Unit 2: Genetic Testing and Genetic Disorders
Genetic Testing Overview
Genetic testing involves various laboratory techniques designed to identify genetic variations that affect an individual’s risk for diseases, diagnosis, prognosis, and therapeutic response. Advances in molecular genetics have made it possible to detect both complex multifactorial diseases and single-gene disorders. Genetic testing plays a crucial role in preventive medicine, reproductive decision-making, and personalized treatment plans tailored to the genetic profile of each patient.
Types of Genetic Testing
What is Carrier Screening?
Carrier screening is a genetic test used to identify individuals who carry one mutated copy of a gene responsible for autosomal recessive disorders. Although carriers typically do not show symptoms, they can transmit the mutation to their offspring. This test is especially significant for prospective parents, particularly in populations with a higher prevalence of specific inherited conditions.
Common Disorders Detected Through Carrier Screening
| Disorder | Inheritance Pattern | Population Significance |
|---|---|---|
| Cystic fibrosis | Autosomal recessive | Predominantly affects individuals of European descent |
| Sickle cell disease | Autosomal recessive | Common in individuals of African ancestry |
| Tay-Sachs disease | Autosomal recessive | Frequent in Ashkenazi Jewish populations |
Carrier screening provides couples with critical insights into genetic risks, enabling informed reproductive choices and risk management.
What is Prenatal Diagnosis?
Prenatal diagnosis refers to genetic testing conducted during pregnancy to evaluate the fetus’s genetic health. It is recommended for all pregnant individuals, especially those with risk factors such as advanced maternal age, family history of genetic diseases, or abnormal prenatal screening results.
Common Prenatal Diagnostic Techniques
| Method | Description |
|---|---|
| Amniocentesis | Sampling fetal cells from amniotic fluid |
| Chorionic Villus Sampling (CVS) | Sampling placental tissue |
| Preimplantation Genetic Diagnosis (PGD) | Testing embryos during IVF |
| Cell-Free Fetal DNA Testing | Analyzing fetal DNA circulating in maternal blood |
These diagnostic tools enable early detection of chromosomal abnormalities and inherited disorders, allowing for timely counseling and medical management.
What is Presymptomatic Genetic Testing?
Presymptomatic testing identifies individuals carrying mutations associated with adult-onset genetic conditions before any symptoms develop. Examples include BRCA gene mutations linked to hereditary breast cancer and variants related to familial colon cancer. Early identification enables proactive monitoring, preventive interventions, and lifestyle modifications that improve long-term outcomes.
What is Pharmacogenetic Testing?
Pharmacogenetic testing examines genetic variations that influence how individuals respond to medications. By understanding these differences, healthcare providers can tailor drug regimens to enhance effectiveness, reduce adverse effects, and optimize therapeutic strategies.
Reasons for Genetic Screening
| Purpose | Clinical Importance |
|---|---|
| Predicting disease risk | Identifies individuals at increased susceptibility |
| Early diagnosis | Enables timely medical intervention |
| Risk reduction | Facilitates preventive measures |
| Guiding drug therapy | Supports personalized medicine approaches |
Chromosomal Aneuploidy Disorders
Turner Syndrome
What is Turner Syndrome and How Common Is It?
Turner syndrome is a chromosomal disorder resulting from monosomy X (45,X), where one X chromosome is missing. This condition affects females who exhibit distinctive developmental abnormalities. Turner syndrome occurs in approximately 1 in 2,500 female births and was first identified by Dr. Henry Turner in 1938.
What Causes Turner Syndrome?
The syndrome arises due to the absence or structural defect of one X chromosome. Individuals typically have nonfunctional ovaries replaced by fibrous tissue, resulting in a lack of estrogen and progesterone production. This leads to impaired sexual development and infertility. Some patients exhibit mosaicism, where some cells have normal chromosomes, leading to milder symptoms and better prognosis.
What Are the Clinical Features of Turner Syndrome?
| System Affected | Common Manifestations |
|---|---|
| Growth | Short stature |
| Cardiovascular | Coarctation of the aorta |
| Reproductive | Primary amenorrhea, infertility |
| Skeletal | Osteoporosis |
| Cognitive | Generally normal IQ, some spatial reasoning challenges |
How is Turner Syndrome Diagnosed and Managed?
Diagnosis is confirmed by karyotyping blood cells. Management includes hormone replacement therapy (estrogen and growth hormone), fertility counseling, and comprehensive multidisciplinary care to monitor and address associated health concerns.
Klinefelter Syndrome
What Is Klinefelter Syndrome and Its Prevalence?
