Science.gov

Sample records for chromosome 1q juvenile

  1. Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome 1 q

    SciTech Connect

    Richards, J.E.; Lichter, P.R.; Torrez, D.; Wong, D.; Johnson, A.T.; Boehnke, M.; Uro, J.L.A. )

    1994-01-01

    A large Caucasian family is presented, in which a juvenile-onset form of open-angle glaucoma is transmitted in an autosomal dominant fashion. Sixteen affected family members were identified from 31 at-risk individuals descended from the affected founder. Affected patients developed high intraocular pressures (sometimes >40 mm Hg) within the first 2 decades of life. Linkage analysis between the disease phenotype and 12 microsatellite repeat markers located on chromosome 1 q gave a maximum lod score of 8.38 at a recombination fraction of zero for marker D1S210. Analysis of recombinant haplotypes suggests a total inclusion region of about 14 cM between markers D1S194 and D1S218 at 1q21-q31. This represents the second juvenile-glaucoma family, in which the disease has been mapped to the long arm of chromosome 1. 57 refs., 2 figs., 3 tabs.

  2. Further evidence for a locus for autosomal dominant juvenile glaucoma on chromosome 1q and evidence for genetic heterogeneity

    SciTech Connect

    Wiggs, J.; Paglinauan, C.; Stawski, S.

    1994-09-01

    Glaucoma is a term used to describe a group of disorders which have in common a characteristic degeneration of the optic nerve associated with typical visual field defects and usually associated with elevated intraocular pressure. Two percent of white Americans and 6-10% of black Americans are affected by the disease. Compelling data indicate that susceptibility to many types of glaucoma is inherited. Hereditary juvenile glaucoma is one form of glaucoma that develops in children and is inherited as an autosomal dominant trait with high penetrance. Using a single large Caucasian pedigree affected with autosomal dominant juvenile glaucoma, Sheffield discovered positive linkage to a group of markers that map to a 30 cM region on the long arm of chromosome 1 (1q21-q31). We have subsequently identified three unrelated Caucasian pedigrees affected with autosomal dominant juvenile glaucoma that also demonstrate linkage to this region on chromosome 1, with the highest combined lod score of 5.12 at theta = .05 for marker D1S218. The identification of critical recombinant individuals in our three pedigrees has allowed us to further localize the disease gene to a 12 cM region between markers D1S242 and D1S431. In addition, we have identified several pedigrees which do not demonstrate linkage to chromosome 1q, including a black family affected with autosomal dominant juvenile glaucoma that is indistinguishable clinically from the disorder affecting the caucasian pedigrees and three pedigrees affected with pigmentary dispersion syndrome, a form of glaucoma that also affects the juvenile population and is also inherited as an autosomal dominant trait. These findings provide evidence for genetic heterogeneity in juvenile glaucoma.

  3. Linkage analysis of primary open-angle glaucoma excludes the juvenile glaucoma region on chromosome 1q

    SciTech Connect

    Wirtz, M.K.; Acott, T.S.; Samples, J.R. |

    1994-09-01

    The gene for one form of juvenile glaucoma has been mapped to chromosome 1q21-q31. This raises the possibility of primary open-angle glaucoma (POAG) also mapping to this region if the same defective gene causes both diseases. To ask this question linkage analysis was performed on a large POAG kindred. Blood samples or skin biopsies were obtained from 40 members of this family. Individuals were diagnosed as having POAG if they met two or more of the following criteria: (1) Visual field defects compatible with glaucoma on automated perimetry; (2) Optic nerve head and/or nerve fiber layer analysis compatible with glaucomatous damage; (3) high intraocular pressures (> 20 mm Hg). Patients were considered glaucoma suspects if they only met one criterion. These individuals were excluded from the analysis. Of the 40 members, seven were diagnosed with POAG; four were termed suspects. The earliest age of onset was 38 years old, while the average age of onset was 65 years old. We performed two-point and multipoint linkage analysis, using five markers which encompass the region 1q21-q31; specifically, D1S194, D1S210, D1S212, D1S191 and LAMB2. Two-point lod scores excluded tight linkage with all markers except D1S212 (maximum lod score of 1.07 at theta = 0.0). In the multipoint analysis, including D1S210-D1S212-LAMB2 and POAG, the entire 11 cM region spanned by these markers was excluded for linkage with POAG; that is, lod scores were < -2.0. In conclusion, POAG in this family does not map to chromosome 1q21-q31 and, thus, they carry a gene that is distinct from the juvenile glaucoma gene.

  4. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  5. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.

    PubMed Central

    Avramopoulos, D; Kitsos, G; Economou-Petersen, E; Grigoriadou, M; Vassilopoulos, D; Papageorgiou, C; Psilas, K; Petersen, M B

    1996-01-01

    A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG) was recently assigned to chromosome region 1q21-q31. In the present study, a large Greek family with autosomal dominant adult onset POAG was investigated using microsatellite markers. Exclusion of linkage of the adult onset POAG gene to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data provide evidence that juvenile and adult onset POAG are genetically distinct disease entities. PMID:9004141

  6. Exclusion of candidate genes from the chromosome 1q juvenile glaucoma region and mapping of the peripheral cannabis receptor gene (CNR2) to chromosome 1

    SciTech Connect

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M.

    1994-09-01

    Juvenile onset primary open angle glaucoma has been mapped by linkage to 1q21-q31. Several candidate genes were evaluated in the same family used to identify the primary linkage. Atrionatriuretic peptide receptor A (NPR1) and laminin C1 (LAMC1) have been previously mapped to this region and could putatively play a role in the pathogenesis of glaucoma. A third gene, the peripheral cannabis receptor (CNR2) was not initially mapped in humans but was a candidate because of the relief that cannabis affords some patients with primary open angle glaucoma. Microsatellites associated with NPR1 and LAMC1 revealed multiple recombinations in affected members of this pedigree. CNR2 was shown to be on chromosome 1 by PCR amplification of a 150 bp fragment of the 3{prime} untranslated region in monochromosomal somatic cell hybrids (NIGMS panel No. 2). These primers also revealed a two allele single strand conformation polymorphism which showed multiple recombinants with juvenile onset primary open angle glaucoma in large pedigrees, segregating this disorder. The marker was then mapped to 1p34-p36 by linkage, with the most likely location between liver alkaline phosphatase (ALPL) and alpha-L-1 fucosidase (FUCA1).

  7. A single gene for juvenile and middle-age onset open-angle glaucomas confined within a small interval on chromosome 1q

    SciTech Connect

    Raymond, V.; Dumont, M.; Plante, M.

    1994-09-01

    Primary open-angle glaucoma (POAG) encompasses a complex of ocular disease entities characterized by an optic neuropathy causing progressive loss of the visual fields and usually associated with elevated intraocular pressure. POAG can be subdivided into two groups according to age of onset: (1) the more prevalent middle to late-age onset chronic open-angle glaucoma (COAG) diagnosed after age 40 and (2) the less common form, juvenile open-angle glaucoma (JOAG), which occurs between 3 years of age and early adulthood. Susceptibility to either COAG or JOAG has been found to be inherited. We studied 141 members of a huge multigeneration French Canadian family affected with an autosomal dominant form of POAG. Both JOAG and COAG were diagnosed in 43 patients. To first position the disease gene, AFM microsatellites markers specific to chromosome 1q21-q31 were selected since linkage of JOAG to this region was recently demonstrated in two Caucasian families. Tight linkage was observed between the JOAG/COAG phenotype and 7 microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 at {theta}=0 was obtained with AFM278ye5. Using a recombination mapping strategy based on a unique founder effect, a characteristic JOAG/COAG haplotype spanning 12 cM was next recognized between loci D1S196 and D1S212. Two key recombination events in affected patients further confined the disease locus within a 5 cM interval between loci D1S445 and D1S452/D1S210. These results are the first to demonstrate that JOAG and one adult form of POAG map at a single locus on chromosome 1q23-q25. They also provide members of this family with a new diagnostic tool to identify the at-risk individuals.

  8. Evaluation of chromosome 1q gain in intracranial ependymomas.

    PubMed

    Rajeshwari, Madhu; Sharma, Mehar Chand; Kakkar, Aanchal; Nambirajan, Aruna; Suri, Vaishali; Sarkar, Chitra; Singh, Manmohan; Saran, Ravindra Kumar; Gupta, Rakesh Kumar

    2016-04-01

    Ependymomas are relatively uncommon gliomas with poor prognosis despite recent advances in neurooncology. Molecular pathogenesis of ependymomas is not extensively studied. Lack of correlation of histological grade with patient outcome has directed attention towards identification of molecular alterations as novel prognostic markers. Recently, 1q gain has emerged as a potential prognostic marker, associated with decreased survival, especially in posterior fossa, high grade tumors. Cases of intracranial ependymomas were retrieved. Tumors were graded using objective criteria to supplement WHO grading. Fluorescence in situ hybridization for 1q gain was performed on formalin-fixed paraffin embedded sections. Eighty-one intracranial ependymomas were analyzed. Pediatric (76%) and infratentorial (70%) ependymomas constituted the majority. 1q gain was seen in 27 cases (33%), was equally frequent in children (34%) and adults (32%), supratentorial (37%) and infratentorial (32%) location, grade II (33%) and III (25%) tumors. Recurrence was noted in 24 cases and death in 7 cases with 5-year progression-free and overall-survival rates of 37% and 80%, respectively. Grade II tumors had a better survival than grade III tumors; histopathological grade was the only prognostically significant marker. 1q gain had no prognostic significance. 1q gain is frequent in ependymomas in Indian patients, seen across all ages, sites and grades, and thus is likely an early event in pathogenesis. The prognostic value of 1q gain, remains uncertain, and multicentric pooling of data is required. A histopathological grading system using objective criteria correlates well with patient outcome and can serve as an economical option for prognostication of ependymomas. PMID:26725097

  9. Assignment of the phosducin (PDC) gene to human chromosome 1q25-1q32. 1 by somatic cell hybridization and in situ hybridization

    SciTech Connect

    Sparkes, R.S.; Kojis, T.; Klisak, I.; Heinzmann, C.; Bateman, J.B. ); Lee, R.H. ); Shinohara, T. ); Craft, C.M. )

    1993-11-01

    Phosducin is a soluble photoreceptor phosphoprotein that probably modulates phototransduction in the retina and thus qualifies as a potential candidate gene for retinitis pigmentosa. Using both human/mouse somatic cell hybrids and in situ hybridization to human metaphase chromosomes, the authors have mapped this gene to chromosome 1q25-1q32.1. 18 refs., 2 figs.

  10. Exclusion of chromosome 1q21-q31 from linkage to three pedigrees affected by the pigment-dispersion syndrome

    SciTech Connect

    Paglinauan, C.; Haines, J.L.; Del Bono, E.A.; Schuman, J.; Stawski, S.; Wiggs, J.L.

    1995-05-01

    The pigment-dispersion syndrome is a form of open-angle glaucoma that usually affects individuals in the first 3 decades of life. In addition to the typical optic-nerve degeneration seen in all types of glaucoma, the pigment-dispersion syndrome is characterized by distinctive clinical features including the deposition of pigment granules from the iris epithelium on a variety of ocular structures including the trabecular meshwork. Frequently this disorder affects young myopic individuals. In the early stages of the disease, affected individuals may have clinical evidence of dispersed pigment without an associated elevation of intraocular pressure and optic-nerve degeneration. However, as the disease process progresses, many affected individuals ({approximately}50%) will develop elevated intraocular pressure and degeneration of the optic nerve, causing a permanent loss of sight. The pigment-dispersion syndrome shares several clinical features with the form of autosomal dominant juvenile open-angle glaucoma that recently has been mapped to the 1q21-q31 region of chromosome 1. Our results indicate that the pigment-dispersion syndrome, a form of glaucoma that may also affect the juvenile population, is genetically unrelated to the autosomal dominant form of juvenile glaucoma caused by a defect in a gene located in the 1q21-q31 region of chromosome 1. 15 refs., 2 figs., 1 tab.

  11. Polymorphisms in the phosducin (PDC) gene on chromosome 1q25-32

    SciTech Connect

    Humphries, P.; Mansergh, F.C.; Farrar, G.J.

    1994-09-01

    Phosducin (33 kDa protein or MEKA) is a principal water-soluble phosphoprotein in the rod and cone photoreceptor cells and pinealocytes. This protein modulates the phototransduction cascade by binding to the beta and gamma subunit complexes of transducin. The PDC gene has been mapped to 1q25-32, the region of linkage of two hereditary retinal degenerative disorders; autosomal dominant juvenile-onset open-angle glaucoma and one form of autosomal recessive RP. Using previously published sequence data, PCR primers were designed to amplify the coding and 5{prime} flanking regions of the PDC gene. Direct sequencing revealed three polymorphisms in the 5{prime} flanking region, two of which were in regions highly homologous between humans and mice. Analysis of the polymorphisms was then extended to larger population samples using SSCPE and denaturing gel analysis. The first polymorphism PDC1 resulted from an insertion of a G residue at position -653/4. Allele frequencies were determined to be 0.51 (insG) and 0.49 (normal) giving a PIC value of 0.50. A deletion of a T residue at position -488 was the basis of the PDC2 polymorphism with allele frequencies of 0.88 (normal) and 0.12 (delT) and a PIC value of 0.21. Interestingly, the allele with an inserted G residue in PDC1 always segregrated with the deleted T allele in PDC2. The third polymorphism PDC3 was caused by a T or G residue at position -1083. Allele frequencies of 0.26 (G residue) and 0.74 (T residue) were determined from an analysis of 80 individuals with an overall PIC value of 0.39. The identification of these three polymorphisms in the PDC gene will be useful for future genetic linkage studies of chromosome 1q in inherited retinopathies.

  12. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

    PubMed

    Schumacher, Fredrick R; Wang, Zhaoming; Skotheim, Rolf I; Koster, Roelof; Chung, Charles C; Hildebrandt, Michelle A T; Kratz, Christian P; Bakken, Anne C; Bishop, D Timothy; Cook, Michael B; Erickson, R Loren; Fosså, Sophie D; Greene, Mark H; Jacobs, Kevin B; Kanetsky, Peter A; Kolonel, Laurence N; Loud, Jennifer T; Korde, Larissa A; Le Marchand, Loic; Lewinger, Juan Pablo; Lothe, Ragnhild A; Pike, Malcolm C; Rahman, Nazneen; Rubertone, Mark V; Schwartz, Stephen M; Siegmund, Kimberly D; Skinner, Eila C; Turnbull, Clare; Van Den Berg, David J; Wu, Xifeng; Yeager, Meredith; Nathanson, Katherine L; Chanock, Stephen J; Cortessis, Victoria K; McGlynn, Katherine A

    2013-07-01

    Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk. PMID:23462292

  13. Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q

    SciTech Connect

    Shephard, E.A.; Fox, M.F.; Povey, S. ); Dolphin, C.T.; Phillips, I.R.; Smith, R. )

    1993-04-01

    The authors have used the polymerase chain reaction to map the gene encoding human flavin-containing monooxygenase (FMO) form II (N. Lomri, Q. Gu, and J. R. Cashman, 1992, Proc. Natl. Acad. Sci. USA 89: 1685--1689) to chromosome 1. They propose the designation FMO3 for this gene as it is the third FMO gene to be mapped. The two other human FMO genes identified to date, FMO1 and FMO2, are also located on chromosome 1 (C. Dolphin, E. A. Shephard, S. Povey, C. N. A. Palmer, D. M. Ziegler, R. Ayesh, R. L. Smith, and 1. R. Phillips, 1991, J. Biol. Chem. 266: 12379--12385; C. Dolphin, E. A. Shephard, S. F. Povey, R. L. Smith, and I. R. Phillips, 1992, Biochem. J. 286: 261--267). The localization of FMO1, FMO2, and FMO3 has been refined to the long arm of chromosome 1. Analysis of human metaphase chromosomes by in situ hybridization confirmed the mapping of FMO1 and localized this gene more precisely to 1 q23-q25. 28 refs., 3 figs., 2 tabs.

