Linkage map of two HLA-SBβ and two HLA-SBα-related genes: an intron in one of the SBβ genes contains a processed pseudogene

Trowsdale, John; Kelly, Adrian; Lee, Janet; Carson, Susan; Austin, Penelope; Travers, Paul

doi:10.1016/0092-8674(84)90546-4

Cited by 110 publications

(26 citation statements)

References 36 publications

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“…2. Double stranded probes were labeled by the random priming technique (29), and single stranded M13 probes were labeled by primer extension (30). Final by a sequence similar to Vi,, which contains the cysteine, tryptophan, and glutamine residues characteristic of V regions in the immunoglobulin superfamily (11,12,19) (underlined residues in Fig.…”

Section: Methodsmentioning

confidence: 99%

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Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells.

Marche¹,

Kindt²

1986

Proc. Natl. Acad. Sci. U.S.A.

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Information relevant to allelic exclusion in T cells has been obtained by a study of cDNA clones corresponding to a-chain genes of the T-cell receptor in the rabbit T-cell line RL-5. One clone contains a variable-joining-constant (VJC) sequence encoding a complete a chain of the T-cell receptor. A second has an identical constant region and includes a distinct variable-joining (VJ) sequence. However, a single-base deletion in the variable region places the remainder of the second transcript out-of-phase and appears to be the product of a rearrangement involving a variable region of the T-cell receptor a-chain pseudogene. Presence of two variablejoining-constant (VJC) transcripts in the same cell line indicates that a-chain gene rearrangement is not affected by transcription of a complete a-chain mRNA and suggests that steps after mRNA synthesis are involved in the allelic exclusion process for a-chain genes. Comparison of rabbit a-chain sequences with those of man and mouse revealed interspecies conservation in constant and variable regions. Genomic Southern blot analyses using a rabbit constant region of the T-cell receptor a-chain probe revealed the presence of a single constant region gene. Hybridization with variable region probes defried two distinct multigenic subfamilies. Homology between certain rabbit and murine variable regions of the T-cell receptor a-chain sequences suggests that the existence of subfamilies predated divergence of these species.The phenomenon of allelic exclusion was described 20 years ago for immunoglobulin-producing cells of rabbit (1) 2190 variable regions of the TCR A-chain (TCR-P) genes with one of the two diversity segments of the TCR-,p and thirteen joining regions of the TCR-A gene segments available (7,8,(11)(12)(13). Like the TCR-A genes, a chain of the TCR (TCR-a) genes were found to be rearranged and expressed in cells of the T lineage (14)(15)(16)(17)(18). Murine and human a-chain gene complexes include a single constant region of the TCR-a (Ca) gene and, in marked contrast with TCR-,8 genes, a large number of variable regions of the TCR-a (Va) and joining regions of the TCR-a (Ja) gene segments appear to be used in the generation of diversity (19)(20)(21)(22).The present study describes characterization oftwo TCR-a cDNA clones isolated from the rabbit T-cell line RL-5. Sequence comparison shows structural similarity among Ca of rabbit, man, and mouse. The rabbit, like mouse and man, has a single constant region gene and multiple copies of Va genes. The two variable regions transcribed by RL-5 cells have close counterparts in two different murine Va subfamilies. The presence of two complete TCR-a transcripts in the RL-5 cell line places constraints on models explaining allelic exclusion of the TCR genes. MATERIALS AND METHODSCloning of TCR-a cDNA. Poly(A)+ mRNA from RL-5 cells was used to construct a cDNA library by the Okayama-Berg procedure as described (23,24) were estimated by using ALIGN programs from the NIH DEC10 computer system.Abbreviations: Ca, the co...

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Section: Methodsmentioning

confidence: 99%

“…Analyses of the TCR-p repertoire of the mouse further reveal that diversity is mostly due to recombination of [20][21][22][23][24][25][26][27][28][29][30] The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

mentioning

confidence: 99%

Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells.

