According to current estimates, as many as one in three Ashkenazi Jews, those with Eastern European descent, are carriers for certain genetic diseases, including Gaucher disease. Researchers think Ashkenazi genetic diseases arise because of the common ancestry many Jews share. While people from any ethnic group can develop genetic diseases, Ashkenazi Jews are at higher risk for certain diseases because of specific gene mutations.
Scientists call this propensity to developing disease the Founder Effect. Hundreds of years ago, mutations occurred in the genes of certain Ashkenazi Jews. The carriers of these newly mutated genes were unaffected by them, but their descendants were at greater risk for developing genetic diseases as a result of inheriting mutated genes. Over the course of Jewish history, many mutated genes, including the gene responsible for Gaucher disease, GBA1, were passed on from generation to generation.
How are Ashkenazi Genetic Diseases Inherited?
For a child to develop one of the genetic diseases prevalent among Ashkenazi Jews, they must inherit two mutations for the same disease. In every living person, genes are paired – in each pair, one gene comes from the mother and the other comes from the father. For recessive inheritance of a genetic disease to occur, both genes in a pair must be abnormal.
If two parents that carry a mutation in the same gene have a child, several outcomes are possible:
Karen Arnovitz Grinzaid, a genetic counseling instructor and executive director of the JScreen Jewish Genetic Screening Program based out of Emory University School of Medicine explains, “Two people who are carriers for the same disease can each pass the mutated gene to each child they have together. If a child inherits two copies of the mutated gene, one from each parent, he has no protection against the disease and will be affected.”
Which Genetic Diseases are Most Common Among Ashkenazi Jews?
Certain genetic disorders are more common in Ashkenazi Jews, and carrier frequencies for these diseases are higher in the Jewish population than in other groups. Carrier frequency is a measure of how often a mutated gene appears within a certain population group; with each disease, the carrier frequency is represented by the proportion of Ashkenazi Jews who have a copy of a mutated gene.
Because of mutations in certain genes and high carrier frequencies, five diseases are especially common among Ashkenazi Jews:
- Gaucher Disease (1 in 10)
The most common Ashkenazi genetic disease is Gaucher disease, with one out of every 10 Ashkenazi Jews carrying the mutated gene that causes the disease. Doctors classify Gaucher disease into three different types, resulting from a deficiency of glucocerebrosidase (GCase) within the body. Type 1, which is treatable, is the most common form among Ashkenazi Jews.
- Cystic Fibrosis (1 in 24)
Normally, cells in the lungs and digestive system produce a thin, slippery mucus as part of normal physiological processes. In people with cystic fibrosis, this mucus becomes much thicker and stickier, which damages internal organs, especially the lungs. It is possible to manage this condition with medications and daily care, but those who develop this disease have shortened life spans, typically only living into the mid- to late 30s.
- Tay-Sachs Disease (1 in 27)
Certain mutations on the HEXA gene cause Tay-Sachs disease, which is characterized by progressive deterioration of nerve cells (neurons) in both the brain and spinal cord. This destruction results from a shortage of an enzyme required to break down fatty substances in the body. There is currently no cure for Tay-Sachs disease.
- Familial Dysautonomia (1 in 31)
Typically, symptoms of this disease are already present when a baby is born. Familial dysautonomia is characterized by changes to nerves in the autonomic nervous system. These nerves are responsible for many involuntary bodily functions, including blood pressure, heart rate, and digestion. While there has been progress in developing effective treatments for this disease, people with the condition usually have shortened lifespans.
- Spinal Muscular Atrophy (1 in 41)
There are several different types of this disease, but all affect the control of muscle movement due to a decline in the number of specialized nerve cells, called motor neurons, in both the spinal cord and brainstem. Life expectancy varies widely depending on the type. There is no cure for Spinal Muscular Atrophy, but treatment may be effective at managing the symptoms and complications.
Efforts to Identify Carriers Early With Jewish Genetic Screening
In 2016, NGF and JScreen, a national community-based public health initiative based out of Emory University School of Medicine, launched a collaborative carrier screening program to increase awareness of and screening for Gaucher disease and other genetic diseases common to Jews. The initiative ensures the first 1000 people who sign up through December 31, 2017 can obtain an at-home testing kit that screens for more than 200 genetic diseases that affect people from all ethnic groups, including diseases that are most common among the Ashkenazi Jewish population.
The first step in the process is to complete online registration and consent forms. Then, JScreen faxes an order to your healthcare provider notifying them of your intent to pursue genetic testing and asking them to acknowledge and approve the request. Ms. Grinzaid says, “Unlike some of the direct-to-consumer services, we’re making sure a medical team is involved throughout this process.”
JScreen will then mail a saliva collection kit to your home. You collect a small saliva sample and send it to a laboratory for testing. Genetic counselors review the results of your test and invite you to take part in a genetic counseling session. You won’t be charged any additional fees. The purpose of the counseling session is to provide you with more information and resources to help ensure the best possible outcome for any children you might have.
Challenges to Screening Initiatives – Increasing Awareness Among Ashkenazi Jews
Even though the screening initiative has been successful, both NGF and JScreen are committed to raising awareness of the importance of genetic screening so that people in high-risk groups are better able to plan for their families’ future. In many cases, couples in high-risk ethnic populations are only offered carrier screening after pregnancy has already occurred.
Ms. Grinzaid says, “We want people to understand that most conditions we’re screening for are inherited in an autosomal recessive way. In order for a child to be affected, both parents need to be carriers for the same disease. Each time they have a pregnancy, there’s a 25 percent risk. In almost 80 percent of cases where a baby is born with one of these genetic conditions, they’re born to a couple with no family history of this condition. When people don’t see anything in their family history, they think they don’t need to worry so they don’t pursue testing or think it’s important.” Couples with Jewish heritage would benefit from genetic testing before beginning a family.
“The only two ways to know you’re a carrier are to have an affected child, because that would prove you’re a carrier, or to undergo screening, which is what we’re trying to encourage,” says Ms. Grinzaid.
The main goal of the JScreen and NGF collaboration is to offer as much information as possible to populations with higher prevalence of Gaucher disease, like those with an Ashkenazi Jewish heritage. The hope is that more people will take advantage of genetic screening in order to be more informed of their chances of being affected by Gaucher and of available treatments.
- Autosomal recessive. U.S. National Library of Medicine. https://medlineplus.gov/ency/article/002052.htm
- Gaucher’s disease. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/gauchers-disease/basics/definition/con-20031396
- Cystic fibrosis. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/home/ovc-20211890
- Tay-Sachs Disease Information Page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Tay-Sachs-Disease-Information-Page
- Familial dysautonomia. U.S. National Library of Medicine. https://medlineplus.gov/ency/article/001387.htm