  14. Localization of the L-glutamine synthetase gene to chromosome 1q23.

    PubMed

    Clancy, K P; Berger, R; Cox, M; Bleskan, J; Walton, K A; Hart, I; Patterson, D

    1996-12-15

    Glutamine synthetase (E.C. 6.3.1.2) is expressed throughout the body and plays an important role in controlling body pH and in removing ammonia from the circulation. The enzyme clears L-glutamate, the major neurotransmitter in the central nervous system, from neuronal synapses. The enzyme is a very sensitive marker of many disease and aging processes, especially those involving reactive oxygen species. This report describes the localization of the enzyme to chromosome 1 by PCR analysis of a human/rodent somatic cell hybrid panel. We also describe the localization of a recently described pseudogene to chromosome 9. Further localization of the glutamine synthetase gene locus to 1q23 was accomplished by fluorescence in situ hybridization. The glutamine synthetase gene was mapped to five CEPH megaYACs between the polymorphic PCR markers D1S117 and D1S466 by analysis of the Whitehead Institute's recently described chromosome 1 contig map. PMID:8975719

  15. Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric Phenotypes

    PubMed Central

    Mefford, Heather C.; Sharp, Andrew J.; Baker, Carl; Itsara, Andy; Jiang, Zhaoshi; Buysse, Karen; Huang, Shuwen; Maloney, Viv K.; Crolla, John A.; Baralle, Diana; Collins, Amanda; Mercer, Catherine; Norga, Koen; de Ravel, Thomy; Devriendt, Koen; Bongers, Ernie M.H.F.; de Leeuw, Nicole; Reardon, William; Gimelli, Stefania; Bena, Frederique; Hennekam, Raoul C.; Male, Alison; Gaunt, Lorraine; Clayton-Smith, Jill; Simonic, Ingrid; Park, Soo Mi; Mehta, Sarju G.; Nik-Zainal, Serena; Woods, C. Geoffrey; Firth, Helen V.; Parkin, Georgina; Fichera, Marco; Reitano, Santina; Giudice, Mariangela Lo; Li, Kelly E.; Casuga, Iris; Broomer, Adam; Conrad, Bernard; Schwerzmann, Markus; Räber, Lorenz; Gallati, Sabina; Striano, Pasquale; Coppola, Antonietta; Tolmie, John L.; Tobias, Edward S.; Lilley, Chris; Armengol, Lluis; Spysschaert, Yves; Verloo, Patrick; De Coene, Anja; Goossens, Linde; Mortier, Geert; Speleman, Frank; van Binsbergen, Ellen; Nelen, Marcel R.; Hochstenbach, Ron; Poot, Martin; Gallagher, Louise; Gill, Michael; McClellan, Jon; King, Mary-Claire; Regan, Regina; Skinner, Cindy; Stevenson, Roger E.; Antonarakis, Stylianos E.; Chen, Caifu; Estivill, Xavier; Menten, Björn; Gimelli, Giorgio; Gribble, Susan; Schwartz, Stuart; Sutcliffe, James S.; Walsh, Tom; Knight, Samantha J.L.; Sebat, Jonathan; Romano, Corrado; Schwartz, Charles E.; Veltman, Joris A.; de Vries, Bert B.A.; Vermeesch, Joris R.; Barber, John C.K.; Willatt, Lionel; Tassabehji, May; Eichler, Evan E.

    2009-01-01

    BACKGROUND Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P = 1.1×10−7). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in the nine children with mental retardation or autism spectrum disorder and other variable features (P = 0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype. PMID:18784092

  16. Construction and characterization of a NotI linking library from human chromosome region 1q25-qter

    SciTech Connect

    Talmadge, C.B.; Zhen, Dong-Kai; Wang, Ji-Yi

    1995-09-01

    Chromosome 1q25-qter-specific NotI linking clones have been isolated from a NotI linking library that was constructed using DNA from MCH206.1 somatic cell hybrid cells. These cells contain chromosome 1q25-qter translocated to human chromosome Xp22 as the only human genetic material in mouse background. Sixty-eight NotI linking clones have been mapped by a combination of fluorescence in situ hybridization and R-banding to cytogenetic bands on the long arm of chromosome 1. The relative order of 11 NotI clones and their relation to known chromosome 1 markers have also been determined in 1q32 and 1q41, where the genes of Van der Woude and Usher syndrome type IIa have been previously mapped: cen-chr1.14-chr1.79-chr1.56-chr1.11-chr1.95-chr1.58 (chr1.74)-D1S70-chr1.15-chr1.82 (chr1.143)-chr1.62-D1S81-tel. The 1q32- and 1q41-specific NotI linking clones were sequenced in the vicinity of the NotI site. They were analyzed in terms of nucleotide composition, G+C content, frequency of CpG dinucleotides, and protein coding potentials. Most of the 1q32-q41-specific NotI linking clones were derived from CpG islands. Sequences of three NotI linking clones proved to be identical with known genes. Six of the remaining eight had a high potential for coding regions and shared short homologous regions with sequences in the GenBank database. The NotI linking clones and the identified CpG islands will provide valuable resources for constructing a long-range restriction map of chromosome 1q25-q44 and for the eventual isolation of disease genes of Van der Woude syndrome (1q32-q41) and Usher syndrome type IIa (1q41). 29 refs., 2 figs., 3 tabs.

  17. Fine Mapping of the Body Fat QTL on Human Chromosome 1q43

    PubMed Central

    Aissani, Brahim; Wiener, Howard W.; Zhang, Kui

    2016-01-01

    Introduction Evidence for linkage and association of obesity-related quantitative traits to chromosome 1q43 has been reported in the Quebec Family Study (QFS) and in populations of Caribbean Hispanic ancestries yet no specific candidate locus has been replicated to date. Methods Using a set of 1,902 single nucleotide polymorphisms (SNPs) genotyped in 525 African American (AA) and 391 European American (EA) women enrolled in the NIEHS uterine fibroid study (NIEHS-UFS), we generated a fine association map for the body mass index (BMI) across a 2.3 megabase-long interval delimited by RGS7 (regulator of G-protein signaling 7) and PLD5 (Phospholipase D, member 5). Multivariable-adjusted linear regression models were fitted to the data to evaluate the association in race-stratified analyses and meta-analysis. Results The strongest associations were observed in a recessive genetic model and peaked in the 3’ end of RGS7 at intronic rs261802 variant in the AA group (p = 1.0 x 10−4) and in meta-analysis of AA and EA samples (p = 9.0 x 10−5). In the EA group, moderate associations peaked at rs6429264 (p = 2.0 x 10−3) in the 2 Kb upstream sequence of RGS7. In the reference populations for the European ancestry in the 1,000 genomes project, rs6429264 occurs in strong linkage disequilibrium (D’ = 0.94) with rs1341467, the strongest candidate SNP for total body fat in QFS that failed genotyping in the present study. Additionally we report moderate associations at the 3’ end of PLD5 in meta-analysis (3.2 x 10−4 ≤ p ≤ 5.8 x 10−4). Conclusion We report replication data suggesting that RGS7, a gene abundantly expressed in the brain, might be a putative body fat QTL on human chromosome 1q43. Future genetic and functional studies are required to substantiate our observations and to potentially link them to the neurobehavioral phenotypes associated with the RGS7 region. PMID:27111224

  18. Fluorescence in situ hybridization (FISH) mapping of human chromosome 1: Cytogenetic band localization of 71 NotI linking clones on chromosome 1q25

    SciTech Connect

    Sumegi, J.; Talmadge, C.G.; Zhen, D.K.

    1994-09-01

    Seventy-one human chromosome 1q25-qter-specific lambda clones have been isolated from NotI-linking libraries which were constructed using DNA from MCH206.1 somatic cell hybrid cells. These cells contain chromosome 1q25 translocated to chromosome Xp22 as the only human chromosomes in a mouse background. The NotI-linking clones have been mapped to cytogenetic bands. The relative order of ten NotI clones in 1q32 and 1q41 and their relation to known chromosome 1 markers have been also determined. Portions of these ten NotI-linking clones were sequenced. Most of the NotI-linking clones were derived from CpG islands, which are often associated with genes. DNA sequence homologies were searched for these ten NotI-linking clones in sequences available in GeneBank. One of the NotI clones carries sequences identical to TGF-beta 2. The NotI-linking clones described here will be useful for constructing a long-range restriction map of chromosome 1q25-qter and may contribute to the cloning of disease genes.

  19. Genetic Linkage of the Muckle-Wells Syndrome to Chromosome 1q44

    PubMed Central

    Cuisset, Laurence; Drenth, Joost P. H.; Berthelot, Jean-Marie; Meyrier, Alain; Vaudour, Gérard; Watts, Richard A.; Scott, David G. I.; Nicholls, Anne; Pavek, Sylvana; Vasseur, Christian; Beckmann, Jacques S.; Delpech, Marc; Grateau, Gilles

    1999-01-01

    Summary The Muckle-Wells syndrome (MWS) is a hereditary inflammatory disorder characterized by acute febrile inflammatory episodes comprising abdominal pain, arthritis, and urticaria. Progressive nerve deafness develops subsequently, and, after several years, the disease is complicated by multiorgan AA-type amyloidosis (i.e., amyloidosis derived from the inflammatory serum amyloid–associated protein) (MIM 191900) with renal involvement and end-stage renal failure. The mode of inheritance is autosomal dominant, but some sporadic cases have also been described. No specific laboratory findings have been reported. The genetic basis of MWS is unknown. Using a genomewide search strategy in three families, we identified the locus responsible for MWS, at chromosome 1q44. Our results indicate that the gene is located within a 13.9-cM region between markers D1S2811 and D1S2882, with a maximum two-point LOD score of 4.66 (recombination fraction .00) at D1S2836 when full penetrance is assumed. Further identification of the specific gene that is responsible for MWS will therefore provide the first biological element for characterizing MWS, other than doing so on the basis of its variable clinical expression. PMID:10486324

  20. Variance-component analysis of obesity in type 2 diabetes confirms loci on chromosomes 1q and 11q.

    PubMed

    van Tilburg, Jonathan H O; Sandkuijl, Lodewijk A; Strengman, Eric; Pearson, Peter L; van Haeften, Timon W; Wijmenga, Cisca

    2003-11-01

    To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome-wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of approximately 75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores > or =1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine-mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31-q42 and 11q14-q24. PMID:14627748

  1. Localization of human flavin-containing monooxygenase genes FMO2 and FMO5 to chromosome 1q

    SciTech Connect

    McCombie, R.R.; Shephard, E.A.; Dolphin, C.T.

    1996-06-15

    The human flavin-containing monooxygenase (FMO) gene family comprises at least five distinct members (FMO1 to FMO5) that code for enzymes responsible for the oxidation of a wide variety of soft nucleophilic substrates, including drugs and environmental pollutants. Three of these genes (FMO1, FMO3, and FMO4) have previously been localized to human chromosome 1q, raising the possibility that the entire gene family is clustered in this chromosomal region. Analysis by polymerase chain reaction of DNA isolated from a panel of human-rodent somatic cell hybrids demonstrates that the two remaining identified members of the FMO gene family, FMO2 and FMO5, also are located on chromosome 1q. 19 refs., 1 fig., 1 tab.

  2. Multiple hits for the association of uterine fibroids on human chromosome 1q43.

    PubMed

    Aissani, Brahim; Wiener, Howard; Zhang, Kui

    2013-01-01

    Uterine leiomyomas (or fibroids) are the most common tumors in women of reproductive age. Early studies of two familial cancer syndromes, the multiple cutaneous and uterine leiomyomatosis (MCUL1), and the hereditary leiomyomatosis and renal cell cancer (HLRCC), implicated FH, a gene on chromosome 1q43 encoding the tricarboxylic acid cycle fumarate hydratase enzyme. The role of this metabolic housekeeping gene in tumorigenesis is still a matter of debate and pseudo-hypoxia has been suggested as a pathological mechanism. Inactivating FH mutations have rarely been observed in the nonsyndromic and common form of fibroids; however, loss of heterozygosity across FH appeared as a significant event in the pathogenesis of a subset of these tumors. To assess the role of FH and the linked genes in nonsyndromic uterine fibroids, we explored a two-megabase interval spanning FH in the NIEHS Uterine fibroid study, a cross-sectional study of fibroids in 1152 premenopausal women. Association mapping with a dense set of single nucleotide polymorphisms revealed several peaks of association (p = 10(-2)-8.10(-5)) with the risk and/or growth of fibroids. In particular, genes encoding factors suspected (cytosolic FH) or known (EXO1 - exonuclease 1) to be involved in DNA mismatch repair emerged as candidate susceptibility genes whereas those acting in the autophagy/apoptosis (MAP1LC3C - microtubule-associated protein) or signal transduction (RGS7 - Regulator of G-protein and PLD5- Phospoholipase D) appeared to affect tumor growth. Furthermore, body mass index, a suspected confounder altered significantly but unpredictably the association with the candidate genes in the African and European American populations, suggesting the presence of a major obesity gene in the studied region. With the high potential for occult tumors in common conditions such as fibroids, validation of our data in family-based studies is needed. PMID:23555580

  3. Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees

    SciTech Connect

    Wiggs, J.L.; Paglinauan, C.; Fine, A.; Sporn, C.; Lou, D. ); Haines, J.L. )

    1994-05-15

    Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. The authors describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM. 27 refs., 2 figs., 1 tab.

  4. Common variable immunodeficiency associated with microdeletion of chromosome 1q42.1-q42.3 and inositol 1,4,5-trisphosphate kinase B (ITPKB) deficiency

    PubMed Central

    Louis, Ankmalika G; Yel, Leman; Cao, Jia N; Agrawal, Sudhanshu; Gupta, Sudhir

    2016-01-01

    Common variable immunodeficiency (CVID) is a heterogenous disorder characterized by hypogammaglobulinemia and impaired specific antibody response and increased susceptibility to infections, autoimmunity and malignancies. A number of gene mutations, including ICOS, TACI and BAFF-R, and CD19, CD20, CD21, CD81, MSH5 and LRBA have been described; however, they account for approximately 20–25% of total cases of CVID. In this study, we report a patient with CVID with an intrinsic microdeletion of chromosome 1q42.1-42.3, where gene for inositol 1,3,4, trisphosphate kinase β (ITPKB) is localized. ITPKB has an important role in the development, survival and function of B cells. In this subject, the expression of ITPKB mRNA as well as ITKPB protein was significantly reduced. The sequencing of ITPKB gene revealed three variants, two of them were missense variants and third was a synonymous variant; the significance of each of them in relation to CVID is discussed. This case suggests that a deficiency of ITPKB may have a role in CVID. PMID:26900472

  5. The genes for nicein/kalinin 125- and 100-kDa subunits, candidates for junctional epidermiolysis bullosa, map to chromosomes 1q32 and 1q25-q31

    SciTech Connect

    Vailly, J.; Ortonne, J.P.; Meneguzzi, G.; Szepetowski, P.; Pedeutour, F. ); Mattei, M.G. ); Burgeson, R. )

    1994-05-01

    Expression of nicein is specifically hampered in the severe form of junctional epidermolysis bullosa (JEB), a recessive genodermatosis characterized by blister formation of integument believed to be due to defects in hemidesmosomes. Nicein genes are therefore the prime candidates for involvement in JEB. To map the gene encoding the 125-kDa subunit of nicein, the authors used the cDNA Kal5.5C coding for the amino-terminal domain of the protein. In situ hybridization was carried out on chromosomes in phytohemagglutinin-stimulated blood lymphocytes of healthy donors. In 100 metaphases examined, 153 silver grains were found associated with chromosomes; 45 (29%) of these were located on chromosome 1, and 33 (73%) of these 45 grains mapped to region 1q32.1-q41 with a maximum in band 1q32. To confirm the regional localization of the genes for nicein subunits of 100 and 125 kDa, fluorescence in situ hybridization was performed on normal lymphocytes from two unrelated normal males and fibroblast cell lines GM00257 (karyotype 46,XX, t(1;2)(1q32;2p23)) and GM004088 (46,XY,t(1;4)(q32;p16)). It was thus confirmed that the genes for nicein 125- and 100-kDa subunits are localized at 1q32 and 1q25-q31, respectively. 9 refs., 1 fig.

