Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse.

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Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L

Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse.

Genome Res. 2003 Dec;13(12):2621-36.

PubMed ID
14656967 [ View in PubMed
]
Abstract

In mammals, the Major Histocompatibility Complex class I and II gene clusters are separated by an approximately 700-kb stretch of sequence called the MHC class III region, which has been associated with susceptibility to numerous diseases. To facilitate understanding of this medically important and architecturally interesting portion of the genome, we have sequenced and analyzed both the human and mouse class III regions. The cross-species comparison has facilitated the identification of 60 genes in human and 61 in mouse, including a potential RNA gene for which the introns are more conserved across species than the exons. Delineation of global organization, gene structure, alternative splice forms, protein similarities, and potential cis-regulatory elements leads to several conclusions: (1) The human MHC class III region is the most gene-dense region of the human genome: >14% of the sequence is coding, approximately 72% of the region is transcribed, and there is an average of 8.5 genes per 100 kb. (2) Gene sizes, number of exons, and intergenic distances are for the most part similar in both species, implying that interspersed repeats have had little impact in disrupting the tight organization of this densely packed set of genes. (3) The region contains a heterogeneous mixture of genes, only a few of which have a clearly defined and proven function. Although many of the genes are of ancient origin, some appear to exist only in mammals and fish, implying they might be specific to vertebrates. (4) Conserved noncoding sequences are found primarily in or near the 5'-UTR or the first intron of genes, and seldom in the intergenic regions. Many of these conserved blocks are likely to be cis-regulatory elements.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Valine--tRNA ligaseP26640Details
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2O95865Details
Tumor necrosis factorP01375Details
Sialidase-1Q99519Details
Lymphotoxin-alphaP01374Details
Complement factor BP00751Details
Choline transporter-like protein 4Q53GD3Details
Apolipoprotein MO95445Details
Chloride intracellular channel protein 1O00299Details
Casein kinase II subunit betaP67870Details
Advanced glycosylation end product-specific receptorQ15109Details