Ashkenazi diseases[edit]
Although there is no reason to think that the Ashkenazi Jewish population has any more or fewer mutations than other ethnic groups, evidence for a significant population bottleneck suggests that deleterious alleles may have become more prevalent in the population due to genetic drift.[14] As a result, this group has been particularly intensively-studied, so many mutations have been identified as common in Ashkenazis.[15] 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[16]
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[edit]
Tay–Sachs disease, a fatal illness of children that causes mental deterioration prior to death, was historically more prevalent among Ashkenazi Jews,[17] although high levels of the disease are also found in some Pennsylvania Dutch, Southern Louisiana Cajun and Eastern Quebec French Canadian populations.[18] Since the 1970s, however, proactive genetic testing has been quite effective in eliminating Tay–Sachs from the Ashkenazi Jewish population.[19]
Lipid transport diseases[edit]
Gaucher's disease, in which lipids accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews;[20] the disease is carried by roughly 1 in every 15 Ashkenazi Jews, compared to 1 in 100 of the general American population.[21] 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[22] and Niemann–Pick disease,[23] the latter of which can prove fatal.
The occurrence of several lysosomal storage disorders in the same population suggests that the alleles responsible might have conferred some selective advantage in the past.[24] 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.[25]
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).[26][27] 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 any specific selectivity towards lysosomal disorders.[28]
Familial dysautonomia[edit]
Familial dysautonomia (Riley–Day Syndrome), which causes vomiting, speech problems, an inability to cry, and false sensory perception, is almost exclusive to Ashkenazi Jews;[29] Ashkenazi Jews are almost 100 times more likely to carry the disease than anyone else.[30]
Other Ashkenazi diseases and disorders[edit]
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:
Colorectal cancer due to hereditary nonpolyposis colorectal cancer (HNPCC) [31]
Congenital adrenal hyperplasia (non-classical form) [32]
Congenital insensitivity to pain with anhidrosis (CIPA)[33]
Crohn's disease (the NOD2/CARD15 locus appears to be implicated) [34]
Kaposi's sarcoma[35]
Maple Syrup Urine Disease [36]
Mucolipidosis IV [37]
Nonsyndromic hearing loss and deafness, DFNB1 (Connexin 26) [38]
Parkinson's disease (G2019S/LRRK2 mutation).[39] 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".[40][41]
Pemphigus vulgaris[42]
Von Gierke disease[43]
Zellweger syndrome [44]
Bookmarks