chr15·hg38·102.0 Mb

Chromosome 15

The imprinting chromosome — where parent-of-origin rewrites the rules, a single SNP determines eye color for a continent, and segmental duplications make it the most rearrangement-prone acrocentric in the genome.

Physical Properties

Length102.0 Mb

Centromeresubmetacentric

p-arm17.1 Mb

q-arm82.3 Mb

GC content42.2%

Genomic Features

Protein-coding genes613

Gene density6.0 / Mb

CpG islands9,626

EPIC v2 probes32,021

Notable

Largest geneRORA (730 kb)

Disease associations

Prader-Willi syndrome

Angelman syndrome

Marfan syndrome

· 15q11-13 imprinting: paternal deletion → Prader-Willi, maternal → Angelman

· PML-RARA fusion t(15;17) defines acute promyelocytic leukemia

· Acrocentric chromosome

Genomic Architecture

BP1-BP2 — interval (~0.5 Mb): Contains four non-imprinted genes (NIPA1, NIPA2, CYFIP1, TUBGCP5) deleted in the "Type I" Prader-Willi/Angelman deletion

BP2-BP3 — interval (~4 Mb): The Prader-Willi/Angelman critical region (PWACR), containing all known imprinted genes

BP3-BP4 — and **BP4-BP5** intervals: Contain the GABAA receptor gene cluster (GABRB3, GABRA5, GABRG3) and other non-imprinted genes

Evolutionary History

Chimpanzee — Human chromosome 15 corresponds to chimpanzee chromosome 16

Gorilla/Orangutan — The syntenic block is preserved with the same acrocentric morphology

Deep Cuts

The snoRNA that controls hunger — SNORD116, a cluster of 29 small nucleolar RNAs at 15q11.2, is now considered the critical gene for Prader-Willi syndrome's defining feature — insatiable hunger. These snoRNAs have no known rRNA targets (unlike canonic…

One SNP, one continent's eye color — The rs12913832 variant in HERC2 intron 86 is a single nucleotide change (A>G) that explains 74% of eye color variation in Europeans. The blue-eye G allele disrupts a chromatin loop connecting a HERC2 intronic enhancer…

The dup15q EEG signature — Children with isodicentric chromosome 15 (tetrasomy of 15q11-q13) show a distinctive EEG pattern — persistent high-amplitude beta activity (20-30 Hz) that closely resembles the EEG signature of benzodiazepine administ…

§ Deep dive

BP1-BP2interval (~0.5 Mb): Contains four non-imprinted genes (NIPA1, NIPA2, CYFIP1, TUBGCP5) deleted in the "Type I" Prader-Willi/Angelman deletion

BP2-BP3interval (~4 Mb): The Prader-Willi/Angelman critical region (PWACR), containing all known imprinted genes

BP3-BP4and **BP4-BP5** intervals: Contain the GABAA receptor gene cluster (GABRB3, GABRA5, GABRG3) and other non-imprinted genes

These LCRs mediate non-allelic homologous recombination (NAHR), making 15q11-q13 one of the most rearrangement-prone regions in the human genome. The recurrence rate for de novo deletions is ~1 in 12,000-20,000 births

SINEs/AluEnriched relative to genome average, particularly in the proximal 15q region. The segmental duplications at BP1-BP5 contain Alu elements at their boundaries, and Alu-Alu recombination contributes to smaller rearrangements within the PWACR

LINEsNear genome average overall

The HERC2 gene at 15q13.1 is itself a segmental duplication — HERC2 duplicons are scattered across 15q11-q13 and have been a major driver of genomic instability in this region

FRA15A(15q22): Aphidicolin-sensitive fragile site

The proximal 15q region, while not a classical fragile site, is effectively a "structural fragility hotspot" due to the density of segmental duplications