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Results for “Locus Control Region”

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At least 955 records · Page 53Linked to original sources
PubMed2000

Complex segregation analysis of deafness in Dalmatians.

OBJECTIVE: To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. ANIMALS: 605 purebred Dalmatians from 42 families. PROCEDURE: Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. RESULTS: Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.

Alleles↗
PubMed2004

Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA.

MHC class II (MHC-II) genes are regulated by an enhanceosome complex containing two gene-specific transcription factors, regulatory factor X complex (RFX) and CIITA. These factors assemble on a strictly conserved regulatory module (S-X-X2-Y) found immediately upstream of the promoters of all classical and nonclassical MHC-II genes as well as the invariant chain (Ii) gene. To identify new targets of RFX and CIITA, we developed a computational approach based on the unique and highly constrained architecture of the composite S-Y motif. We identified six novel S'-Y' modules situated far away from the promoters of known human RFX- and CIITA-controlled genes. Four are situated at strategic positions within the MHC-II locus, and two are found within the Ii gene. These S'-Y' modules function as transcriptional enhancers, are bona fide targets of RFX and CIITA in B cells and IFN-gamma-induced cells, and induce broad domains of histone hyperacetylation. These results reveal a hitherto unexpected level of complexity involving long distance control of MHC-II expression by multiple distal regulatory elements.

Acetylation↗
PubMed2006

Epigenetic histone modifications do not control Igkappa locus contraction and intranuclear localization in cells with dual B cell-macrophage potential.

Somatic rearrangement of the Ig genes during B cell development is believed to be controlled, at least in part, by accessibility of the loci to the recombinational machinery. Accessibility is poorly understood, but appears to be controlled by a combination of histone posttranslational modifications, large scale Ig locus contractions, and changes in intranuclear localization of the loci. These changes are regulated by developmental stage-specific as well as tissue-specific mechanisms. We previously isolated a murine B cell lymphoma line, Myc5, that can oscillate between the B cell and macrophage lineages depending upon growth conditions. This line provides an opportunity to study tissue-specific regulation of epigenetic mechanisms operating on the Ig loci. We found that when Myc5 cells are induced to differentiate from B cells into macrophages, expression of macrophage-specific transcripts was induced (M-CSFR, F4/80, and CD14), whereas B cell-specific transcripts decreased dramatically (mb-1, E47, IRF4, Pax5, and Igkappa). Loss of Igkappa transcription was associated with reduced Igkappa locus contraction, as well as increased association with heterochromatin protein-1 and association of the Igkappa locus with the nuclear periphery. Surprisingly, however, we found that histone modifications at the Igkappa locus remained largely unchanged whether the cells were grown in vivo as B cells, or in vitro as macrophages. These results mechanistically uncouple histone modifications at the Igkappa locus from changes in locus contraction and intranuclear localization.

Alleles↗
PubMed1999

[An analysis of the linkage of hypertrophic cardiomyopathy and the delta locus of the T-cell receptor (TCRD) chain in the family of P].

AIM: To estimate probability of location of the gene determining family hypertrophic cardiomyopathy (HCMP) in family P. on the 14th chromosome in segment 14q11 using parametric method "lod score". MATERIALS AND METHODS: The family of proband P. had multiple cases of HCMP. Dinucleotide GT repeat and NT 256 point variation located in the cluster of genes coding synthesis of TCRD (14q11 chromosome segment) were used as markers of HCMP gene (FHC-1 gene 14q1 chromosome segment). Allele polymorphism of the two markers was defined at polymerase chain reaction, restriction of the amplificate by restrictase BamHI (for NT 256 point variation) and vertical electrophoresis in polyacrylamide and agar gels. RESULTS: Basing on the distribution of the above markers in P. family, lod score estimates in all the standard values of recombination frequency were determined (0-0,45, step 0.05). The maximal estimate corresponded to zero recombination frequency and was equal to 1.17 (this was below the critical value 3). However, the obtained lod score value satisfied the chance ratio 15:1 in favor of the link presence. CONCLUSION: The data obtained evidence for the presence of the link of HCMP gene with marker locus TCRD which is nearby the identified locus of the disease (FHC-1-14q11.2 segment). This suggests that HCMP in family P may be due to mutant allele of the gene coding synthesis of beta-polypeptide chains of cardial myosin.

Adolescent↗
PubMed2000

[New approaches to construction of transgenic animals with high level tissue-specific expression of foreign genes: construction and reconstruction of genomic domains].

The major problems in constructing transgenic animals and approaches to their solution are discussed. Modern views of the structural-functional organization of the eukaryotic genome are considered. The domain hypothesis of the genome organization is analyzed in detail, as many problems associated with a low level and a lack of tissue specificity of transgene expression can be solved at the step of construction (or reconstruction of existing domains).

Animals↗
PubMed2002

Association of psoriasis vulgaris with HLA class I and class II antigens in the Turkish population, according to the age at onset.