  6. Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31.

    PubMed

    Williamson, C; Cavaco, B M; Jauch, A; Dixon, P H; Forbes, S; Harding, B; Holtgreve-Grez, H; Schoell, B; Pereira, M C; Font, A P; Loureiro, M M; Sobrinho, L G; Santos, M A; Thakker, R V; Jausch, A

    1999-02-01

    A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors. PMID:9933477

  7. Linkage of morbid obesity with polymorphic microsatellite markers on chromosome 1q31 in a three-generation Canadian kindred

    SciTech Connect

    Murray, J.D.; Bulman, D.E.; Ebers, G.C. |

    1994-09-01

    Obesity is the most common nutritional disorder affecting Western societies. An estimated 3.7 million Canadians are considered to be overweight, a condition associated with hypertension, accelerated atherosclerosis, diabetes and a host of other medical problems. We have identified a 3 generation kindred in which morbid obesity appears to segregate in an autosomal dominant manner. All individuals were examined. Mass (kg) and heights (m) were measured in order to determine a body mass index (BMI) for each individual. Those individuals with BMI of greater than or equal to 30.0 were designated as affected. In the pedigree studied 25 individuals met this criteria and 12 of these were morbidly obese (BMI greater or equal to 40.0). A search of candidate genes proved unfruitful. A linkage study was initiated. All individuals in the pedigree were genotyped for microsatellite markers which were spaced every 20 centimorgans (cM). Positive evidence of linkage was detected with markers which map to 1q31-32 (lod score of 3.6 at {theta} = 0.05). Notably, strong effects for fatness in pigs have been found on pig chromosome 4 which has synteny with human chromosome 1q21-32. We are currently attempting to refine the position of this gene using linkage analysis with other microsatellite markers from this region of the genome. In addition we are screening other families in which obesity segregates for linkage to 1q31.

  8. Distinctive Phenotype in 9 Patients with Deletion of Chromosome 1q24-q25

    PubMed Central

    Burkardt, Deepika D’Cunha; Rosenfeld, Jill A.; Helgeson, Maria; Angle, Brad; Banks, Valerie; Smith, Wendy; Gripp, Karen W.; Moline, Jessica; Moran, Rocio; Niyazov, Dmitriy M.; Stevens, Cathy; Zackai, Elaine; Lebel, Robert Roger; Ashley, Douglas; Kramer, Nancy; Lachman, Ralph S.; Graham, John M.

    2011-01-01

    Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170135865–172099327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome. PMID:21548129

  9. Genetic and physical mapping of the Chediak-Higashi syndrome on chromosome 1q42-43

    SciTech Connect

    Barrat, F.J.; Auloge, L.; Pastural, E.

    1996-09-01

    The Chediak-Higashi syndrome (CHS) is a severe autosomal recessive condition, features of which are partial oculocutaneous albinism, increased susceptibility to infections, deficient natural killer cell activity, and the presence of large intracytoplasmic granulations in various cell types. Similar genetic disorders have been described in other species, including the beige mouse. On the basis of the hypothesis that the murine chromosome 13 region containing the beige locus was homologous to human chromosome 1, we have mapped the CHS locus to a 5-cM interval in chromosome segment 1q42.1-q42.2. The highest LOD score was obtained with the marker D1S235 (Z{sub max} = 5.38; {theta} = 0). Haplotype analysis enabled us to establish D1S2680 and D1S163, respectively, as the telomeric and the centromeric flanking markers. Multipoint linkage analysis confirms the localization of the CHS locus in this interval. Three YAC clones were found to cover the entire region in a contig established by YAC end-sequence characterization and sequence-tagged site mapping. The YAC contig contains all genetic markers that are nonrecombinant for the disease in the nine CHS families studied. This mapping confirms the previous hypothesis that the same gene defect causes CHS in human and beige phenotype in mice and provides a genetic framework for the identification of candidate genes. 36 refs., 4 figs., 1 tab.

  10. Pre- and Postnatal Analysis of Chromosome 1q44 Deletion in Agenesis of Corpus Callosum

    PubMed Central

    Shetty, Mitesh; Srikanth, Ambika; Kadandale, Jayarama; Hegde, Sridevi

    2015-01-01

    Agenesis of corpus callosum (ACC) is one of the common brain abnormalities and also a common finding in children with mental disability. ACC is heterogeneous and can occur as an isolated condition or as part of a syndrome. ACC can be accurately identified by the absence of the cavum septum pallucidum and tear drop effect of the lateral ventricle after 18 weeks of pregnancy in an ultrasound scan. Genetic causes have been attributed to 30-45% of cases with ACC. Submicroscopic deletions of 1q43q44 have been reported in several cases of ACC. The AKT3 gene, mapped to 1q44, is required for the development of the callosum and brain size. It is considered to be a candidate gene for ACC. We studied a total of 22 cases with ACC, in pre- and postnatal samples using FISH probes. None of the samples showed a deletion in 1q44, implying that the AKT3 gene may not be associated with ACC. PMID:26648835

  11. Evidence of the presence of both oncogene and tumor suppressor gene on chromosome 1q in primary breast cancer, together with a genic dosage effect

    SciTech Connect

    Bieche, I.; Champeme, M.H.; Lidereau, R.

    1994-09-01

    Alterations of the long arm of chromosome 1 are the most consistent cytogenetic abnormalities found in human breast carcinoma. We examined genetic alterations on chromosome 1q in 124 human breast tumors, using restriction fragment length polymorphism (RFLP) markers mapping to the long (thirteen markers) and the short arm (four markers). Imbalance of heterozygosity at one or more loci on the long arm was observed in 80 (65%) of the 124 tumors. Among these 80 tumor DNAs, 38 showed a gain of heterozygosity (GOH), 16 a loss of heterozygosity (LOH) and one both GOH and LOH, at each locus on the long arm, indicating that 55 tumor DNAs had a gain and/or loss of the entire long arm of chromosome 1. Detailed alteration mapping of the other 25 tumors showing partial alterations of chromosome 1q identified two distinct altered regions: a smallest common deleted region at 1q21-31 and a smallest common overrepresented region at 1q41-q44. The results suggest that both oncogene(s) and tumor suppressor gene(s) are present on chromosome 1q and are associated with breast carcinomas. Moreover, the frequent loss or gain of a whole copy of chromosome 1q suggests that involvement a genic dosage effect in the pathogenesis of breast cancer.

  12. Localization of the adenosine A1 receptor subtype gene (ADORA1) to chromosome 1q32.1

    SciTech Connect

    Townsend-Nicholson, A.; Schofield, P.R.; Baker, E.

    1995-03-20

    Adenosine, acting through its receptors, exerts effects on almost all organ systems, influencing a diversity of physiological responses, including the inhibition of neurotransmitter release, the modulation of cardiac rhythmicity and contractility, and the potentiation of IgE-dependent mediator release. Adenosine receptors belong to the G protein-coupled receptor superfamily, a class of cell-surface receptors that, when activated, couple to a heterotrimeric G protein complex to effect signal transduction. Molecular cloning and subsequent pharmacological and biochemical analyses have led to the identification of four different subtypes of adenosine receptor. The A3 receptor has been localized to chromosome 3 in the mouse by interspecific backcross analysis, suggesting a human chromosomal localization of 1p13 from known mouse-human linkage homologies. We have previously mapped the A2b adenosine receptor subtype to chromosome 17p11.2-p12 using fluorescence in situ hybridization (FISH) and PCR-based screening of somatic cell hybrid DNAs. A previous report has concluded that the Al and A2a receptor subtypes are localized on chromosome 22q11.2-q13.1 and 11q11-q13, respectively, but conflicts with that of MacCollin et al., who have mapped the A2a gene to chromosome 22. In this report, we show that the human A1 adenosine receptor subtype does not map to chromosome 22q11.2-q13.1, but is instead localized on chromosome 1q32. 13 refs., 1 fig.

  13. Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence

    SciTech Connect

    Sztrolovics, R.; Grover, J.; Roughley, P.J.

    1994-10-01

    This report describes the cloning of the 3{prime}-untranslated region of the human fibromodulin cDNA and its use to map the gene. For somatic cell hybrids, the generation of the PCR product was concordant with the presence of chromosome 1 and discordant with the presence of all other chromosomes, confirming that the fibromodulin gene is located within region q32 of chromosome 1. The physical mapping of genes is a critical step in the process of identifying which genes may be responsible for various inherited disorders. Specifically, the mapping of the fibromodulin gene now provides the information necessary to evaluate its potential role in genetic disorders of connective tissues. The analysis of previously reported diseases mapped to chromosome 1 reveals two genes located in the proximity of the fibromodulin locus. These are Usher syndrome type II, a recessive disorder characterized by hearing loss and retinitis pigmentosa, and Van der Woude syndrome, a dominant condition associated with abnormalities such as cleft lip and palate and hyperdontia. The genes for both of these disorders have been projected to be localized to 1q32 of a physical map that integrates available genetic linkage and physical data. However, it seems improbable that either of these disorders, exhibiting restricted tissue involvement, could be linked to the fibromodulin gene, given the wide tissue distribution of the encoded proteoglycan, although it remains possible that the relative importance of the quantity and function of the proteoglycan may avry between tissues. 11 refs., 1 fig.

  14. A gene involved in control of human cellular senescence on human chromosome 1q

    SciTech Connect

    Hensler, P.J.; Pereira-Smith, O.M. ); Annab, L.A.; Barrett, J.C. )

    1994-04-01

    Normal cells in culture exhibit limited division potential and have been used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite division. Fusion of normal human diploid fibroblasts with immortal human cells yielded hybrids having limited life spans, indicating that cellular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. The purpose of this study was to determine whether human chromosome 1 could complement the recessive immortal defect of human cell lines assigned to one of the four complementation groups. Using microcell fusion, the authors introduced a single normal human chromosome 1 into immortal human cell lines representing the complementation groups and determined that it caused loss of proliferative potential of an osteosarcoma-derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras[sup +]-transformed derivative of TE85 (143B TK[sup [minus

  15. Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III

    SciTech Connect

    Takano, Takako; Yamanouchi, Yasuko; Mori, Yosuke

    1997-01-20

    We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,de1(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient. 16 refs., 4 figs.

  16. Hereditary Hyperparathyroidism–Jaw Tumor Syndrome: The Endocrine Tumor Gene HRPT2 Maps to Chromosome 1q21-q31

    PubMed Central

    Szabó, József; Heath, Brett; Hill, Virginia M.; Jackson, Charles E.; Zarbo, Richard J.; Mallette, Lawrence E.; Chew, Shern L.; Besser, Gordon M.; Thakker, Rajesh V.; Huff, Vicki; Leppert, Mark F.; Heath, Hunter

    1995-01-01

    The syndrome of hereditary hyperparathyroidism and jaw tumors (HPT-JT) is characterized by inheritance, in an autosomal dominant pattern, of recurrent parathyroid adenomas, fibro-osseous tumors of the mandible and/or maxilla, Wilms tumor, and parathyroid carcinoma. This syndrome is clinically and genetically distinct from other endocrine neoplasia syndromes and appears to result from mutation of an endocrine tumor gene designated “HRPT2.” We studied five HPT-JT families (59 persons, 20 affected); using PCR-based markers, we instituted a genomewide linkage search after excluding several candidate genes. Lod scores were calculated at various recombination fractions (θ), penetrance 90%. We mapped HRPT2 to the long arm of chromosome 1 (1q21-q31). The maximal lod score was 6.10 at θ = .0 with marker D1S212, or >106 odds in favor of linkage. In six hereditary Wilms tumor families (96 persons, 29 affected), we found no linkage to 1q markers closely linked with HRPT2 (lod scores −15.6 [D1S191] and −17.8 [D1S196], θ = .001). Nine parathyroid adenomas and one Wilms tumor from nine members of three HPT-JT families were examined for loss of heterozygosity at linked loci. The parathyroid adenomas and Wilms tumor showed no loss of heterozygosity for these DNA markers. Our data establish that HRPT2, an endocrine tumor gene on the long arm of chromosome 1, is responsible for the HPT-JT syndrome but not for the classical hereditary Wilms tumor syndrome. ImagesFigure 1 PMID:7717405

  17. Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31

    SciTech Connect

    Szabo, J.; Heath, B.; Hill, V.M.; Heath, H. III; Leppert, M.F.; Jackson, C.E.; Zarbo, R.J.; Mallette, L.E.; Huff, V.; Chew, S.L.

    1995-04-01

    The syndrome of hereditary hyperparathyroidism and jaw tumors (HPT-JT) is characterized by inheritance, in an autosomal dominant pattern, of recurrent parathyroid adenomas, fibro-osseous tumors of the mandible and/or maxilla, Wilms tumor, and parathyroid carcinoma. This syndrome is clinically and genetically distinct from other endocrine neoplasia syndromes and appears to result from mutation of an endocrine tumor gene designated {open_quotes}HRPT2{close_quotes}. We studied five HPT-JT families (59 persons, 20 affected); using PCR-based markers, we instituted a genome-wide linkage search after excluding several candidate genes. Lod scores were calculated at various recombination fractions ({theta}), penetrance 90%. We mapped HRPT2 to the long arm of chromosome 1 (1q21-q31). The maximal lod score was 6.10 at {theta} = .0 with marker D1S212, or >10{sup 6} odds in favor of linkage. In six hereditary Wilms tumor families (96 persons, 29 affected), we found no linkage to 1q markers closely linked with HRPT2 (lod scores -15.6 [D1S191] and -17.8 [D1S196], {theta} = .001). Nine parathyroid adenomas and one Wilms tumor from nine members of three HPT-JT families were examined for loss of heterozygosity at linked loci. The parathyroid adenomas and Wilms tumor showed no loss of heterozygosity for these DNA markers. Our data establish that HRPT2, an endocrine tumor gene on the long arm of chromosome 1, is responsible for the HPT-JT syndrome but not for the classical hereditary Wilms tumor syndrome. 32 refs., 2 figs., 2 tabs.

