Linkage Disequilibrium between Two Loci (5’ Untranslated Exon 1 and Intron 5-Ddel) of the Antithrombin III Gene in Three Ethnic Groups in Singapore

1995 ◽  
Vol 45 (4) ◽  
pp. 192-198 ◽  
Author(s):  
Y. Liu ◽  
N. Saha ◽  
P.S. Low ◽  
J.S.H. Tay
Keyword(s):  
Linkage Disequilibrium ◽  
Ethnic Groups ◽  
Antithrombin Iii ◽  
Untranslated Exon ◽  
Exon 1

scholarly journals Ikaros Is Regulated through Multiple Histone Modifications and Deoxyribonucleic Acid Methylation in the Pituitary

2007 ◽  
Vol 21 (5) ◽  
pp. 1205-1215 ◽  
Author(s):  
Xuegong Zhu ◽  
Sylvia L. Asa ◽  
Shereen Ezzat
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Cpg Island ◽  
Chromatin Accessibility ◽  
Dominant Negative ◽  
Nurd Complex ◽  
Human Pituitary ◽  
Untranslated Exon ◽  
Exon 1 ◽  
Mouse Pituitary

Abstract The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been identified in human tumors. Ik modulates chromatin accessibility through associations with members of the NURD complex including histone deacetylase complexes. We show here that Ik expression in mouse pituitary corticotroph cells is itself regulated through histone modifications as well as DNA methylation. Examination of primary human pituitary specimens also identified a correlation of loss of Ik expression with the presence of DNA methylation in the untranslated exon 1 CpG island. These findings have important implications for the understanding of Ikaros’ role in epigenetic functions and suggest a potential role for demethylating agents in the treatment of related disorders.

scholarly journals Functional Cooperation between Multiple Regulatory Elements in the Untranslated Exon 1 Stimulates the Basal Transcription of the Human GnRH-II Gene

2003 ◽  
Vol 17 (7) ◽  
pp. 1175-1191 ◽  
Author(s):  
Chi Keung Cheng ◽  
Ruby L. C. Hoo ◽  
Billy K. C. Chow ◽  
Peter C. K. Leung
Keyword(s):  
Gene Transcription ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Mutational Analysis ◽  
Regulatory Elements ◽  
Start Codon ◽  
Basal Transcription ◽  
Untranslated Exon ◽  
E Box ◽  
Exon 1

Abstract The wide distribution of GnRH-II and conservation of its structure over all vertebrate classes suggest that the neuropeptide possesses vital biological functions. Although recent studies have shown that the expression of the human GnRH-II gene is regulated by cAMP and estrogen, the molecular mechanisms governing its basal transcription remain poorly understood. Using the neuronal TE-671 and placental JEG-3 cells, we showed that the minimal human GnRH-II promoter was located between nucleotide −1124 and −750 (relative to the translation start codon) and that the untranslated exon 1 was important to produce full promoter activity. Two putative E-box binding sites and one Ets-like element were identified within the first exon, and mutational analysis demonstrated that these cis-acting elements functioned cooperatively to stimulate the human GnRH-II gene transcription. EMSAs, UV cross-linking, and Southwestern blot analyses indicated that the basic helix-loop-helix transcription factor AP-4 bound specifically to the two E-box binding sites, whereas an unidentified protein bound to the Ets-like element. The functional importance of AP-4 in controlling human GnRH-II gene transcription was demonstrated by overexpression of sense and antisense full-length AP-4 cDNAs. Taken together, our present data demonstrate a novel mechanism in stimulating basal human GnRH-II gene transcription mediated by cooperative actions of multiple regulatory elements within the untranslated first exon of the gene.

