Jewish diseases are rare genetic disorders that occur more often in individuals who are of Jewish descent than in the general population. The diseases in this panel do occur in people of all ethnic backgrounds but are more common in people of Ashkenazi Jewish background. The genetics of Ashkenazi Jewish people have been well studied, due to a number of skilled Jewish geneticists with an interest in inherited diseases and the willingness of the Jewish people to understand, and prevent, these diseases. All of these diseases are inherited in an autosomal recessive pattern, which means two copies of a defective gene must be inherited before disease symptoms manifest. Disease carriers are people that carry just one defective copy of the specific disease-associated gene (and one normal copy) and do not show any symptoms, but can still pass the defective gene to the next generation. Some of the diseases in this panel are very severe and fatal at a young age (e.g. Tay-Sachs disease), while others can be effectively managed, particularly if diagnosed at a young age (e.g. maple syrup urine disease).
Why are these Diseases more Common in People with Ashkenazi Jewish Heritage?
As with all other inherited genetic disorders, changes in specific genes cause the genetic diseases that occur more commonly in people with Ashkenazi Jewish ancestry. These diseases are more common in poeple of Ashkenazi Jewish heritage because of two main reasons, the founder effect and genetic drift.
The founder effect happens when a small number of people (from an original larger population), known as ‘founders’, give rise to a large population of people in a fairly short period of time. These founders had minor genetic defects that were amplified over time, causing many of the Ashkenazi Jewish individuals to be affected by, or become carriers of, genetic diseases. Although carriers themselves do not show any disease symptoms, if two carriers have a child, there is a 25% chance that their child will inherit two copies of the defective gene and suffer from the disease. Many ethnic groups (including Ashkenazi Jewish people) marry within their ethnic group for cultural and/or religious reasons and these populations become genetically isolated. There is no new, different DNA introduced into the group to dilute out the disease alleles so the disease alleles remain at higher frequencies within the population.
Genetic drift is the change in frequency of a specific gene variant or allele in a population. Different alleles (e.g. disease allele versus normal allele) are randomly sampled from each parent. Carriers have a 50% chance of passing the defective disease allele to the next generation but this is just a ‘chance’ and by no means an accurate value. For example, a carrier could easily pass the disease allele to all of his or her children, or to only half their children, or not pass the disease allele on at all. This random sampling can affect the frequency of a specific disease allele. In large populations, this random sampling tends to even itself out so the allele frequencies do not change much. However, in smaller, genetically isolated populations, (such as Ashkenazi Jews) specific alleles (e.g. disease alleles) can easily become more prevalent in the population just by chance.
Genetics of Jewish Diseases
All of the Jewish genetic diseases tested in this panel are autosomal recessive. Autosomal indicates that the disease-associated gene is located on an autosome. We each have 22 pairs of autosomes and two sex chromosomes. We inherit two copies of every gene located on an autosome, one from each parent. Recessive indicates that two copies of the defective disease allele are required before disease symptoms occur – i.e. inheriting one defective disease allele from each parent. People that carry one disease allele and one normal allele for a disease-associated gene are unaffected and known as carriers.
Approximately 25% of people of Ashkenazi Jewish ancestry are carriers for a genetic change that can cause a Jewish disease. This frequency is slightly higher in the US, where between 1 in 2 and 1 in 3 people of Ashkenazi Jewish heritage are estimated to be carriers. When two carriers of a specific disease have a child, there is a 25% chance that the child will inherit a defective disease allele from each parent and be affected by the disease. There is also a 50% chance that the child will only inherit one defective disease allele and also be a carrier, and there is a 25% that the child will inherit two normal alleles and be unaffected and not carry the disease allele.
Carrier status is very important for people of Ashkenazi Jewish heritage because of the high carrier frequency, so the chance of two carriers meeting and choosing to have children is much higher than in the general population. Carrier screening and genetic counseling is recommended for people who are of Ashkenazi Jewish descent choosing to have children.
Gaucher disease, Tay-Sachs disease, familial dysautonomia, Canavan disease and cystic fibrosis are the most common genetic diseases affecting people of Ashkenazi Jewish heritage. Cystic fibrosis is one of the most common life-threatening inherited genetic disorders in Caucasians worldwide with a carrier frequency of up to 1 in 25. It does not have a higher frequency in people of Ashkenazi Jewish heritage (compared to other Caucasians) so is not included in this panel. However, cystic fibrosis information and genetic testing is also available here, and carrier screening is recommended for people of Ashkenazi Jewish heritage.
How Common are the Jewish Diseases?
||Disease Prevalence in Ashkenazi Jewish Individuals
||Carrier Frequency in Ashkenazi Jewish Individuals
||1 in 40,000-50,000
||1 in 100-134
||1 in 6400-13,500
||1 in 40-60
||1 in 3600-3700
||1 in 30-32
|Fanconi Anemia Group C
||1 in 32,000
||1 in 89-100
||1 in 850-1000
||1 in 7-18
|Glycogen Storage Disease Type IA
||1 in 16,000-20,000
||1 in 64-71
|Maple Syrup Urine Disease Type 1A & 1B
||1 in 38,000-50,000
||1 in 81-113
|Mucolipidosis Type IV
||1 in 62,500
||1 in 89-127
|Niemann-Pick Type A and B
||1 in 32,000-40,000
|| 1 in 90-115
||1 in 3000-3600
||1 in 25-31
Ferreira JC, Schreiber-Agus N, Carter SM, Klugman S, Gregg AR, Gross SJ. (2014) Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. Am J Obstet Gynecol. 211(3): 197-204.