Klinefelter syndrome is a condition where males possess one or more extra X chromosomes, most commonly 47,XXY. It affects about 1 in 1,000 male births. The additional X chromosomes often correlate with more pronounced physical and cognitive impairments.
What Are the Signs of Klinefelter Syndrome?
Symptoms typically include small testes, infertility, gynecomastia (breast tissue development), sparse body hair, tall stature, and varying cognitive challenges. Mosaic forms may present with milder symptoms.
Cri du Chat Syndrome (5p Deletion Syndrome)
What Genetic Change Causes Cri du Chat Syndrome?
Cri du Chat syndrome is caused by a deletion on the short arm of chromosome 5. The severity of symptoms depends on the extent of this deletion. Most cases occur sporadically, though some are inherited.
What Are the Key Clinical Features?
| Feature | Description |
|---|---|
| Cry | High-pitched, cat-like cry |
| Neurological | Severe intellectual disability |
| Craniofacial | Microcephaly, micrognathia |
| Musculoskeletal | Hypotonia (low muscle tone) |
| Cardiac | Congenital heart defects |
Diagnosis is confirmed through cytogenetic analysis. Treatment is supportive and focuses on improving physical, occupational, and speech functions.
Down Syndrome (Trisomy 21)
What Causes Down Syndrome?
Down syndrome results from an extra copy of chromosome 21, making it the most frequent autosomal aneuploidy compatible with life. It affects approximately 1 in 800 live births worldwide.
What Are the Clinical Characteristics?
| Category | Findings |
|---|---|
| Cognitive | Intellectual disability, IQ typically 25–70 |
| Facial Features | Flat nasal bridge, epicanthal folds |
| Cardiac | Congenital heart defects |
| Immune | Increased susceptibility to infections |
| Neurological | Alzheimer-like changes by middle adulthood |
Immunity and Genetic Influence
What Constitutes Innate Immunity?
Innate immunity represents the body’s first line of defense, present from birth. It includes physical barriers such as skin and mucous membranes, mechanical defenses like coughing and urination, and biochemical agents including stomach acid and lysozyme. Immune cells such as neutrophils, macrophages, natural killer cells, and dendritic cells contribute to rapid, nonspecific responses. Inflammation is a key innate response characterized by redness, warmth, swelling, and pain.
What Is Adaptive Immunity?
Adaptive immunity develops progressively and targets specific pathogens. It involves humoral immunity, mediated by B cells producing antibodies, and cell-mediated immunity, involving T cells. Memory cells formed during this process provide long-lasting protection, enabling quicker responses upon subsequent exposures to the same pathogens.
Inheritance Patterns of Genetic Disorders
What Are the Main Modes of Genetic Inheritance?
Autosomal Dominant Disorders: These require only one mutated gene copy for the disease to manifest. Each child of an affected parent has a 50% chance of inheriting the disorder. Huntington’s disease is a classic example.
Autosomal Recessive Disorders: Manifestation occurs only if two mutated alleles are inherited, usually from asymptomatic carrier parents. Examples include cystic fibrosis and sickle cell disease.
X-Linked Disorders: These involve mutations on the X chromosome.
| Type | Key Features | Example |
|---|---|---|
| X-linked dominant | No male-to-male transmission | Rett syndrome |
| X-linked recessive | Primarily affects males | Duchenne muscular dystrophy |
Case Study: Systemic Lupus Erythematosus (SLE)
What Is the Pathophysiology of SLE?
SLE is a chronic autoimmune disorder characterized by antinuclear antibodies. It arises from a combination of genetic predisposition and environmental triggers such as ultraviolet radiation. These factors lead to immune complex formation, causing type III hypersensitivity reactions and widespread inflammation affecting multiple organ systems.
How Is SLE Diagnosed and Treated?
Diagnosis requires meeting at least four clinical and immunological criteria, including malar rash, arthritis, kidney involvement, hematologic abnormalities, and presence of autoantibodies. Treatment focuses on reducing disease flare-ups and preventing organ damage using corticosteroids, immunosuppressive drugs, and lifestyle modifications.
References
American College of Obstetricians and Gynecologists. (2020). Carrier screening in the age of genomic medicine. ACOG Practice Bulletin.
Centers for Disease Control and Prevention. (2023). Genetic testing and screening.
Kumar, V., Abbas, A. K., & Aster, J. C. (2021). Robbins and Cotran pathologic basis of disease (10th ed.). Elsevier.
National Institutes of Health. (2022). Genetic and rare diseases information center.
Strachan, T., & Read, A. (2018). Human molecular genetics (5th ed.). Garland Science.