Human chromosome 1

Ideogram of human chromosome 1

Human chromosome 1 is the largest of human chromosomes , one of 22 human autosomes . The chromosome contains more than 248 million base pairs , ^[1] which represents approximately 8% of the total DNA material of a human cell ^[2] .

Currently, it is estimated that there are 4505 genes on chromosome ¹ , ^[1] which is higher than previously made predictions about the number of genes that were based on chromosome sizes.

According to the cytogenetic classification, chromosome 1 belongs to the chromosomes of group A, which means that this chromosome belongs to the group of the largest human chromosomes and is a metacentric, that is, it has shoulders (p- and q-) of approximately equal length. Chromosome 1 has a large heterochromatic region, which includes two centromere bands 1p11 and 1q11, as well as a centromeric band 1q12, together constituting about 5% of the length of chromosome 1 ^[3] .

Chromosome 1 contains fewer repetitive dispersed sequences than the average for the human genome (32.49% vs. 45%, respectively). This difference is mainly due to the lower content of long dispersed nuclear elements (LINEs - long interspersed nuclear elements), which in chromosome 1 contains 11.34% of the entire length of the chromosome, while on average the human genome contains about 20% of LINE-sequences ^{[ 3]} .

The work on determining the nucleotide sequence of the 1st chromosome was coordinated by the Sanger Institute , it was received and published last ^[4] ^[5] in the framework of the Human Genome Project two decades after it began.

Genes

Chromosome 1 has an average gene density of about 14.2 genes per 1 million base pairs, which is almost twice as high as the average for the human genome (7.8 genes per 1 million base pairs). Thus, chromosome 1 is one of the richest in human chromosome genes ^[2] .

Chromosome 1 contains several clusters of genes encoding functionally and / or structurally related transcripts . The most significant is the cluster of epidermal differentiation genes, occupying 2.5 million base pairs in a 1q21 band. This cluster contains 14 genes that are specifically expressed during the calcium-dependent keratinocyte differentiation, and 13 additional genes belonging to the S100 family of calcium-binding proteins ^[3] .

Chromosome 1 contains two gene clusters of canonical histones : in the 1q21 band, there is a HIST2 cluster containing 6 histone genes, and in the 1q42 band, there is a HIST3 cluster consisting of three genes ^[6] .

On the q-arm in the 1q22-q23 bands there is a cluster of genes encoding CD1 antigens (CD1A - CD1E), and also on this shoulder in the 1q23-q25 bands is a cluster of genes encoding flavin-containing monooxygenases (FM01 - FM05).

On the p-arm, the most significant clusters are the cluster of genes encoding amylases (AMY1A - AMY1C, AMY2A, AMY2AB), which is in the 1p21 band, the cluster of connexin genes (GJA4, GJA10, GJB3 - GJB5) in the band 1p34-p35.1, and also the glutathione -S-transferase gene cluster (GSTM1 - GSTM5) in the 1p13.3 band ^[3] .

Listed below are some genes located on chromosome 1 .

