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Euphemia Leung Randal W. Berg Ries Langley John Greene Lisa A. Raymond Meena Augustus Jian Ni Kenneth C. Carter Nigel Spurr K. H. Andy Choo G. W. Krissansen 《Immunogenetics》1997,46(2):111-119
MAdCAM-1, the endothelial addressin cell adhesion molecule-1, interacts preferentially with the leukocyte β7 integrin LPAM-1
(α4β7), but also with L-selectin, and with VLA-4 (α4β1) on myeloid cells, and serves to direct leukocytes into mucosal and
inflamed tissues. Overlapping cosmid and phage λ genomic clones were isolated, revealing that the human MAdCAM-1 gene contains five exons where the signal peptide, two Ig domains, and mucin domain are each encoded by separate exons. The
transmembrane domain, cytoplasmic domain, and 3′ untranslated region are encoded together on exon 5. The mucin domain contains
eight repeats in total that are subject to alternative splicing. Despite the absence of a human counterpart of the third IgA-homologous
domain and lack of sequence conservation of the mucin domain, the genomic organizations of the human and mouse MAdCAM-1 genes are similar. An alternatively spliced MAdCAM-1 variant was identified that lacks exon 4 encoding the mucin domain,
and may mediate leukocyte adhesion to LPAM-1 without adhesion to the alternate receptor, L-selectin. The MAdCAM-1 gene was located at p13.3 on chromosome 19, in close proximity to the ICAM-1 and ICAM-3 genes (p13.2-p13.3). PMA-inducible promotor activity was contained in a 700 base pair 5’ flanking fragment conserved with
the mouse MAdCAM-1 gene including tandem NF-kB sites, and an Sp1 site; and in addition multiple potential AP2, Adh1 (ETF), PEA3, and Sp1 sites.
In summary, the data establish that the previously reported human MAdCAM-1 cDNA does indeed encode the human homologue of mouse MAdCAM-1, despite gross dissimilarities in the MAdCAM-1 C-terminal structures.
Received: 5 December 1996 / Revised: 2 January 1997 相似文献
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van Rietschoten JG Smits HH Westland R Verweij CL den Hartog MT Wierenga EA 《Immunogenetics》2000,51(1):30-36
The interleukin-12 receptor (IL-12R) is composed of two subunits, referred to as β1 and β2. Both chains are necessary for
high-affinity IL-12 binding and signalling, although only the IL-12Rβ2 chain contains the intracellular tyrosine residues
responsible for STAT4 activation. This study presents the intron-exon organization of the human IL-12Rβ2-chain gene. Polymerase
chain reaction (PCR) primers designed across the cDNA (U46198) were used to trace introns, by comparing PCR product sizes
obtained using cDNA and genomic DNA as templates. PCR products spanning introns were sequenced to determine the exact splice
sites and flanking regions. The coding region of the gene was found to consist of 15 exons and 14 introns. All intron-exon
boundaries are consistent with the consensus sequence for splice junctions (5′ GT/AG 3′). Comparison of the intron-exon organization
with the human GCSFR gene indicated a remarkably well conserved genomic organization between these two class I cytokine receptors. Interestingly,
we identified an alternatively spliced mRNA, encoding a putative, truncated protein, lacking all signalling potential.
Received: 21 July 1999 / Revised: 2 September 1999 相似文献
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Nellie Y. Loh Helen J. Ambrose Lisa M. Guay-Woodford Srimita DasGupta Ralph A. Nawrotzki Derek J. Blake Kay E. Davies 《Mammalian genome》1998,9(11):857-862
β-Dystrobrevin, a dystrophin-related protein that is expressed in non-muscle tissues, is highly homologous to α-dystrobrevin,
a member of the dystrophin-associated protein complex (DPC). β-Dystrobrevin associates with Dp71 and syntrophin and is believed
to have a role in non-muscle DPCs. Here we report the characterization and mapping of the mouse β-dystrobrevin gene. The mouse
β-dystrobrevin gene is organized into 21 exons spanning over 130 kb of DNA. We provide evidence that this gene is transcribed
from at least two promoter regions but appears to utilize a common translation initiation site. We show that the similarity
between β-dystrobrevin and α-dystrobrevin is reflected in the conservation of their exon-intron junctions. β-Dystrobrevin
has been localized to proximal mouse Chromosome (Chr) 12 by backcross mapping. A database search revealed that two mouse genetic
diseases involving tissues expressing β-dystrobrevin have been mapped to this region, namely, congenital polycystic kidneys
(cpk) and fatty liver dystrophy (fld). However, refined mapping analysis has excluded β-dystrobrevin as a candidate gene for either disease.
