Cytochrome b-245 Alpha Chain Gene Variants and Arterial Function in Indonesian Short Stature Children

There is a relationship between IgE levels and expression of high-affinity IgE receptors (FcεRI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the FcεRI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the FcεRI alpha chain gene with genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by using single-stranded conformational polymorphism analysis. No nonsynonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A/C transversion at −770 from the translation start site; a G/A transition at −664; and a T/C transition at −335. No differences in allele frequencies were detected between asthmatic subjects and controls. Homozygosity for the C variant at locus −335 was more common in Caucasian asthmatic patients with IgE levels in the lower quartile than in the upper quartile ( P = 0.032). An analysis of highly polymorphic SNPs indicated that this association is unlikely to be due to population substructure. We conclude that homozygosity for the C allele of FcεRI alpha chain variant is associated with lower IgE levels.

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A frameshift mutation in Exon V of the A alpha-chain gene leading to truncated A alpha-chains in the homozygous dysfibrinogen Milano III

Journal of Biological Chemistry ◽

10.1016/s0021-9258(20)30106-x ◽

1994 ◽

Vol 269 (52) ◽

pp. 33129-33134

Author(s):

M Furlan ◽

C Steinmann ◽

M Jungo ◽

C Bögli ◽

F Baudo ◽

...

Keyword(s):

Frameshift Mutation ◽

Chain Gene ◽

Alpha Chain

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Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene FCGRT by MicroRNA-3181

Pharmaceutical Research ◽

10.1007/s11095-017-2294-0 ◽

2018 ◽

Vol 35 (1) ◽

Cited By ~ 5

Author(s):

Daniel C. Ferguson ◽

Javier G. Blanco

Keyword(s):

Chain Gene ◽

Receptor Alpha ◽

Alpha Chain ◽

Receptor Alpha Chain

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A delta T-cell receptor deleting element transgenic reporter construct is rearranged in alpha beta but not gamma delta T-cell lineages.

Molecular and Cellular Biology ◽

10.1128/mcb.15.12.7022 ◽

1995 ◽

Vol 15 (12) ◽

pp. 7022-7031 ◽

Cited By ~ 14

Author(s):

J Shutter ◽

J A Cain ◽

S Ledbetter ◽

M D Rogers ◽

R D Hockett

Keyword(s):

T Cells ◽

T Cell ◽

Cell Receptor ◽

Chain Gene ◽

Gamma Delta ◽

Alpha Chain ◽

Chain Locus ◽

Discrete Population ◽

Alpha Beta ◽

Gamma Delta T Cell

T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell.

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High Prevalence of Growth Plate Gene Variants in Children With Familial Short Stature Treated With GH

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-02288 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4273-4281 ◽

Cited By ~ 8

Author(s):

Lukas Plachy ◽

Veronika Strakova ◽

Lenka Elblova ◽

Barbora Obermannova ◽

Stanislava Kolouskova ◽

...

Keyword(s):

Short Stature ◽

Growth Plate ◽

Single Gene ◽

Gene Variants ◽

Genetic Etiology ◽

Associated Proteins ◽

Genetic Mechanisms ◽

Standards And Guidelines ◽

Minimum Height ◽

Severe Short Stature

AbstractContextFamilial short stature (FSS) is a term describing a growth disorder that is vertically transmitted. Milder forms may result from the combined effect of multiple genes; more severe short stature is suggestive of a monogenic condition. The etiology of most FSS cases has not been thoroughly elucidated to date.ObjectivesTo identify the genetic etiology of severe FSS in children treated with GH because of the diagnosis of small for gestational age or GH deficiency (SGA/GHD).Design, Settings, and PatientsOf 736 children treated with GH because of GHD/SGA, 33 with severe FSS (life-minimum height −2.5 SD or less in both the patient and shorter parent) were included in the study. The genetic etiology was known in 5 of 33 children prior to the study [ACAN (in 2], NF1, PTPN11, and SOS1). In the remaining 28 of 33, whole-exome sequencing was performed. The results were evaluated using American College of Medical Genetics and Genomics standards and guidelines.ResultsIn 30 of 33 children (90%), we found at least one variant with potential clinical significance in genes known to affect growth. A genetic cause was elucidated in 17 of 33 (52%). Of these children, variants in growth plate-related genes were found in 9 of 17 [COL2A1, COL11A1, and ACAN (all in 2), FLNB, FGFR3, and IGF1R], and IGF-associated proteins were affected in 2 of 17 (IGFALS and HMGA2). In the remaining 6 of 17, the discovered genetic mechanisms were miscellaneous (TRHR, MBTPS2, GHSR, NF1, PTPN11, and SOS1).ConclusionsSingle-gene variants are frequent among families with severe FSS, with variants affecting the growth plate being the most prevalent.

