chr1·hg38·249.0 Mb

Chromosome 1

The behemoth of the human karyotype: 249 million base pairs encoding more protein-coding genes than any other chromosome, yet the last to be fully sequenced — not completed until May 2006, three years after the Human Genome Project declared victory.

Physical Properties

Length249.0 Mb

Centromeremetacentric

p-arm122.0 Mb

q-arm124.0 Mb

GC content41.3%

Genomic Features

Protein-coding genes2,058

Gene density8.3 / Mb

CpG islands28,846

EPIC v2 probes97,108

Notable

Largest geneRYR2 (790 kb)

Disease associations

Charcot-Marie-Tooth 1B

Gaucher disease

Hereditary leiomyomatosis

· Largest human chromosome at 249 Mb

· Contains ~2,000 protein-coding genes

· 1p36 deletion is the most common terminal deletion syndrome

Genomic Architecture

Isochore structure — Chromosome 1 is a mosaic of all five isochore families (L1, L2, H1, H2, H3). The telomeric 1p36 region is notably GC-rich, while the pericentromeric heterochromatin at 1q12 is deeply AT-rich — one of the largest const…

Segmental duplications — The pericentromeric region is a hotspot for segmental duplications (SDs). One-third of human-specific SDs reside within pericentromeric regions, and chromosome 1 contributes disproportionately. A human-lineage-specifi…

Repeat content — ~45% interspersed repeats (LINE-1 enriched in q-arm Giemsa-dark bands; Alu enriched in GC-rich, gene-dense regions of 1p). The 1q12 heterochromatin block contains megabases of classical satellite DNA that is notorious…

Evolutionary History

Ancestral origins — Comparative cytogenetics indicates that the ancestral eutherian karyotype contained a chromosome homologous to human chromosome 1 as a single syntenic block. This synteny is conserved across most placental mammals — t…

Pericentric inversion — After the human-chimpanzee split (~6 Mya), a pericentric inversion occurred between 1p13 and 1q23 in the human lineage. This inversion is one of nine major karyotypic differences between humans and chimpanzees (the ot…

Deep Cuts

Last chromosome sequenced — Despite being chromosome number 1, it was the *last* human chromosome to have its sequence completed (Gregory et al., Nature 2006). The difficulty arose from its sheer size, the complex pericentromeric segmental dupli…

The "1qh" polymorphism — The size of the 1q12 heterochromatic block varies up to 3-fold between individuals and is one of the most common cytogenetic heteromorphisms reported in prenatal diagnostics. It is entirely benign but has historically…

Chromosome 1 and schizophrenia — The 1q21.1 locus is one of the most replicated structural variant associations in psychiatric genetics. Deletions increase schizophrenia risk ~8-fold; duplications increase autism risk ~3-fold. The same genomic interv…

§ Deep dive

Isochore structureChromosome 1 is a mosaic of all five isochore families (L1, L2, H1, H2, H3). The telomeric 1p36 region is notably GC-rich, while the pericentromeric heterochromatin at 1q12 is deeply AT-rich — one of the largest constitutive heterochromatin blocks in the genome (sometimes called the "1qh" region), composed primarily of satellite II and III repeats visible as a C-band.

Segmental duplicationsThe pericentromeric region is a hotspot for segmental duplications (SDs). One-third of human-specific SDs reside within pericentromeric regions, and chromosome 1 contributes disproportionately. A human-lineage-specific pericentric inversion distinguishes human chromosome 1 from the chimpanzee homolog.

Repeat content~45% interspersed repeats (LINE-1 enriched in q-arm Giemsa-dark bands; Alu enriched in GC-rich, gene-dense regions of 1p). The 1q12 heterochromatin block contains megabases of classical satellite DNA that is notoriously difficult to assemble.

Fragile sitesHouses several common fragile sites including FRA1A (1p36), FRA1B (1p32), FRA1E (1p21.3), FRA1F (1q21), and FRA1H (1q42). The rare folate-sensitive fragile site FRAXA is on the X chromosome, but FRA1A at 1p36 is among the most frequently expressed common fragile sites in the genome.

Evolutionary breakpointsA pericentric inversion between 1p13 and 1q23 occurred after the human-chimpanzee divergence, making it one of nine major chromosomal inversions distinguishing human and chimpanzee karyotypes.