Medical genetics of Jewish people
Encyclopedia
The medical genetics of Jewish people is the study, screening and treatment of genetic disorder
s that are more common in particular Jewish populations than in the population as a whole. 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. Several 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.
, even being described in the Talmud
. 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.
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, 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.
However, most populations contain hundreds of allele
s 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 more thoroughly than most other human populations because:
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." 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.
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. This "healthy aging" phenotype may be due to higher levels of telomerase
in these individuals.
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. A few diseases are unique to this group: for example familial dysautonomia
is almost unknown in other populations.
, although high levels of the disease are also found in some Pennsylvania Dutch, Southern Louisiana Cajun and Eastern Quebec French Canadian populations. Since the 1970s, however, proactive genetic testing has been quite effective in eliminating Tay–Sachs from the Ashkenazi Jewish population.
, in which lipid
s accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews; the disease is carried by roughly 1 in every 15 Ashkenazi Jews, compared to 1 in 100 of the general American population. Gaucher's disease can cause brain damage
and seizure
s, 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 disease
s, particularly in the form of lipid storage disorder
s. They more frequently act as carriers of mucolipidosis
, than do other ethnic groups. and Niemann–Pick disease, which can prove fatal. 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.
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
). 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
). 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.
(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.
populations. Among Ashkenazi Jews, a higher incidence of specific genetic disorders and hereditary disease
s have been verified, including:
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 4–5 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 USA, 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 & 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.
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. 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. 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.
Related:
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s that are more common in particular Jewish populations than in the population as a whole. The genetics of Ashkenazi Jews
Ashkenazi Jews
Ashkenazi Jews, also known as Ashkenazic Jews or Ashkenazim , are the Jews descended from the medieval Jewish communities along the Rhine in Germany from Alsace in the south to the Rhineland in the north. Ashkenaz is the medieval Hebrew name for this region and thus for Germany...
have been particularly well-studied, resulting in the discovery of many genetic disorders that are associated with this ethnic group
Ethnic group
An ethnic group is a group of people whose members identify with each other, through a common heritage, often consisting of a common language, a common culture and/or an ideology that stresses common ancestry or endogamy...
. 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. Several organizations, such as Dor Yeshorim
Dor Yeshorim
Dor Yeshorim , also called Committee for Prevention of Genetic Diseases, is an organization that offers genetic screening to members of the worldwide Jewish community...
, 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.
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 historyJewish history
Jewish history is the history of the Jews, their religion and culture, as it developed and interacted with other peoples, religions and cultures. Since Jewish history is over 4000 years long and includes hundreds of different populations, any treatment can only be provided in broad strokes...
, even being described in the Talmud
Talmud
The Talmud is a central text of mainstream Judaism. It takes the form of a record of rabbinic discussions pertaining to Jewish law, ethics, philosophy, customs and history....
. However, the scientific study of hereditary disease in Jewish populations was initially hindered by the shadow of the racist and unscientific ideas of eugenics
Eugenics
Eugenics is the "applied science or the bio-social movement which advocates the use of practices aimed at improving the genetic composition of a population", usually referring to human populations. The origins of the concept of eugenics began with certain interpretations of Mendelian inheritance,...
and "racial hygiene", which tried to describe various ethnic groups as inferior.
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, 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.
However, most populations contain hundreds of allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s that could potentially cause disease and most people are heterozygotes for one or two recessive
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
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
University of Haifa
The University of Haifa is a university in Haifa, Israel.The University of Haifa was founded in 1963 by Haifa mayor Abba Hushi, to operate under the academic auspices of the Hebrew University of Jerusalem....
, 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 endogamyEndogamyEndogamy is the practice of marrying within a specific ethnic group, class, or social group, rejecting others on such basis as being unsuitable for marriage or other close personal relationships. A Greek Orthodox Christian endogamist, for example, would require that a marriage be only with another...
, 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." 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.
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. This "healthy aging" phenotype may be due to higher levels of telomerase
Telomerase
Telomerase is an enzyme that adds DNA sequence repeats to the 3' end of DNA strands in the telomere regions, which are found at the ends of eukaryotic chromosomes. This region of repeated nucleotide called telomeres contains non-coding DNA material and prevents constant loss of important DNA from...
in these individuals.