  18. Chromosomal anomalies at 1q, 3, 16q, and mutations of SIX1 and DROSHA genes underlie Wilms tumor recurrences

    PubMed Central

    Gamba, Beatrice; Torri, Federica; Terenziani, Monica; Collini, Paola; Macciardi, Fabio; Radice, Paolo; Perotti, Daniela

    2016-01-01

    Approximately half of children suffering from recurrent Wilms tumor (WT) develop resistance to salvage therapies. Hence the importance to disclose events driving tumor progression/recurrence. Future therapeutic trials, conducted in the setting of relapsing patients, will need to prioritize targets present in the recurrent lesions. Different studies identified primary tumor-specific signatures associated with poor prognosis. However, given the difficulty in recruiting specimens from recurrent WTs, little work has been done to compare the molecular profile of paired primary/recurrent diseases. We studied the genomic profile of a cohort of eight pairs of primary/recurrent WTs through whole-genome SNP arrays, and investigated known WT-associated genes, including SIX1, SIX2 and micro RNA processor genes, whose mutations have been recently proposed as associated with worse outcome. Through this approach, we sought to uncover anomalies characterizing tumor recurrence, either acquired de novo or already present in the primary disease, and to investigate whether they overlapped with known molecular prognostic signatures. Among the aberrations that we disclosed as potentially acquired de novo in recurrences, some had been already recognized in primary tumors as associated with a higher risk of relapse. These included allelic imbalances of chromosome 1q and of chromosome 3, and CN losses on chromosome 16q. In addition, we found that SIX1 and DROSHA mutations can be heterogeneous events (both spatially and temporally) within primary tumors, and that their co-occurrence might be positively selected in the progression to recurrent disease. Overall, these results provide new insights into genomic and genetic events underlying WT progression/recurrence. PMID:26802027

  19. Chromosomal anomalies at 1q, 3, 16q, and mutations of SIX1 and DROSHA genes underlie Wilms tumor recurrences.

    PubMed

    Spreafico, Filippo; Ciceri, Sara; Gamba, Beatrice; Torri, Federica; Terenziani, Monica; Collini, Paola; Macciardi, Fabio; Radice, Paolo; Perotti, Daniela

    2016-02-23

    Approximately half of children suffering from recurrent Wilms tumor (WT) develop resistance to salvage therapies. Hence the importance to disclose events driving tumor progression/recurrence. Future therapeutic trials, conducted in the setting of relapsing patients, will need to prioritize targets present in the recurrent lesions. Different studies identified primary tumor-specific signatures associated with poor prognosis. However, given the difficulty in recruiting specimens from recurrent WTs, little work has been done to compare the molecular profile of paired primary/recurrent diseases. We studied the genomic profile of a cohort of eight pairs of primary/recurrent WTs through whole-genome SNP arrays, and investigated known WT-associated genes, including SIX1, SIX2 and micro RNA processor genes, whose mutations have been recently proposed as associated with worse outcome. Through this approach, we sought to uncover anomalies characterizing tumor recurrence, either acquired de novo or already present in the primary disease, and to investigate whether they overlapped with known molecular prognostic signatures. Among the aberrations that we disclosed as potentially acquired de novo in recurrences, some had been already recognized in primary tumors as associated with a higher risk of relapse. These included allelic imbalances of chromosome 1q and of chromosome 3, and CN losses on chromosome 16q. In addition, we found that SIX1 and DROSHA mutations can be heterogeneous events (both spatially and temporally) within primary tumors, and that their co-occurrence might be positively selected in the progression to recurrent disease. Overall, these results provide new insights into genomic and genetic events underlying WT progression/recurrence. PMID:26802027

  20. Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21–q22

    PubMed Central

    Shiina, Takashi; Ando, Asako; Suto, Yumiko; Kasai, Fumio; Shigenari, Atsuko; Takishima, Nobusada; Kikkawa, Eri; Iwata, Kyoko; Kuwano, Yuko; Kitamura, Yuka; Matsuzawa, Yumiko; Sano, Kazumi; Nogami, Masahiro; Kawata, Hisako; Li, Suyun; Fukuzumi, Yasuhito; Yamazaki, Masaaki; Tashiro, Hiroyuki; Tamiya, Gen; Kohda, Atsushi; Okumura, Katsuzumi; Ikemura, Toshimichi; Soeda, Eiichi; Mizuki, Nobuhisa; Kimura, Minoru; Bahram, Seiamak; Inoko, Hidetoshi

    2001-01-01

    Human chromosomes 1q21–q25, 6p21.3–22.2, 9q33–q34, and 19p13.1–p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21–25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21–q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides. [The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank databases under

  1. Molecular characterization of the complement C1q, C2 and C4 genes in Brazilian patients with juvenile systemic lupus erythematosus

    PubMed Central

    Liphaus, Bernadete L; Umetsu, Natalia; Jesus, Adriana A; Bando, Silvia Y; Silva, Clovis A; Carneiro-Sampaio, Magda

    2015-01-01

    OBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3′ non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation. CONCLUSIONS: Silent mutations and single-base changes in the 3′ non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis. PMID:26017655

  2. The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2

    SciTech Connect

    Weier, H.U.G.; Greulich, K.M.; George, C.X.; Samuel, C.E.

    1995-11-20

    The interferon-inducible double-stranded RNA-specific adenosine deaminase is an RNA-modifying enzyme implicated in the generation of biased hypermutations of viral RNAs and the site-selective editing of mammalian mRNAs of neural origin. The gene for the dsRNA-specific adenosine deaminase has been mapped by fluorescence in situ hybridization (FISH) of genomic clones to a single locus on human chromosome 1 bands q21.1-21.2. Simultaneous multicolor FISH including X clones and yeast artificial chromosomes showed a localization of the gene in band 1q21 centromeric of D1S1705. 22 refs., 1 fig.

  3. Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma.

    PubMed

    Araki, Asuka; Chocholous, Monika; Gojo, Johannes; Dorfer, Christian; Czech, Thomas; Heinzl, Harald; Dieckmann, Karin; Ambros, Inge M; Ambros, Peter F; Slavc, Irene; Haberler, Christine

    2016-01-01

    Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and

  4. Confirmation and refinement of an autosomal dominant congenital motor nystagmus locus in chromosome 1q31.3-q32.1.

    PubMed

    Li, Lin; Xiao, Xueshan; Yi, Changxian; Jiao, Xiaodong; Guo, Xiangming; Hejtmancik, James Fielding; Zhang, Qingjiong

    2012-12-01

    Congenital motor nystagmus (CMN) is characterized by early-onset bilateral ocular oscillations. To identify the disease locus for autosomal dominant CMN in a Chinese family 86001, clinical data, including slit lamp and funduscopic examination and blood samples were collected from family. Genomic DNA was prepared from leukocytes, and a genome-wide linkage scan was performed using 382 polymorphic microsatellite markers and two-point linkage analysis using the logarithm of odds (LOD) score method as implemented in the LINKAGE program package. Maximum two-point scores were calculated using ILINK, and LINKMAP was used for multipoint analysis. All nine affected individuals in the family showed typical phenotypes for CMN. Maximum two-point LOD scores (3.61 at θ=0) were obtained with D1S2619, D1S2877 and D1S2622.The 24.6 cM (28.07 Mb) linked region is flanked by markers D1S218 and D1S2655, placing the disease locus on chromosome 1q25.2-1q32.1. Multipoint analysis confirmed linkage to the region of D1S218 and D1S2655 with Maximum two-point scores of 3.61. The linkage interval overlaps with that of a newly reported CMN locus on 1q31-q32.2 and narrows down the linked region to 5.90 cM (5.92 Mb). This study confirms and refines a novel locus for autosomal dominant CMN to chromosome 1q31.3-q32.1 (5.90 cM) and demonstrates its presence in the Chinese population. PMID:22914672

  5. Pituitary deficiency and congenital infiltrating lipomatosis of the face in a girl with deletion of chromosome 1q24.3q31.1.

    PubMed

    Capra, V; Severino, M; Rossi, A; Nozza, P; Doneda, C; Perri, K; Pavanello, M; Fiorio, P; Gimelli, G; Tassano, E; Di Battista, E

    2014-02-01

    Interstitial deletions of the long arm of chromosome 1 are rare and they are classified as proximal or intermediate. The intermediate interstitial deletions span 1q24-1q32. We describe a 6-year-old girl with multiple pituitary hormone deficiency, severe cognitive impairment, bilateral cleft lip and palate, midline facial capillary malformation, erythema of hands and feet and dysplastic cranial vessels, low anti-thrombin III activity, hemifacial overgrowth due to progressive infiltrating lipomatosis with bone overgrowth, marked vascular proliferation and erythema of hands and feet, and abnormal cranial vessels. The girl's karyotype showed an apparently de novo interstitial deletion 1q24.3q31.1, which was defined by array-CGH. The deleted region contains numerous genes, but only eight (CENPL, LHX4, LAMC1, LAMC2, PTGS2, ANGPTL1, TNN, and TNR) are good candidates to explain, at least partially, the phenotype of the proposita. We, therefore, discuss the involvement of these genes and the observed phenotype. PMID:24311370

  6. Physical mapping of the chromosome 7 breakpoint region in an SLOS patient with t(7;20)X(q32.1;q13.2)

    SciTech Connect

    Alley, T.L.; Wallace, M.R.; Scherer, S.W.

    1997-01-31

    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by multiple congenital anomalies and mental retardation. SLOS has an associated defect in cholesterol biosynthesis, but the molecular genetic basis of this condition has not yet been elucidated. Previously our group reported a patient with a de novo balanced translocation [t(7;20)(q32.1;q13.2)] fitting the clinical and biochemical profile of SLOS. Employing fluorescence in situ hybridization (FISH), a 1.8 Mb chromosome 7-specific yeast artificial chromosome (YAC) was identified which spanned the translocation breakpoint in the reported patient. The following is an update of the on-going pursuit to physically and genetically map the region further, as well as the establishment of candidate genes in the 7q32.1 breakpoint region. 11 refs., 1 fig.

  7. Novel Association of Odontogenic Myxoma with Constitutional Chromosomal 1q21 Microduplication: Case Report and Review of the Literature.

    PubMed

    Best-Rocha, Alejandro; Patel, Kalyani; Hicks, John; Edmonds, Joseph L; Paldino, Michael J; Wu, Hao

    2016-01-01

    Odontogenic myxoma (OM) is a rare, benign, and locally aggressive tumor. It tends to occur in the posterior maxilla and mandible and is often associated with root resorption and perforation of cortex. Histopathologically, there is a proliferation of spindle, bipolar, and stellate cells, with bland nuclei within a myxoid to infrequently fibromyxoid extracellular matrix. Long, thin residual bony trabeculae are often seen floating within the spindle cell proliferation because of the infiltrating nature of this tumor, and these trabeculae impart a "soap bubble" or "tennis-racket" radiologic appearance. No syndromic association of OM has been reported. Although similar histopathologic features are shared with cardiac myxoma and soft tissue myxoma, mutations in the GNAS gene have not been identified in OM to date, and only 2 of 17 OMs showed mutations in the PRKAR1A gene. In this report, we describe a case of OM in a patient with constitutional 1q21 microduplication, a locus that harbors genes encoding certain proteins in the cAMP-dependent protein kinase A (PKA) signaling pathway, including G-protein-coupled receptors and 1 phosphodiesterase interacting protein. Review of the literature describes the key clinical features and molecular pathogenesis of 1q21 microduplication, as well as highlighting the role of PKA signaling pathway in the pathogenesis of myxomas in general. PMID:26230961

  8. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q

    PubMed Central

    Heit, John A.; Armasu, Sebastian M.; Asmann, Yan W.; Cunningham, Julie M.; Matsumoto, Martha E.; Petterson, Tanya M.; de Andrade, Mariza

    2012-01-01

    Summary Objectives To identify venous thromboembolism (VTE) disease-susceptibility genes. Patients/Methods We performed in silico genome wide association (GWAS) analyses using genotype data imputed to ~2.5 million single nucleotide polymorphisms (SNPs) from adults with objectively-diagnosed VTE (n=1503), and controls frequency-matched on age and sex (n=1459; discovery population). SNPs exceeding genome-wide significance were replicated in a separate population (VTE cases, n=1407; controls, n=1418). Genes associated with VTE were resequenced. Results Seven SNPs exceeded genome-wide significance (P < 5 × 10-8); four on chromosome 1q24.2 (F5 rs6025 [Factor V Leiden], BLZF1 rs7538157, NME7 rs16861990 and SLC19A2 rs2038024) and three on chromosome 9q34.2 (ABO rs2519093 [ABO intron 1], rs495828, rs8176719 [ABO blood type O allele]). The replication study confirmed a significant association of F5, NME7, and ABO with VTE. However, F5 was the main signal on 1q24.2 as only ABO SNPs remained significantly associated with VTE after adjusting for F5 rs6025. This 1q24.2 region was shown to be inherited as a haplotype block. ABO resequencing identified 15 novel single nucleotide variations (SNV) in ABO intron 6 and the ABO 3’ UTR that were strongly associated with VTE (P < 10-4) and belonged to three distinct linkage disequilibrium (LD) blocks; none were in LD with ABO rs8176719 or rs2519093. Our sample size provided 80% power to detect odds ratios=2.0 and 1.51 for minor allele frequencies=0.05 and 0.5, respectively (α=1 × 10-8; 1% VTE prevalence). Conclusions Aside from F5 rs6025, ABO rs8176719 and rs2519093, and F2 rs1799963, additional common and high VTE-risk SNPs among whites are unlikely. PMID:22672568

  9. Unbalanced chromosome 1 abnormalities leading to partial trisomy 1q in four infants with Down syndrome and acute megakaryocytic leukemia

    PubMed Central

    Silva, Maria Luiza Macedo; do Socorro Pombo-de-Oliveira, Maria; Raimondi, Susana C; Mkrtchyan, Hasmik; Abdelhay, Eliana; de Figueiredo, Amanda Faria; de Souza, Mariana Tavares; Garcia, Daniela Ribeiro Ney; de Ventura, Eliane Maria Soares; de Sousa, Adriana Martins; Liehr, Thomas

    2009-01-01

    Background Children with Down syndrome (DS) have an increased risk of childhood acute leukemia, especially acute megakaryoblastic leukemia (AMKL) also called acute myeloid leukemia (AML) type M7. Here four yet unreported infants with such malignancies are reported. Results An unbalanced translocation involving chromosome 1 was identified by GTG banding in all cases. These were characterized in more detail by molecular cytogenetic approaches. Additional molecular analysis revealed in three of the four cases mutations in exon 2 of the GATA binding protein 1 (globin transcription factor 1), located in Xp11.23. Conclusion Our results corroborate that abnormalities of chromosome 1 are common in DS-associated AMKL. Whether this chromosomal region contains gene(s) involved in hematopoietic malignant transformation remains to be determined. PMID:19228396

  10. Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32

    SciTech Connect

    Rousseau-Merck, M.F.; Derre, J.; Berger, R.

    1995-11-20

    Vasopressin exerts its physiological effects on liver metabolism, fluid osmolarity, and corticotrophic response to stress through a set of at least three receptors, V1a, V2, and V3 (also called V1b), respectively. These receptors constitute a distinct group of the superfamily of G-protein-coupled cell surface receptors. When bound to vasopressin, they couple to G proteins activating phospholipase C for the V1a and V3 types and adenylate cyclase for the V2. The vasopressin receptor subfamily also includes the receptor for oxytocin, a structurally related hormone that signals through the activation of phospholipase C. The chromosomal position of the V2 receptor gene has been assigned to Xq28-qter by PCR-based screening of somatic cell hybrids, whereas the oxytocin receptor gene has been mapped to chromosome 3q26.2 by fluorescence in situ hybridization (FISH). The chromosomal location of the V1a gene is currently unknown. We recently cloned the cDNA and the gene coding for the human pituitary-specific V3 receptor (HGMW-approved symbol AVPR3). We report here the chromosomal localization of this gene by two distinct in situ hybridization techniques using radioactive and fluorescent probes. 11 refs., 1 fig.

  11. Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome 1q23-q25

    SciTech Connect

    Belmouden, A.; Adam, M.F.; De Dinechin, S.D. |

    1997-02-01

    Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (AMB1, ATP2B4, ATPlA2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene. 59 refs., 3 figs., 3 tabs.

  12. Chromosomal localization of the genes encoding the kinetochore proteins CENPE and DENPF to human chromosomes 4q24{r_arrow}q25 and 1q32{r_arrow}q41, respectively, by fluorescence in situ hybridization

    SciTech Connect

    Testa, J.R.; Zhou, J.Y.; Bell, D.W.; Yen, T.J.

