7.7 Genetic Testing - Tagged

Genetic Testing

Pedigree Analysis

• Purpose of Pedigree Information

  • Helps in tracking traits through family lines, providing visualization of how traits are passed on through generations.

  • Allows for assessment of risk regarding trait inheritance (Linkage Analysis), crucial in understanding familial connections and influences in genetic disorders.

Research and Counseling Implications

• Aids genetic counselors, medical researchers, and families in determining the likelihood of passing traits to future generations. This is particularly important for hereditary diseases.

• When combined with genetic testing and genome-wide association studies, it helps identify specific genes responsible for certain diseases or traits, their function in healthy individuals, and potential treatment methods, enhancing personalized medicine approaches.

Resources

• OMIM (Online Mendelian Inheritance in Man)

  • An extensive online catalog of human genes and genetic disorders, providing updated information concerning clinical features and phenotypes.

  • Useful for searching information related to genes, genetic diseases, and inheritance patterns. This resource is instrumental in both research and clinical settings.

Cystic Fibrosis and Treatments

• Pre- and Post-Kalydeco Treatment Landscape

  • Highlighting the advancements and treatment options available for cystic fibrosis, especially before and after the introduction of Kalydeco (a groundbreaking medication). Kalydeco represents a significant breakthrough in treating specific mutations in the CFTR gene, demonstrating the impact of targeted therapy.

Genetic Disease Detection Techniques

• Prenatal Detection Methods:

  • Techniques for Different Disorders:

    • Chromosome Abnormalities: Karyotype examination via amniocentesis or chorionic villus sampling (CVS) is essential for detecting aneuploidies like Down syndrome.

    • Cleft Lip/Palate: Detected through ultrasound, which can reveal physical malformations.

    • Cystic Fibrosis: Identified via DNA analysis from amniocentesis or CVS, providing critical early diagnosis to manage care.

    • Dwarfism and Hemophilia: Detected by ultrasound or DNA analysis through amniocentesis.

    • Neural-tube Defects: Screened with maternal blood tests (e.g., alpha-fetoprotein) and confirmed via biochemical tests on amniotic fluid.

    • Sickle-cell Anemia and Tay-Sachs Disease: Diagnosed using fetal blood sampling or DNA analysis from amniocentesis, providing vital information for family planning and management.

Genetic Testing Overview

• Candidates for Genetic Testing:

  • Applicable to embryos, fetuses, children, and adults, allowing early intervention and planning for genetic conditions.

  • Key areas include preimplantation diagnosis, screening for fetal abnormalities, and diagnosing genetic diseases across all ages. This breadth of application emphasizes the role of genetic testing in a diverse range of clinical scenarios.

IVF Process

• Stages of In Vitro Fertilization (IVF):

  • Step 1: Stimulation of ovaries using hormonal medications to produce multiple eggs.

  • Step 2: Egg retrieval and fertilization, where retrieved eggs are combined with sperm in a laboratory setting.

  • Following Stages: Development of embryos, embryo transfer to the uterus, and pregnancy testing, which together facilitate conception for individuals facing infertility.

Prenatal Testing Techniques

• Ultrasonography:

  • Uses sound waves to visualize the fetus, facilitating the identification of size, position, and potential defects like neural tube or skeletal issues.

• Amniocentesis:

  • A needle guided by ultrasound is used to withdraw amniotic fluid for analysis of fetal cells, cultured and examined for genetic analysis, identifying various chromosomal disorders.

• Chorionic Villus Sampling (CVS):

  • A catheter, guided by ultrasound, collects chorion cells for immediate genetic testing, enabling quicker diagnosis of certain genetic issues without waiting for cell culture.

Analysis Techniques for Genetic Testing

• Karyotyping:

  • Cells from amniocentesis or CVS can be used to create karyotypes for chromosomal analysis, crucial for identifying chromosomal abnormalities.

• In Situ Hybridization:

  • Utilizes DNA probes to locate and visualize genes within cells using methods like FISH (Fluorescence In Situ Hybridization), aiding in specific gene detection.

• Cell-Free DNA Testing:

  • Analysis of fetal DNA in maternal blood detects genetic markers related to diseases, assessing risk for conditions like trisomy based on fetal DNA found in maternal circulation, signifying a non-invasive testing method.

Neonatal Testing Recommendations

• Conditions for Mandatory Screening:

  • Includes medium-chain acyl-CoA dehydrogenase deficiency, congenital hypothyroidism, phenylketonuria, cystic fibrosis, and more, ensuring the early detection of life-threatening conditions.

DNA Analysis Methods

• Restriction Fragment Length Polymorphisms (RFLP):

  • Compares DNA banding patterns between affected and unaffected family members, a classic approach in identifying genetic disorders.

• Short Tandem Repeats (STRs):

  • Identifies variations in repetitive DNA sequences, which can indicate disease predispositions, utilized in forensic analysis and paternity testing.

• DNA Fingerprinting:

  • A technique for identifying individuals based on DNA variability, increasingly used in criminal justice and ancestry research.

Exome Sequencing and GWAS

• Exome Sequencing:

  • Targets only the protein-coding regions of the genome, representing about 1% of the total genome, to identify relevant genetic issues, allowing efficient identification of mutations.

• Genome-Wide Association Studies (GWAS):

  • Investigates associations between traits and specific alleles, offering insight into genetic influences on health, revolutionizing understanding of complex diseases.

Applications of Genetic Testing

• Presymptomatic Genetic Testing:

  • Determines genetic predispositions in healthy adults, including risks for hereditary illnesses such as Huntington's disease.

• Heterozygote Screening:

  • Identifies carriers of genetic conditions, crucial for family planning.

• Pharmacogenetic Testing:

  • Assesses how genetics influence drug effectiveness and safety, customizing medication plans to enhance efficacy and minimize adverse effects.

Considerations of Genetic Testing

• Evaluation of Genetic Tests:

  • ACCE framework assessing analytical validity, clinical utility, and ethical implications ensures dependable testing.

• EGAPP regarding genomic applications in practice reviews guidelines for integrating genetic testing into clinical practice effectively.

• Ethical and Social Concerns:

  • Issues surrounding privacy, insurance, employment, and protections under GINA (Genetic Information Nondiscrimination Act) established in 2008 are critical when discussing genetic testing, as they impact the public's willingness to utilize such services.