A New Cluster of Genes Within the Human Major Histocompatibility Complex

Abstract

A 435-kilobase (kb) DNA segment, which is centromeric to HLA-B in the human major histocompatibility complex, was isolated by chromosome walking with overlapping cosmids. Within the cloned region, the genes for the tumor necrosis factors (TNFs) alpha and beta and HLA-B were 210 kb apart. The human homolog of a mouse gene, B144, was located next to TNF alpha. Moreover, the presence of additional genes was suggested by a large cluster of CpG islands. With cosmid probes, several distinct transcripts were detected in RNA samples from a variety of cell lines. Altogether, five novel genes were identified by isolation of corresponding complementary DNA clones. These "HLA-B-associated transcripts" (BATs) were mapped to different locations within a 160-kb region that includes the genes for TNF alpha and TNF beta. The presence of the genes for BAT1 and BAT5 in the vicinity of HLA-B again raises the question of which gene in this region determines susceptibility to ankylosing spondylitis.

Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes.

“…An additional six genes have recently been identified in the region between the genes encoding C4 and tumor necrosis factor ,8 (40). The function of the products of these recently identified genes is presently unknown, although several of them are actively transcribed in B cells (38,40). It seems possible that the C4A and/or C2 RFLPs observed in this study are in linkage disequilibrium with defective alleles of one or more of the newly identified, or other as yet unidentified, MHC class III genes.…”

“…This region of chromosome 6 is located between the MHC class I and class II gene clusters and contains the genes encoding complement proteins C2, factor B, C4A, and C4B, as well as the microsomal cytochrome P-450 21-OHase (36). Other genes that have been mapped in this region include genes encoding the tumor necrosis factors a and 8 (36) and a protein with an unusual periodic structure, termed RD (37), the human homolog of the mouse gene B144 (38), a duplicated gene encoding the major heat shock protein HSP70 (39), and five genes encoding "HLA-B-associated transcripts" (38). An additional six genes have recently been identified in the region between the genes encoding C4 and tumor necrosis factor ,8 (40).…”

LST1/A Is a Myeloid Leukocyte-specific Transmembrane Adaptor Protein Recruiting Protein Tyrosine Phosphatases SHP-1 and SHP-2 to the Plasma Membrane

“…The human gene LST1 and its mouse homologue Lst1 (also known as B144) are located in the MHC class III locus, which is rich in immunologically important genes (1)(2)(3)(4). The human LST1 primary transcript has been reported to undergo extensive alternative splicing resulting in a large number of splice variants.…”

HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53

“…Bat3 (HLA-B-associated transcript 3) was originally identified as a gene within the class III region of the human major histocompatibility complex on chromosome 6 (Spies et al 1989;Banerji et al 1990). The biological function of Bat3 is currently unknown.…”