Genetics

Human genetics in the clinical lab often deals with variations within a relatively stable (per generation) but complex genome to understand inherited risk and disease. Microbial genetics contends with highly dynamic and diverse genomes, focusing on identification and the rapid evolution of clinically critical traits like drug resistance, primarily driven by HGT

Human Genetics vs. Microbial Genetics

Both fields explore how genetic information encoded in nucleic acids dictates function, variation, and disease. However, their context and the types of questions asked in the clinical lab are distinct

Human Genetics (Focus: The Host Blueprint)

• Genome Structure: Large (~3 billion bp), diploid (2n=46), linear chromosomes complexed with histones into chromatin, located within a nucleus. Contains vast amounts of non-coding DNA, including introns
• Gene Regulation: Complex, involving transcription factors, enhancers/silencers, chromatin remodeling, extensive RNA processing (splicing of introns/exons), and epigenetics (methylation, histone modification)
• Variation & Inheritance
  • Mutations (point, CNVs, rearrangements) arise but at a slower rate relative to organism lifespan
  • Inheritance is primarily vertical (parent to offspring) via sexual reproduction, following Mendelian (AD, AR, XL) and Non-Mendelian (Mitochondrial, Imprinting, Triplet Repeats) patterns
  • Focus on germline mutations (inherited diseases) and somatic mutations (cancer)
• Clinical Focus
  • Diagnosing inherited monogenic disorders (e.g., CF, Sickle Cell)
  • Identifying chromosomal abnormalities (e.g., Down syndrome)
  • Cancer genetics: Detecting inherited predispositions (e.g., BRCA) and somatic mutations guiding targeted therapy (e.g., EGFR, KRAS)
  • Pharmacogenomics: Predicting drug response based on genetic variants
  • Carrier screening and prenatal diagnosis

Microbial Genetics (Focus: Pathogen/Commensal Blueprints)

• Genome Structure: Highly diverse!
  • Bacteria: Typically smaller (~1-10 million bp), haploid, single circular chromosome in a nucleoid (no nucleus). Often contain crucial plasmids. Genes densely packed, often in operons; introns are rare
  • Viruses: Tiny genomes; can be DNA/RNA, ss/ds, linear/circular/segmented. Rely heavily on host machinery
  • Fungi/Parasites: Eukaryotic, with nuclear chromosomes, but generally smaller genomes than humans
• Gene Regulation: Primarily geared towards rapid adaptation. Operons allow coordinated response. Transcription/translation often coupled (bacteria)
• Variation & Inheritance
  • High mutation rates due to rapid replication cycles
  • Massive role of Horizontal Gene Transfer (HGT): sharing genes between organisms via transformation, transduction, conjugation
  • Mobile Genetic Elements (MGEs): like plasmids, transposons, and integrons are key drivers of variation and spread of traits like resistance
• Clinical Focus
  • Pathogen Identification: Detecting specific microbial DNA/RNA for diagnosis
  • Antimicrobial Resistance (AMR): Detecting specific genes (mecA, blaKPC, vanA) or mutations conferring resistance to guide treatment (MAJOR FOCUS)
  • Virulence Factor Detection: Identifying genes associated with pathogenicity
  • Epidemiology/Strain Typing: Tracking outbreaks and transmission using genetic markers or sequencing
  • Viral load monitoring and genotyping

Key Contrasts for the Clinical Lab

Feature	Human Genetics Emphasis	Microbial Genetics Emphasis
Primary Goal	Diagnose inherited disease, cancer genetics	Diagnose infection, detect AMR, track outbreaks
Key Variation Source	Germline/Somatic Mutations, CNVs	Mutations, HGT via MGEs
Genome Complexity	High, large, linear, chromatin	Diverse, often simpler, plasmids crucial (bacteria)
Major Diagnostic Methods	Sequencing, CMA, PCR, FISH, Karyotyping	PCR/RT-PCR, Sequencing, specialized AMR assays
Therapeutic Implication	Targeted cancer therapy, gene therapy (emerging)	Antibiotic selection, antiviral therapy