Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human.

Blatt, Cila; Eversole-Cire, Pamela; Cohn, Vivian H.; Zollman, Susan; Fournier, R. E. K.; Mohandas, L T; Nesbitt, Muriel N.; Lugo, Tracy G.; Jones, David T.; Reed, Randall R.

doi:10.1073/pnas.85.20.7642

Cited by 129 publications

(39 citation statements)

References 42 publications

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“…In these tumors, mutations ofthe gene encoding the a chain of the Gs protein, which has been localized to chromosome 20 (42), behaved like dominantly acting oncogenes. Our investigation for Gsa mutations in 11 of 13 patients with somatotrophinomas revealed gsp mutations in two tumors (Fig.…”

Section: Discussionmentioning

confidence: 99%

Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations.

Thakker

Pook²,

Wooding³

et al. 1993

J. Clin. Invest.

137

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The molecular pathology of somatotrophinomas has been investigated by a combined search for dominant mutations of the gene encoding the Gsa protein and for recessive mutations involving chromosome 11q13, which contains the gene causing multiple endocrine neoplasia type I (MENI ). Somatotrophinomas and peripheral leukocytes were obtained from thirteen patients with acromegaly; one patient also suffered from MENi. Five DNA probes identifying restriction fragment length polymorphisms from 1 Iq revealed allele loss in pituitary tumors from five (four non-MENI and one MEN1) patients. Deletion mapping revealed that the region of allele loss common to the somatotrophinomas involved 1 1q13. An analysis for similar allelic deletions at 12 other loci from chromosomes 1-5, 7-9, 12-14, and 17 did not reveal generalized allele loss in the somatotrophinomas. These results, which represent the first report of chromosome 11 allele loss occurring in non-MEN1 somatotrophinomas, indicate that a recessive oncogene on 11q13 is specifically involved in the monoclonal development of somatotrophinomas. In addition Gsa mutations were detected in two non-MENi somatotrophinomas, one of which also revealed allele loss of chromosome 11. Thus, our results reveal that the development of somatotrophinomas is associated with alterations in both dominant and recessive oncogenes and further characterization of these genetic abnormalities will help to elucidate the multistep etiology and progression of somatotrophinomas. (J. Clin. Invest. 1993. 2815-2821

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Section: Discussionmentioning

confidence: 99%

Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations.

Thakker

Pook²,

Wooding³

et al. 1993

J. Clin. Invest.

137

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“…On chromosome 9, Gnai-2, one of the alpha inhibitory subunits of G protein, has been mapped to within 10 centimorgans of our peak LOD for adiposity between the D9Mit]l and D9MitJ8 markers (23). The G protein is of particular interest since it modulates second messenger formation in the majority of hormonal and neurotransmitter systems (24) and therefore a defect in G protein function could be involved in many different phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

West¹,

Goudey-Lefevre²,

York³

et al. 1994

J. Clin. Invest.

140

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Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice. AKR/J mice are sensitive to dietary obesity when fed a high fat diet while SWR/J mice are resistant. Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity. Using an F2 mapping population of 931 male mice we found significant linkage with a QTL on chromosome 9 (Likelihood of the Odds [LOD] ratio of 4.85) and another QTL on chromosome 15 (LOD = 3.93). The presence of a QTL on chromosome 15 was confirmed in a separate mapping population of 375 male F1 x SWR/J mice (LOD = 3.82). These two loci are designated dietary obese 2 (Do2) and dietary obese 3 (Do3) for the chromosome 9 and 15 loci, respectively. Both of these chromosomal regions contain candidate genes which may contribute to variation in the phenotype. These loci also exert a significant control over individual adipose depot weights. (J. Clin. Invest. 1994. 94:1410-1416

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“…The Gnas locus: alternative promoters, splicing and regulation by genomic imprinting Although the location of the Ga s encoding Gnas gene on mouse distal chromosome 2/human chromosome 20q13.2-q13.3 and its exon-intron structure had been known for some time (Blatt et al 1988, Kozasa et al 1988, Gejman et al 1991, Levine et al 1991, Rao et al 1991, Peters et al 1994, and despite some early indications for alternative upstream promoters (Ishikawa et al 1990, Swaroop et al 1991, the full complexity of the Gnas locus was only discovered through work in a different field, i.e. genomic imprinting.…”

Section: The Ga S Variant Xla S Also Stimulates Camp Signalling From mentioning

confidence: 99%

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

Plagge

Kelsey

Germain‐Lee

2007

Journal of Endocrinology

104

137

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The stimulatory a-subunit of trimeric G-proteins Ga s , which upon ligand binding to seven-transmembrane receptors activates adenylyl cyclases to produce the second messenger cAMP, constitutes one of the archetypal signal transduction molecules that have been studied in much detail. Over the past few years, however, genetic as well as biochemical approaches have led to a range of novel insights into the Ga s encoding guanine nucleotide binding protein, a-stimulating (Gnas) locus, its alternative protein products and its regulation by genomic imprinting, which leads to monoallelic, parental origin-dependent expression of the various transcripts. Here, we summarise the major characteristics of this complex gene locus and describe the physiological roles of Ga s and its 'extra large' variant XLa s at post-natal and adult stages as defined by genetic mutations. Opposite and potentially antagonistic functions of the two proteins in the regulation of energy homeostasis and metabolism have been identified in Gnasand Gnasxl (XLa s )-deficient mice, which are characterised by obesity and leanness respectively. A comparison of findings in mice with symptoms of the corresponding human genetic disease 'Albright's hereditary osteodystrophy'/'pseudohypoparathyroidism' indicates highly conserved functions as well as unresolved phenotypic differences.

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Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human.

Cited by 129 publications

References 42 publications

Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations.

Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations.

Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

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