Fine mapping of the autosomal dominant juvenile open angle glaucoma (GLC1A) region and evaluation of candidate genes.

Sunden, Sara L.F.; Alward, Wallace L.M.; Nichols, Brian E.; Rokhlina, Tatiana; Nystuen, Arne; Stone, Edwin M; Sheffield, Val C.

doi:10.1101/gr.6.9.862

Cited by 45 publications

(29 citation statements)

References 23 publications

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“…30,31 From these we selected three single-nucleotide polymorphisms (SNPs) in FAS and two in FASL, and genotyped the 681 family members of 126 American multiplex SLE pedigrees for these as well as a FASL microsatellite in the 3 0 UTR. 32 Of the FAS polymorphisms evaluated, two were located to the promoter: À690C4T (dbSNP rs 2234758) in a possible mutational hotspot and À670G4A (dbSNP rs 1800682) in a GAS (gamma activation site) binding site. 21 The third is a silent mutation in codon214 (ACC to ACT) (dbSNP rs 2234978) in exon 7, which does not lead to an aminoacid change.…”

Section: Association Studiesmentioning

confidence: 99%

Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

et al. 2005

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Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens and tissue injury. Defective apoptosis of activated immune cells leads to the development of autoantibodies in SLE. FasL initiated apoptosis is central for peripheral tolerance. Fas deficiencies in humans and mice predispose toward systemic autoimmunity. SLE is conferred by many genes. The genetic effects may be concentrated by familial clustering or by stratifying of subphenotypes. We have tested polymorphisms and haplotypes in FAS and FASL for association to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC C/T as well as the FASÀ670G4A 0 -codon214 AC C/T 0 haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE in other populations and demonstrate that the activity depends on the allelic variants as well as on the haplotype. The presence of FASÀ670G, which affects STAT1 binding, leads to the highest activity. FASLÀ844C activity is modified by the cis acting À478A and, hence, the haplotype and not the individual variant, determines the promoter activity. We conclude that the FAS/FASL promoter haplotypes are functional and that polymorphisms in FAS may contribute to thrombocytopenia in SLE.

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Section: Association Studiesmentioning

confidence: 99%

Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

et al. 2005

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“…The markers were ordered based on previously published physical maps of the region. [10][11][12]24,25 The lod scores for the markers are indicated in Table 3. The highest lod score, a ϭ 0, was obtained using an expressed polymorphism identified in the FV gene (see below), which gave a lod score of 7.22.…”

Section: Multipoint Linkage and Haplotype Analysismentioning

confidence: 99%

“…[10][11][12][24][25][26] Polymorphic markers were used to narrow the critical region. The PACs and BACs for contig 195, which completely covers the critical interval, were sequenced by the Sanger Centre.…”

Section: Construction Of the Bac Map For The Critical Intervalmentioning

confidence: 99%

“…The intragenic AT3 marker and microsatellite markers from chromosome 1 were selected using the most recent Massachusetts Institute of Technology (MIT) STS map, 6 the GDB database, 7 the CHLC database, 8 and previous physical maps of this region. [9][10][11][12] The forward primer of each polymerase chain reaction (PCR) primer pair (Research Genetics, Huntsville, AL) was end-radiolabeled with phosphorous-33 ␥-adenosine 5Ј-triphosphate ( 33 P-␥ATP) using polynucleotide kinase. The amplifications were performed in a final volume of 25 L containing 50 ng DNA, 50 ng of each primer, 10 ng end-labeled primer, 0.25 M each dinucleoside 5Ј-triphosphate (dNTP), 1.5 mM magnesium dichloride (MgCl 2 ), 1 times Taq buffer, and 0.5 U Taq polymerase (Gibco-BRL Life Technologies, Rockville, MD).…”

Section: Genotypingmentioning

confidence: 99%

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Characterization of a novel autosomal dominant bleeding disorder in a large kindred from east Texas

Kuang¹,

Hasham²,

Phillips³

et al. 2001

Blood

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A large east Texas family with autosomal dominant inheritance of a novel bleeding disorder has been identified. The disorder is characterized clinically by easy bruising, life-threatening bleeding with trauma or surgery, and menorrhagia in affected women. Laboratory studies demonstrated prolongation of the prothrombin time and activated partial thromboplastin time in affected individuals. Paradoxically, assays of known coagulation factors are all within normal limits. To determine the molecular basis of this disease, a candidate gene linkage analysis in this kindred was done. Initially it was hypothesized that the cause of the disease in this family could be an antithrombin III (AT3) mutation that resulted in a constitutively active AT3 in the absence of heparin binding. Linkage studies using DNA from the family and an intragenic polymorphic marker within the AT3 gene showed that the disease mapped to this locus. The coding region and intron/exon junctions of AT3 were sequenced using the proband's DNA, but this analysis failed to identify a mutation.

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“…Sheffield et al (1993) used genetic linkage analysis to map JOAG to chromosome 1. This GLC1A locus was subsequently refined (Sunden et al 1996) and the disease-causing gene was identified using a combination of positional cloning and candidate gene studies (Stone et al 1997). The gene codes for a protein that was initially named trabecular meshwork glucocorticoid response protein (TIGR) .…”

mentioning

confidence: 99%

Characterization and Comparison of the Human and MouseGLC1A Glaucoma Genes

Fingert¹,

Ying²,

Swiderski³

et al. 1998

Genome Res.

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The GLC1A gene (which encodes the protein myocilin) has been associated with the development of primary open angle glaucoma. Bacterial artificial chromosomes containing the human GLC1A gene and its mouse ortholog were subcloned and sequenced to reveal the genomic structure of the genes. Comparison of the coding sequences of the human and mouse GLC1A genes revealed a high degree of amino acid homology (82%) and the presence of several conserved motifs in the predicted GLC1A proteins. The expression of GLC1A was examined by Northern blot analysis of RNA from adult human tissues. GLC1A expression was observed in 17 of 23 tissues tested, suggesting a wider range of expression than was recognized previously. The comparison of the human and mouse GLC1A genes suggests that the mouse may be a useful model organism in studying the molecular pathophysiology of glaucoma.

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Fine mapping of the autosomal dominant juvenile open angle glaucoma (GLC1A) region and evaluation of candidate genes.

Cited by 45 publications

References 23 publications

Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

Characterization of a novel autosomal dominant bleeding disorder in a large kindred from east Texas

Characterization and Comparison of the Human and MouseGLC1A Glaucoma Genes

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