BACKGROUND: Association of psoriasis vulgaris with HLA antigens reference to age at onset has been reported in different racial or ethnic populations. OBJECTIVE: Our purpose was to determine the distribution of HLA markers in the Turkish population according to the age at onset of the psoriasis vulgaris. METHODS: HLA class I and class II antigens were performed by serologic methods in a group of 100 Turkish patients with psoriasis and 201 control subjects. Patients with psoriasis were subdivided into two groups based on age at onset (below or above 40 years of age) and family history. RESULTS: The frequency of HLA A30, Cw3, Cw6, DR7, DR14, DQ8, and DQ9 antigens were significantly increased in the Turkish psoriatic patients whereas HLA A66, Cw2, Cw4 and DR11 were found to be negatively associated with psoriasis. However, there were striking differences in HLA antigens according to the age at onset of the disease. Type I, early onset was associated with a high frequency of A30, B50, Cw6 and DR7 antigens whereas patients with type II, late onset had an increased frequency of Cw7. CONCLUSIONS: We conclude that psoriasis is probably a genetically determined disease and suggest that HLA-Cw6 antigen seems to associate commonly with early onset of psoriasis in Turkish patients.

Adolescent↗
PubMed2003

[The frequency of reversion of the opaque2 locus mutable alleles controlled by the Bg-rbg system of mobile elements in maize].

Maize lines differing in the frequency of reversion of the opaque2 (o2) mutable alleles controlled by the system of Bg-rbg transportable elements were studied. In the presence of the Bg regulatory element, these alleles can revert to normal. When reversion occurs prior to the first division of the primary endosperm nucleus, either phenotypically normal kernels or whole endosperm revertants (WER) develop. Low frequency of whole endosperm revertant formation may be produced by different genetic mechanisms. The frequency of WER formation was shown to nonlinearly depend on the dose of the Bg-hf regulatory element. A dose increase from two to three failed to cause an essential increase in the number of revertants. The regulatory elements Bg-lf and Bg-hf differed in ability to induce excision of the receptor element at the same dose. The frequency of reversion of the receptive alleles was shown to be regulated by epigenetic mechanisms so that high frequency of reversion of receptive alleles requires preliminary premeiotic association between the regulatory and receptor elements. The inheritance of the maize alleles o2-hf and o2-lf proved to be similar to that an3 mutable alleles in petunia.

Alleles↗
PubMed1999

Predominant expression of human Agamma--in contrast with beta-globin gene in MEL cells transfected with the construct muLCRAgamma psibeta deltabeta.

A cosmid construct muLCRAgamma psibeta deltabeta were induced into mouse erythroleukemia cell lines 585 that expresses murine adult globin only and MEL GM-979 that expresses both murine embryonic and adult globins. Similar patterns of human globin gene expression were displayed in the two MEL cell lines transfected with the construct. Inducible expression of the Agamma- and beta-gene was observed during induced cell differentiation. However, the expression level of the Agamma-globin gene is much higher than that of the beta-globin gene in either uninduced or induced MEL transformants. No gamma to beta switching happened in the stable MEL transformants following a continuous culture. The much more effective enhance of the muLCR on the Agamma-globin gene than that on the beta-globin gene is resulted probably from the fact that the distance between the LCR and the beta-globin gene is much longer than that between the LCR and the Agamma-globin gene in the construct, in comparison with other constructs containing HS2 or muLCR linked to both of gamma- and beta-globin genes in different order. Two suggestions can be derived from these results: 1) A competition between the gamma- and beta-globin gene for interaction with the LCR may indeed present, but only an enough long distance difference between the LCR to the gamma- and to the beta-gene can effectively influence the competition; 2) Unlike transgenic mice, MEL cells are incapable of reconstructing the regulatory information involved in developmental control when it is provided by a fragment of the beta-globin gene cluster with limited length.

Animals↗
PubMed2005

A two-stage approach identifies a Q344X mutation in the rhodopsin gene of a Chinese Singaporean family with autosomal dominant retinitis pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP) is a group of hereditary retinal diseases in which photoreceptor cells degenerate. It is both clinically and genetically heterogenous. Using a two-stage approach by combining linkage analysis with mutation detection, we have rapidly identified the gene locus and the mutation site of a Chinese Singaporean family with autosomal dominant RP. MATERIALS AND METHODS: Three Chinese Singaporean families were tested. One family showed autosomal dominant inheritance pattern, while the other two could be recessive or sporadic. Twelve di-nucleotide markers tightly linked to 6 genes known to be responsible for either autosomal dominant or recessive RP were selected for linkage analysis. Cosegregation of marker and disease inheritance pattern permits identification of the target candidate gene. RFLP (restriction fragment length polymorphism) markers were added to confirm the linkage result prior to the detailed mutation detection study. RESULTS: With this two-stage strategy, the autosomal dominant RP family showed the rhodopsin locus segregating concordantly with the disease. Mutation screening later identified a nonsense mutation 5261C>T in the last exon of rhodopsin gene. It predicted a Q344X changes at the C-terminus of the gene product, truncating it by 5 amino acids. CONCLUSION: This systematic approach facilitates molecular diagnosis of a genetically heterogenous disease like RP. This is the first report of an RP mutation in Singapore. This 5261C>T mutation has been reported in the Caucasian, but not the Chinese population. The relatively milder phenotype in this family showed similarity to the reported US family, indicating the correlation of mutation site to severity of disease regardless of ethnicity.

