Genetic Medicine & Medical Tools Quiz

Prenatal Genomics

• Antenatal screening is offered to pregnant women as part of routine standard care during pregnancy
• Methods of antenatal screening:
  • Non-genomic technologies (e.g. pregnancy ultrasound)
  • Genomic non-invasive prenatal testing (NIPT) using cell-free fetal DNA (cffDNA) to detect conditions caused by an atypical number of chromosomes
• Prenatal genomics: diagnostic testing
  • Invasive diagnostic testing (e.g. chorionic villus sampling (CVS), amniocentesis) to detect chromosomal or genomic variants
  • Pre-implantation genetic diagnosis (PGD) to test early embryos in vitro
  • Non-invasive prenatal diagnosis (NIPD) using maternal blood to detect fetal DNA

Congenital Adrenal Hyperplasia (CAH)

• Autosomal recessive inherited condition affecting the adrenal gland
• Symptoms include increased production of male hormones, leading to atypical genital development in females
• Early diagnosis is crucial, and prenatal diagnosis can inform treatment decisions

Rapid Fetal Whole Exome Sequencing (RP-WES)

• Analyzes fetal DNA to identify genetic variants associated with development during pregnancy
• Improves parental counseling and pregnancy management

Genetics of Polygenic and Multifactorial Disorders

• Access to polygenic risk scores can target higher-risk individuals for screening opportunities (e.g., mammograms)
• Variations in multiple genes can contribute to disease risk (e.g., breast cancer)

Aneuploidies

• Presence of an abnormal number of chromosomes in a cell or person's DNA
• Examples: Trisomy 21 (Down syndrome), Trisomy 18 (Edward's syndrome), Trisomy 13 (Patau syndrome)

Genomics of Rare Disorders

• Rare diseases are rare individually but collectively affect 3.5 million people in the UK
• Many rare diseases have a genetic cause
• Whole-genome sequencing has increased diagnostic possibilities

Mitochondrial DNA

• Mitochondria have multiple copies of circular mitochondrial DNA (mtDNA)
• Mitochondrial DNA has a higher rate of spontaneous mutation than nuclear DNA
• Heteroplasmy: mixture of mutant and wild-type mtDNA within each cell and among tissues

Gene Therapy

• Transfer of a section of DNA to cells to treat genetic disorders
• Somatic gene therapy: non-germline cells, effects not passed to offspring
• Germline gene therapy: germline cells, effects passed to offspring

CRISPR-Cas9

• Part of bacterial defense against viruses and pathogens
• Adapted for use in genetic editing in any organism, including humans
• Applications: treating genetic diseases, including cancer and hepatitis B

Artificial Intelligence in Diagnostics and Therapeutics

• AI enables understanding of complex genomics data, precision medicine, and preventative care

• AI requires ethical consideration and healthcare professionals should be aware of policies and standards### Disease Types and Inheritance

• Polygenic diseases are caused by several sets of alleles

• Multifactorial diseases are caused by multiple genetic variants and environmental factors

• Common diseases affect a large portion of the population, while rare diseases affect less than 1 in 2000 people

• Monogenic diseases are caused by a single gene, while mitochondrial diseases are caused by mutations in the mitochondrial DNA (mtDNA)

• Aneuploidies are diseases caused by differences in the number of chromosomes

Polygenic and Multifactorial Disorders

• Polygenic conditions or traits are caused by a combination of multiple genetic variants (loci) and do not have clear inheritance patterns
• Multifactorial inheritance refers to polygenic conditions or traits influenced by environmental factors
• Examples of multifactorial diseases include heart disease, cancer, diabetes, and arthritis
• Polygenic score or predisposition is the likelihood of a person developing a disease or trait based on their genetic profile

Family History and Genetic Pedigree

• X-linked recessive inheritance is a pattern of inheritance where a single gene variant on the X chromosome causes a disease
• Queen Victoria was a carrier of the recessive allele for haemophilia, and her sons had a 50% chance of having the disorder, while her daughters had a 50% chance of being carriers
• Mitochondrial DNA is inherited solely from the mother
• Microarray-based comparative genomic hybridization (array-CGH) is a technique that detects small deletions (microdeletions) and duplications (microduplications) in the genome

Microarray-Based Comparative Genomic Hybridization (array-CGH)

• Array-CGH involves labelling patient and reference DNA with different coloured fluorescent dyes and hybridizing them to an array of DNA probes
• The probes are spotted on the array slide in a non-even distribution, providing "backbone" coverage of the genome
• The array slide is washed and scanned, and the fluorescence emitted at each probe location is measured
• Computer software analyzes the data, and the results are presented as a ratio of patient to reference DNA signals
• Yellow indicates equal patient and reference DNA present, red indicates a deletion, and green indicates a duplication

Gene Therapy

• Gene therapy involves introducing DNA into a patient to treat a genetic disease
• The new DNA usually contains a functioning gene to correct the effects of a disease-causing mutation or inhibits the expression or blocks the activity of a defective gene