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P Denny

Publications and source records attributed to P Denny.

At least 37 records · Page 2Linked to original sources
PubMed1999

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.

Animals↗
PubMed1999

The gene mutated in bare patches and striated mice encodes a novel 3beta-hydroxysteroid dehydrogenase.

X-linked dominant disorders that are exclusively lethal prenatally in hemizygous males have been described in human and mouse. None of the genes responsible has been isolated in either species. The bare patches (Bpa) and striated (Str) mouse mutations were originally identified in female offspring of X-irradiated males. Subsequently, additional independent alleles were described. We have previously mapped these X-linked dominant, male-lethal mutations to an overlapping region of 600 kb that is homologous to human Xq28 (ref. 4) and identified several candidate genes in this interval. Here we report mutations in one of these genes, Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein, in two independent Bpa and three independent Str alleles. Quantitative analysis of sterols from tissues of affected Bpa mice support a role for Nsdhl in cholesterol biosynthesis. Our results demonstrate that Bpa and Str are allelic mutations and identify the first mammalian locus associated with an X-linked dominant, male-lethal phenotype. They also expand the spectrum of phenotypes associated with abnormalities of cholesterol metabolism.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Localization of two insulin-dependent diabetes (Idd) genes to the Idd10 region on mouse chromosome 3.

Multiple genes control the development of autoimmune diabetes both in humans and in the nonobese diabetic (NOD) strain of mouse. Previously, three insulin-dependent diabetes (Idd) genes, Idd3, Idd10, and Idd17, were localized to mouse Chromosome (Chr) 3. The B10- or B6-derived resistance alleles at Idd10 and Idd3 together provide the NOD mouse with nearly complete protection from diabetes. In the present study, the 10.2-cM region encoding Idd10 was defined further with newly developed congenic strains. A locus, located in the centromeric 2.1 cM of the 10.2 cM region, contributed to the Idd10 trait. However, this locus did not account for the full effect of Idd10, suggesting the presence of a second gene in the distal portion of the 10.2-cM region. This second gene is designated as Idd18 and is localized to a 5.1-cM region. The resolution of the originally defined Idd3 locus into at least four separate loci, Idd3, Idd10, Idd17, and Idd18, illustrates the complex polygenic nature of diabetes.

Animals↗
PubMed1998

[Diagnostic imaging of idiopathic segmental infarct of the greater omentum. Diagnostic and physiopathologic considerations].

Primary infarction of the greater omentum is a rare cause of acute abdominal syndrome. Rate of occurrence may nevertheless be underestimated. We report a series of six cases observed over a 30-month period with US and CT imaging. We assessed early signs and their course. CT-scans depicted fatty oval-shaped masses below the right anterior or anterolateral parietal wall, associated with a thickening of the anterior parietal peritoneum, explaining symptom pathogenesis. Torsion can be identified, but has no specific impact on prognosis. Follow-up CT scan may evidence spontaneous, but sometimes slow, resolution.

Abdomen, Acute↗
PubMed1998

[Radiologic aspects of infarction of the appendix epiploica].

Clinical, US, CT and MR findings were reviewed in 5 patients with primary epiploic appendagitis (3 men, 2 women, mean age 38 years, age range 29-62 years) seen between December 1994 and December 1997. Diagnosis was reached in all cases with CT, with US in 3 and with MR in 1. Follow-up CT was performed in 2 cases and clinical follow-up in 4. One patient underwent surgery. Initial US, CT or MR examinations revealed a fatty oval-shaped nodule located anteriorly or anterolaterally to the left colon. The greater diameter ranged from 20 to 30 mm. Perinodular lesions with strands of periappendicular fat and thickened parietal peritoneum were visualized in all cases without any other inflammatory process in the abdomen. Symptoms resolved within 4 days in all patients. Signs of fatty inflammatory processes resolved in the 2 patients who had follow-up CTs. Primary epiploic appendagitis has characteristic US, CT and MR features which help guide medical treatment.