Asian People↗
PubMed1996

In vivo footprinting analysis of the hepatic control region of the human apolipoprotein E/C-I/C-IV/C-II gene locus.

Expression of both the apolipoprotein (apo)E and apoC-I genes in the liver is specified by a 319-nucleotide hepatic control region (HCR-1) that is located 15 kilobase pairs downstream of the apoE gene and 5 kilobase pairs downstream of the apoC-I gene. In vivo footprint analysis of HCR-1 in intact nuclei revealed several liver-specific protein-binding sites that were not detectable by in vitro methods. In addition to three previously identified in vitro footprints, four in vivo footprints were identified in a region of HCR-1 that is required for directing gene expression to hepatocytes. Prominent liver-specific DNase I-hypersensitive sites were associated with these footprints. Liver-specific nuclear protein binding to these sites was confirmed by oligonucleotide gel-retention assays. The in vivo analysis also identified a cluster of nuclear protein-binding sites in the Alu family repeat segment adjacent to the domain required for liver expression. Micrococcal nuclease digestion indicated the presence of a nucleosome in the central domain of HCR-1 in liver chromatin that was in phase with the nucleosome location in tissues that did not express the transgene. These results suggest that HCR-1 functions in a highly structured chromatin environment requiring a complex interaction of liver-enriched transcription factors.

Apolipoprotein C-I↗
PubMed1986

A unique immune response control locus mapping with the H-2D class I region.

The immune response to the polysaccharide antigen Trinitrophenyl (TNP)-ficoll is controlled by two complementing loci in the murine major histocompatibility complex. One locus of control is present in the I-A subregion and the second is located between the S and D regions. A monoclonal antibody 48-21.7 was selected for its ability to significantly block the in vitro primary response to TNP-ficoll. This antibody bound to antigen-presenting cells does not interfere with the presentation of other antigens. Experiments are presented to demonstrate that the monoclonal antibody 48-21.7 precipitates a unique protein of approximately 40,000 daltons. Sequential immunoprecipitation with monoclonal antibodies to the class I Db antigen and to relevant Ia antigens demonstrated no cross-reactivity. Amino acid sequencing has found unique amino acids to be present at three class I N-terminal invariant positions. These observations indicate the presence of a unique class I-like molecule coded for by genes mapping between S and D and involved in the response to the polysaccharide ficoll.

Animals↗
PubMed1985

A new dispensable genetic locus of the terminus region involved in control of cell division in Escherichia coli.

Temperature-sensitive mutants defective in cell division were isolated after localised mutagenesis of the terminus region of the Escherichia coli chromosome. The defective gene in one of these mutants, dicA, was mapped at 34.9 min by linkage with manA and with three physically characterized Tn10 insertions. Temperature-sensitivity conferred by mutation dicA1 in a recA background [corrected] was suppressed by the presence of hybrid plasmids carrying the wild-type gene. In addition, the mutation was suppressed either by tranposon inactivation of a nearby gene, dicB, or by deletion of the entire dicA-dicB interval. These results define the dicA-dicB locus as a new dispensable genetic cluster involved in the control of cell division.

Escherichia coli↗
PubMed1984

Allotypes of murine factor B controlled by a locus within the S region of the H-2 complex.

Bf protein was directly precipitated from a mixture of EDTA-plasma from 13 different, inbred strains and rabbit IgG anti-mouse Bf, and was isolated by SDS-PAGE. The gel pieces containing Bf protein were digested by trypsin after labeling with 125I-Na, and then peptides of Bf protein with each mouse strain were compared by two-dimensional peptide mapping. The results for the peptide patterns with the standard B10 congenic strains (all of which Bf phenotypes had been already designated as Bf.1 because of the identical isoelectric point values) revealed two distinct peptide patterns. The peptide pattern of Bf protein appeared to be identical in each of the inbred strains, but only one of the 36 spots in the fingerprint observed either with B10 or B10.BR (designated tentatively as Bf.1 (b.k.) ) was not detected in that from B10.D2 and B10.S (designated tentatively as Bf.1 (d.s.) ). The results of peptide mapping with intra-H-2 recombinant inbred strains show that this structural variant was mapped to the S region, which is direct evidence that allotypes of murine Bf are encoded by a structural gene within the MHC.

Animals↗