chr17·hg38·83.3 Mb

Chromosome 17

The evolutionary black sheep: the most rearranged chromosome in the primate lineage, the densest in cancer genes, and home to a 900-kb inversion that may have shaped the European mind.

Physical Properties

Length83.3 Mb

Centromeresubmetacentric

p-arm22.8 Mb

q-arm56.6 Mb

GC content45.5%

Genomic Features

Protein-coding genes1,197

Gene density14.4 / Mb

CpG islands15,438

EPIC v2 probes43,584

Notable

Largest geneNF1 (350 kb)

Disease associations

Li-Fraumeni syndrome

Breast cancer (BRCA1/HER2)

Neurofibromatosis type 1

· TP53 is mutated in >50% of all human cancers

· Most gene-dense chromosome per Mb along with chr19

· HER2 amplification defines ~20% of breast cancers

Genomic Architecture

Isochore structure — Predominantly GC-rich H2/H3 isochores — unusual for this size.

LCR architecture — 17p11.2 and 17p12 harbor complex low-copy repeats mediating recurrent microdeletions/microduplications (CMT1A-REPs, SMS-REPs).

Evolutionary breakpoints — 20 rearrangement breakpoints in human lineage vs only 3 in mouse — the most dramatic interspecific contrast for any autosome. Nearly all co-localize with segmental duplications.

Evolutionary History

"Evolutionary black sheep" — 20 breakpoints in human lineage vs 3 in mouse — most dramatic contrast for any autosome. Yet interchromosomal synteny is perfectly preserved across mammals.

17q21.31 inversion polymorphism — ~900-kb inversion containing MAPT. H2 (ancestral, inverted) found ~20% in Europeans, nearly absent elsewhere. Under positive selection — associated with increased female fecundity.

Deep Cuts

H2 fertility paradox — The H2 haplotype is under positive selection because carrier women have more children — yet it predisposes to the 17q21.31 microdeletion causing intellectual disability. Selection favors the haplotype despite its path…

Genes within genes — NF1 harbors OMGP, EVI2B, and EVI2A transcribed from the opposite strand inside its introns — exceedingly rare architecture.

Smith-Magenis inverted clock — The only known genetic syndrome with a fully inverted circadian melatonin pattern — peak during daytime.

§ Deep dive

Isochore structurePredominantly GC-rich H2/H3 isochores — unusual for this size.

LCR architecture17p11.2 and 17p12 harbor complex low-copy repeats mediating recurrent microdeletions/microduplications (CMT1A-REPs, SMS-REPs).

Evolutionary breakpoints20 rearrangement breakpoints in human lineage vs only 3 in mouse — the most dramatic interspecific contrast for any autosome. Nearly all co-localize with segmental duplications.