Linkage disequilibrium pattern and age-at-diagnosis are critical for replicating genetic associations across ethnic groups in leprosy

2012 ◽  
Vol 132 (1) ◽  
pp. 107-116 ◽  
Author(s):  
Andrea Alter ◽  
Vinicius Medeiros Fava ◽  
Nguyen Thu Huong ◽  
Meenakshi Singh ◽  
Marianna Orlova ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Ethnic Groups ◽  
Age At Diagnosis ◽  
Linkage Disequilibrium Pattern ◽  
Genetic Associations

The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5′ untranslated exon 1

2016 ◽  
Vol 61 ◽  
pp. 48-53 ◽  
Author(s):  
Valeria Fiorentino ◽  
Valentina Brancaleoni ◽  
Francesca Granata ◽  
Giovanna Graziadei ◽  
Elena Di Pierro
Keyword(s):  
Variegate Porphyria ◽  
Untranslated Exon ◽  
Exon 1 ◽  
Noncoding Variant

Analysis of the CC chemokine receptor 3 gene reveals a complex 5′ exon organization, a functional role for untranslated exon 1, and a broadly active promoter with eosinophil-selective elements

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2346-2354 ◽  
Author(s):  
Nives Zimmermann ◽  
Bruce L. Daugherty ◽  
Jessica L. Kavanaugh ◽  
Faisal Y. El-Awar ◽  
Elizabeth A. Moulton ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Messenger Rna ◽  
Direct Sequencing ◽  
Cell Types ◽  
Northern Analysis ◽  
Strong Activity ◽  
Exon 2 ◽  
Cc Chemokine ◽  
Untranslated Exon ◽  
Exon 1

Abstract To understand the regulation of CC chemokine receptor 3 (CCR3) expression, its gene structure and promoter have been characterized. The CCR3 gene contains 4 exons that give rise to multiple messenger RNA (mRNA) species by alternative splicing. Exon 1 is present in all transcripts, whereas exon 2 or 3 is present at low frequency (< 10%). Exon 4 contains the open reading frame and 11 bp of the 5′ untranslated region. Northern analysis revealed 4 species of CCR3 mRNA. Direct sequencing revealed that the first 1 kb of the promoter and exon 1 contained only one mutation in 19 individuals, indicating that the CCR3 promoter and exon 1 are conserved between individuals. The first 1.6 kb of the 5′ flanking region of exon 1 contained promoter elements including a TATA box and motifs for myeloid transcription factors and had strong promoter activity in eosinophilic, lymphoid, myeloid, and respiratory epithelial cell lines. Deletion analysis revealed differential regulation of the CCR3 promoter in eosinophilic and epithelial cells suggesting the presence of lineage-specific elements. Interestingly, exon 1 enhanced the activity of the promoter and this effect was especially prominent in eosinophilic cells. Thus, the humanCCR3 gene has a complex 5′ exon structure, a conserved promoter with strong activity in multiple cell types, and a functional 5′ untranslated exon.

scholarly journals The promoter and first, untranslated exon of the human glucocorticoid receptor gene are GC rich but lack consensus glucocorticoid receptor element sites.

1990 ◽  
Vol 10 (10) ◽  
pp. 5580-5585 ◽  
Author(s):  
J Zong ◽  
J Ashraf ◽  
E B Thompson
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Gene ◽  
Flanking Sequence ◽  
Exon 2 ◽  
Transcription Start Sites ◽  
Untranslated Exon ◽  
Glucocorticoid Response ◽  
Glucocorticoid Receptor Gene ◽  
Exon 1 ◽  
Glucocorticoid Receptor Mrna

Glucocorticoid receptor mRNA is regulated by glucocorticoids. We found no consensus glucocorticoid response element, TATA box, or CAAT box but many GC boxes in approximately 3 kilobases of the 5'-flanking sequence of the human glucocorticoid receptor gene. We identified several transcription start sites, an untranslated exon 1, and the coding content of exon 2.

scholarly journals Genetic Variation at the Locus Encompassing 11-β Hydroxylase and Aldosterone Synthase Accounts for Heritability in Cortisol Precursor (11-Deoxycortisol) Urinary Metabolite Excretion