Marche¹,

Kindt²

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…scribed; at present seven P3 chain (two DP, two DQ, and three DR) and five a chain (two DP, two DQ, and one DR) gene loci have been identified (4)(5)(6)(7)(8)(9). Although their precise genetic order is not yet known, the DP locus is known to be centromeric to both DQ and DR, which in turn are centromeric to the class I loci, HLA-A, -B, and -C (10).…”

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confidence: 99%

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Moriuchi¹,

Moriuchi²,

Silver³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Three families of human Ia molecules, DP, DQ, and DR, have previously been defined. A cDNA clone, pDSH-9.1, encoding the a chain of a DQ molecule derived from an HLA-DRw9 homozygous cell line has been isolated and sequenced. Comparison of the nucleotide and predicted protein sequence to those of other DQ a subunits reveals that DQ a subunits derived from DR4, -7, and -9 cells are very similar to each other but quite different from a DQ a subunit derived from a DRw6 cell line. These studies suggest that certain Ia haplotypes have a common evolutionary history. Furthermore, in the context of current serologic and biochemical knowledge, they suggest that the gene encoding the DQ a subunit is in strong linkage disequilibrium with the DR locus.The Ia region of the major histocompatibility complex (MHC) consists of a series of closely linked loci encoding cell surface molecules that regulate the immune response. These Ia molecules may be divided into three groups, DP (formerly known as SB) (1), DQ (formerly known as DS) (2), and DR (3), that are structurally distinct. Ia molecules consist of two subunits, a and ,3, with molecular weights of approximately 28,000 and 33,000. Within each group, DP, DQ, and DR, multiple a-and /8-chain gene loci have been described; at present seven P3 chain (two DP, two DQ, and three DR) and five a chain (two DP, two DQ, and one DR) gene loci have been identified (4-9). Although their precise genetic order is not yet known, the DP locus is known to be centromeric to both DQ and DR, which in turn are centromeric to the class I loci, HLA-A, -B, and -C (10). Recombinational analysis indicates that both DP and the class I loci are approximately 1 centimorgan from the DQ and DR loci (10,11). No recombinational event between DQ and DR has yet been confirmed, suggesting a relatively low frequency of recombination. Biochemical studies (2,(12)(13)(14)(15)(16)(17)(18) and analysis of cDNA clones (19)(20)(21)(22)(23)(24)(25)(26) indicate that a majority of the Ia genes are expressed as products. Ia gene products belonging to the same group are highly related (greater than 95% protein homology) while those belonging to different groups are only approximately 60% related.The Ia system is highly polymorphic. At least 11 alleles at the DR locus (designated numerically-i.e., DR1-DR11) have been defined serologically (27). Similarly, at least 6 alleles at the DQ locus and 6 at the DP locus have been defined biochemically and by cellular assays, respectively (27,28 (29). Similarly, cells typing as DR1, -2, and -6 frequently display the MB1 antigenic determinant (30).Although the molecular basis for these antigenic determinants is not known, in some instances, the gene products expressing them have been identified. Thus, MB1, which is expressed on Drl, -2, and -6 cells, and MB3, which is expressed on DR4 and DR5 cells, are both present on different allelic forms of DQ molecules (28,31,32). In other instances, the molecular assignment has been more controversial; MT3 has been localized to DR-like mol...

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“…The following probes were employed: pDAc~13b (specific for HLA-DP~; Trowsdale et al 1985); pll-13 (specific for HLADPcx; Trowsdale et al 1984); p6 (3" flanking sequence, specific for HLA-B; Ragoussis et al 1989); LG2-E2 (3" untranslated sequence, specific for HLA-E; Ulbrecht et al 1992); p259 (SalI-PstI fragment, contains the 5" untranslated sequence and the first exon of HLA-H; unpublished); HLA-A2 (3" flanking sequence, specific for HLA-A; Ragoussis et al 1989); 21133" UT specific for TUBB; Lee et al 1983). …”

Section: Dna Probesmentioning

confidence: 99%

Presence of an expressed ?-tubulin gene (TUBB) in the HLA class I region may provide the genetic basis for HLA-linked microtubule dysfunction

Volz

Weiß²,

Trowsdale³

et al. 1994

Hum Genet

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Abstract. An expressed I]-tubulin gene (TUBB) has previously been localized to chromosome region 6pter-p21 in man. By using a panel of deletion mutant cell lines and radiation-reduced hybrids containing fragments of chromosome 6, the TUBB locus could be mapped to the HLA class I region at 6p21.3. A long range restriction map including TUBB and several HLA class I genes was then generated by rotating field gel electrophoresis. The results show that TUBB maps to a segment 170-370 kb telomeric of HLA-C. This location suggests that a mutation at the TUBB locus could be the cause for certain forms of HLAlinked microtubule dysfunction, including immotile cilia syndrome.

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Linkage map of two HLA-SBβ and two HLA-SBα-related genes: an intron in one of the SBβ genes contains a processed pseudogene

Cited by 110 publications

References 36 publications

Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells.

Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells.

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Presence of an expressed ?-tubulin gene (TUBB) in the HLA class I region may provide the genetic basis for HLA-linked microtubule dysfunction

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