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. 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 glucocerebrosidaseGlucocerebrosidase
β-Glucocerebrosidase is an enzyme with glucosylceramidase activity that is needed to cleave, by hydrolysis, the beta-glucosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism...
gene causes Gaucher's disease
Gaucher's disease
Gaucher's disease is a genetic disease in which a fatty substance accumulates in cells and certain organs.Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid...
in Ashkenazis, 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
Familial dysautonomia
Familial dysautonomia is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms including: insensitivity to pain, inability to produce...
is almost unknown in other populations.
| Disease | Mode of inheritance | Gene | Carrier frequency |
|---|---|---|---|
| Bloom syndrome Bloom syndrome Bloom's syndrome , also known as Bloom–Torre–Machacek syndrome, is a rare autosomal recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's chromosomes. The condition was discovered and first described by dermatologist Dr... |
Autosomal recessive | BLM Bloom syndrome protein Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is expressed in Bloom syndrome.The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities... |
1/100 |
| Breast cancer Breast cancer Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas... and ovarian cancer Ovarian cancer Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses.... |
Autosomal dominant | BRCA1 BRCA1 BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990... or BRCA2 BRCA2 BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available.... |
1/100 and 1/75, respectively |
| Canavan disease Canavan disease Canavan disease, also called Canavan-Van Bogaert-Bertrand disease, aspartoacylase deficiency or aminoacylase 2 deficiency, is an autosomal recessive degenerative disorder that causes progressive damage to nerve cells in the brain. Canavan disease is also one of the most common degenerative... |
Autosomal recessive | ASPA | 1/60 |
| Congenital deafness | Autosomal recessive | GJB2 GJB2 Gap junction beta-2 also known as connexin-26 is a protein that in humans is encoded by the GJB2 gene. Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1, also known as Connexin 26 deafness or GJB2-related deafness.- Function :Gap... or GJB6 |
1/25 |
| Cystic fibrosis Cystic fibrosis Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine... |
Autosomal recessive | CFTR Cystic fibrosis transmembrane conductance regulator Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes... |
1/25 |
| Haemophilia C Haemophilia C Haemophilia C is a mild form of haemophilia affecting both sexes. However, it predominantly occurs in Jews of Ashkenazi descent. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B... |
Autosomal recessive | F11 Factor XI Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene.... |
1/12 |
| Familial dysautonomia Familial dysautonomia Familial dysautonomia is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms including: insensitivity to pain, inability to produce... |
Autosomal recessive | IKBKAP IKBKAP IKBKAP is a human gene that provides instructions to make the IKAP protein, which is found in a variety of cells throughout the body, including brain cells... |
1/30 |
| Familial hypercholesterolemia Familial hypercholesterolemia Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein , in the blood and early cardiovascular disease... |
Autosomal dominant | LDLR | 1/69 |
| Familial hyperinsulinism | Autosomal recessive | ABCC8 ABCC8 ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.-External links:* *... |
1/125–1/160 |
| Fanconi anemia C Fanconi anemia Fanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair... |
Autosomal recessive | FACC | 1/100 |
| Gaucher disease | Autosomal recessive | GBA Glucocerebrosidase β-Glucocerebrosidase is an enzyme with glucosylceramidase activity that is needed to cleave, by hydrolysis, the beta-glucosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism... |
1/7–1/18 |
| Glycogen Storage Disease type 1a Glycogen storage disease type I Glycogen storage disease type I or von Gierke's disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase. This deficiency impairs the ability of the liver to produce free glucose from glycogen and from... |
Autosomal recessive | G6PC G6PC Glucose-6-phosphatase is an enzyme that in humans is encoded by the G6PC gene.-Further reading:... |
1/71 |
| Mucolipidosis IV | Autosomal recessive | MCOLN1 | 1/110 |
| Niemann–Pick (type A) | Autosomal recessive | SMPD1 | 1/90 |
| Nonclassical 21 OH deficiency Congenital adrenal hyperplasia due to 21-hydroxylase deficiency Congenital adrenal hyperplasia due to 21-hydroxylase deficiency , in all its forms, accounts for over 95% of diagnosed cases of congenital adrenal hyperplasia, and "CAH" in most contexts refers to 21-hydroxylase deficiency... |
Autosomal recessive | CPY21 | 1/6 |
| Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system... |
Autosomal dominant | LRRK2 LRRK2 Leucine-rich repeat kinase 2 , also known as dardarin, is an enzyme that in humans is encoded by the LRRK2 gene. LRRK2 is a member of the leucine-rich repeat kinase family... |
1/42 |
