Medical genetics of Jews

There are several autosomal recessive genetic disorders that are more common in ethnically Jewish populations, particularly Ashkenazi Jews, than the population as a whole. This is due to population bottlenecks that occurred relatively recently in the past as well as a practice of consanguineous marriage. These two phenomena lead to a decrease in genetic diversity and a higher likelihood 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, as the phenomenon affects them the most. This has resulted in the discovery of many genetic disorders associated with this ethnic group. In contrast, the medical genetics of Sephardic Jews and Mizrahi Jews are more complicated, since they are more genetically diverse, and consequently 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 non-Jewish organizations, such as Dor Yeshorim, 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.

Nazism and Controversy

Further information: Nazism

This field of study was identified as Nazism by International Law following the Holocaust through the Berlin Agreements and Potsdam Conference of 1945 creating a good deal of controversy on the subject. Though the Nazi Party was not the first to being stereotyping Jews and other minorities with genetic defects the Nazi Party was pivotal in providing eugenics studies present in this article with it's credibility by including it as a fundamental part of the Nazi political belief system to demonize Jews by law under the Nuremberg Laws as well as create a basis for hate by incorporating such "science" in the national curriculum. In fact to this very day such ideologies such as attributing genetic disorders in greater or lesser amounts to Jew as well as other minorities is defined as "Nazism" by most major dictionaries.

This rhetoric of belief was not only outlawed internationally by law, but also was disproven during the Nazi era as well as today resulting in a large protest from the Jewish community of such studies taking place. In Israel the Hebrew University in Jerusalem has continually built upon the works of the scientist who dispelled the fabricated claims made by Nazi ecumenists since the end of the Holocaust. Additionally the Israeli Supreme Court has weighed in on this several times in order to construct the Law of Return which does not recognize genetics as having a role in determining someone's Jewish character. While hammering out the Israeli Law of Return the question of using genetics was considered and rejected by the court as Israeli Chief Justice Chaim Cohen said, “It is one of the bitterest ironies of the State that the same racist approach that was propagated by the Nazis and characterized the infamous Nuremburg laws should, because of an alleged sacrosanct Jewish tradition, become the basis for official determination or rejection of Jewishness in the State of Israel.”. Chief Rabbi David Lau of the Israeli Rabbinate was quoted on this subject of including genetics as a means for verification of Jewish identity in 2019 saying, “We would never force someone to do this though. And it should be emphasized that a DNA test is not used to determine Jewish status in accordance with Jewish law and only to assist in the clarification [process].” after seeking a DNA test to confirm the identity of couple seeking marriage who had already supplied proof of Judaism through the appropriate measures.

This question was also answered by the US Supreme Court who struck down the ideology in the gene patent case of 2013 affirming that within the USA there is no proof of there being a Jewish Gene or other common genetic variation found among Jews of any variety. Following this determination by the US Supreme Court the Jewish Federation of San Diego attempted to launch an investigation into the practice of dropping those who did not voluntarily identify as Jewish from all genetic studies creating a bias within data collection in order to obtain a desired result. The case to have the rhetoric removed was not selected resulting in the curriculum remaining in place in California as well as nationally. Then in 2019 Hayden B. Siegel opened a case with the Office of Civil Rights to review the inclusion of Nazism (genetic studies on minorities) in the National Curriculum of the United States but again the case was not selected for review due to jurisdictional reasons citing internal departmental bias and antisemitism.

The majority of the controversy revolves around the "science" used to establish a link between Jews as well as other minorities and genetic disorders being unverified. For example in this Wikipedia article's citations there is there is no methodology for verification of Jewishness of study participants included but rather the opposite of admissions that the studies were formed entirely on self-reported data and assumptions. Moreover there is proof that no such genetic characteristic could exist by people who are verifiably Jewish calling into question the credibility of those who assert, without any verification method being included, that Jews are any more or less afflicted by any given genetic disorder. Additionally those who have created studies which identified Jews as carriers of any form of genetic whether it be positive or negative have consistently been identified by the Anti-Defamation League and other Jewish Civil Rights agencies as antisemites such as Nobel Prize Winner James Watson. James Watson was later stripped of his Nobel for his antisemitic views resulting in the appointment of Eric Landers by President Biden being called into question by the Jewish community of America due to his friendship with James Watson as well as citions of his work in several papers which echoed the antisemitic beliefs of the former Nobel Prize winner.