    1994-10-01

    CENPE and CENPF are human kinetochore proteins of 312 and {approximately}400 kDa, respectively. As part of an effort to characterize the functions of these two proteins, we have used their respective cDNAs to map their human chromosomal locations by fluorescence in situ hybridization. The gene that encodes CENPE, a kinetochore-associated motor protein that is postulated to segregate chromosomes during mitosis, maps to chromosome 4q24{r_arrow}q25. The CENPF gene, which encodes a structural protein of the kinetochore, maps to chromosome 1q32{r_arrow}q41 within close proximity to the genetic locus that is linked to Van der Woude syndrome. 8 refs., 1 fig.

  13. Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease

    SciTech Connect

    Craig, R.W.; Zhou, P.; Kozopas, K.M.

    1994-09-15

    The MCL1 gene, recently identified in a myeloid leukemia cell line, has sequence similarity to BCL2, the gene at the t(14;18) translocation in follicular lymphoma. The chromosomal location of MCL1 has now been determined. The human locus (MCL1) was mapped to the long arm of human chromosome 1q21, using the methods of in situ hybridization and somatic cell hybrid analysis. In the mouse, MCL1-related sequences were mapped to positions on two mouse chromosomes (chromosomes 3 and 5), using haplotype analysis of an interspecific cross. The location of the locus on mouse chromosome 3 (Mcl1) was homologous to that of MCL1 on human chromosome 1; the second locus (Mcl-rs on mouse chromosome 5) may represent a pseudogene. The proximal long arm of human chromosome 1, where MCL1 is located, is duplicated and/or rearranged in a variety of preneoplastic and neoplastic diseases including hematologic diseases and solid tumors. MCL1 is thus a candidate gene for involvement in cancer. 46 refs., 2 figs., 3 tabs.

  14. Spread of X-chromosome inactivation into chromosome 15 is associated with Prader-Willi syndrome phenotype in a boy with a t(X;15)(p21.1;q11.2) translocation.

    PubMed

    Sakazume, Satoru; Ohashi, Hirofumi; Sasaki, Yuki; Harada, Naoki; Nakanishi, Katsumi; Sato, Hidenori; Emi, Mitsuru; Endoh, Kazushi; Sohma, Ryoichi; Kido, Yasuhiro; Nagai, Toshiro; Kubota, Takeo

    2012-01-01

    X-chromosome inactivation (XCI) is an essential mechanism in females that compensates for the genome imbalance between females and males. It is known that XCI can spread into an autosome of patients with X;autosome translocations. The subject was a 5-year-old boy with Prader-Willi syndrome (PWS)-like features including hypotonia, hypo-genitalism, hypo-pigmentation, and developmental delay. G-banding, fluorescent in situ hybridization, BrdU-incorporated replication, human androgen receptor gene locus assay, SNP microarrays, ChIP-on-chip assay, bisulfite sequencing, and real-time RT-PCR were performed. Cytogenetic analyses revealed that the karyotype was 46,XY,der(X)t(X;15)(p21.1;q11.2),-15. In the derivative chromosome, the X and half of the chromosome 15 segments showed late replication. The X segment was maternal, and the chromosome 15 region was paternal, indicating its post-zygotic origin. The two chromosome 15s had a biparental origin. The DNA methylation level was relatively high in the region proximal from the breakpoint, and the level decreased toward the middle of the chromosome 15 region; however, scattered areas of hypermethylation were found in the distal region. The promoter regions of the imprinted SNRPN and the non-imprinted OCA2 genes were completely and half methylated, respectively. However, no methylation was found in the adjacent imprinted gene UBE3A, which contained a lower density of LINE1 repeats. Our findings suggest that XCI spread into the paternal chromosome 15 led to the aberrant hypermethylation of SNRPN and OCA2 and their decreased expression, which contributes to the PWS-like features and hypo-pigmentation of the patient. To our knowledge, this is the first chromosome-wide methylation study in which the DNA methylation level is demonstrated in an autosome subject to XCI. PMID:21735174

  15. Fine mapping of juvenile primary open angle glaucoma (POAG) on 1q21-q31 and exculsion of adult-POAG from the respective region

    SciTech Connect

    Child, A.; Sarfarazi, M.; Crick, R.P.

    1994-09-01

    Juvenile POAG is an autosomal dominant eye disorder which has recently been mapped to 1q21-q24, in a region of 14-23 cM. We report here linkage analysis of 9 microsatellite repeat markers spanning this region in families from England, Scotland and Sardinia. We have observed no recombinants with D1S433 (Z=2.86) and obtained looser linkage with D1S196 ({theta}=0.03; Z=6.38), D1S431 ({theta}=0.14; Z=2.74), D1S210 ({theta}=0.06; Z=1.32), D1S452 ({theta}=0.18; Z=0.729) and D1S242 ({theta}=0.08; Z=2.29). In one family, a critical recombinant in an affected individual localizes the J-POAG locus between D1S452 and D1S242 in a 3 cM region. However, other recombinants in two normal individuals from different families suggests that J-POAG may be localized in a 1 cM distance between D1S433 and D1S431. These unaffected individuals have well passed the age-of-onset in their respective pedigrees. This result suggests that either these two recombinant individuals are gene carriers (i.e., non-penetrants) or there are more than one gene in this region causing the same disease. The possibility of the latter is less likely, since in addition to a total of 4 non-penetrant individuals in our panel, other such cases have also been reported previously. This in turn suggests that the precentage of non-penetrant cases in J-POAG may be considerably higher than it was previously appreciated. Study of 14 families with adult-onset POAG revealed no segregation with the above-mentioned linked microsatellite markers. Our findings confirm, for the first time, that adult-POAG is genetically distinct from the J-POAG. Genetic linkage study of adult families with additional STRPs is currently in progress.

  16. Confirmation of linkage of Hypokalemic periodic paralysis to chromosome 1q31-32: Further evidence supporting CACNL1A3 as a candidate gene

    SciTech Connect

    Lewis, K.; Knouff, C.; Gaskell, P.C.

    1994-09-01

    Hypokalemic periodic paralysis (HOKPP; MIM 170400) is one entity of a series of periodic paralyses characterized by episodic bouts of weakness with onset in the second to third decades. The hypokalemic form is defined by decreased serum potassium during a paralytic attack. HOKPP can occur in both familial and sporadic forms; the familal form is autosomal dominant with reduced penetrance in female gene carriers. Recently, Fontaine et al. have localized HOKPP to 1q31-32 in three multigenerational HOKPP families. The region of sub-localization includes the CACNL1A3 gene, making it a potential candidate for the genetic defect in HOKPP. We have ascertained and sampled 2 large multigenerational HOKPP pedigrees (N = 55 individuals with DNA) for linkage analysis. The families were initially screened for linkage with over 150 marker loci located throughout the genome. Analysis of the chromosome 1 markers D1S412, D1S413 and F13B gave significant evidence for linkage. The peak two-point lod score realized was Z = 4.34 at theta = 0.0 (D1S413). A sex-dependent penetrance of 80% was assumed, although varying the penetrance did not significantly alter the results. There was no evidence for heterogeneity. Multipoint analysis of the data defined the region between D1S238 and D1S245 (which contains the CACNL1A3 gene) as the most likely region (> 1000 odds) for the location of the HOKPP gene. There were no obligate recombinants among males or affected females for the CACNL1A3 (Z = 3.19, theta = 0.0), although several potential non-penetrant females were identified. These studies confirm linkage of HOPKK to chromosome 1 in an independent data set, lend further support of CACNL1A3 as a potential candidate gene, and give evidence for homogeneity in this disease.

  17. Gene mapping of Usher syndrome type IIa: Localization of the gene to a 2.1-cM segment on chromosome 1q41

    SciTech Connect

    Kimberling, W.J.; Weston, M.D.; Ing, P.S.; Connolly, C.; Sumegi, J.; Moeller, C.; Aarem, A. van; Cremers, C.W.R.J.; Martini, A.; Milani, M.

    1995-01-01

    Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor {beta}2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself. 30 refs., 4 figs., 2 tabs.

  18. Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism.

    PubMed

    Elsemman, Ibrahim E; Mardinoglu, Adil; Shoaie, Saeed; Soliman, Taysir H; Nielsen, Jens

    2016-04-26

    Hepatitis C virus (HCV) infection is a worldwide healthcare problem; however, traditional treatment methods have failed to cure all patients, and HCV has developed resistance to new drugs. Systems biology-based analyses could play an important role in the holistic analysis of the impact of HCV on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular carcinoma (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin sulfate was significantly changed in the cirrhosis stage, whereas the metabolism of acyl-carnitine was significantly changed in the dysplastic nodule and early HCC stages. Our results explained the role of the upregulated expression of BCAT1, PLOD3 and six other methyltransferase genes involved in carnitine biosynthesis and S-adenosylmethionine metabolism in the early and advanced HCC stages. Moreover, GNPAT and BCAP31 expression was upregulated in the early and advanced HCC stages and could lead to increased acyl-CoA consumption. By integrating our results with copy number variation analyses, we observed that GNPAT, PPOX and five of the methyltransferase genes (ASH1L, METTL13, SMYD2, TARBP1 and SMYD3), which are all located on chromosome 1q, had increased copy numbers in the cancer samples relative to the normal samples. Finally, we confirmed our predictions with the results of metabolomics studies and proposed that inhibiting the identified targets has the potential to provide an effective treatment strategy for HCV-associated liver disorders. PMID:27040643

  19. Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg)

    SciTech Connect

    Fukai, Kazuyoshi; Oh, Jangsuk; Karim, M.A.

    1996-09-01

    Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized by hypopigmentation or oculocutaneous albinism and severe immunologic deficiency with neutropenia and lack of natural killer (NK) cell function. Most patients die in childhood from pyogenic infections or an unusual lymphoma-like condition. A hallmark of the disorder is giant inclusion bodies seen in all granule-containing cells, including granulocytes, lymphocytes, melanocytes, mast cells, and neurons. Similar ultrastructural abnormalities occur in the beige mouse, which thus has been suggested to be homologous to human CHS. High-resolution genetic mapping has indicated that the bg gene region of mouse chromosome 13 is likely homologous to the distal portion of human chromosome 1q. Accordingly, we carried out homozygosity mapping using markers derived from distal human chromosome 1q in four inbred families or probands with CHS. Our results indicate that the human CHS gene maps to an 18.8-cM interval in chromosome segment 1q42-q44 and that human CHS therefore is very likely homologous to mouse bg. 43 refs., 2 figs.

  20. Relatives with opposite chromosome constitutions, rec(10)dup(10p)inv(10)(p15.1q26.12) and rec(10)dup(10q)inv(10)(p15.1q26.12), due to a familial pericentric inversion.

    PubMed

    Ciuladaite, Zivile; Preiksaitiene, Egle; Utkus, Algirdas; Kučinskas, Vaidutis

    2014-01-01

    Large pericentric inversions in chromosome 10 are rare chromosomal aberrations with only few cases of familial inheritance. Such chromosomal rearrangements may lead to production of unbalanced gametes. As a result of a recombination event in the inversion loop, 2 recombinants with duplicated and deficient chromosome segments, including the regions distal to the inversion, may be produced. We report on 2 relatives in a family with opposite terminal chromosomal rearrangements of chromosome 10, i.e. rec(10)dup(10p)inv(10) and rec(10)dup(10q)inv(10), due to familial pericentric inversion inv(10)(p15.1q26.12). Based on array-CGH results, we characterized the exact genomic regions involved and compared the clinical features of both patients with previous reports on similar pericentric inversions and regional differences within 10p and 10q. The fact that both products of recombination are viable indicates a potentially high recurrence risk of unbalanced offspring. This report of unbalanced rearrangements in chromosome 10 in 2 generations confirms the importance of screening for terminal imbalances in patients with idiopathic intellectual disability by molecular cytogenetic techniques such as FISH, MLPA or microarrays. It also underlines the necessity for FISH to define structural characteristics of such cryptic intrachromosomal rearrangements and the underlying cytogenetic mechanisms. PMID:25401700

  1. Coarctation of the aorta and mild to moderate developmental delay in a child with a de novo deletion of chromosome 15(q21.1q22.2)

    PubMed Central

    Lalani, Seema R; Sahoo, Trilochan; Sanders, Merideth E; Peters, Sarika U; Bejjani, Bassem A

    2006-01-01

    Background Deletion of 15q21q22 is a rare chromosomal anomaly. To date, there have been nine reports describing ten individuals with different segmental losses involving 15q21 and 15q22. Many of these individuals have common features of growth retardation, hypotonia and moderate to severe mental retardation. Congenital heart disease has been described in three individuals with interstitial deletion involving this region of chromosome 15. Case presentation We report a child with coarctation of the aorta, partial agenesis of corpus callosum and mild to moderate developmental delay, with a de novo deletion of 15q21.1q22.2, detected by the array Comparative Genomic Hybridization (CGH). We utilized chromosome 15-specific microarray-based CGH to define the chromosomal breakpoints in this patient. Conclusion This is the first description of mapping of an interstitial deletion involving the chromosome 15q21q22 segment using the chromosome 15-specific array-CGH. The report also expands the spectrum of clinical phenotype associated with 15q21q22 deletion. PMID:16472378

  2. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques

    PubMed Central

    Han, Liangrong; Jing, Xin; Liu, Hailiang; Yang, Chuanchun; Zhang, Fengting; Hu, Yue; Yue, Hongni; Ning, Ying

    2016-01-01

    Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques. PMID:27218255

  3. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    PubMed

    Pan, Qiong; Hu, Hao; Han, Liangrong; Jing, Xin; Liu, Hailiang; Yang, Chuanchun; Zhang, Fengting; Hu, Yue; Yue, Hongni; Ning, Ying

    2016-01-01

    Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques. PMID:27218255

  4. Asplenia syndrome in a child with a reciprocal translocation of chromosomes 11 and 20 [46,XX,t(11;20)(q13.1;q13.13)

    SciTech Connect

    Freeman, S.B.; Muraldharan, K.; Pettay, D.

    1994-09-01

    Failure to establish the left-right embryonic axis results in abnormalities of laterality; situs solitus is replaced by situs inversus totalis or various degrees of heterotaxy involving the heart, great vessels, lungs, liver, spleen, and/or bowel. Laterality syndromes are likely to be genetically heterogeneous although specific human genes have not been identified. Families with dominant, recessive, and X-linked laterality syndromes have been reported as well as individuals with situs abnormalities and chromosome rearrangements. The latter offer the possibility of narrowing the gene search to specific chromosome regions. A recent report described an infant with polysplenia syndrome and a paracentric inversion of chromosome 11 [46,XX,inv(11)(q13q25)pat]. We report the second case of a child with laterality abnormalities and a chromosome rearrangement involving a similar breakpoint on chromosome 11. The proband is a 6 y/o female with mental retardation, dysmorphic features, pulmonic stenosis, asplenia, Hirschsprung disease, and a balanced, reciprocal translocation involving chromosomes 11 and 20 [46,XX,t(11;20)(q13,1;q13.13)pat]. Using DNA probes we have excluded uniparental disomy for chromosomes 11 and 20. If a gene for determination of laterality lies in the 11q13 region, the proband`s abnormalities could be the result of her receiving an allele disrupted by the paternal translocation as well as a mutant allele from her mother. To investigate this possibility, we are studying the segregation of maternal chromosome 11 markers in the proband and her balanced carrier and non-carrier siblings.

  5. Genetics Home Reference: 1q21.1 microduplication

    MedlinePlus

    ... Genetics Home Health Conditions 1q21.1 microduplication 1q21.1 microduplication Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 1q21.1 microduplication is a chromosomal change in which a ...

  6. Asplenia syndrome in a child with a balanced reciprocal translocation of chromosomes 11 and 20 [46,XX,t(11;20)(q13.1;q13.13)

    SciTech Connect

    Freeman, S.B.; May, K.M.; Blackston, R.D.; Muralidharan, K.

