Molecular Genetics Laboratory

Molecular tests analyze changes in one or more genes and determine the nucleotide sequences of DNA within an individual’s genetic code. This process, known as DNA sequencing, is performed in various forms:

1. Targeted Mutation Testing:
   This type of test seeks a specific change in a particular gene that is known to cause a disorder, such as a specific mutation in the HBB gene causing sickle cell disease. It is commonly performed in families with a known variant to determine whether other members are affected by the familial disorder.

2. Single-Gene Testing:
   These tests analyze genetic variations in a specific gene and are often used to confirm a particular diagnosis, especially when the gene has multiple variants that may cause disease. Single-gene disorders can follow different inheritance patterns:

• Autosomal dominant: Only one copy of the defective gene is required to cause the disease, e.g., Huntington’s disease and Marfan syndrome.

• Autosomal recessive: Two copies of the defective gene are required to manifest the disease, e.g., Cystic Fibrosis and Thalassemia.

• Sex-linked inheritance: The defective gene is located on a sex chromosome (X or Y). Examples include Hemophilia, Duchenne Muscular Dystrophy, and color blindness.

• Mitochondrial inheritance: These genes are exclusively inherited from the mother, and associated symptoms may include seizures, stroke, and gastrointestinal issues. Examples include Leigh syndrome, MELAS, LHON, and MERRF.

3. Gene Panel Testing:
   These tests screen for changes in multiple genes and are useful for precise diagnosis in individuals with similar clinical features across a wide range of conditions, such as genetic epilepsy. Multifactorial disorders, including cardiovascular diseases, diabetes, and cancer, where both genetic and environmental factors play a role, can also be identified using gene panels.

4. Whole Exome or Whole Genome Sequencing:
   These methods analyze a large portion of DNA to detect genetic variations and are typically requested when single-gene or panel testing is inconclusive, when a condition is suspected, or when the genetic cause of a disease is unknown. Whole exome/genome sequencing is also considered a cost-effective alternative to performing multiple single-gene tests.

5. Chromosomal Testing:
   These tests examine the entire set of chromosomes to detect large-scale changes such as chromosomal gain or loss (trisomy or monosomy), deletions, or rearrangements. Certain genetic syndromes are associated with specific chromosomal alterations, such as Williams syndrome, which results from a deletion on chromosome 7.

6. Gene Expression Testing:
   These tests determine which genes are active or inactive in cells. When a gene is active, it produces mRNA, which plays a role in protein synthesis. Gene expression tests study mRNA to identify active genes, as overexpression or underexpression of specific genes may indicate particular disorders, including various types of cancer.

In the modern era, as patients’ awareness of diseases and their causes increases, molecular testing has become widely used in medical genetics centers worldwide for pathogen detection and personalized medicine. These tests can be performed on human, animal, and microbial samples using advanced techniques such as PCR and Sanger sequencing to accurately identify genetic mutations.