Chromosome 2 (human)

Chromosome 2 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second largest human chromosome, spanning more than 237 million base pairs ^[1] (the building material of DNA) and representing almost 8% of the total DNA in cells.

Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 2 likely contains 1,491 genes, including those of the HOXD homeobox gene cluster.^[2]

Evolution

Further information: Genes of the Chromosome 2 fusion site in chimpanzees

All members of Hominidae except humans have 24 pairs of chromosomes. Humans have only 23 pairs of chromosomes. Human chromosome 2 is widely accepted to be a result of an end-to-end fusion of two ancestral chromosomes.^[3][4]

Fusion of ancestral chromosomes left distinctive remnants of telomeres, and a vestigial centromere

The evidence for this includes:

• The correspondence of chromosome 2 to two ape chromosomes. The closest human relative, the chimpanzee, has near-identical DNA sequences to human chromosome 2, but they are found in two separate chromosomes. The same is true of the more distant gorilla and orangutan.^[5][6]
• The presence of a vestigial centromere. Normally a chromosome has just one centromere, but in chromosome 2 there are remnants of a second centromere.^[7]
• The presence of vestigial telomeres. These are normally found only at the ends of a chromosome, but in chromosome 2 there are additional telomere sequences in the middle.^[8]

Chromosome 2 presents very strong evidence in favour of the common descent of humans and other apes. According to researcher J. W. IJdo, "We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2." ^[8]

Genes

Among the genes located on chromosome 2 are these:

• ABCA12: ATP-binding cassette, sub-family A (ABC1), member 12
• ABCG5 and ABCG8: ATP-binding cassette, subfamily A, members 5 and 8
• AGXT: alanine-glyoxylate aminotransferase (oxalosis I; hyperoxaluria I; glycolicaciduria; serine-pyruvate aminotransferase)
• ALMS1: Alstrom syndrome 1
• ALS2: amyotrophic lateral sclerosis 2 (juvenile)
• BMPR2: bone morphogenetic protein receptor, type II (serine/threonine kinase)
• COL3A1: collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant)
• COL4A3: collagen, type IV, alpha 3 (Goodpasture antigen)
• COL4A4: collagen, type IV, alpha 4
• COL5A2: collagen, type V, alpha 2
• HADHA: hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit
• HADHB: hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit
• MSH2: mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
• MSH6: mutS homolog 6 (E. coli)
• NCL: Nucleolin
• NR4A2: nuclear receptor subfamily 4, group A, member 2
• OTOF: otoferlin
• PAX3: paired box gene 3 (Waardenburg syndrome 1)
• PAX8: paired box gene 8
• PELI1: Ubiquitin ligase
• SLC40A1: solute carrier family 40 (iron-regulated transporter), member 1
• SSB: Sjogren syndrome antigen B
• TPO: thyroid peroxidase
• TBR1: T-box, brain, 1
• WDR35 (IFT121: TULP4): intraflagellar transport 121

Related diseases & disorders

The following diseases are related to genes located on chromosome 2:

• 2p15-16.1 microdeletion syndrome
• Autism
• Alport syndrome
• Alström syndrome
• Amyotrophic lateral sclerosis
• Amyotrophic lateral sclerosis, type 2
• Congenital hypothyroidism
• Ehlers–Danlos syndrome
• Ehlers–Danlos syndrome, classical type
• Ehlers–Danlos syndrome, vascular type
• Fibrodysplasia ossificans progressiva
• Harlequin type ichthyosis
• Hemochromatosis
• Hemochromatosis, type 4
• Hereditary nonpolyposis colorectal cancer
• Infantile-onset ascending hereditary spastic paralysis
• Juvenile primary lateral sclerosis
• Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
• Maturity onset diabetes of the young type 6
• Mitochondrial trifunctional protein deficiency
• Nonsyndromic deafness
• Nonsyndromic deafness, autosomal recessive
• Primary hyperoxaluria
• Primary pulmonary hypertension
• Sitosterolemia (knockout of either ABCG5 or ABCG8)
• Sensenbrenner syndrome
• Synesthesia
• Waardenburg syndrome

Intelligence

Recent studies suggest that genes on chromosome 2 may play an important role in human intelligence.^[9]

References

1. ^ Hillier et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature 434 (7034): 724–31. doi:10.1038/nature03466. PMID 15815621. 
2. ^ Vega Homo sapiens Overview of Chromosome 2
3. ^ Human Chromosome 2 is a fusion of two ancestral chromosomes by Alec MacAndrew; accessed 18 May 2006.
4. ^ Evidence of Common Ancestry: Human Chromosome 2 (video) 2007
5. ^ Yunis and Prakash; Prakash, O (1982). "The origin of man: a chromosomal pictorial legacy". Science 215 (4539): 1525–1530. doi:10.1126/science.7063861. PMID 7063861. 
6. ^ Human and Ape Chromosomes; accessed 8 September 2007.
7. ^ Avarello et al. (1992). "Evidence for an ancestral alphoid domain on the long arm of human chromosome 2". Human Genetics 89 (2): 247–9. doi:10.1007/BF00217134. PMID 1587535. 
8. ^ ^{a b} IJdo et al. (1991). "Origin of human chromosome 2: an ancestral telomere-telomere fusion". Proceedings of the National Academy of Sciences 88 (20): 9051–5. doi:10.1073/pnas.88.20.9051. PMC 52649. PMID 1924367. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=52649. 
9. ^ A Linkage Study of Academic Skills Defined by the Queensland Core Skills Test