Medical genetics of Jews

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. 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, such as Dor Yeshorim, 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. 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 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.

Disease	Subspecialty	Mode of inheritance	Gene	Carrier frequency
Favism	Medical genetics	X-linked	G6PD
Bloom syndrome	Medical genetics	Autosomal recessive	BLM	1/100
Breast cancer and ovarian cancer	Oncology	Autosomal dominant	BRCA1 or BRCA2	1/100 and 1/75, respectively
Canavan disease	Endocrinology, neurology	Autosomal recessive	ASPA	1/60
Congenital deafness	Neurology, otorhinolaryngology, audiology	Autosomal recessive	GJB2 or GJB6	1/25
Cystic fibrosis	Pulmonology, hepatology	Autosomal recessive	CFTR	1/25
Haemophilia C	Hematology	Autosomal recessive	F11	1/12
Familial dysautonomia	Neurology	Autosomal recessive	IKBKAP	1/30
Familial hypercholesterolemia	Endocrinology, chemical pathology	Autosomal dominant	LDLR	1/69
Familial hyperinsulinism	Gastroenterology, endocrinology, pediatrics	Autosomal recessive	ABCC8	1/125–1/160
Fanconi anemia C	Hematology	Autosomal recessive	FACC	1/100
Gaucher disease	Endocrinology, neurology	Autosomal recessive	GBA	1/7–1/18
Glycogen Storage Disease type 1a	Endocrinology, hematology, immunology	Autosomal recessive	G6PC	1/71
Mucolipidosis IV	Endocrinology	Autosomal recessive	MCOLN1	1/110
Niemann–Pick	Medical genetics	Autosomal recessive	SMPD1	1/90
Nonclassical 21 OHase deficiency	Endocrinology	Autosomal recessive	CPY21	1/6
Parkinson's disease	Neurology	Autosomal dominant	LRRK2	1/42
Tay–Sachs	Medical genetics	Autosomal recessive	HEXA	1/25–1/30
Torsion dystonia	Neurology	Autosomal dominant	DYT1	1/4000
Usher syndrome	Ophthalmology	Autosomal recessive	PCDH15	1/72
Warsaw breakage syndrome	Medical genetics, pediatrics	Autosomal recessive	DDX11	1/50

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

, 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

, 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:

Alport syndrome
Colorectal cancer due to hereditary nonpolyposis colorectal cancer
Congenital adrenal hyperplasia
Congenital insensitivity to pain with anhidrosis
Crohn's disease
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
Parkinson's disease
Pemphigus vulgaris
Schizophrenia
Von Gierke disease
Zellweger syndrome