These terms all relate to different scopes of genetic material and sequencing approaches. Here’s a breakdown of the differences, keeping it straightforward but precise:

Genome

• Definition: The genome is the complete set of DNA in an organism—every single base pair, including all genes and non-coding regions. In humans, that’s about 3 billion base pairs across 23 pairs of chromosomes.
• Sequencing: Whole-genome sequencing (WGS) reads this entire thing using next-generation sequencing (NGS). It captures coding regions (exons), non-coding regions (introns, regulatory sequences), and everything else.
• Use: Great for discovering new mutations, structural variants (e.g., large deletions), or studying non-coding DNA’s role in disease. It’s the most comprehensive but generates tons of data and can be overkill for specific questions.

Exome

• Definition: The exome is the subset of the genome that codes for proteins—specifically, all the exons. Exons are the parts of genes that get translated into proteins, making up about 1-2% of the human genome (~30 million base pairs).
• Sequencing: Whole-exome sequencing (WES) targets just these regions. During library prep for NGS, probes or baits hybridize to exon-specific sequences, enriching them before sequencing.
• Use: Ideal for finding mutations in protein-coding genes linked to diseases (e.g., Mendelian disorders, cancer driver mutations). It’s cheaper and faster than WGS but misses non-coding variants.

Limited Exome

• Definition: This isn’t a standard term but typically refers to a restricted version of exome sequencing, focusing on a subset of exons—often a panel of specific genes relevant to a condition (e.g., cancer genes like BRCA1 or TP53).
• Sequencing: Similar to WES but with a narrower target, using custom probes for fewer genes. Think of it as a “mini-exome” tailored to a purpose.
• Use: Used in clinical settings for cost-efficiency or when only certain genes matter (e.g., hereditary cancer panels). It’s less comprehensive than a full exome but more focused.

Chromosome

• Definition: A chromosome is a single, long DNA molecule (plus proteins) that contains many genes. Humans have 46 chromosomes (23 pairs), and each carries a chunk of the genome—e.g., chromosome 1 has ~250 million base pairs.
• Sequencing: You wouldn’t typically “sequence a chromosome” in isolation with NGS unless you’re studying something specific (e.g., chromosomal abnormalities). Techniques like karyotyping or FISH (fluorescence in situ hybridization) visualize chromosomes, while NGS might target regions on a chromosome.
• Use: Chromosome-level analysis often focuses on structure (e.g., aneuploidy like Down syndrome—extra chromosome 21) rather than sequence details. Sequencing a whole chromosome would fall under WGS unless narrowed down.

Key Differences

• Scope:
  • Genome = everything (coding + non-coding, all chromosomes).
  • Exome = all coding regions (~1-2% of genome, across all chromosomes).
  • Limited Exome = a curated subset of coding regions.
  • Chromosome = one physical DNA structure (part of the genome, with coding and non-coding DNA).
• Data Size: WGS gives you 100x more data than WES. Limited exome is even smaller. Chromosome-level work depends on the context.
• Cost & Time: WGS > WES > limited exome. Chromosome-specific sequencing isn’t a standard standalone thing.
• Applications:
  • Genome: Broad discovery (e.g., rare diseases, population genetics).
  • Exome: Protein-coding mutations (e.g., genetic disorders).
  • Limited Exome: Targeted diagnostics (e.g., specific cancers).
  • Chromosome: Structural insights (e.g., prenatal testing).

Example

Imagine you’re hunting a genetic cause for a disease:

• WGS: Sequences the whole genome—might find a mutation in a regulatory region.
• WES: Checks all exons—catches a coding mutation in a gene like CFTR (cystic fibrosis).
• Limited Exome: Tests just 50 cancer-related genes—spots a BRCA1 mutation.
• Chromosome: Looks at chromosome 7’s structure—might see a deletion causing a syndrome.