Chromosome and Extrachromosomal Structure

The nuclear genome

Human somatic cells are diploid: 46 chromosomes, 22 pairs of autosomes plus the sex chromosomes (XX or XY), one set from each parent ¹. The haploid set (23 chromosomes, as in an egg or sperm) is about 3.2 billion base pairs, so a somatic cell holds about 6.4 billion ¹, folded into nucleosomes and chromatin (see DNA-Associated Proteins).

The number that matters most for testing: a typical nuclear gene is present at two copies per cell. A haploid human genome weighs about 3.3 picograms, so 10 ng of genomic DNA holds only about 3,000 copies of a single-copy gene (about 1,500 cells), a useful sanity check when an assay looks too sensitive.

Chromosome landmarks and band addresses

• Centromere: the constriction holding sister chromatids together and attaching to the spindle; it splits the chromosome into two arms.
• p arm (short, petit) and q arm (long) ¹.
• Telomeres: TTAGGG repeats capping each end so it isn’t mistaken for a break ¹.

A karyotype shows all chromosomes, arranged by size and centromere position. Staining (G-banding) gives each chromosome a reproducible pattern of light and dark bands, and the bands give addresses: chromosome, arm, region, band, sub-band ¹.

Karyotype shorthand (ISCN) gives count, sex chromosomes, then changes:

The mitochondrial genome

Each mitochondrion carries its own small, circular genome, a relic of its bacterial ancestry ¹:

• 16,569 bp with 37 genes: 13 respiratory-chain proteins, 22 tRNAs, 2 rRNAs. Most mitochondrial proteins are still encoded in the nucleus and imported ¹.
• Maternally inherited through the egg ¹.
• High copy number: many mitochondria per cell, several genomes each - hundreds to thousands of copies per cell ².
• Heteroplasmy: a cell can hold a mix of normal and variant mtDNA, and the proportion affects disease severity.

Plasmids, phage, and viruses

Plasmids are small circular double-stranded DNAs that replicate independently of the bacterial chromosome, often carrying antibiotic-resistance genes that spread between bacteria ¹. Carbapenemase genes like blaKPC travel on plasmids, one reason labs test for resistance genes directly. Plasmids are also the lab’s cloning vectors: insert a sequence, grow the bacteria, harvest many copies ³. Plasmid copy number ranges from one to hundreds per cell.

Bacteriophages infect bacteria and have also been adapted as vectors ¹.

Viral genomes come in every combination: DNA or RNA, single- or double-stranded, linear or circular, sometimes segmented ¹.

RNA viruses need a reverse transcription step before PCR; this is why the extraction and amplification must match the target.

Copy number and sensitivity

The template a specimen holds sets a floor on what an assay can detect ³. Forensic labs use mtDNA for hair shafts and old bone for exactly this reason, and many infectious-disease assays target multicopy genes or rRNA to boost sensitivity.

What to take from this

Human cells carry 46 chromosomes (3.2 Gb per haploid set), so a nuclear gene starts at two copies per cell. Chromosome addresses read chromosome, arm (p short, q long), region, band, sub-band - CFTR is at 7q31.2 - and karyotypes read count, sex chromosomes, changes. mtDNA is a 16,569 bp maternally inherited circle at hundreds to thousands of copies per cell. Plasmids carry resistance genes and serve as vectors, and viral genomes vary in chemistry. Copy number sets the sensitivity floor.