    1996-02-02

    We present a 6-year-old girl with a balanced 11;20 translocation [46,XX,t(11;20)(q13.1;q13.13)pat], asplenia, pulmonic stenosis, Hirschsprung disease, minor anomalies, and mental retardation. This case represents the second report of an individual with situs abnormalities and a balanced chromosome rearrangement involving a breakpoint at 11q13. Segregation analysis of markers in the 11q13 region in the proposita and her phenotypically normal carrier sibs did not show a unique combination of maternal and paternal alleles in the patient. We discuss several possible explanations for the simultaneous occurrence of situs abnormalities and a balanced 11;20 translocation. These include (1) chance, (2) a further chromosome rearrangement in the patient, (3) gene disruption and random situs determination, and (4) gene disruption plus transmission of a recessive or imprinted allele from the mother. 30 refs., 1 fig., 2 tabs.

  7. Karyotype-phenotype insights from 11q14.1-q23.2 interstitial deletions: FZD4 haploinsufficiency and exudative vitreoretinopathy in a patient with a complex chromosome rearrangement.

    PubMed

    Li, Peining; Zhang, Hui Z; Huff, Shannon; Nimmakayalu, Manjunath; Qumsiyeh, Mazin; Yu, Jingwei; Szekely, Anna; Xu, Tian; Pober, Barbara R

    2006-12-15

    We detected a unique de novo complex chromosome rearrangement (CCR) in a patient with multiple abnormalities including growth retardation, facial anomalies, exudative vitreoretinopathy (EVR), cleft palate, and minor digital anomalies. Cytogenetic analysis, fluorescent in situ hybridization, and microsatellite genotyping showed a reciprocal translocation between chromosomes 5 and 8, and a complex translocation-deletion-inversion process in the formation of derivative chromosomes 11 and 16. High-density whole-genome oligonucleotide array comparative genomic hybridization (oaCGH) defined a 35-megabase interstitial deletion of 11q14.1-q23.2 and a 1 megabase deletion of 16q22.3-q23.1. The Frizzled-4 (FZD4) gene is located within this 11q deletion. Parental studies and sequencing analysis confirmed that the patient was hemizygous for FZD4 due to the loss of a paternal allele on the derivative chromosome 11. Mutations in FZD4 are known to cause autosomal dominant exudative vitreoretinopathy (EVR1). Our patient's findings suggest that haploinsufficiency of the FZD4 gene product can also be a disease-causing mechanism for EVR1. We reviewed the clinical manifestations of 23 cases with 11q14-q23 interstitial deletions, with particular scrutiny of the present case and four reported cases characterized by molecular cytogenetics. These findings were used to construct a regional deletion map consisting of a haplosufficient segment at 11q14.3, a flanking centromeric segment at 11q14.1-q14.2, and a flanking telomeric segment at 11q21-q23.3. We propose that deletions of the FZD4 gene located within the centromeric segment cause retinal dysgenesis, while deletions within the telomeric segment account for dysmorphic craniofacial features, growth and mental retardation, and mild digital anomalies. These results provide insight into karyotype-phenotype correlations and prompt a rational analytic approach to cases with interstitial deletions of the 11q14-q23 region. PMID:17103440

  8. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

    PubMed Central

    Petersen, Gloria M.; Amundadottir, Laufey; Fuchs, Charles S.; Kraft, Peter; Stolzenberg-Solomon, Rachael Z.; Jacobs, Kevin B.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gallinger, Steven; Gross, Myron; Helzlsouer, Kathy; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Li, Donghui; Mandelson, Margaret T.; Olson, Sara H.; Risch, Harvey A.; Zheng, Wei; Albanes, Demetrius; Bamlet, William R.; Berg, Christine D.; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Bracci, Paige M.; Canzian, Federico; Clipp, Sandra; Cotterchio, Michelle; de Andrade, Mariza; Duell, Eric J.; Gaziano, J. Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hassan, Manal; Howard, Barbara; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Kaaks, Rudolf; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C.; Lynch, Shannon M.; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Parikh, Hemang; Patel, Alpa V.; Peeters, Petra H.M.; Rajkovic, Aleksandar; Riboli, Elio; Rodriguez, Laudina; Seminara, Daniela; Shu, Xiao-Ou; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Van Den Eeden, Stephen K.; Virtamo, Jarmo; Wactawski-Wende, Jean; Wang, Zhaoming; Wolpin, Brian M.; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Fraumeni, Joseph F.; Hoover, Robert N.; Hartge, Patricia; Chanock, Stephen J.

    2010-01-01

    We conducted a genome-wide association study (GWAS) of pancreatic cancer in 3,851 cases and 3,934 controls drawn from twelve prospective cohort studies and eight case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P=3.27×10−11; per allele odds ratio, OR 1.26, 95% CI=1.18-1.35) and rs9564966 (P=5.86×10−8; per allele OR 1.21, 95% CI=1.13-1.30) map to a non-genic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2; the strongest signal was rs3790844 (P=2.45×10−10; per allele OR 0.77, 95% CI=0.71-0.84). A single SNP, rs401681 (P=3.66×10−7; per allele OR 1.19, 95% CI=1.11-1.27) maps to the CLPTM1L-TERT locus on 5p15.33, associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies. PMID:20101243

  9. A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q

    PubMed Central

    Wiltshire, Steven; Hattersley, Andrew T.; Hitman, Graham A.; Walker, Mark; Levy, Jonathan C.; Sampson, Michael; O’Rahilly, Stephen; Frayling, Timothy M.; Bell, John I.; Lathrop, G. Mark; Bennett, Amanda; Dhillon, Ranjit; Fletcher, Christopher; Groves, Christopher J.; Jones, Elizabeth; Prestwich, Philip; Simecek, Nikol; Rao, Pamidighantam V. Subba; Wishart, Marie; Foxon, Richard; Howell, Simon; Smedley, Damian; Cardon, Lon R.; Menzel, Stephan; McCarthy, Mark I.

    2001-01-01

    Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores ⩾1.18 (P⩽.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest. PMID:11484155

  10. Isolation of region-specific cosmids by hybridization with microdissection clones from human chromosome 10q11. 1-q21. 1

    SciTech Connect

    Karakawa, Katsu; Takami, Koji; Fujita, Shoichi Osaka Univ. Medical School, Fukushima-ku, Osaka ); Nakamura, Tsutomu; Takai, Shin-ichiro; Nishisho, Isamu ); Jones, C. ); Ohta, Tohru; Jinno, Yoshihiro; Niikawa, Norio )

    1993-08-01

    A region-specific plasmid library composed of 20,000 recombinants was constructed by microdissection of human chromosome 10 (10q11.2-q21.1) and subsequent amplification with the primer-linker method of polymerase chain reaction (PCR). Hybridization with total human DNA showed that 32 of 217 microclones studied contained highly repetitive sequences. Further analysis of the remaining 185 microclones proved that 43 microclones, each having an insert longer than 200 bp, contained unique sequences of human chromosome 10 origin. Twenty-five microclones randomly selected from the 43 were used directly as probes to isolate corresponding cosmid clones, resulting in 32 cosmids corresponding to 14 microclones. Of the 25 cosmids that could be mapped by fluorescence in situ hybridization, 24 proved to originate from the microdissected or adjacent region (10p11.2-q22.3)and 1 from a rather distal region (10q24.3-q25.1). In addition, 15 of the 32 cosmids revealed restriction fragment length polymorphisms, including 1 with a variable number of tandem repeats marker. The microdissection library and the obtained cosmids are valuable resources for constructing high-resolution physical and linkage maps of the pericentromeric region of chromosome 10, where the gene predisposing to multiple endocrine neoplasia type 2A (MEN2A) has been mapped. 30 refs., 3 figs., 3 tabs.

  11. Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population

    SciTech Connect

    Van Soest, S.; Ingeborgh Van Den Born, L.; Bergen, A.A.B.

    1994-08-01

    Linkage analysis was carried out in a large family segregating for autosomal recessive retinitis pigmentosa (arRP), originating from a genetically isolated population in The Netherlands. Within the family, clinical heterogeneity was observed, with a major section of the family segregating arRP with characteristic para-arteriolar preservation of the retinal pigment epithelium (PPRPE). In the remainder of the arRP patients no PPRPE was found. Initially, all branches of the family were analyzed jointly, and linkage was found between the marker F13B, located at 1q31-q32.1, and RP12 ({Zeta}{sub max} = 4.99 at 8% recombination). Analysis of linkage heterogeneity between five branches of the family yielded significant evidence for nonallelic genetic heterogeneity within this family, coinciding with the observed clinical differences. Multipoint analysis, carried out in the branches that showed linkage, favored the locus order 1cen-D1S158-(F13B, RP12)-D1S53-1qter ({Zeta}{sub max} = 9.17). The finding of a single founder allele associated with the disease phenotype supports this localization. This study reveals that even in a large family, apparently segregating for a single disease entity, genetic heterogeneity can be detected and resolved successfully. 35 refs., 5 figs.

  12. A novel tRNA variable number tandem repeat at human chromosome 1q23.3 is implicated as a boundary element based on conservation of a CTCF motif in mouse.

    PubMed

    Darrow, Emily M; Chadwick, Brian P

    2014-06-01

    The human genome contains numerous large tandem repeats, many of which remain poorly characterized. Here we report a novel transfer RNA (tRNA) tandem repeat on human chromosome 1q23.3 that shows extensive copy number variation with 9-43 repeat units per allele and displays evidence of meiotic and mitotic instability. Each repeat unit consists of a 7.3 kb GC-rich sequence that binds the insulator protein CTCF and bears the chromatin hallmarks of a bivalent domain in human embryonic stem cells. A tRNA containing tandem repeat composed of at least three 7.6-kb GC-rich repeat units reside within a syntenic region of mouse chromosome 1. However, DNA sequence analysis reveals that, with the exception of the tRNA genes that account for less than 6% of a repeat unit, the remaining 7.2 kb is not conserved with the notable exception of a 24 base pair sequence corresponding to the CTCF binding site, suggesting an important role for this protein at the locus. PMID:24753417

  13. A novel tRNA variable number tandem repeat at human chromosome 1q23.3 is implicated as a boundary element based on conservation of a CTCF motif in mouse

    PubMed Central

    Darrow, Emily M.; Chadwick, Brian P.

    2014-01-01

    The human genome contains numerous large tandem repeats, many of which remain poorly characterized. Here we report a novel transfer RNA (tRNA) tandem repeat on human chromosome 1q23.3 that shows extensive copy number variation with 9–43 repeat units per allele and displays evidence of meiotic and mitotic instability. Each repeat unit consists of a 7.3 kb GC-rich sequence that binds the insulator protein CTCF and bears the chromatin hallmarks of a bivalent domain in human embryonic stem cells. A tRNA containing tandem repeat composed of at least three 7.6-kb GC-rich repeat units reside within a syntenic region of mouse chromosome 1. However, DNA sequence analysis reveals that, with the exception of the tRNA genes that account for less than 6% of a repeat unit, the remaining 7.2 kb is not conserved with the notable exception of a 24 base pair sequence corresponding to the CTCF binding site, suggesting an important role for this protein at the locus. PMID:24753417

  14. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

    PubMed Central

    Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

    1998-01-01

    The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43. PMID:9634513

  15. Linkage analysis excludes the glaucoma locus on 1q from involvement in autosomal dominant glaucoma with iris hypoplasia

    SciTech Connect

    Heon, E.; Sheth, B.P.; Kalenak, J.W.

    1994-09-01

    Genetic factors have been implicated in a variety of types of glaucoma including primary open-angle glaucoma, infantile glaucoma, pigmentary glaucoma, and juvenile open-angle glaucoma. We previously mapped the disease-causing gene for one type of juvenile open angle glaucoma to chromosome 1q21-31. Weatherill and Hart (1969) and Pearce (1983) each noted the association of iris hypoplasia and early-onset autosomal dominant glaucoma. We recently had the opportunity to study a large family (12 affected members) with this phenotype. Affected individuals developed glaucoma at an average age of 30 years. These patients also have a strikingly underdeveloped iris stroma which causes a peculiar eye color. Linkage analysis was able to completely exclude the 1q glaucoma locus from involvement in the disorder that affects this family. A complete clinical description of the family and linkage results at additional candidate loci will be presented.

  16. Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP5O) by exon trapping and mapping to chromosome 21q22.1-q22.2

    SciTech Connect

    Chen, Haiming; Morris, M.A.; Rossier, C.

    1995-08-10

    Exon trapping was used to clone portions of potential genes from human chromosome 21. One trapped sequence showed striking homology with the bovine and rat ATP synthase OSCP (oligomycin sensitivity conferring protein) subunit. We subsequently cloned the full-length human ATP synthase OSCP cDNA (GDB/HGMW approved name ATP50) from infant brain and muscle libraries and determined its nucleotide and deduced amino acid sequence (EMBL/GenBank Accession No. X83218). The encoded polypeptide contains 213 amino acids, with more than 80% identity to bovine and murine ATPase OSCP subunits and over 35% identity to Saccharomyces cerevisiae and sweet potato sequences. The human ATP5O gene is located at 21q22.1-q22.2, just proximal to D21S17, in YACs 860G11 and 838C7 of the Chumakov et al. YAC contig. The gene is expressed in all human tissues examined, most strongly in muscle and heart. This ATP5O subunit is a key structural component of the stalk of the mitochondrial respiratory chain F{sub 1}F{sub 0}-ATP synthase and as such may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome (trisomy 21). 39 refs., 5 figs.

  17. Fatty acid induced glioma cell growth is mediated by the acyl-CoA synthetase 5 gene located on chromosome 10q25.1-q25.2, a region frequently deleted in malignant gliomas.