2005 ◽  
Vol 90 (2) ◽  
pp. 1072-1077 ◽  
Author(s):  
Bernard Keavney ◽  
Bongani Mayosi ◽  
Nicole Gaukrodger ◽  
Helen Imrie ◽  
Michelle Baker ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Linkage Disequilibrium ◽  
Left Ventricular Hypertrophy ◽  
Plasma Levels ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Chromosome 8 ◽  
Strong Linkage Disequilibrium ◽  
Aldosterone Synthase ◽  
Exon 1

Genetic variation in the gene encoding aldosterone synthase (CYP11B2) has previously been shown to be associated with hypertension and left ventricular hypertrophy. The intermediate phenotype most consistently associated with variation at this locus is that of elevated plasma 11-deoxycortisol (S). However, in normal subjects, aldosterone synthase does not metabolize S, which is converted to cortisol (F) by the enzyme 11β hydroxylase, encoded by the gene CYP11B1, which lies adjacent to CYP11B2 on chromosome 8. It is possible that the quantitative trait locus for the phenotype is within CYP11B1 and that linkage disequilibrium across the extended locus could account for these observations. However, variation across the whole CYP11B1/B2 locus had not been extensively characterized with respect to these phenotypes. We genotyped six polymorphisms in the CYP11B2 gene and three polymorphisms in the CYP11B1 gene in 248 Caucasian nuclear families comprising 1428 individuals. We measured plasma levels of S and F in 460 individuals from 86 families and urinary excretion rates of tetrahydrodeoxycortisol (THS) and tetrahydrodeoxycorticosterone in 573 individuals from 105 families. We examined heritability of the phenotypes and their association with genotypes and haplotypes at this locus. All steroid phenotypes except urinary tetrahydrodeoxycorticosterone were highly heritable (P < 0.00001). There was strong linkage disequilibrium across the CYP11B1/B2 locus. There was modest evidence for association between polymorphisms of CYP11B2 and plasma levels of S (P = 0.02 for T4986C polymorphism) and the plasma S to F ratio, reflecting the activity of 11-β hydroxylase (P = 0.01 for T4986C polymorphism). There was strong evidence for association between polymorphisms of both CYP11B1 and CYP11B2 and urinary THS, which was strongest for the CYP11B1 exon 1 polymorphism (P = 0.00002). Addition of other marker data to CYP11B1 exon 1 did not improve the fit of a log-linear model. Genotype at CYP11B1 explained approximately 5% of the variance in urinary THS excretion in the population. Thus, it is likely that linkage disequilibrium between causative CYP11B1 variants and CYP11B2 polymorphisms account for the previous observations. Further fine-mapping studies across the CYP11B1 locus are required to localize the causative variant(s) for the biochemical phenotype; this may also identify susceptibility alleles for hypertension and left ventricular hypertrophy.

scholarly journals Large deletion of the 5' end of the ROMK1 gene causes antenatal Bartter syndrome.

1998 ◽  
Vol 9 (12) ◽  
pp. 2357-2359
Author(s):  
D Feldmann ◽  
J L Alessandri ◽  
G Deschênes
Keyword(s):  
Homozygous Deletion ◽  
Large Deletion ◽  
Bartter Syndrome ◽  
Thick Ascending Limb ◽  
Consanguineous Family ◽  
Medullary Thick Ascending Limb ◽  
Untranslated Exon ◽  
Exon 1

Mutations in exon 5 of the ROMK1 gene (KCNJ1) have recently been observed in antenatal Bartter syndrome patients. This study describes a homozygous deletion removing KCNJ1 exons 1 and 2 observed in a consanguineous family with antenatal Bartter syndrome. Absence of the untranslated exon 1 led to the deletion of transcription elements located in this exon that may cause the disease. Deletion of exon 1 transcription elements should lead to the absence of hROMK2-K5 transcripts, whereas hROMK1 transcripts should normally be transcripted. Consequently, probably only hROMK2-K5 transcripts are expressed in the medullary thick ascending limb of Henle.

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