Next Generational Genetic Screening

Next generation sequencing (NGS) technologies offer the possibility to map entire genomes at affordable costs. This brings the genetic testing procedure to a higher level of complexity. The positive aspect is the ease to cope with the complex diagnosis of genetically heterogeneous disorders and to identify novel disease genes. The sequence variants/mutations detected by NGS have been widely used for disease diagnosis, prognosis, therapeutic decision, and follow up of patients. The capacity of its massive parallel sequencing offers new opportunities for personalized precision medicine. One of the advantages of NGS is to interrogate many targets at the same time on the scale of hundreds and thousands or even millions of targets. Such capacity gives NGS huge potential application in clinical settings.

Who is Genetic Counselor?

A genetic counselor is a kind of genetic specialist. Genetic counselors are part of a healthcare team. Their role is to help you understand and make decisions about genetic testing, genetic conditions and related issues. These may include medical and emotional concerns for you and your family. Genetic counselors can provide information and answer questions about:

1. The science behind genetic conditions
2. Your risk for genetic disease
3. Genetic testing
4. Management and prevention of genetic conditions
5. Available resources

When you meet with our genetic counselor, he or she will take your personal and family health history to help better understand your risk for having a genetic condition. Overall, our genetic counselor can help you and your family make informed decisions.

At supreme dermatology and specialist hospital, we run the best next generation genetic sequencing laboratory in Nigeria. We offer the most accurate Non-Invasive Prenatal Screening Test (NIPT), the Genetic Carrier Screening premarital Test, Preimplantation Genetic Screening/Diagnosis (PGS/PGD) preventative and predictive genetic screening

• Prenatal genetic testing: This gives parents information about genetic disorders or birth abnormalities the fetus may have. Prenatal genetic testing is optional. A person’s chromosomes or genes cause genetic disorders. A gene is part of your body’s cells that stores instructions for how your body works. A chromosome holds your genes. Congenital disorders are present at birth, and healthcare providers can diagnose some of these conditions before birth.

There are two different kinds of tests: screening tests and diagnostic tests.

What types of prenatal screening tests is available?

Screening tests don’t diagnose genetic conditions, and an abnormal result doesn’t mean the fetus has a condition. It means there’s a higher risk for a genetic disorder. In some cases, diagnostic testing may be recommended by our specialist.

Some examples of prenatal genetic screening tests are:

Carrier screening

Carrier screening is a blood test that we offer you and your partner. This type of testing can identify small changes in the genes that increase the risk that the fetus could inherit serious medical conditions. These are often called single-gene conditions. Examples include cystic fibrosis, sickle cell disease and spinal muscular atrophy. If your blood test shows you’re a carrier for a genetic risk, your partner should also undergo screening. If both parents are carriers of the same genetic risk, the fetus could have a more severe form of the disease. You only need to complete carrier screening tests once in your lifetime.

Screening for an abnormal chromosome number

Chromosomes should be inherited in pairs — one half of the pair from each parent. Sometimes, nature makes mistakes during fertilization, resulting in missing, or extra, parts of the chromosome pair. Examples include Down syndrome (an extra chromosome 21) and Turner’s syndrome (a missing X chromosome). These test results will be different for each pregnancy. Types of tests include:

1. Cell-free fetal DNA screening: This is popularly known as non-invasive prenatal testing (NIPT). Our specialist look for some common forms of abnormal chromosome numbers in small bits of fetal DNA found in your blood. Because fetal DNA is present in very small amounts, the test cannot be done until 10 weeks gestation.
2. Serum screening: This type of test is also done on your blood sample. It doesn’t look directly at fetal DNA. Instead, these tests analyze various protein levels in your blood to determine the risk for abnormal chromosome numbers. Examples of this type of test include sequential screening, quad screening and first trimester serum screening. Each of these tests must occur at very specific times during pregnancy. These tests will not be carried out until the 11th week of pregnancy.

Screening for physical abnormalities

Sometimes, missing or extra chromosomes cause changes in your baby’s physical structure. For example, the chromosomes are normal but your baby has a physical defect. During pregnancy, ultrasound and blood tests can help determine the fetus’s risk for physical abnormalities and assess whether or not they may be due to genetic abnormalities.

