A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13.

Ansari-Lari, M. Ali; Muzny, Donna M.; Lü, Jing; Lü, Fei; Lilley, Caroline E.; Spanos, S; Malley, Tracy M.; Gibbs, Richard A.

doi:10.1101/gr.6.4.314

Cited by 96 publications

(74 citation statements)

References 37 publications

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“…Human GNB3 is located in a gene-rich cluster on chromosome 12p13 [37,38]-a locus that has shown linkage with an autosomal-dominant form of hypertension [39] and with BMI [40] and fasting serum total cholesterol levels [41]. Initially, the 825T allele was found to be associated with an increased risk of hypertension in a sample of approximately 850 subjects [1], and this observation was confirmed in independent studies of various sample sizes [5,17].…”

Section: Introductionmentioning

confidence: 55%

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

et al. 2005

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Aims/hypothesis: The 825C>T polymorphism in the gene encoding the G protein β3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with divergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome. Materials and methods: The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish subjects using mass spectrometry analysis of PCR products. Case-control studies were undertaken for obesity, hypertension, type 2 diabetes and the metabolic syndrome, and a meta-analysis including data from the present study and previous studies of hypertension was performed. Quantitative trait studies of metabolic variables were carried out in 4,387 glucose-tolerant subjects. Results: We observed minor differences in 825C>T genotype distributions for type 2 diabetes (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007); however, after correction for multiple testing, these were not statistically significant. No association was found with hypertension, obesity or the metabolic syndrome. Curiously, the T allele was associated with nominally lower systolic and diastolic blood pressure levels-a finding in contrast with most previous studies-but not with other metabolic variables. Meta-analysis demonstrated a high degree of heterogeneity between study populations of different ethnic origin. Although there was a tendency towards an increased risk of hypertension among 825T allele carriers, this was not statistically significant. Conclusions/interpretation: The present study suggests no major involvement of the GNB3 825C>T polymorphism in components of the metabolic syndrome.

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Section: Introductionmentioning

confidence: 55%

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

et al. 2005

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“…1). The CD4 gene is composed of 10 exons in both humans and chickens, with each exon containing a separate domain of the CD4 molecule: exons 1 and 10 encode the 5Ј and 3Ј untranslated regions, respectively, exon 2 codes for the signal peptide, domain 1 is divided between exons 3 and 4, extracellular domains 2, 3 and 4 are encoded on exons 5, 6, and 7, and exons 8 and 9 code for the transmembrane and intracellular regions, respectively (8,39). Although the exons containing the 5Ј untranslated region of tCD4 have not been sequenced, it is clear that the coding region of tCD4 is divided in an identical manner as the other vertebrate CD4 genes, supporting its analogy with CD4.…”

Section: Cd4 and Cd4rel Cdna And Genomic Sequencesmentioning

confidence: 99%

Evolution of the CD4 Family: Teleost Fish Possess Two Divergent Forms of CD4 in Addition to Lymphocyte Activation Gene-3

Laing

Zou

Purcell

et al. 2006

The Journal of Immunology

115

117

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The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig superfamily and is essential for cell-mediated immunity. Two different genes were identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes four extracellular Ig domains reminiscent of mammalian CD4, whereas the other (CD4REL) codes for two Ig domains. Structural motifs within the amino acid sequences suggest that the two Ig domains of CD4REL duplicated to generate the four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3. Here we present evidence that both of these molecules in trout are homologous to mammalian CD4 and that teleosts encode an additional CD4 family member, lymphocyte activation gene-3, which is a marker for activated T cells. The syntenic relationships of similar genes in other teleost and non-fish genomes provide evidence for the likely evolution of CD4-related molecules in vertebrates, with CD4REL likely representing the primordial form in fish. Expression of both CD4 genes is highest in the thymus and spleen, and mRNA expression of these genes is limited to surface IgM− lymphocytes. consistent with a role for T cell functionality. Finally, the intracellular regions of both CD4 and CD4REL possess the canonical CXC motif involved in the interaction of CD4 with p56LCK, implying that similar mechanisms for CD4+ T cell activation are present in all vertebrates. Our results therefore raise new questions about T cell development and functionality in lower vertebrates that cannot be answered by current mammalian models and, thus, is of fundamental importance for understanding the evolution of cell-mediated immunity in gnathosomes.

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“…More likely, the J19 project may represent a problematic sequence. This region contains a large number of repetitive elements and was difficult to sequence (Ansari-Lari et al 1996). These data demonstrate the differences between projects and the need for increased redundancy of sequencing for a few difficult sequences.…”

Section: Analysis Of Sequence Qualitymentioning

confidence: 99%

Analysis of the Quality and Utility of Random Shotgun Sequencing at Low Redundancies

Bouck¹,

Miller²,

Gorrell³

et al. 1998

Genome Res.

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The currently favored approach for sequencing the human genome involves selecting representative large-insert clones (100-200 kb), randomly shearing this DNA to construct shotgun libraries, and then sequencing many different isolates from the library. This method, entitled directed random shotgun sequencing, requires highly redundant sequencing to obtain a complete and accurate finished consensus sequence. Recently it has been suggested that a rapidly generated lower redundancy sequence might be of use to the scientific community. Low-redundancy sequencing has been examined previously using simulated data sets. Here we utilize trace data from a number of projects submitted to GenBank to perform reconstruction experiments that mimic low-redundancy sequencing. These low-redundancy sequences have been examined for the completeness and quality of the consensus product, information content, and usefulness for interspecies comparisons.The data presented here suggest three different sequencing strategies, each with different utilities.(1) Nearly complete sequence data can be obtained by sequencing a random shotgun library at sixfold redundancy. This may therefore represent a good point to switch from a random to directed approach. (2) Sequencing can be performed with as little as twofold redundancy to find most of the information about exons, EST hits, and putative exon similarity matches. (3) To obtain contiguity of coding regions, sequencing at three-to fourfold redundancy would be appropriate. From these results, we suggest that a useful intermediate product for genome sequencing might be obtained by three-to fourfold redundancy. Such a product would allow a large amount of biologically useful data to be extracted while postponing the majority of work involved in producing a high quality consensus sequence.

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A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13.

Cited by 96 publications

References 37 publications

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

Evolution of the CD4 Family: Teleost Fish Possess Two Divergent Forms of CD4 in Addition to Lymphocyte Activation Gene-3

Analysis of the Quality and Utility of Random Shotgun Sequencing at Low Redundancies

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