    PubMed

    Yamashita, Y; Kumabe, T; Cho, Y Y; Watanabe, M; Kawagishi, J; Yoshimoto, T; Fujino, T; Kang, M J; Yamamoto, T T

    2000-11-30

    Acyl-CoA synthetase (ACS) ligates fatty acid and CoA to produce acyl-CoA, an essential molecule in fatty acid metabolism and cell proliferation. ACS5 is a recently characterized ACS isozyme highly expressed in proliferating 3T3-L1 cells. Molecular characterization of the human ACS5 gene revealed that the gene is located on chromosome 10q25.1-q25.2, spans approximately 46 kb, comprises 21 exons and 22 introns, and encodes a 683 amino acid protein. Two major ACS5 transcripts of 2.5- and 3.7-kb are distributed in a wide range of tissues with the highest expression in uterus and spleen. Markedly increased levels of ACS5 transcripts were detected in a glioma line, A172 cells, and primary gliomas of grade IV malignancy, while ACS5 expression was found to be low in normal brain. Immunohistochemical analysis also revealed strong immunostaining with an anti-ACS5 antibody in glioblastomas. U87MG glioma cells infected with an adenovirus encoding ACS5 displayed induced cell growth on exposure to palmitate. Consistent with the induction of cell growth, the virus infected cells displayed induced uptake of palmitate. These results demonstrate a novel fatty acid-induced glioma cell growth mediated by ACS5. PMID:11127823

  18. Genomewide Search for Type 2 Diabetes–Susceptibility Genes in French Whites: Evidence for a Novel Susceptibility Locus for Early-Onset Diabetes on Chromosome 3q27-qter and Independent Replication of a Type 2–Diabetes Locus on Chromosome 1q21–q24

    PubMed Central

    Vionnet, Nathalie; Hani, El Habib; Dupont, Sophie; Gallina, Sophie; Francke, Stephan; Dotte, Sébastien; De Matos, Frédérique; Durand, Emmanuelle; Leprêtre, Frédéric; Lecoeur, Cécile; Gallina, Philippe; Zekiri, Lirije; Dina, Christian; Froguel, Philippe

    2000-01-01

    Despite recent advances in the molecular genetics of type 2 diabetes, the majority of susceptibility genes in humans remain to be identified. We therefore conducted a 10-cM genomewide search (401 microsatellite markers) for type 2 diabetes–related traits in 637 members of 143 French pedigrees ascertained through multiple diabetic siblings, to map such genes in the white population. Nonparametric two-point and multipoint linkage analyzes—using the MAPMAKER-SIBS (MLS) and MAXIMUM-BINOMIAL-LIKELIHOOD (MLB) programs for autosomal markers and the ASPEX program for chromosome X markers—were performed with six diabetic phenotypes: diabetes and diabetes or glucose intolerance (GI), as well as with each of the two phenotypes associated with normal body weight (body-mass index<27 kg/m2) or early age at diagnosis (<45 years). In a second step, high-resolution genetic mapping (∼2 cM) was performed in regions on chromosomes 1 and 3 loci showing the strongest linkage to diabetic traits. We found evidence for linkage with diabetes or GI diagnosed at age <45 years in 92 affected sib pairs from 55 families at the D3S1580 locus on chromosome 3q27-qter using MAPMAKER-SIBS (MLS = 4.67, P=.000004), supported by the MLB statistic (MLB-LOD=3.43, P=.00003). We also found suggestive linkage between the lean diabetic status and markers APOA2–D1S484 (MLS = 3.04, P=.00018; MLB-LOD=2.99, P=.00010) on chromosome 1q21-q24. Several other chromosomal regions showed indication of linkage with diabetic traits, including markers on chromosome 2p21-p16, 10q26, 20p, and 20q. These results (a) showed evidence for a novel susceptibility locus for type 2 diabetes in French whites on chromosome 3q27-qter and (b) confirmed the previously reported diabetes-susceptibility locus on chromosome 1q21-q24. Saturation on both chromosomes narrowed the regions of interest down to an interval of <7 cM. PMID:11067779

  19. Localization of juvenile, but not late-infantile, neuronal ceroid lipofuscinosis on chromosome 16

    SciTech Connect

    Wenliang Yan; Ozelius, L.; Breakefield, X.O.; Gusella, J.F. Harvard Medical School, Boston, MA ); Boustany, R.M.N. ); Konradi, C.; Lerner, T.; Trofatter, J.A.; Haines, J.L. ); Julier, C. )

    1993-01-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders characterized by the deposition of autofluorescent proteinaceous fingerprint or curvilinear bodies. The authors have found that CLN3, the gene underlying the juvenile form of NCL, is very tightly linked to the dinucleotide repeat marker D16S285 on chromosome 16. Integration of D16S285 into the genetic map of chromosome 16 by using the Centre d'Etude du Polymorphisme Humain panel of reference pedigrees yielded a favored marker order in the CLN3 region of qtel-D16S150-.08-D16S285-.04-D16S148-.02-D16S67-ptel. The most likely location of the disease gene, near D16S285 in the D16S150-D16S148 interval, was favored by odds of greater than 10[sup 4]:1 over the adjacent D16S148-D16S67 interval, which was recently reported as the minimum candidate region. Analysis of D16S285 in pedigrees with late-infantile NCL virtually excluded the CLN3 region, suggesting that these two forms of NCL are genetically distinct. 23 refs., 3 figs., 2 tabs.

  20. Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25.

    PubMed

    Jay, G D; Tantravahi, U; Britt, D E; Barrach, H J; Cha, C J

    2001-07-01

    We have previously identified megakaryocyte stimulating factor (MSF) gene expression by synovial fibroblasts as the origin of lubricin in the synovial cavity. Lubricin is a mucinous glycoprotein responsible for the boundary lubrication of articular cartilage. MSF has a significant homology to vitronectin and is composed of 12 exons. RNA was purified from human synovial fibroblasts and articular chondrocytes grown in vitro from tissue explants obtained from subjects without degenerative joint disease. RT-PCR was used with multiple complimentary primer pairs spanning the central mucin expressing exon 6 of the MSF gene and individual exons on both the N- and C-terminal sides of exon 6. Exons 2, 4 and 5 appear to be variably expressed by synovial fibroblasts and articular chondrocytes. Lubricating mucin, in the form of MSF, is expressed by both chondrocytes and synovial fibroblasts in vitro. Both lubricin and superficial zone protein (SZP), a related proteoglycan, share a similar primary structure but could differ in post-translational modifications with O-linked oligosaccharides which are predominant in lubricin and with limited amounts chondroitin and keratan sulfate found in SZP. Since most of the MSF exons are involved in the expression of lubricating mucin, a strong homology to vitronectin persists. It is therefore appropriate to consider that both SZP and lubricin occupy a new class of biomolecules termed tribonectins. Screening of a human genome bacterial artificial chromsome (BAC) library with a cDNA primer pair complimentary for exon 6 identified two clones. Both clones were complimentary for chromosome 1q25 by in situ hybridization. This same locus was previously implicated in camptodactyl-arthropathy-pericarditis syndrome (CAP) by genetic mapping. It is hypothesized that CAP, a large joint arthropathy, may be associated with ineffective boundary lubrication provided by synovial fluid. PMID:11518279

  1. Juvenile myoclonic epilepsy in chromosome 6p12-p11: Locus heterogeneity and recombinations

    SciTech Connect

    Liu, A.W.; Delgado-Escueta, A.V.; Serratosa, J.M.

    1996-06-14

    We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome-wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Z{sub max} > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Z{sub max} were 4.230 for D6S294 ({theta}{sub m=f} at 0.133) and 4.442 for D6S466 ({theta}{sub m=f} at 0.111). Admixture test (H{sub 2} vs. H{sub 1}) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, {alpha}, was 0.50 (95% confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257. 44 refs., 3 figs., 4 tabs.

  2. Neurological aspects of del(1q) syndrome.

    PubMed

    Murayama, K; Greenwood, R S; Rao, K W; Aylsworth, A S

    1991-09-15

    We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions. PMID:1746617

  3. Chromosome 16 microdeletion in a patient with juvenile neuronal ceroid lipofuscinosis (Batten disease)

    SciTech Connect

    Taschner, P.E.M.; Vos, N. de; Thompson, A.D.; Callen, D.F.; Doggett, N.; Mole, S.E.; Dooley, T.P.; Barth, P.G.; Breuning, M.H. |

    1995-03-01

    The gene that is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease - CLN3 - has been localized to 16p12, and the mutation shows a strong association with alleles of microsatellite markers D16S298, D16S299, and D16S288. Recently, haplotype analysis of a Batten patient from a consanguineous relationship indicated homozygosity for a D16S298 null allele. PCR analysis with different primers on DNA from the patient and his family suggests the presence of a cytogenetically undetectable deletion, which was confirmed by Southern blot analysis. The microdeletion is embedded in a region containing chromosome 16-specific repeated sequences. However, putative candidates for CLN3, members of the highly homologous sulfotransferase gene family, which are also present in this region in several copies, were not deleted in the patient. If the microdeletion in this patient is responsible for Batten disease, then we conclude that the sulfotransferase genes are probably not involved in JNCL. By use of markers and probes flanking D15S298, the maximum size of the microdeletion was determined to be {approximately}29 kb. The microdeletion may affect the CLN3 gene, which is expected to be in close proximity to D16S298. 27 refs., 6 figs.

  4. Genome-wide and fine-mapping linkage studies of type 2 diabetes and glucose traits in the Old Order Amish: evidence for a new diabetes locus on chromosome 14q11 and confirmation of a locus on chromosome 1q21-q24.

    PubMed

    Hsueh, Wen-Chi; St Jean, Pamela L; Mitchell, Braxton D; Pollin, Toni I; Knowler, William C; Ehm, Margaret G; Bell, Callum J; Sakul, Hakan; Wagner, Michael J; Burns, Daniel K; Shuldiner, Alan R

    2003-02-01

    We conducted a genome scan using a 10-cM map to search for genes linked to type 2 diabetes in 691 individuals from a founder population, the Old Order Amish. We then saturated two regions on chromosomes 1 and 14 showing promising linkage signals with additional markers to produce a approximately 2-cM map for fine mapping. Analyses of both discrete traits (type 2 diabetes and the composite trait of type 2 diabetes and/or impaired glucose homeostasis [IGH]), and quantitative traits (glucose levels during a 75-g oral glucose challenge, designated glucose 0-180 and HbA(1c)) were performed. We obtained significant evidence for linkage to type 2 diabetes in a novel region on chromosome 14q11 (logarithm of odds [LOD] for diabetes = 3.48, P = 0.00005). Furthermore, we observed evidence for the existence of a diabetes-related locus on chromosome 1q21-q24 (LOD for type 2 diabetes/IGH = 2.35, P = 0.0008), a region shown to be linked to diabetes in several other studies. Suggestive evidence for linkage to glucose traits was observed on three other regions: 14q11-q13 (telomeric to that above with LOD = 1.82-1.85 for glucose 150 and 180), 1p31 (LOD = 1.28-2.30 for type 2 diabetes and glucose 120-180), and 18p (LOD = 3.07, P = 0.000085 for HbA(1c) and LOD = 1.50 for glucose 0). In conclusion, our findings provide evidence that type 2 diabetes susceptibility genes reside on chromosomes 1, 14, and 18. PMID:12540634

  5. Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA)

    PubMed Central

    Hamaoui, Raja; Bryant, Annette; Hinks, Anne; Ursu, Simona; Wedderburn, Lucy R.; Thomson, Wendy; Lewis, Cathryn M.; Woo, Patricia

    2012-01-01

    Background The cytokine IL-10 and its family members have been implicated in autoimmune diseases and we have previously reported that genetic variants in IL-10 were associated with a rare group of diseases called juvenile idiopathic arthritis (JIA). The aim of this study was to fine map genetic variants within the IL-10 cytokine family cluster on chromosome 1 using linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (tSNPs) approach with imputation and conditional analysis to test for disease associations. Methodology/Principal Findings Fifty-three tSNPs were tested for association between Caucasian paediatric cohorts [219 systemic JIA (sJIA), 187 persistent oligoarticular JIA (pOJIA), and 139 extended OJIA (eOJIA) patients], and controls (Wellcome Trust control cohort, WTCCC2). Significant association with sJIA was detected at rs1400986 in the promoter of IL-20 (odds ratio 1.53; 95% CI 1.21–1.93; p = 0.0004), but in no other subtypes. Imputation analysis identified additional associated SNPs for pOJIA at IL-20 and IL-24, including a rare, functional, missense variant at IL-24 with a p = 0.0002. Penalised logistic regression analysis with HyperLasso and conditional analysis identified several further associations with JIA subtypes. In particular, haplotype analysis refined the sJIA association, with a joint effect at rs1400986 and rs4129024 in intron 1 of MAPKAPK2 (p = 3.2E−5). For pOJIA, a 3-SNP haplotype including rs1878672 in intron 3 of IL-10 showed evidence for association (p = 0.0018). In eOJIA, rs10863962 (3′UTR of FCAMR) and rs12409577 (intron of IL-19) haplotype showed some evidence of association (p = 0.0003). Conclusions This study supports previous association of IL-20 with sJIA. Haplotype analyses provided stronger association signals than single point analyses, while a penalised logistic regression approach also suggested multiple independent association signals. Replication studies are required to confirm or

  6. Juvenile polyposis of infancy associated with paracentric inversion and deletion of chromosome 10 in a Hispanic patient: a case report.

    PubMed

    Vargas-González, Roberto; de la Torre-Mondragón, Luis; Aparicio-Rodríguez, Juan Manuel; Paniagua-Morgan, Froylan; López-Hernández, Gerardo; Garrido-Hernández, Miguel Angel; Nuñez-Barrera, Sandra

    2010-01-01

    Juvenile polyposis of infancy is a rare genetic disorder, involving multiple hamartomatous polyps of the gastrointestinal tract, which usually has a very aggressive clinical course and is often fatal. It is characterized by early onset (during the 1st months of life) and by diffuse juvenile polyposis with anemia, recurrent gastrointestinal bleeding, diarrhea, rectal prolapse, intussusception, protein-losing enteropathy, starvation, and malnutrition. There is a hypothesis that mutation of the tumor-suppressor genes BMPR1A and PTEN, located on the long arm of chromosome 10, is associated with the development of this disease. Medical treatment for this disorder is challenging and should be conservative whenever possible. We present the case of a 3-year-old girl with juvenile polyposis of infancy who eventually died from mesenteric artery thrombosis during surgical colectomy. Karyotype of the patient showed a paracentric inversion in 10q and a deletion in 10p. We will briefly comment on some genetic considerations of this disease. PMID:20334546

  7. Chromosome

    MedlinePlus

    ... if you are born a boy or a girl (your gender). They are called sex chromosomes: Females have 2 X chromosomes. Males have 1 X and 1 Y chromosome. The mother gives an X chromosome to the ... baby is a girl or a boy. The remaining chromosomes are called ...

  8. Chromosome

    MedlinePlus

    ... genes . It is the building block of the human body. Chromosomes also contain proteins that help DNA exist ... come in pairs. Normally, each cell in the human body has 23 pairs of chromosomes (46 total chromosomes). ...

  9. Overlap of Juvenile polyposis syndrome and Cowden syndrome due to de novo chromosome 10 deletion involving BMPR1A and PTEN: implications for treatment and surveillance.

    PubMed

    Alimi, Adebisi; Weeth-Feinstein, Lauren A; Stettner, Amy; Caldera, Freddy; Weiss, Jennifer M

    2015-06-01

    We describe a patient with a severe juvenile polyposis phenotype, due to a de novo deletion of chromosome 10q22.3-q24.1. He was initially diagnosed with Juvenile polyposis syndrome (JPS) at age four after presenting with hematochezia due to multiple colonic juvenile polyps. He then re-presented at 23 years with recurrent hematochezia from juvenile polyps in his ileoanal pouch. He is one of the earliest reported cases of JPS associated with a large deletion of chromosome 10. Since his initial diagnosis of JPS further studies have confirmed an association between JPS and mutations in BMPR1A in chromosome band 10q23.2, which is in close proximity to PTEN. Mutations in PTEN cause Cowden syndrome (CS) and other PTEN hamartoma tumor syndromes. Due to the chromosome 10 deletion involving contiguous portions of BMPR1A and PTEN in our patient, he may be at risk for CS associated cancers and features, in addition to the polyps associated with JPS. This case presents new challenges in developing appropriate surveillance algorithms to account for the risks associated with each syndrome and highlights the importance of longitudinal follow-up and transitional care between pediatric and adult gastroenterology for patients with hereditary polyposis syndromes. PMID:25846706

  10. Refined localization of the [alpha][sub 1]-subunit of the skeletal muscle L-type voltage-dependent calcium channel (CACNL1A3) to human chromosome 1q32 by in situ hybridization

    SciTech Connect

    Iles, D.E.; Segers, B.; Wieringa, B.; Weghuis, D.O.; Suijerbuijk, R. ); Mikala, G.; Schwartz, A. )

    1994-02-01

    The authors isolated and partially sequenced a cosmid clone containing the human skeletal muscle L-type voltage-dependent calcium channel gene (CACNL1A3). The cosmid clone, which was also found to contain a novel dinucleotide repeat marker for the CACNL1A3 gene, was used for the chromosomal localization of CACNL1A3 by in situ hybridization. The results refine the localization of CACNL1A3 on the long arm of human chromosome 1 to band q32. 15 refs., 2 figs., 1 tab.

  11. A 11 Mb YAC-based contig spanning the familial juvenile nephronophthisis region (NPH1) located on chromosome 2q

    SciTech Connect

    Konrad, M.; Saunier, S.; Silbermann, F.