| Tay–Sachs | Autosomal recessive | HEXA HEXA Hexosaminidase A , also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene.Hexosaminidase A and the cofactor GM2 activator protein catalyze the degradation of the GM2 gangliosides and other molecules containing terminal N-acetyl hexosamines... |
1/25–1/30 |
| Torsion dystonia Torsion dystonia Torsion dystonia is a disease characterized by painful muscle contractions resulting in uncontrollable distortions. This specific type of dystonia is found in children, with symptoms starting around the ages of 11 or 12. It commonly begins with contractions in one general area such as an arm or a... |
Autosomal dominant | DYT1 | 1/4000 |
| Usher syndrome Usher syndrome Usher syndrome is a relatively rare genetic disorder that is a leading cause of deafblindness and that is associated with a mutation in any one of 10 genes. Other names for Usher syndrome include Hallgren syndrome, Usher-Hallgren syndrome, rp-dysacusis syndrome and dystrophia retinae dysacusis... |
Autosomal recessive | PCDH15 PCDH15 Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.-External Links:* -Further reading:... |
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 JewsAshkenazi Jews
Ashkenazi Jews, also known as Ashkenazic Jews or Ashkenazim , are the Jews descended from the medieval Jewish communities along the Rhine in Germany from Alsace in the south to the Rhineland in the north. Ashkenaz is the medieval Hebrew name for this region and thus for Germany...
, although high levels of the disease are also found in some Pennsylvania Dutch, Southern Louisiana Cajun and Eastern Quebec French Canadian populations. 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 diseaseGaucher's disease
Gaucher's disease is a genetic disease in which a fatty substance accumulates in cells and certain organs.Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid...
, in which lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews; the disease is carried by roughly 1 in every 15 Ashkenazi Jews, compared to 1 in 100 of the general American population. Gaucher's disease can cause brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
and seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, 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
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, although it generally has only a minor impact on life expectancy.
Ashkenazi Jews are also highly affected by other lysosomal storage disease
Lysosomal storage disease
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function...
s, particularly in the form of lipid storage disorder
Lipid storage disorder
Lipid storage disorders are a group of inherited metabolic disorders in which harmful amounts of lipids accumulate in some of the body’s cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize lipids or they produce enzymes that do...
s. They more frequently act as carriers of mucolipidosis
Mucolipidosis
Mucolipidosis is a group of inherited metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cells....
, than do other ethnic groups. and Niemann–Pick disease, which can prove fatal. The occurrence of several lysosomal storage disorders in the same population suggested the idea that the alleles responsible might have conferred some selective advantage
Selection
In the context of evolution, certain traits or alleles of genes segregating within a population may be subject to selection. Under selection, individuals with advantageous or "adaptive" traits tend to be more successful than their peers reproductively—meaning they contribute more offspring to the...
in the past.
This would be similar to the partial immunity to malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
that is conferred by having one copy of the allele that causes sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
in people with two copies of the allele (an effect called heterozygote advantage
Heterozygote advantage
A heterozygote advantage describes the case in which the heterozygote genotype has a higher relative fitness than either the homozygote dominant or homozygote recessive genotype. The specific case of heterozygote advantage is due to a single locus known as overdominance...
). It has been proposed that some of these disorders became common in this population due to selection for high levels of intelligence
Intelligence
Intelligence has been defined in different ways, including the abilities for abstract thought, understanding, communication, reasoning, learning, planning, emotional intelligence and problem solving....
(see ashkenazi intelligence
Ashkenazi intelligence
Whether Ashkenazi Jews have higher intelligence than other ethnic groups has been an occasional subject of scientific controversy. The 2005 paper "Natural History of Ashkenazi Intelligence" by Cochran, Hardy, and Harpending, argued on the basis of inherited diseases and the peculiar economic...
). 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.
Familial dysautonomia
Familial dysautonomiaFamilial dysautonomia
Familial dysautonomia is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms including: insensitivity to pain, inability to produce...
(Riley–Day Syndrome), which causes vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, speech problems, an inability to cry
Cry
Cry usually refers to crying, the act of shedding tears.Cry may also refer to:* Cry, Yonne, a commune in France* CRY , worldwide non-profit organization-Songs:* "Cry" , 1951...
