRK2 mutation on the main haplotype, shared by Ashkenazi Jews, North Africans, and Europeans, initially arose in the Near East at least 4000 years ago. Because of a founder effect, the ancestors of present-day Ashkenazi Jews may have kept the low-frequency G2019S mutation through the different diasporas, whereas Near Eastern daughter populations lost the mutation. The mutation might then have been "reintroduced by recurrent gene flow from Ashkenazi populations to other Jewish, European, and North African populations. The present-day frequency of the mutation in control populations (0.05% in Europeans, 0.5% in North-African Arabs and 1% in Ashkenazi Jews) may support this scenario".) Pemphigus vulgaris Schizophrenia (NDST3 gene variation) Von Gierke disease Zellweger syndrome
Sephardi and Mizrahi diseases In contrast to the Ashkenazi population, Sephardic and Mizrahi Jews are much more divergent groups, with ancestors from Spain, Portugal, Morocco, Tunisia, Algeria, Italy, Libya, the Balkans, Iran, Kurdistan, Turkey, India, and Yemen, with specific genetic disorders found in each regional group, or even in specific subpopulations in these regions.