chr11·hg38·135.1 Mb

Chromosome 11

The genome's most gene-dense autosome and birthplace of the olfactory receptor superfamily — home to the beta-globin cluster that taught us gene regulation, the IGF2/H19 imprinting paradigm, and more disease genes per megabase than almost any other chromosome.

Physical Properties

Length135.1 Mb

Centromeremetacentric

p-arm51.1 Mb

q-arm80.7 Mb

GC content41.6%

Genomic Features

Protein-coding genes1,298

Gene density9.6 / Mb

CpG islands14,556

EPIC v2 probes49,497

Notable

Largest geneDLG2 (2.2 Mb)

Disease associations

Sickle cell disease

Beta-thalassemia

Beckwith-Wiedemann syndrome

· Contains the beta-globin cluster (HBE1, HBG1/2, HBD, HBB)

· 11p15.5 is an imprinted region — Beckwith-Wiedemann syndrome

· KMT2A (MLL) rearrangements define infant leukemia

Genomic Architecture

Olfactory receptor (OR) megacluster — 369 of the genome's 856 OR genes (43%) reside on chromosome 11, distributed across 28 single- and multi-gene clusters. This is by far the richest OR chromosome — ORs represent >10% of all chromosome 11 genes. Two clus…

Isochore structure — Heterogeneous — 11p15 is GC-rich and gene-dense; central 11q contains large L1/L2 isochore domains; distal 11q is moderately GC-rich

Segmental duplications — Pericentromeric region heavily duplicated; OR gene clusters themselves represent massive tandem and interspersed segmental duplications, with evidence of ongoing copy-number variation

Evolutionary History

Ancestral origin — Chromosome 11 corresponds largely to a single ancestral mammalian chromosome that has been conserved as a syntenic block across placental mammals. It shows extensive synteny with mouse chromosome 7 (proximal and dista…

OR gene origin — The concentration of both Class I and Class II olfactory receptors — with 9 of 13 Class II families represented — strongly supports chromosome 11 as the evolutionary birthplace of the vertebrate OR repertoire. The OR4…

Deep Cuts

The first molecular disease — Sickle cell disease (HBB Glu6Val) was identified as a "molecular disease" by Linus Pauling in 1949, then pinpointed to a single amino acid by Vernon Ingram in 1956. This was the founding event of molecular medicine, a…

The 2.7 kb gap — Tyrosine hydroxylase (TH) and insulin (INS) are separated by only 2.7 kb of DNA on 11p15.5. The rate-limiting enzyme for catecholamine synthesis sits essentially on top of the hormone that regulates glucose metabolism…

Olfactory receptor graveyard — Of the 369 OR genes on chromosome 11, a large fraction are pseudogenes — "dead" olfactory receptors inactivated during primate evolution as the visual system expanded and olfaction became less critical. Chromosome 11 …

§ Deep dive

Olfactory receptor (OR) megacluster369 of the genome's 856 OR genes (43%) reside on chromosome 11, distributed across 28 single- and multi-gene clusters. This is by far the richest OR chromosome — ORs represent >10% of all chromosome 11 genes. Two clusters exceed 100 OR genes each, the largest in the genome. The OR4 superfamily cluster (48.1—55.2 Mb) was fractured into four pieces by centromere insertion, a heterochromatic block, and an intrachromosomal duplication. Chromosome 11 is the only chromosome containing Class I olfactory receptors and has 9 of 13 Class II families — strong evidence that it was the evolutionary birthplace of the OR repertoire

Isochore structureHeterogeneous — 11p15 is GC-rich and gene-dense; central 11q contains large L1/L2 isochore domains; distal 11q is moderately GC-rich

Segmental duplicationsPericentromeric region heavily duplicated; OR gene clusters themselves represent massive tandem and interspersed segmental duplications, with evidence of ongoing copy-number variation

Common fragile sitesFRA11B (11q23.3) maps to the CBL2 locus; FRA11A is folate-sensitive at 11q13.3. The 11q23 region is a recurrent breakpoint zone in leukemia

Repeat contentThe OR gene clusters are interspersed with LINE elements that may have facilitated their tandem expansion; Alu density is elevated in the gene-dense 11p15 region