1. Nuchal translucency: Uses ultrasound to measure the thickness of the back of the fetus’s neck. A thick nuchal translucency gives us clues about the risk for abnormal chromosome number and for physical abnormalities like abnormal fetal heart formation. Providers perform this ultrasound at 11 to 14 weeks gestation.
2. AFP screening (maternal serum screen): our specialist draws some of your blood to measure the level of AFP in your blood. High levels may indicate physical problems with the fetus’s abdomen, face or spine. This occurs at 15 to 22 weeks gestation.
3. Quad screen: Measures the levels of four substances in your blood and determines the risk of the fetus having chromosomal abnormalities and neural tube defects. This test is also called a multiple marker screen. It’s also done at 15 to 22 weeks gestation.
4. Fetal anatomy scan: Uses ultrasound to evaluate the fetus’s physical structures, including the developing brain, skeleton, heart, kidneys, abdomen, face, arms and legs. This ultrasound is usually done at 18 to 20 weeks gestation.

Remember, prenatal screenings tell you a condition might be present. It doesn’t diagnose a condition.

What types of prenatal diagnostic tests are there?

Diagnostic prenatal tests can confirm if the fetus has a genetic condition. These tests take cells from the amniotic fluid or placenta and test them for specific disorders. Diagnostic testing is only performed when a screening test is abnormal or if you’re at high risk for having a baby with a genetic condition.

The most common diagnostic tests are amniocentesis and chorionic villus sampling (CVS).

1. Amniocentesis: Your provider inserts a needle through your skin into your uterus to remove a sample of amniotic fluid from the amniotic sac. Amniocentesis happens between 16 and 20 weeks of pregnancy.
2. CVS: Your provider inserts a needle into your uterus to remove a small sample of cells from the placenta. The provider will determine if it’s safer to place the needle through your abdomen or your vagina. CVS occurs around 11 to 13 weeks of pregnancy.

Our specialist then sends the samples to the lab for analysis. The lab can perform several types of diagnostic tests, including fluorescence in situ hybridization (FISH), standard karyotyping, and microarray or special panels. Some diagnostic test results can be ready in 72 hours, while others may take more than two weeks to complete.

Who should get genetic testing?

Some of the reasons families will choose diagnostic genetic testing during pregnancy are:

• Irregular result of a genetic screening test.
• Family or personal history of genetic conditions.
• Pregnancy over age 35.
• History of miscarriage or stillbirth.

• Premarital genetic testing- Marriage is the elementary component of society and is a foundation of an emotional and healthy relationship between couples. A healthy marriage assures couples about eluding hereditary and infectious diseases, thus establishing a happy and healthy family. Pre-marital genetic testing and genetic counseling can give an insight into the possibility of recessive disorder that is getting passed on through generations in families. Couples can take informed decisions regarding their future and family planning decisions can be discussed after marriage. Counseling and prenatal testing in such cases can prove to be beneficial and opens multiple options on reproductive choices. Premarital genetic screening (PGS) helps to avoid hereditary diseases; thus, increasing the likelihood of having a happy and stable family.

Why is premarital screening beneficial?

The premarital screening helps the soon-to-be-married couple to identify the potential health risks in themselves and their children. Some of the benefits of premarital screening are:

1. Measure the comprehensive health status of soon-to-be husband and wife
2. It detects infectious diseases such as hepatitis B, HIV infection (AIDS), Hepatitis C, and other sexually-transmissible diseases (STDs).
3. It rules out common genetic blood disorders such as thalassemia, sickle cell anemia, and hemophilia. 

Tests conducted in premarital screening

Tests that are a part of premarital screening are:

Routine investigations:

They provide information on the overall health status of future brides and grooms. They are:

1. Complete urine analysis
2. Complete blood count (CBC)
3. Peripheral blood smear
4. Blood group testing (ABO-Rh): It screens out the Rh-negative women and counsels the couples about the risk related to pregnancy.

Tests to rule out infectious disease:

1. VDRL test for syphilis
2. ELISA or western blot test to detect HIV infection (AIDS)
3. Hepatitis-B screening
4. HCV antibody tests to detect hepatitis-C virus
5. Screening tests for sexually-transmitted diseases(STDs)

Genetic tests:

Genetic tests are a must in the case of consanguineous marriages (marriage in between blood relatives or have common ancestors). Chances of recessive-inherited disease appearance are high in offsprings of consanguineous marriage couples. The closer the blood relationships, the greater the risk of having genetic diseases in their children. Genetic tests are culture-based screening tests, including analyzing blood or tissue samples collected from couples.

Marriage is an auspicious event in a person’s life. Every couple at some point in their life wants to start a family. Before starting a new life, you should take the premarital test to prevent any genetic or infective condition in the child. You have to think about your and your partner’s health before taking this huge step of getting married. When your children get any inherited problem, it may affect their social, psychological, and emotional status. So, to prevent infectious diseases and inherited conditions, don’t neglect premarital screening.

Why choose Supreme Dermatology and Specialist Hospital for premarital screening?