Shoulder p

ACADM (1p31.1) - Acyl CoA dehydrogenase of medium chain fatty acids (MCAD)
ANGPTL3 (1p31.3) - a protein of the angiopoietin -like protein family;
ANGPTL7 (1p36.22) - a protein of the angiopoietin -like protein family;
CASP9 (1p36.21) - caspase 9, apoptosis mediator;
CD2 (1p13.1) - membrane protein , intercellular adhesion molecule;
CD53 (1p13.3) - CD53 antigen, or tetraspanine 25;
COL11A1 (1p21.1) - α ₁ -chain collagen type XI;
CPT2 (1p32.3) - carnitine palmitoyl transferase 2;
CLCN6 (1p36.22) - chloride channel 6;
DAB1 (1p32.2) - homologue of 1 gene for the Drosophila disabled ;
DBT (1p21.2) - branched transacylase E2 dihydrolipoamide ;
DIRAS3 (1p31.3) - RAS-like GTP-binding protein 3 of the DIRAS family;
ENO1 (1p36.23) - α-enolase, or enolase 1;
ESPN (1p36.31) - Espin;
GALE (1p36.11) - UDP-galactose-4-epimerase;
GJB3 (1p34.3) - β ₃ -subunit of the slot contact 31 kDa, or connexin 31;
HMGCL (1p36.11) - 3-hydroxymethyl-3-methylglutaryl-CoA-lyase;
HSD3B1 (1p12) - 3β-hydroxy-Δ ⁵ -steroid dehydrogenase and steroid-Δ-isomerase 1;
HSD3B2 (1p12) - 3β-hydroxy-Δ ⁵ -steroid dehydrogenase and steroid-Δ-isomerase 2;
KCNQ4 (1p34.2) - α-subunit of the potential-dependent potassium channel English. voltage-gated potassium channel , a member of the 4 subfamily KQT-like;
KIF1B (1p36.22) - a member of the 1B kinesin family;
LIN28A (1p36.11) is the homolog A of the lin-28 gene of C. elegans ;
LRP8 (1p32.3) - low density lipoprotein receptor 8, apolipoprotein E receptor;
MFN2 (1p36.22) - mitofuzin 2;
MTHFR (1p36.22) - 5,10-methylenetetrahydrofolate reductase;
MUTYH (1p34.1) - homY gene mutY E. coli ;
NCDN (1p34.3) - neurochondrin;
NGF (1p13.2) - β-subunit of nerve growth factor ;
PARK7 (1p36.23) - an autosomal recessive type associated with Parkinson's disease with early manifestation of gene 7;
PCSK9 (1p32.3) - a hydrolase from the family of proprotein convertases;
PDE4B (1p31.3) - phosphodiesterase 4B;
PINK1 (1p36.12) - PTEN -inducible kinase 1;
PLOD1 (1p36.22) - procollagen-lysine 1, or 2-oxoglutarate-5-dioxygenase 1;
PTPRF (1p34.2) - receptor-like protein tyrosine phosphatase F;
ROR1 (1p31.3) - transmembrane receptor protein tyrosine kinase ROR1;
RPE65 (1p31.3) - an enzyme of retinal cells;
SDC3 (1p35.2) - membrane protein , proteoglycan of the syndecan family;
SESN2 (1p35.3) - protein family sisters;
STMN1 (1p36.11) - statmin 1;
TNFRSF4 (1p36.33) - receptor for the superfamily of tumor necrosis factor receptors (OX40; CD134);
TNFRSF14 (1p36.32) - receptor superfamily of tumor necrosis factor receptors;
TNFRSF18 (1p36.33) - receptor for superfamily of tumor necrosis factor receptors;
TSHB (1p13.2) - β-subunit of thyroid-stimulating hormone ;
UBIAD1 (1p36.22) - prenyltransferase domain-containing protein;
UROD (1p34.1) - uroporphyrinene decarboxylase.