, 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 that are inherited in an autosomal recessive pattern often occur in endogamousEndogamy
Endogamy is the practice of marrying within a specific ethnic group, class, or social group, rejecting others on such basis as being unsuitable for marriage or other close personal relationships. A Greek Orthodox Christian endogamist, for example, would require that a marriage be only with another...
populations. Among Ashkenazi Jews, a higher incidence of specific genetic disorders and hereditary disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s have been verified, including:
- Colorectal cancerColorectal cancerColorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
due to hereditary nonpolyposis colorectal cancerHereditary nonpolyposis colorectal cancerLynch syndrome is an autosomal dominant genetic condition which has a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin...
(HNPCC) - Congenital adrenal hyperplasiaCongenital adrenal hyperplasiaCongenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
(non-classical form) - Congenital insensitivity to pain with anhidrosisCongenital insensitivity to pain with anhidrosisCongenital insensitivity to pain with anhidrosis is an extremely rare inherited disorder of the nervous system which prevents the sensation of pain, heat, cold, or any real nerve-related sensations ; however, patients can still feel pressure. CIPA is the fourth type of hereditary sensory and...
(CIPA) - Crohn's diseaseCrohn's diseaseCrohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
(the NOD2/CARD15 locus appears to be implicated) - Kaposi's sarcomaKaposi's sarcomaKaposi's sarcoma is a tumor caused by Human herpesvirus 8 , also known as Kaposi's sarcoma-associated herpesvirus . It was originally described by Moritz Kaposi , a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more widely known as one of the AIDS defining...
- Maple Syrup Urine DiseaseMaple syrup urine diseaseMaple syrup urine disease , also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia...
- Mucolipidosis IV
- Nonsyndromic hearing loss and deafness, DFNB1 (ConnexinConnexinConnexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions . Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules...
26) - Parkinson's diseaseParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
(G2019S/LRRK2 mutation). According to the most extensive and thorough study by Lesage et al. in 2010, estimations indicated that 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. According to the authors, 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 vulgarisPemphigus vulgarisPemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but which are often painful.-Pathophysiology:...
- Von Gierke disease
- Zellweger syndromeZellweger syndromeZellweger syndrome, also called cerebrohepatorenal syndrome is a rare, congenital disorder, characterized by the reduction or absence of functional peroxisomes in the cells of an individual. It is one of a family of disorders called leukodystrophies...
- Parkinson's diseaseParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
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.| Disease | Mode of inheritance | Gene | Carrier frequency | Populations |
|---|---|---|---|---|
| Oculocutaneous albinism Oculocutaneous albinism Oculocutaneous albinism is a form of albinism involving the eyes , skin , and in rare instances, the hair as well.Four types of oculocutaneous albinism have been described, all caused by a disruption of melanin synthesis and all autosomal recessive disorders.Common Albinism requires genes from both... |
Autosomal recessive | TYR Tyrosinase Tyrosinase also known as monophenol monooxygenase is an enzyme that catalyses the oxidation of phenols and is widespread in plants and animals... |
1/30 | Morocco |
| Ataxia telangiectasia Ataxia telangiectasia Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease... |
Autosomal recessive | ATM | 1/80 | Morocco, Tunisia |
| Creutzfeldt–Jakob disease | Autosomal dominant | PRNP PRNP Major prion protein also known as CD230 is a protein that in humans is encoded by the PRNP gene... |
1/24,000 | Libya |
| Cerebrotendinous xanthomatosis | Autosomal recessive | CYP27A1 CYP27A1 CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the mitochondria. It is most prominently involved in the biosynthesis of bile acids.-Function:CYP27A1 participates in the... |
1/70 | Morocco |
| Cystinuria Cystinuria Cystinuria is an inherited autosomal recessive disease that is characterized by the formation of cystine stones in the kidneys, ureter, and bladder.-Signs and symptoms:Cystinuria is a cause of persistent kidney stones... |
Autosomal recessive | SLC7A9 SLC7A9 Solute carrier family 7 , member 9 also known as SLC7A9 is a protein which in humans is encoded by the SLC7A9 gene.- Function :... |
1/25 | Libya |
| Familial Mediterranean fever Familial Mediterranean fever Familial Mediterranean fever is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin.... |
Autosomal recessive | MEFV MEFV MEFV is a human gene that provides instructions for making a protein called pyrin . Pyrin is produced in certain white blood cells that play a role in inflammation and in fighting infection... |