We help you and your spouse undergo thorough and unbiased premarital screening. The test results will pave your way for peaceful married life by putting all these worries at bay. If test results come negative, our expert team will help in treatment. So, don’t stress on these frugal matters and consult with us.

• Predictive and presymptomatic testing- Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hereditary hemochromatosis(an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.

Our health professional would review your results with you to make sure you understand your options. The results from a predictive test may affect:

1. Your life plan
2. Your health choices
3. Your mental and emotional state

Test results also may show information about your relatives. Carefully think about your results and the effect they can have on family members.

Testing Types and Results

There are two different types of predictive genetic testing:

1. Presymptomatic Testing: Positive tests results show that you will develop symptoms of a disease. For example, this type of test is used to check for mutations linked to Huntington’s Disease.
2. Predispositional Testing: Positive tests results show that you are more likely than others to develop symptoms of a disease. But, doctors cannot know for sure if you will get sick. For example, this type of test is used to check for mutations linked to breast cancer.

We will not do a predictive genetic test until certain things have been explained to you. This may include information about the test that you are getting and what the results mean.

Most predictive tests have some uncertainty about:

• If a condition will develop,
• When it might develop, and
• How sick you will get.

Your next steps will depend on the type of test you took. With a positive presymptomatic test result, get ready for symptoms in the future. With a positive predisposition test result, think about what you can do to avoid disease. In both cases, you can always talk to our healthcare professional.

• Preimplantation Genetic Screening/Diagnosis (PGS/PGD)

Pregnant women whose babies are at risk of having a genetic condition serious enough to warrant consideration of termination of pregnancy may be offered prenatal diagnostic tests such as amniocentesis and chorionic villus biopsy. For some couples, however, such tests are not acceptable, and preimplantation genetic diagnosis is an alternative.

Preimplantation genetic diagnosis involves testing the early embryo after in vitro fertilisation. One or two cells (blastomeres) are removed at biopsy from the preimplantation embryo at the 6-10 cell stage (day 3 of development), thus allowing replacement into the uterus of unaffected embryos.

Preimplantation genetic diagnosis can be offered for three major categories of disease. Firstly, it can be used to determine the sex of the embryo for sex linked disorders where the specific genetic defect at a molecular level is unknown, highly variable, or unsuitable for testing on single cells—for example Duchenne muscular dystrophy.¹ Secondly, it can be used to identify single gene defects such as cystic fibrosis, where the molecular abnormality is testable with molecular techniques after polymerase chain reaction (PCR) amplification of DNA extracted from single cells.² Thirdly, it can be used in chromosomal disorders, where fluorescence in situ hybridisation has been developed to detect a variety of chromosomal rearrangements, including translocations, inversions, and chromosome deletions.³ Some potential parents who carry a chromosomal rearrangement may never have achieved a viable pregnancy before requesting preimplantation genetic diagnosis if each previous conception resulted in a chromosomally unbalanced embryo which miscarried spontaneously.

Indications for preimplantation genetic screening

Preimplantation genetic screening (PGS) is recommended when couples risk transmitting a known genetic abnormality to their children. Only healthy and normal embryos are transferred into the mother’s uterus, thus diminishing invasive prenatal diagnoses, late pregnancy termination, or the birth of a child with a serious genetic disease.

Primary candidates for PGTS

These include the following:

1. Carriers of autosomal recessive diseases (for carriers of autosomal recessive diseases, the risk an embryo may be affected is 25%)
2. Carriers of autosomal dominant diseases (for carriers of autosomal dominant disease, the risk an embryo may be affected is 50%)
3. Couples with a family history of X-linked disorders (couples with a family history of X-linked disease have a 25% risk of having an affected embryo [half of the male embryos])
4. Couples with chromosomal translocation, which can cause implantation failure, recurrent pregnancy loss, or mental or physical problems in offspring 

Two main techniques are used for the genetic assessment:

• Polymerase chain reaction (PCR)- In PCR, multiple copies of the gene of interest are made by a process of amplification. This amplification process allows the identification of very small amounts of DNA to make the diagnosis.
• Fluorescent in situ hybridization (FISH)- FISH allows the laboratory to count the number of chromosomes in an isolated cell. This technique is used primarily for expected abnormalities in chromosome number, such as Down syndrome, or translocations (defects in the structure of the chromosome).

At Supreme Dermatology and Specialist Hospital, our embryology laboratory staff has extensive experience with embryo micromanipulation and biopsy. Our genetic counselor is available to coordinate your cycle with the IVF team and the PGD laboratory, to make the process as smooth as possible. Call on +2348101407128 for enquiries and consultation.