chr10·hg38·133.8 Mb

Chromosome 10

The tumor suppressor's home — where PTEN guards the genome and RET wires the nervous system, all on a chromosome whose two arms were once separate chromosomes in our primate ancestors.

Physical Properties

Length133.8 Mb

Centromeresubmetacentric

p-arm39.7 Mb

q-arm92.2 Mb

GC content41.0%

Genomic Features

Protein-coding genes733

Gene density5.5 / Mb

CpG islands12,462

EPIC v2 probes43,266

Notable

Largest geneNRG3 (1.1 Mb)

Disease associations

Cowden syndrome

MEN type 2

Endometrial cancer

· PTEN is one of the most commonly mutated tumor suppressors

· RET activating mutations cause multiple endocrine neoplasia type 2

· Contains the DMBT1 gene spanning 81 kb

Genomic Architecture

Isochore structure — Predominantly L2/H1 isochores, with GC-rich H2/H3 patches concentrated in the distal 10q telomeric region, consistent with the chromosome's modest gene density

Pericentromeric complexity — The sequences flanking the centromere are a "complex patchwork" of arm-specific sequences, stable duplications, and unstable repeats with homologies to telomeric and other centromeric locations. Two blocks of duplicat…

Segmental duplications — Inter- and intrachromosomal duplications have materially inflated the gene count; duplicated segments cluster in pericentromeric regions. 53% of evolutionary rearrangement breakpoints genome-wide associate with segmen…

Evolutionary History

Ancestral origin — Human chromosome 10 derives from the fusion of two ancestral primate chromosomes. In prosimian ancestors, 10p and 10q existed as separate chromosomes (designated PHYL-10p and PHYL-10q). These fused into a single chrom…

New World monkey configuration — In platyrrhines (New World monkeys), PHYL-10p remained a separate chromosome, while PHYL-10q was associated with material homologous to human chromosome 16

Deep Cuts

The dual-personality gene — RET is one of very few genes where activating mutations cause cancer (MEN2) and inactivating mutations cause a developmental disorder (Hirschsprung disease). The same cysteine residues in the extracellular domain can …

DiGeorge phenocopy — DGS2 on 10p is clinically indistinguishable from classic DiGeorge syndrome (22q11.2 deletion) — the two chromosomes converge on the same pharyngeal arch/neural crest developmental pathway, suggesting a shared regulato…

FRA10B breaks the rules — Most fragile sites break because they replicate late; FRA10B breaks despite normal replication timing, driven purely by its AT-rich secondary structure. It is the key counterexample to the late-replication model of ch…

§ Deep dive

Isochore structurePredominantly L2/H1 isochores, with GC-rich H2/H3 patches concentrated in the distal 10q telomeric region, consistent with the chromosome's modest gene density

Pericentromeric complexityThe sequences flanking the centromere are a "complex patchwork" of arm-specific sequences, stable duplications, and unstable repeats with homologies to telomeric and other centromeric locations. Two blocks of duplicated segments (~250 kb and ~150 kb) are separated by ~300 kb of unique DNA on each arm. Zinc-finger gene triads (ZNF11A/ZNF33A/ZNF37A on 10p; ZNF11B/ZNF33B/ZNF37B on 10q) are inverted across the centromere

Segmental duplicationsInter- and intrachromosomal duplications have materially inflated the gene count; duplicated segments cluster in pericentromeric regions. 53% of evolutionary rearrangement breakpoints genome-wide associate with segmental duplications (vs. 18% expected by chance)

Common fragile sitesTwo notable fragile sites:

FRA10A(10q23.3) — folate-sensitive, caused by CGG repeat expansion (>200 repeats trigger CpG methylation) in the FRA10AC1 gene encoding a conserved nuclear protein

FRA10B(10q25.2) — BrdU-inducible, caused by expansion of a ~42 bp AT-rich minisatellite. Unusually, FRA10B does not replicate late — a striking exception to the "late replication" model of fragile site expression

Repeat contentTypical LINE/SINE representation; no exceptional Alu enrichment or depletion reported relative to similarly sized chromosomes