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 HEXA Hexosaminidase A , also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene.Hexosaminidase A and the cofactor GM2 activator protein catalyze the degradation of the GM2 gangliosides and other molecules containing terminal N-acetyl hexosamines... |
1/110 | Morocco |
| 11-β-hydroxylase deficiency | Autosomal recessive | CYP11B1 | 1/30–1/128 | Morocco |
| Disease | Mode of inheritance | Gene | Carrier frequency | Populations |
|---|---|---|---|---|
| Beta-thalassemia Beta-thalassemia Beta-thalassemias are a group of inherited blood disorders caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated... |
Autosomal recessive | HBB HBB Beta globin Beta globin Beta globin (HBB, β-globinprotin that, along with alpha globin (HBA), makes up the most common form of hemoglobin in adult humans. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains.-Gene locus:... |
1/6 | Iran, Iraq, Kurdistan |
| Factor VII deficiency | Autosomal recessive | F7 Factor VII Factor VII is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients... |
1/40 | Iran |
| Familial Mediterranean fever Familial Mediterranean fever Familial Mediterranean fever is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin.... |
Autosomal recessive | MEFV MEFV MEFV is a human gene that provides instructions for making a protein called pyrin . Pyrin is produced in certain white blood cells that play a role in inflammation and in fighting infection... |
1/5–1/7 | Iraq, Iran, Armenia, North-African Jews, Ashkenazi |
| Glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is... |
X-linked | G6PD | 1/4 | Iraq |
| Inclusion body myopathy | Autosomal recessive | GNE GNE (gene) Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is an enzyme that in humans is encoded by the GNE gene.-External links:*-Further reading:... |
1/12 | Iran |
| Metachromatic leukodystrophy Metachromatic leukodystrophy Metachromatic leukodystrophy is a lysosomal storage disease which is commonly listed in the family of leukodystrophies. Leukodystrophies affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibers throughout the central and peripheral nervous... |
Autosomal recessive | ARSA | 1/50 | Yemen |
| Oculopharyngeal muscular dystrophy Oculopharyngeal muscular dystrophy Oculopharyngeal muscular dystrophy is an autosomal dominant neuromuscular disease which appears in early middle age . OPMD is an example of a trinucleotide repeat disorder caused by expanding 10 to 11-17 at the 5' end of the coding region for PABPN1... |
Autosomal, recessive or dominant | PABPN1 PABPN1 Polyadenylate-binding protein 2 also known as polyadenylate-binding nuclear protein 1 is a protein that in humans is encoded by the PABPN1 gene.- Function :... |
1/7 | Bukhara |
| Phenylketonuria Phenylketonuria Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine... |
Autosomal recessive | PAH Phenylalanine hydroxylase Phenylalanine hydroxylase is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PheOH is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for... |
1/35 | Yemen |
Genetic testing in Jewish populations
One of the first genetic testingGenetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
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 4–5 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 USA, 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
CIGNA
Cigna , headquartered in Bloomfield, Connecticut, is a global health services company, owing to its expanding international footprint and the fact that it provides administrative services only to approximately 80 percent of its clients...
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.
In the orthodox community
Orthodox Judaism
Orthodox Judaism , is the approach to Judaism which adheres to the traditional interpretation and application of the laws and ethics of the Torah as legislated in the Talmudic texts by the Sanhedrin and subsequently developed and applied by the later authorities known as the Gaonim, Rishonim, and...
an organization called Dor Yeshorim
Dor Yeshorim
Dor Yeshorim , also called Committee for Prevention of Genetic Diseases, is an organization that offers genetic screening to members of the worldwide Jewish community...
carries out anonymous genetic screening of couples before marriage in order 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 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. 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.
See also
- Jewish medical ethicsJewish medical ethicsJewish medical ethics is a modern scholarly and clinical approach to medical ethics that draws upon Jewish thought and teachings. Pioneered by Rabbi Immanuel Jakobovits in the 1950s, Jewish medical ethics centers mainly around an applied ethics drawing upon traditional rabbinic law...
Related:
- Population groups in biomedicine
- Ethnicity and health
- Ancestry and health
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 TimesThe New York TimesThe New York Times is an American daily newspaper founded and continuously published in New York City since 1851. The New York Times has won 106 Pulitzer Prizes, the most of any news organization...