Adipose Tissue↗
PubMed1997

Congenic mapping of the insulin-dependent diabetes (Idd) gene, Idd10, localizes two genes mediating the Idd10 effect and eliminates the candidate Fcgr1.

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is under the control of multiple insulin-dependent diabetes (Idd) genes. The Idd3 gene, originally defined as a broad peak of linkage on mouse chromosome 3, was subsequently identified as two genes, Idd3 and Idd10, separated by at least 20 cM. The resistance alleles of Idd3 and Idd10 individually confer only partial protection from diabetes but, in combination, result in profound resistance to disease due to an epistatic genetic interaction. In this study, we used newly developed congenic strains to further localize Idd10. Surprisingly, we found that Idd10 itself comprises at least two linked loci: Idd10 and the newly designated Idd17. Idd17 was localized to a 1.1-cM region between D3Mit26 and D3Mit40, proximal to Fcgr1, a candidate gene encoding the high affinity Fc receptor for IgG. Idd10 was localized to a 10-cM region between D3Mit213 and D3Mit106, distal to Fcgr1. Thus, Fcgr1 was excluded as a candidate for either Idd10 or Idd17, despite the fact that the NOD strain expresses a mutant form of the receptor. Interestingly, although Idd10 and Idd17 participate in a genetic interaction with each other, Idd10 but not Idd17 participates in the genetic interaction with Idd3. Our study on chromosome 3 begins to reveal the extent of the polygenic nature of autoimmune diabetes, and demonstrates that the use of congenic strains is an effective mapping strategy, even in the dissection of multiple, linked genes with subtle effects.

Alleles↗
PubMed1997

Thiostrepton binds to malarial plastid rRNA.

Binding of the thiazolyl peptide antibiotic thiostrepton to the GTPase domain of 23S rRNA involves a few crucial nucleotides, notably A1067 (E. coli). Small RNA transcripts were prepared corresponding to the GTPase domain of the plastid 23S rRNA and the two forms of cytosolic 28S rRNAs found in the human malaria parasite Plasmodium falciparum, as well as the plastid form of rRNA of the AIDS-related pathogen Toxoplasma gondii. Binding affinities of the wild type and mutated RNA sequences were as predicted; the malarial plastid sequence had by far the highest affinity, whereas that from toxoplasma did not bind thiostrepton.

Animals↗
PubMed1997

HOSEpipe--a WWW-hosted data management and analysis system for STS content mapping projects.

We have developed a data management system, 'HOSEpipe' (High Output STS Evaluation pipeline) to aid sample tracking and data analysis in STS content mapping projects. The system is based around a World Wide Web (WWW) server that provides a number of pages including forms for sample processing and data entry accessible via a standard WWW browser application. The system is split into two main modules: firstly, a sequence evaluation and annotation module that takes de novo sequence for a potential STS, screens it against existing STSs and DNA sequence databases, followed by appropriate primer sequence design; secondly, a module that handles YAC library STS screening and includes facilities for both sample tracking and experimental data analysis. We present the design and rationale of the HOSEpipe system and its development to support a whole chromosomal physical mapping project. This software and design approach is potentially applicable to physical mapping projects of varying sizes and resolution and to similar projects, such as sample sequencing and the construction of sequence-ready maps.

Animals↗
PubMed1997

Mapping of the IDDM locus Idd3 to a 0.35-cM interval containing the interleukin-2 gene.

Currently, 16 loci that contribute to the development of IDDM in the NOD mouse have been mapped by linkage analysis. To fine map these loci, we used congenic mapping. Using this approach, we localized the Idd3 locus to a 0.35-cM interval on chromosome 3 containing the Il2 gene. Segregation analysis of the known variations within this interval indicated that only one variant, a serine-to-proline substitution at position 6 of the mature interleukin-2 (IL-2) protein, consistently segregates with IDDM in crosses between NOD and a series of nondiabetic mouse strains. These data, taken together with the immunomodulatory role of IL-2, provide circumstantial evidence in support of the hypothesis that Idd3 is an allelic variation of the Il2 gene, or a variant in strong linkage disequilibrium.