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Evidence that platelet and plasma fibrinogen have the same A-alpha chain gene product

Fibrin formation and Fibrinolysis ◽

10.1515/9783110871951-004 ◽

1986 ◽

pp. 15-22

Author(s):

Christopher Southan ◽

Irina Knight ◽

Helen Ireland ◽

David A. Lane

Keyword(s):

Gene Product ◽

Plasma Fibrinogen ◽

Chain Gene ◽

Alpha Chain

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Delineation of an enhancerlike positive regulatory element in the interleukin-2 receptor alpha-chain gene.

Molecular and Cellular Biology ◽

10.1128/mcb.10.2.850 ◽

1990 ◽

Vol 10 (2) ◽

pp. 850-853 ◽

Cited By ~ 22

Author(s):

B B Lin ◽

S L Cross ◽

N F Halden ◽

D G Roman ◽

M B Toledano ◽

...

Keyword(s):

Regulatory Element ◽

Interleukin 2 ◽

Chain Gene ◽

Enhancer Activity ◽

Enhancer Element ◽

Receptor Alpha ◽

Alpha Chain ◽

Interleukin 2 Receptor ◽

Positive Regulatory Element ◽

Receptor Alpha Chain

We have delineated a positive regulatory element in the interleukin-2 receptor alpha-chain gene (IL-2R alpha) between positions -299 and -243 that can potently activate a heterologous (herpesvirus thymidine kinase [tk]) promoter in phorbol myristate acetate (PMA)-induced Jurkat T cells and is functional when cloned in either orientation. This enhancerlike element contains a site (-268/-257) that can bind NF-kappa B; however, unlike the immunoglobulin kappa gene kappa B enhancer element, the IL-2R alpha kappa B-like site alone can only weakly activate a heterologous promoter. Adjacent 5' and 3' sequences also weakly activate the tk-CAT vector, but constructs combining the IL-2R alpha kappa B-like site plus adjacent 5' and 3' sequences potently activate gene expression. This combination of regions is essential for potent PMA-induced transcription from the tk promoter. Experiments using constructs in which IL-2R alpha upstream sequences are sequentially deleted suggested that there is a region 5' of position -299 which can suppress IL-2R alpha promoter and/or enhancer activity. Thus, it is possible that both positive and negative elements may be important in the regulation of IL-2R alpha gene transcription.

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Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.85.14.5215 ◽

1988 ◽

Vol 85 (14) ◽

pp. 5215-5219 ◽

Cited By ~ 82

Author(s):

P. E. Newburger ◽

R. A. Ezekowitz ◽

C. Whitney ◽

J. Wright ◽

S. H. Orkin

Keyword(s):

Gene Expression ◽

Cytochrome B ◽

Interferon Gamma ◽

Heavy Chain ◽

Chain Gene ◽

Heavy Chain Gene

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Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel.

Molecular and Cellular Biology ◽

10.1128/mcb.12.9.4067 ◽

1992 ◽

Vol 12 (9) ◽

pp. 4067-4075 ◽

Cited By ~ 38

Author(s):

T H Tan ◽

G P Huang ◽

A Sica ◽

P Ghosh ◽

H A Young ◽

...

Keyword(s):

T Cell Activation ◽

Interleukin 2 ◽

Regulatory Elements ◽

Chain Gene ◽

Nf Kappa B ◽

Receptor Alpha ◽

Alpha Chain ◽

Interleukin 2 Receptor ◽

Alpha Gene ◽

Receptor Alpha Chain

The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R alpha) gene contain a potent kappa B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa B-binding protein NF-kappa B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa B element in the IL-2R alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R alpha promoter, but not the kappa B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the kappa B site of the IL-2R alpha promoter. Finally, induction of surface IL-2R alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R alpha kappa B site. Our study identified c-Rel as one component of the Rel/NF-kappa B-family proteins involved in the kappa B-dependent activation of IL-2R alpha gene expression. Furthermore, our results suggest that a Re1NA-like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c-Re1 during T-cell activation.

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