Ancestry-Based Genetic Screening: Know Your Chances & Your Options
Preconception screening and genetic counseling is offered to people or couples with an increased chance for passing certain genetic disorders onto their children. Care begins with a personalized risk assessment followed by counseling and screening for those genetic conditions appropriate to the patient's ancestral background (sometimes referred to as ethnic background; where your ancestors are from). If test results indicate that either partner carries a hereditary disease, care teams will provide education and support needed to make informed reproductive decisions.
- Personalized risk assessment
- Carrier screening
- Discussion of reproductive options for carriers
What are Ancestry-Based Genetic Conditions?
Many people don't know what genetic conditions or diseases are, or that they can affect people of certain ancestry at higher rates than other members of the population. All people are likely to be carriers of several autosomal recessive genetic conditions, but it is not always clear as to which conditions are most likely to be carried by your family. Autosomal recessive conditions are diseases that require both reproductive partners to be carriers of the same genetic condition in order to have an affected child. A carrier is a healthy person who has one normal copy of a gene and one copy of the gene that does not work properly. If both members of a reproductive pair are found to be carriers, they have a 25 percent chance of passing that genetic condition on to their baby with each pregnancy. Carriers for these conditions are healthy themselves, so they are often surprised by the birth of a child with a recessive condition. A simple blood or saliva test is all that it takes to find out if you are a carrier prior to pregnancy. This allows for reproductive planning if desired.
Genetic counseling and carrier screening are available to allow people to make informed reproductive decisions. Advanced technologies can allow for reproductive partners who are carriers of the same condition to reduce the chance of having a baby with that condition. Our team can provide genetic counseling, screening, and treatment to anyone who suspects their family ancestry may place them in a high-risk category as well as those who have no known increased chance of being a carrier.
If one member of reproductive pair is known to be a carrier, the other member may need to seek genetic counseling in order to make sure that the most sensitive test is used to assess carrier status, as not all carrier methods can detect genetic changes in people of all ancestries.
Below is a chart of diseases frequently carried by people of specific ancestral backgrounds. More information about each condition can be found below
1 in 10-12
1 in 15
1 in 20
1 in 25
French Canadian, Cajun
1 in 25
1 in 40-60
1 in 20-30
Many people are of mixed ancestral background or do not know where their ancestors are originally from. For these people, screening for cystic fibrosis and spinal muscular atrophy is recommended, screening for anemia may be indicated to determine risk for sickle cell anemia and thalassemias, and (pan-ethnic) expanded carrier screening is available. Expanded carrier screening is a blood or saliva test that includes screening for a large number of serious recessive, and sometime X-linked, genetic conditions. Sequencing technology (reading all letters of the genetic code) is now used, in order to detect carriers from all ancestral backgrounds and to look at many conditions using one test.
Alpha thalassemia is a blood condition that can result in fatigue, pallor, weakness, and serious complications. People with this condition have low levels of hemoglobin, which is needed to carry oxygen in the blood. The body tries to produce more blood cells to make up for the lack of hemoglobin, and this can change the shape of some bones where blood is made. Some people need transfusions of blood, which can result in complications, such as heart disease or infections in rare cases. It is most common in people with ancestors from Southeast Asia, Mediterranean countries, North Africa, the Middle East, India, and Central Asia
The genetics of alpha thalassemia is complex, as we have two different copies of the alpha globin genes, HBA1 and HBA2. If missing four copies, the fetus often presents with full body swelling during the pregnancy and often will not survive. If missing three copies of the gene, the child will present with alpha thalassemia in childhood.
Screening for this condition is by a blood test called hemoglobin electrophoresis. If you or your partner has an abnormal screen, your provider will discuss next steps for determining whether your offspring may have an increased chance of having this condition.
Beta thalassemia is a blood condition that can result in fatigue, pallor, weakness, and serious complications. It is similar to alpha thalassemia in many ways. People with this condition have low levels of hemoglobin, which is needed to carry oxygen in the blood. The body tries to produce more blood cells to make up for the lack of hemoglobin, and this can result in changing the shape of some bones where blood is made. Some people need transfusions of blood, which can result in complications, such as heart disease or infections in rare cases. It is most common in people with ancestors from Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia.
Beta thalassemia can present at birth (thalassemia major) or later in childhood (thalassemia intermedia), depending on the level of hemoglobin loss of function.
Screening for this condition is by a blood test called hemoglobin electrophoresis. If you or your partner has an abnormal screen, your provider will discuss next steps for determining whether your offspring may have an increased chance for this condition.
Cystic fibrosis (CF) is a disease that most severely affects the lungs and pancreas. Due to an abnormality in salt transport in people with CF, very thick mucus is produced in the lungs, causing difficulty breathing and increasing the frequency of serious lung infections. The pancreas is unable to produce important enzymes necessary for the proper absorption and processing of fats. This often results in decreased life expectancy. CF is a disease seen with equal frequency in those of European and Ashkenazi Jewish ancestry, in which approximately 1 in 25 people carries a disease-causing variant. This condition can also be carried by people of all other backgrounds but at a lower frequency. Carriers are detected by a blood DNA test. Many blood tests for CF are aimed at detecting the genetic changes common in those with European and Ashkenazi Jewish ancestry. These tests are referred to as genotyping. People of other background may need a more detailed DNA test; sequencing is recommended as the most sensitive screening test for CF.
Familial dysautonomia (FD), also known as Riley-Day Syndrome, is a condition that causes the autonomic and sensory nervous systems to not work properly. The autonomic nervous system controls bodily functions such as swallowing and digestion, regulation of blood pressure and body temperature and the body’s response to stress. The sensory nervous system helps the body to taste, recognize hot and cold and identify painful sensations. The condition is also known as HSAN III (hereditary sensory and autonomic neuropathy, type III).