Amino Acid Sequence↗
PubMed1997

[MRI aspect of hepatic adenomatosis].

We report a case of hepatic adenomatosis demonstrated with MR imaging. The diagnosis can be suspected when this technique shows multiple hepatic lesions which present an iso-signal intensity on T1-wi, a hyperintense signal on T2-wi and rapid wash-in and wash-out of gadolinium. Injection of superparamagnetic iron oxide mag be useful in the characterization of the lesion: a decreased signal intensity after injection rules out the diagnosis of metastasis. Because of the unknown course of hepatic adenomatosis, histological proof and radiological follow-up are recommended.

Adenoma↗
PubMed1995

The Sry-related HMG box-containing gene Sox6 is expressed in the adult testis and developing nervous system of the mouse.

We have cloned and sequenced a full-length cDNA for the HMG box-containing, SRY-related gene Sox6 from mouse. The deduced protein sequence of Sox6 has considerable homology with that of the previously determined Sox5 sequence. It seems likely that these genes have diverged more recently than other members of the SOX gene family, although the two genes map to different chromosomes in the mouse. In common with Sox5, Sox6 is highly expressed in the adult mouse testis and the HMG domains of both proteins bind to the sequence 5'-AACAAT-3'. This suggests that the two genes may have overlapping functions in the regulation of gene expression during spermatogenesis in the adult mouse. However, Sox6 may have an additional role in the mouse embryo, where it is specifically expressed in the developing nervous system.

Amino Acid Sequence↗
PubMed1994

DNA binding and bending properties of the post-meiotically expressed Sry-related protein Sox-5.

Sox-5 is one of a family of genes which show homology to the HMG box region of the testis determining gene SRY. We have used indirect immunofluorescence to show that Sox-5 protein is localized to the nucleus of post-meiotic round spermatids in the mouse testis. In vitro footprinting and gel retardation assays demonstrate that Sox-5 binds specifically to the sequence AACAAT with moderately high affinity (Kd of approximately 10(-9) M). Moreover, interaction of Sox-5 with its target DNA induces a significant bend in the DNA, characteristic of HMG box proteins. Circular dichroism spectroscopy of the Sox-5 HMG box and its specific complex with DNA shows an alteration in the DNA spectrum, perhaps as a consequence of DNA bending, but none in the protein spectrum on complex formation. The dependence of the change in the CD spectrum with protein to DNA ratio demonstrates the formation of a 1:1 complex. Analysis of the structure of the Sox-5 HMG box by 2D NMR suggests that both the location of helical secondary structure as well as the tertiary structure is similar to that of HMG1 box 2.

Amino Acid Sequence↗
PubMed1992

An SRY-related gene expressed during spermatogenesis in the mouse encodes a sequence-specific DNA-binding protein.

SRY, the testis determining gene, encodes a member of a family of DNA binding proteins characterized by an amino acid sequence motif known as the HMG box. Using degenerate primers and the polymerase chain reaction, we have isolated SRY-related cDNAs from adult murine testis RNA. One of these, Sox-5, encodes a 43 kDa HMG-box protein with similarities to transcription activating proteins. Anti-Sox-5 antibody was used to analyse expression of Sox-5 in pre-pubertal testis and in fractionated spermatogenic cells. Sox-5 is restricted to post-meiotic germ cells, being found at highest levels in round spermatids. Sox-5 is a DNA binding protein and binding site selection assays suggest that it can bind specifically to oligonucleotides containing the consensus motif AACAAT. Sry can also bind to this motif, indicating that the Sry family may have overlapping sequence specificities.

Amino Acid Sequence↗