Genetics of Jewish populations

Further information: Genetic studies on Jews

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. 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.

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. 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.

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 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 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

Due to their historical endogamy over the centuries, today's 10 million Ashkenazi Jews can trace their ancestry to members of a population of only 350 individuals who lived about 600–800 years ago. That population derived from both Europe and the Middle East. There is evidence that the population bottleneck may have allowed deleterious alleles to become more prevalent in the population due to genetic drift. As a result, this group has been particularly intensively studied, so many mutations have been identified as common in Ashkenazim. 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 Ashkenazim, which is their most common genetic disease, but only one of these mutations is found in non-Jewish groups. A few diseases are unique to this group; for example, familial dysautonomia is almost unknown in other populations.

Genetic disorders common in Ashkenazi Jews

Disease	Mode of inheritance	Gene	Carrier frequency
Favism	X-linked	G6PD
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 OHase deficiency	Autosomal recessive	CPY21	1/6
Parkinson's disease	Autosomal dominant	LRRK2	1/42
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, 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.

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 sufferers 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.

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:

• 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

Non-Ashkenazi disorders

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, Iraq, India, and Yemen, with specific genetic disorders found in each regional group, or even in specific subpopulations in these regions.

Genetic disorders common in Sephardic and Mizrahi Jews

Disease	Mode of inheritance	Gene or enzyme	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	1/5–7	All MENA (Middle Eastern and North African countries).
Glycogen storage disease III	Autosomal recessive	AGL	1/35	Morocco, North Africa
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 Mizrahi Jews

Disease	Mode of inheritance	Gene or enzyme	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, but heterozygous carriers also can show clinical manifestations.	MEFV	1/5–1/7	Iraq, Iran, Armenia, North African Jews, Ashkenazi
Glucose-6-phosphate dehydrogenase deficiency	X-linked	G6PD	1/4	Iraq, esp. Kurdistan, Syria and all MENA countries. Female heterozygotes can also show clinical symptoms due to lyonization (X-inactivation) especially during pregnancy.
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. 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 four or five per year. 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. In the US, these screening programs have been widely accepted by the Ashkenazi community, and have greatly reduced the frequency of the disorders.

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 and 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 disease, Canavan disease, cystic fibrosis, and familial dysautonomia as part of routine obstetrical care.

In the orthodox community, an organization called Dor Yeshorim carries out anonymous genetic screening of couples before marriage to reduce the risk of children with genetic diseases being born. 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 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. However, this program has 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 disease.

See also

• Ethnicity and health
• Finnish heritage disease
• Genetic studies on Jews
• Jewish genealogy
• Jewish medical ethics
• Health status of Asian Americans
• Health of Filipino Americans

Further reading

• Abel EL (2001). Jewish genetic disorders: a layman's guide. Jefferson, N.C: McFarland. ISBN 0-7864-0941-X.
• Goodman RM (1979). Genetic disorders among the Jewish people. Baltimore: Johns Hopkins University Press. ISBN 0-8018-2120-7.
• Goldstein DI (2009). Jacob's Legacy: A Genetic View of Jewish History. New Haven, Conn: Yale University Press. ISBN 978-0-300-15128-2.
• Guha S, Rosenfeld JA, Malhotra AK, Lee AT, Gregersen PK, Kane JM, Pe'er I, Darvasi A, Lencz T (January 2012). "Implications for health and disease in the genetic signature of the Ashkenazi Jewish population". Genome Biology. 13 (1): R2. doi:10.1186/gb-2012-13-1-r2. PMC 3334583. PMID 22277159.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

• Chicago Center for Jewish Genetic Disorders
• Ashkenazi Jews – The Hebrew University of Jerusalem
• Jewish Diseases Genetic Testing – The Center for Medical Genetics
• Ashkenazi Jewish Genetic Diseases – Victor Center for Jewish Genetic Diseases
• Ashkenazi Jewish Diseases – Tufts Medical Center
• Jewish Genetic Disease Consortium
• Center for Jewish Genetic Diseases – Mount Sinai Medical Center
• Mendelian disorders among Jews – Israeli National Genetic Database
• Studies Show Jews’ Genetic Similarity by The New York Times