The hallmark of FD is the lack of overflow tears with emotional crying. Children with FD may have difficulty feeding. They also may be unable to feel pain, and can break bones or burn themselves without realizing they've been injured.
FD is caused by mutations in the IKBKAP gene. An estimated one in 30 people of Ashkenazi Jewish descent carries the FD gene change, found on chromosome 9. Carriers don’t display any symptoms or warning signs of FD.
Currently, there is no cure for FD. The lifespan of those affected with FD is often shortened. Treatments aim at controlling symptoms and avoiding complications. Treatment strategies can include using special feeding techniques and special therapies, medications, artificial tears, respiratory care, and orthopedic management.
There are three different types of Gaucher (pronounced go-shay) disease (type I, II, III). Type I is the most common form of this condition; an estimated 1 in 14 people of Ashkenazi Jewish descent is a carrier. The gene is located on chromosome 1. The signs and symptoms of Gaucher disease vary greatly and can appear at any age. The most common symptom of type I Gaucher disease is painless enlargement of the spleen and/or liver with absence of central nervous system involvement. Other symptoms may include bruising, bone pain, frequent nosebleeds, and a lack of energy. Also, children with type I Gaucher disease are often shorter than their peers and may have delayed puberty.
People with Gaucher disease lack an enzyme called glucocerebrosidase and are unable to break down a fatty substance in their cells. This fatty substance builds up in the liver, spleen, bone marrow, and other areas of the body. This build-up leads to the medical complications of Gaucher disease.
Although there is no cure for Gaucher disease, there are some treatments available for managing and relieving the symptoms. Enzyme replacement therapy is an effective form of treatment, but it is quite expensive and time-consuming. The treatment consists of a modified form of the glucocerebrosidase enzyme given intravenously. A newer therapy oral therapy, miglustat, is available for those patients who are not suitable candidates for enzyme therapy. These therapies can lead to improved quality of life for affected individuals and their families.
Tay-Sachs disease is an inherited, genetic condition that causes progressive degeneration and destruction of the central nervous system in affected individuals. Babies born with Tay-Sachs disease appear typical at birth, and symptoms of the disease do not appear until the infants are approximately four-to-six months of age. It is at this time that these children begin to lose previously attained skills, such as sitting up or rolling over. They gradually lose their sight, hearing and swallowing abilities. There is severe developmental delay. These children usually die by the age of four.
Individuals with Tay-Sachs disease lack a substance in their body called hexosaminidase A (Hex A). Hex A is responsible for breaking down a certain type of fat called GM2-ganglioside. When Hex A is missing from the body, it cannot break down this fat. The fatty substance accumulates to toxic levels in the body, mainly in the brain and nervous system. There is no cure for Tay-Sachs, although research is on-going regarding possible treatment options including gene therapy
An estimated 1 in every 25 people of Ashkenazi Jewish and French-Canadian ancestry is a carrier for Tay-Sachs disease. TSD is also carried at a high rate in people of Cajun and Irish descent.
Screening for Tay-Sachs was historically performed by enzyme analysis (which must be performed on blood) and now is often performed via DNA sequencing which can be performed on blood, saliva, or a cheek swab. Older DNA panels (genotyping tests) often only looked for those genetic changes seen in those of Ashkenazi Jewish ancestry and should not be used for the general population.
Sickle cell anemia
One out of 10 to 12 people of African ancestry are carriers for sickle cell anemia (SCA). SCA is a condition that causes the blood cells to be in a sickle shape instead of their usual shape and have more difficulty moving through small vessels in the body to carry oxygen. People with SCA can have a "crisis" in which they experience significant pain in the bones and may need IV fluids and transfusions of blood. Certain medications can decrease the risk for these crises. Carriers of this condition may say they have “sickle cell trait”. Carriers generally are well, but can occasionally have complications at high altitudes. Carriers can be detected using a blood test called hemoglobin electrophoresis in most cases. DNA testing can also be performed to identify the specific genetic change for reproductive purposes.
Spinal Muscular Atrophy (SMA)
Spinal muscular atrophy (SMA) refers to a group of diseases which affect the motor neurons of the spinal cord and brain stem, which are responsible for supplying electrical and chemical signals to muscle cells. Without proper signals, muscle cells do not function properly and thus become much smaller (atrophy). This leads to muscle weakness. Individuals affected with SMA have progressive muscle degeneration and weakness, eventually leading to death.
There are several forms of SMA, depending on the age of onset and the severity of the disease. Two genes, SMN1 and SMN2, have been linked to SMA types I, II, III and IV. Type I is the most severe form of SMA and is characterized by muscle weakness present from birth, often manifested by difficulties with breathing and swallowing, and death usually by age 2 to 3 years. Type II has onset of muscle weakness after 6 months of age, and can obtain some early physical milestones like sitting without support. Type III is a milder form of SMA, with onset of symptoms after 10 months of age. Individuals with Type III SMA often achieve the ability to walk, but may have frequent falls and difficulty with stairs. The weakness is more in the extremities, and affects the legs more than the arms. Type IV is the mildest form and is characterized by adult onset of muscle weakness.
SMA is most often caused by a deletion of a segment of DNA, called Exon 7 and Exon 8, in the SMN1 gene located on chromosome 5. Rarely, SMA is caused by a point mutation in the SMN1 gene. Carrier testing for SMA measures the number of copies of the deleted segment in the SMN1 gene. A non-carrier is expected to have 2 copies present (no deletion), while a carrier will have only 1 copy present (a deletion of one copy). However, carrier testing will not identify carriers of point mutations.