Shoulder q

AGT (1q42.2) - angiotensinogen;
AIM2 (1q23.1 — q23.2) - cytokine ;
APOA2 (1q23.3) - apolipoprotein A-II;
ARNT (1q21.3) - nuclear aromatic receptor translocator ( AHR )
AQP10 (1q21.3) - water channel of a group of aquaporins
ASPM (1q31.3 ^[7] ) - an asp Drosophila asp homolog associated with microcephaly ;
CD34 (1q32.2) - stem cell adhesion molecule;
CD46 (1q32.2) - inhibitory receptor of complement;
CRB1 (1q31.3) - homologue of 1 gene of Drosophila crumbs ;
CRP (1q23.2) - C-reactive protein;
DDR2 (1q23.3) - membrane protein, receptor tyrosine kinase ;
DISC1 (1q42.2) - “1 disrupted in schizophrenia”;
F5 (1q24.2) - coagulation factor V, or proaccelerin, or labile factor;
FMO3 (1q24.3) - flavin-containing monooxygenase 3;
GBA (1q22) - acidic β-glucosidase;
HFE2A (1q21.1) - gene 2 associated with juvenile hemochromatosis type II, or hemo-juvelin;
HPC1 (1q25.3) - gene 1 associated with hereditary prostate cancer ;
HSD11B1 (1q32.2) - 11-β-hydroxysteroid dehydrogenase type 1;
IRF6 (1q32.2) - interferon-regulating factor 6;
ITGA10 (1q21.1) is a glycoprotein from the integrin superfamily (alpha-10);
LAMB3 (1q32.2) - β ³ chain of laminins ;
LMNA (1q22) - Lamin A and Lamin C;
LYST (1q42.3) - a regulator of lysosomal transport ;
MPZ (1q23.3) is the main protein of myelin;
MTR (1q43) - 5-methyltetrahydrofolate-homocysteine methyltransferase (methionine synthetase);
MUC1 (1q22) - mucin , a protective protein of the surface of epithelial cells;
MYOC (1q24.3) - myocilin, or a protein that induces the glucocorticoid response of the trabecular network ;
NCF2 (1q25.3) - neutrophil cytosolic factor 2;
NGFR (17q21.33) - nerve growth factor receptor ;
NID1 (1q42.3) - nidogen 1;
NLRP3 (1q44) - cryopyrin;
NOS1AP (1q23.3) - adapter protein of neuronal NO synthase;
NTRK1 (1q23.1) - neurotrophic receptor tyrosine kinase 1;
PLXNA2 (1q32.2) - plexin A2;
PPOX (1q23.3) - protoporphyrinogen oxidase;
PTPRC (1q31.3-q32.1) - receptor type tyrosine protein phosphatase C (CD45);
PSEN2 (1q42.13) - presenilin 2;
RGS4 (1q23.3) - regulator of G-protein activity;
SELE (1q24.2) - E-selectin;
SELL (1q24.2) - L-selectin;
SELP (1q24.2) - P-selectin;
SDHB (1p36.13) - subunit B succinate dehydrogenase ;
SHC1 (1q21.3) - adapter protein signaling cascade of growth factors;
SLAMF1 (1q23.3) is a lymphocyte receptor (CD150).
TNFSF4 (1q25.1) - a cytokine of the family of tumor necrosis factors (OX40L);
TNNT2 (1q32.1) - cardiac troponin T, type 2;
USH2A (1q41) is a gene associated with Asher syndrome 2A.

Diseases and disorders

About 350 genetic diseases associated with chromosome 1 are known ^[2] ; rearrangements and mutations in this chromosome lead to cancer and many other diseases. The following are some of the diseases associated with genes of the 1st chromosome:

non-syndromic deafness ( nonsyndromic deafness ) of autosomal recessive type 36 and autosomal dominant type 2 - ESPN and KCNQ4 ;
Alzheimer's disease - PSEN2 ;
types I, II and III Gaucher disease - GBA ;
urine disease with the smell of maple syrup type 2 - CPT2 ;
Parkinson's disease - GBA , PARK7 and PINK1 ;
hyperhomocysteinemia - MTHFR ;
Charcot – Marie – Tut disease of types 1B, 2A and 2B1 - MPZ , KIF1B and LMNA ;
variegate porphyria ( English variegate porphyria ) - PPOX ;
congenital hypothyroidism - TSHB ;
galactosemia type 3 - GALE ;
hemochromatosis type 2A - HFE2 ;
hepatoerythropoietic porphyria ( English hepatoerythropoietic porphyria ) - UROD ;
type 2 hypertrophic cardiomyopathy - TNNT2 ;
Glaucoma - GLC1A ;
homocystinuria ( eng. homocystinuria );
3-hydroxy-3-methylglutaryl-CoA-lyase deficiency ( English 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ) - HMGCL ;
carnitine palmitoyltransferase II deficiency ( English carnitine palmitoyltransferase II deficiency ) - CPT2 ;
medium chain acyl-coenzyme A dehydrogenase deficiency - ACADM ;
Schneider Corneal Dystrophy - UBIAD1 ;
gelatinous teardrop-shaped corneal dystrophy - TACSTD2 ;
collagenopathy type XI ( eng. collagenopathy, type XI ) - COL11A1 ;
primary autosomal recessive microcephaly - ASPM ;
late skin porphyria ( eng. porphyria cutanea tarda ) - UROD ;
breast cancer ;
prostate cancer - HPC1 ;
familial adenomatous polyposis ( English familial adenomatous polyposis ) - MUTYH ;
Asher syndrome type II (2A) - USH2A ;
Van der Woude syndrome - IRF6 ;
Muckle-Wells syndrome ( Muckle – Wells syndrome ) - CIAS1 ;
Marshall syndrome ( eng. Marshall syndrome ) - COL11A1 ;
popliteal pterygium syndrome ( English popliteal pterygium syndrome ) - IRF6 ;
Stickler syndrome type COL11A1 - COL11A1 ;
Hutchinson's syndrome - Gilford - LMNA ;
Ehlers syndrome - Danlos kyphoscoliotic type - PLOD1 ;
trimethylaminuria - FMO3 ;
thrombophilia associated with factor V mutation Leiden ( English Factor V Leiden thrombophilia ) - F5 ;
Congenital amegakaryocytic thrombocytopenia ( eng. Congenital_amegakaryocytic_thrombocytopenia ) - the C-mpl gene ( eng. Thrombopoietin receptor ). ICD code D69.6. Mutations in the MPL gene in a homozygous or compound heterozygous state are found in patients. The MPL gene is located on the first chromosome at the 1p34 locus and contains 12 exons.
pheochromocytoma - SDHB .