Received: 1 June 1998 / Accepted: 16 July 1998 相似文献
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The α2u-globulins are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a
subset of secretory tissues in rats. The many α2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity,
individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental
regulation. Analysis suggests that there are approximately 20 α2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the α2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated
by pulsed field gel electrophoresis indicated that the α2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing α2u-globulin genes indicated that the α2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the α2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the
mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have
consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.
Received: 12 August 1998 / Accepted: 13 January 1999 相似文献
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Genomic organization of the complex α-gliadin gene loci in wheat 总被引:1,自引:0,他引:1
Gu YQ Crossman C Kong X Luo M You FM Coleman-Derr D Dubcovsky J Anderson OD 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2004,109(3):648-657
To better understand the molecular evolution of the large -gliadin gene family, a half-million bacterial artificial chromosome (BAC) library clones from tetraploid durum wheat, Triticum turgidum ssp. durum (2n=4x=28, genome AB), were screened for large genomic segments carrying the -gliadin genes of the Gli-2 loci on the group 6 homoeologous chromosomes. The resulting 220 positive BAC clones—each containing between one and four copies of -gliadin sequences—were fingerprinted for contig assembly to produce contiguous chromosomal regions covering the Gli-2 loci. While contigs consisting of as many as 21 BAC clones and containing up to 17 -gliadin genes were formed, many BAC clones remained as singletons. The accuracy of the order of BAC clones in the contigs was verified by Southern hybridization analysis of the BAC fingerprints using an -gliadin probe. These results indicate that -gliadin genes are not evenly dispersed in the Gli-2 locus regions. Hybridization of these BACs with probes for long terminal repeat retrotransposons was used to determine the abundance and distribution of repetitive DNA in this region. Sequencing of BAC ends indicated that 70% of the sequences were significantly similar to different classes of retrotransposons, suggesting that these elements are abundant in this region. Several mechanisms underlying the dynamic evolution of the Gli-2 loci are discussed. 相似文献
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Kira K. Lueders Rosemary W. Elliott Ingo Marenholz Dietmar Mischke Michael DuPree Dean Hamer 《Mammalian genome》1999,10(9):900-905
As a first step in determining whether there are polymorphisms in the nicotinic acetylcholine receptor (nAChR) genes that
are associated with nicotine addiction, we isolated genomic clones of the β2-nAChR genes from human and mouse BAC libraries.
Although cDNA sequences were available for the human gene, only the promoter sequence had been reported for the mouse gene.
We determined the genomic structures by sequencing 12 kb of the human gene and over 7 kb of the mouse gene. While the sizes
of exons in the mouse and human genes are the same, the introns differ in size. Both promoters have a high GC content (60–80%)
proximal to the AUG and share a neural-restrictive silencer element (NRSE), but overall sequence identity is only 72%. Using
a 6-Mb YAC contig of Chr 1, we mapped the human β2-nAChR gene, CHRNB2, to 1q21.3 with the order of markers cen, FLG, IVL,
LOR, CHRNB2, tel. The mouse gene, Acrb2, had previously been mapped to Chr 3 in a region orthologous to human Chr 1. We refined mapping of the mouse gene and other
markers on a radiation hybrid panel of Chr 3 and found the order cen, Acrb2, Lor, Iv1, Flg, tel. Our results indicate that this cluster of markers on human Chr 1 is inverted with respect to its orientation on the
chromosome compared with markers in the orthologous region of mouse Chr 3.
Received: 26 January 1999 / Accepted: 10 May 1999 相似文献
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Human C8 is one of five complement components (C5b, C6, C7, C8, C9) that interact to form the cytolytic C5b-9 complex on target membranes. It is composed of three nonidentical subunits (C8, C8, C8) encoded by separate genes. C8 and C8 are linked on chromosome 1p32, whereas C8 is located on 9q22.3-q32. In this study, overlapping genomic clones were isolated and used to decipher the organization of the human C8 gene. The gene contains at least 11 exons spanning 70kb of DNA. When compared to C6, C8 and C9, there is a remarkable similarity in genomic organization, consistent with amino acid sequence comparisons that suggest these proteins are ancestrally related. Regions of each protein that are structurally similar are encoded in exons of correspondingly similar lengths with highly conserved boundaries and phases. Availability of genomic sequence also facilitated a more detailed analysis of C8 and C8 linkage. Based on analysis of genomic digests with cDNA probes, the loci were previously reported to be physically linked (< 2.5kb) and in a 5- 3 orientation. In the present study, results obtained using exon-specific probes indicate the loci are not as closely linked as initially believed. Furthermore, they suggest that cDNA probes used earlier yielded misleading information because they encode exons that are distributed across large segments of genomic DNA. 相似文献
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The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M74721. 相似文献