Notes

↑ ¹ ² Human chromosome 1 map view (English) . Vertebrate Genome Annotation (VEGA) database . The Wellcome Trust Sanger Institute . - Map of the chromosome and its main parameters: size, number of genes, etc. Archived April 5, 2012. (Checked November 13, 2009)
↑ ¹ ² ³ SG Gregory, KF Barlow, KE McLay, et al. The human chromosome 1 ( Nature ) // Nature . - May 2006 . - No. 441 . - P. 315–321 . DOI : 10.1038 / nature04727 . PMID 16710414 . (Checked November 13, 2009)
² ¹ ² ³ ⁴ Nature encyclopedia of the human genome / David N. Cooper. - London, New York and Tokyo: Nature Publishing group, 2003. - Vol. 1. - P. 551-559. - ISBN 0-333-80386-8 .
↑ Landmark HGP Papers (English) . Human Genome Project Information . Human Genome Project . Archived April 5, 2012. (Checked August 3, 2009)
↑ Final genome 'chapter' published . BBC News . BBC . Archived April 5, 2012. (Checked August 4, 2009)
↑ Marzluff, WF, Gongidi, P., Woods, KR, Jin, J., Malta. LJ The mouse and replication-dependent histone genes (eng.) // Genomics : journal. - Academic Press , 2002. - November ( vol. 80 , no. 5 ). - P. 487-498 . - PMID 12408966 . Archived March 5, 2016.
↑ Ada Hamosh. 605481 - ABNORMAL SPINDLE-LIKE, MICROCEPHALY-ASSOCIATED; ASPM (English) . OMIM (7 September 2018). The appeal date is December 17, 2018.

[vega-1] ¹ ² Human chromosome 1 map view (English) . Vertebrate Genome Annotation (VEGA) database . The Wellcome Trust Sanger Institute . - Map of the chromosome and its main parameters: size, number of genes, etc. Archived April 5, 2012. (Checked November 13, 2009)

[gregory2006-2] ¹ ² ³ SG Gregory, KF Barlow, KE McLay, et al. The human chromosome 1 ( Nature ) // Nature . - May 2006 . - No. 441 . - P. 315–321 . DOI : 10.1038 / nature04727 . PMID 16710414 . (Checked November 13, 2009)

[ehg-3] ² ¹ ² ³ ⁴ Nature encyclopedia of the human genome / David N. Cooper. - London, New York and Tokyo: Nature Publishing group, 2003. - Vol. 1. - P. 551-559. - ISBN 0-333-80386-8 .

[hgpjournal-4] Landmark HGP Papers (English) . Human Genome Project Information . Human Genome Project . Archived April 5, 2012. (Checked August 3, 2009)

[bbcnews-5] Final genome 'chapter' published . BBC News . BBC . Archived April 5, 2012. (Checked August 4, 2009)

[Marzluff-1-6] Marzluff, WF, Gongidi, P., Woods, KR, Jin, J., Malta. LJ The mouse and replication-dependent histone genes (eng.) // Genomics : journal. - Academic Press , 2002. - November ( vol. 80 , no. 5 ). - P. 487-498 . - PMID 12408966 . Archived March 5, 2016.

[7] Ada Hamosh. 605481 - ABNORMAL SPINDLE-LIKE, MICROCEPHALY-ASSOCIATED; ASPM (English) . OMIM (7 September 2018). The appeal date is December 17, 2018.