    1995-12-10

    A gene (NPH1) responsible for approximately 90% of the purely renal form of familial juvenile nephronophthisis, a progressive tubulo-interstitial kidney disorder, maps to human chromosome 2. We report the construction of a YAC-based contig spanning the critical NPH1 region and the flanking genetic markers. This physical map was integrated with a refined genetic map that restricted the NPH1 interval to about 2 cM; this interval corresponds to a maximum physical distance of 3.5 Mb. The entire contig covers 9 cM between the loci D2S135 and D2S121. The maximum physical distance between these two markers is approximately 11.3 Mb. Forty-five sequence-tagged sites, including six genes, have been located within this contig. PAX8, a member of the human paired box gene family, that is expressed in the developing kidney, was assigned outside the restricted NPH1 critical region and cannot therefore be regarded as a candidate gene. This set of overlapping clones represents a useful resource for further targeted development of genetic markers and for the characterization of candidate genes responsible for juvenile nephronophthisis. 26 refs., 2 figs., 3 tabs.

  12. Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.

    PubMed

    Wight, Jenny E; Nguyen, Viet-Huong; Medina, Marco T; Patterson, Christopher; Durón, Reyna M; Molina, Yolly; Lin, Yu-Chen; Martínez-Juárez, Iris E; Ochoa, Adriana; Jara-Prado, Aurelio; Tanaka, Miyabi; Bai, Dongsheng; Aftab, Sumaya; Bailey, Julia N; Delgado-Escueta, Antonio V

    2016-03-01

    Juvenile myoclonic epilepsy (JME), the most common genetic epilepsy, remains enigmatic because it is considered one disease instead of several diseases. We ascertained three large multigenerational/multiplex JME pedigrees from Honduras with differing JME subsyndromes, including Childhood Absence Epilepsy evolving to JME (CAE/JME; pedigree 1), JME with adolescent onset pyknoleptic absence (JME/pA; pedigree 2), and classic JME (cJME; pedigree 3). All phenotypes were validated, including symptomatic persons with various epilepsies, asymptomatic persons with EEG 3.5-6.0 Hz polyspike waves, and asymptomatic persons with normal EEGs. Two-point parametric linkage analyses were performed with 5185 single-nucleotide polymorphisms on individual pedigrees and pooled pedigrees using four diagnostic models based on epilepsy/EEG diagnoses. Haplotype analyses of the entire genome were also performed for each individual. In pedigree 1, haplotyping identified a 34 cM region in 2q21.2-q31.1 cosegregating with all affected members, an area close to 2q14.3 identified by linkage (Z max = 1.77; pedigree 1). In pedigree 2, linkage and haplotyping identified a 44 cM cosegregating region in 13q13.3-q31.2 (Z max = 3.50 at 13q31.1; pooled pedigrees). In pedigree 3, haplotyping identified a 6 cM cosegregating region in 17q12. Possible cosegregation was also identified in 13q14.2 and 1q32 in pedigree 3, although this could not be definitively confirmed due to the presence of uninformative markers in key individuals. Differing chromosome regions identified in specific JME subsyndromes may contain separate JME disease-causing genes, favoring the concept of JME as several distinct diseases. Whole-exome sequencing will likely identify a CAE/JME gene in 2q21.2-2q31.1, a JME/pA gene in 13q13.3-q31.2, and a cJME gene in 17q12. PMID:27066514

  13. Mapping of the human SAP1 (SRF accessory protein 1) gene and SAP2, a gene encoding a related protein, to chromosomal bands 1q32 and 12q23, respectively

    SciTech Connect

    Shipley, J.; Sheer, D.; Patel, K.

    1994-10-01

    SAP1, SAP2, and ELK1 form a related subgroup of ETS-domain proteins that can form ternary complexes with the transcription factor SRF at the c-fos serum response element (SRE). SAP1 was identified by a genetic screen for proteins interacting with SRF expressed in yeast, and SAP2 by its homology with SAP1; ELK1 was previously identified by its homology to the ETS domain. cDNA probes were used to isolate cosmid and phage clones harboring genes encoding SAP1 and SAP2. These clones were subsequently used to map the genes to 1q32 and 12q23, respectively, by fluorescence in situ hybridization. 17 refs., 1 fig.

  14. Constitutional partial 1q trisomy mosaicism and Wilms tumor.

    PubMed

    Mark, Hon Fong L; Wyandt, Herman; Pan, Agen; Milunsky, Jeff M

    2005-10-15

    We report on a female patient with severe-profound mental retardation, multiple congenital anomalies, as well as a history of mosaicism for partial 1q trisomy in the amniotic fluid and a previous Wilms tumor specimen. Peripheral blood and fibroblasts were studied and did not demonstrate the mosaicism initially detected for 1q. Array comparative genomic hybridization yielded negative results. Additional cytogenetic studies helped clarify the previous findings and revealed evidence of partial 1q trisomy mosaicism in normal kidney tissue and in a kidney lesion. GTG-banded results showing low-percentage mosaicism for the structural rearrangement der(1)t(1;1)(p36.1;q23) in both tissues were corroborated by fluorescence in situ hybridization studies. We hypothesize that the partial 1q trisomy predisposed the target tissue (in this case kidney) to neoplasia. This study provides further support for the hypothesis that certain constitutional chromosomal abnormalities can predispose to cancer. As detection of a low-percentage mosaicism may be hampered by the limits imposed by currently available technology and the constraint of a finite sample size, extra vigilance in monitoring other somatic tissues will be needed throughout the patient's lifetime. Anticipatory clinical guidance and prognostication are meaningful only if given accurate cytogenetic diagnoses. To the best of our knowledge, this is the first reported case of Wilms tumor associated with constitutional partial 1q trisomy, either in pure or mosaic form, with the particular 1q23 breakpoint in conjunction with a break on 1p36.1. PMID:16213366

  15. Deletion (11)(q14.1q21)

    SciTech Connect

    Stratton, R.F.; Lazarus, K.H.; Ritchie, E.J.L.; Bell, A.M.

    1994-02-01

    The authors report on a 4-year-old girl with moderate development delay, horseshoe kidney, bilateral duplication of the ureters with right upper pole obstruction, hydronephrosis and nonfunction, and subsequent Wilms tumor of the right lower pole. She had an interstitial deletion of the long arm of chromosome 11 involving the region 11(q14.1q21). 22 refs., 2 figs., 1 tab.

  16. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells.

    PubMed

    Bigler, Cornelia; Schaller, Monica; Perahud, Iryna; Osthoff, Michael; Trendelenburg, Marten

    2009-09-01

    Autoantibodies against complement C1q (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE). They strongly correlate with the occurrence of severe lupus nephritis, suggesting a pathogenic role in SLE. Because anti-C1q are known to recognize a neoepitope on bound C1q, but not on fluid-phase C1q, the aim of this study was to clarify the origin of anti-C1q by determining the mechanism that renders C1q antigenic. We investigated anti-C1q from serum and purified total IgG of patients with SLE and hypocomplementemic urticarial vasculitis as well as two monoclonal human anti-C1q Fab from a SLE patient generated by phage display. Binding characteristics, such as their ability to recognize C1q bound on different classes of Igs, on immune complexes, and on cells undergoing apoptosis, were analyzed. Interestingly, anti-C1q did not bind to C1q bound on Igs or immune complexes. Neither did we observe specific binding of anti-C1q to C1q bound on late apoptotic/necrotic cells when compared with binding in the absence of C1q. However, as shown by FACS analysis and confocal microscopy, anti-C1q specifically targeted C1q bound on early apoptotic cells. Anti-C1q were found to specifically target C1q bound on cells undergoing apoptosis. Our observations suggest that early apoptotic cells are a major target of the autoimmune response in SLE and provide a direct link between human SLE, apoptosis, and C1q. PMID:19648280

  17. Mapping of a gene for familial juvenile nephronophthisis: Refining the map and defining flanking markers on chromosome 2

    SciTech Connect

    Hildebrandt, F.; Singh-Sawhney, I.; Schnieders, B.; Centofante, L.; Omran, H.; Pohlmann, A.; Schmaltz, C.; Wedekind, H.; Schubotz, D.; Brandis, M. ); Antignac, C. ); Weber, J.L. )

    1993-12-01

    Familial juvenile nephronophthisis (NPH) is an autosomal recessive kidney disease that leads to end-stage renal failure in adolescence and is associated with the formation of cysts at the cortico-medullary junction of the kidneys. NPH is responsible for about 15% of end-stage renal disease in children, as shown by Kleinknecht and Habib. NPH in combination with autosomal recessive retinitis pigmentosa is known as the Senior-Loken syndrome (SLS) and exhibits renal pathology that is identical to NPH. The authors had excluded 40% of the human genome from linkage with a disease locus for NH or SLS when Antignac et al. first demonstrated linkage for an NPH locus on chromosome 2. The authors present confirmation of linkage of an NPH locus to microsatellite markers on chromosome 2 in nine families with NPH. By linkage analysis with marker AFM262xb5 at locus D2S176, a maximum lod score of 5.05 at a [theta][sub max] = .03 was obtained. In a large NPH family that yielded at D2S176 a maximum lod score of 2.66 at [theta][sub max] = .0, markers AFM172xc3 and AFM016yc5, representing loci D2S135 and D2S110, respectively, were identified as flanking markers, thereby defining the interval for an NPH locus to a region of approximately 15 cM. Furthermore, the cytogenetic assignment of the NPH region was specified to 2p12-(2q13 or adjacent bands) by calculation of linkage between these flanking markers and markers with known unique cytogenic assignment. The refined map may serve as a genetic framework for additional genetic and physical mapping of the region. 26 refs., 3 figs., 1 tab.

  18. Renormalons and 1/Q2 corrections

    NASA Astrophysics Data System (ADS)

    Akhoury, R.; Zakharov, V. I.

    1997-06-01

    We argue that the appearance of the Landau pole in the running coupling of QCD introduces 1/Q2 power corrections in current correlator functions. These terms are not accounted for by the standard operator product expansion and is the price to be paid for the lack of a unique definition of the running coupling at the 1/Q2 level. We review also possible phenomenological implications of the 1/Q2 terms in an alternative language of ultraviolet renormalon.

  19. Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27

    SciTech Connect

    Matsumine, Hiroto; Shimoda-Matsubayashi, Satoe; Nakagawa-Hattori, Yuko

    1997-03-01

    An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 ({theta} = .03) and D6S253 ({theta} = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons. 38 refs., 4 figs., 1 tab.

  20. C1q and systemic lupus erythematosus.

    PubMed

    Walport, M J; Davies, K A; Botto, M

    1998-08-01

    In this chapter we review the association between SLE and C1q. In the first part of the chapter we discuss the clinical associations of C1q deficiency, and tabulate the available information in the literature relating to C1q deficiency and autoimmune disease. Other clinical associations of C1q deficiency are then considered, and we mention briefly the association between other genetically determined complement deficiencies and lupus. In the review we explore the relationship between C1q consumption and lupus and we discuss the occurrence of low molecular weight (7S) C1q in lupus, which raises the possibility that increased C1q turnover in the disease may result in unbalanced chain synthesis of the molecule. Anti-C1q antibodies are also strongly associated with severe SLE affecting the kidney, and with hypocomplementaemic urticarial vasculitis, and these associations are also examined. We address the question of how C1q deficiency may cause SLE, discussing the possibility that this may be due to abnormalities of immune complex processing, which have been well characterised in a umber of different human models. There is clear evidence that immune complex processing is abnormal in patients with hypocomplementaemia, and this is compatible with the hypothesis that ineffective immune complex clearance could cause tissue injury, and this may in turn stimulate an autoantibody response. We have also considered the possibility that C1q-C1q receptor interactions are critical in the regulation of apoptosis, and we explore the hypothesis that dysregulation of apoptosis could explain important features in the development of autoimmune disease associated with C1q deficiency. An abnormally high rate of apoptosis, or defective clearance of apoptotic cells, could promote the accumulation of abnormal cellular products that might drive an autoimmune response. Anti-C1q antibodies have been described in a number of murine models of lupus, and these are also briefly discussed. We focus

  1. Linkage disequilibrium between the juvenile neuronal ceroid lipofuscinosis gene and marker loci on chromosome 16p12. 1

    SciTech Connect

    Lerner, T.J.; MacCormack, K.; Gleitsman, J.; Schlumpf, K.; Breakefield, X.O.; Gusella, J.F.; Haines, J.L. )

    1994-01-01

    The neuronal ceroid lipofuscinoses (NCL; Batten disease) are a collection of autosomal recessive disorders characterized by the accumulation of autofluorescent lipopigments in the neurons and other cell types. Clinically, these disorders are characterized by progressive encephalopathy, loss of vision, and seizures. CLN3, the gene responsible for juvenile NCL, has been mapped to a 15-cM region flanked by the marker loci D16S148 and D16S150 on human chromosome 16. CLN2, the gene causing the late-infantile form of NCL (LNCL), is not yet mapped. The authors have used highly informative dinucleoide repeat markers mapping between D16S148 and D16S150 to refine the localization of CLN3 and to test for linkage to CLN2. The authors find significant linkage disequilibrium between CLN3 and the dinucleotide repeat marker loci D16S288 (X[sup 2](7) = 46.5, P < .005), D16S298 (X[sup 2](6) = 36.6, P < .005), and D16S299 (X[sup 2](7) = 73.8, P < .005), and also a novel RFLP marker at the D16S272 locus (X[sup 2](1) = 5.7, P = .02). These markers all map to 16p12.1. The D16S298/D16S299 haplotype [open quotes]5/4[close quotes] is highly overrepresented, accounting for 54% of CLN3 chromosomes as compared with 8% of control chromosomes (X[sup 2] = 117, df = 1, P < .001). Examination of the haplotypes suggests that the CLN3 locus can be narrowed to the region immediately surrounding these markers in 16p12.1. Analysis of D16S299 in LNCL pedigrees supports the previous finding that CLN3 and CLN2 are different genetic loci. This study also indicates that dinucleotide repeat markers play a valuable role in disequilibrium studies. 23 refs., 1 fig., 4 tabs.

  2. Localization of cofilin gene to 1q25

    SciTech Connect

    Hung, W.Y.; Deng, H.X.; Hentati, H.A.

    1994-09-01

    Cofilin is a 21 kD actin-binding protein which has recently been identified as an important intracellular messenger that activates resting T-lymphocytes for clonal growth and expression of their functional repertoires. To determine the chromosomal location of the cofilin gene, a cDNA fragment, 276 bp downstream from initial codon to poly A tail, was used as a probe to screen a human genomic DNA lamda phage library. Four positive phage clones were isolated from 400,000 phage plaques. The size of the genomic inserts ranged from 14 kb to 20 kb. The DNA from these phage clones were labeled with digoxigenin and hybridized to metaphase chromosome preparations. The hybridization signals were detected with sheep anti-digoxigenin and FITC-conjugated rabbit anti-sheep antibodies. Fluorescence signal was amplified once with FITC-conjugated goat anti-rabbit antibody. The results indicate that cofilin gene is located at chromosome 1q25.

  3. Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: Linkage to convulsions and electroencephalography trait

    SciTech Connect

    Liu, A.W.; Delgado-Escueta, A.V.; Serratosa, J.M.

    1995-08-01

    Despite affecting 4 million Americans and 100-200 million persons worldwide, the precise molecular mechanisms of human epilepsies remain unknown. Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. In this epilepsy, electroencephalographic (EEG) 15-30 Hz multispikes produce myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Moreover, EEG 3.5-6 Hz multispike wave complexes appear in clinically asymptomatic family members. We first studied 38 members of a four-generation LA-Belize family with classical JME but with no pyknoleptic absences. Five living members had JME; four clinically asymptomatic members had EEG multispike wave complexes. Pairwise analysis tightly linked microsatellites centromeric to HLA, namely D6S272 (peak lod score [Z{sub max}]=3.564-3.560 at male-female recombination [{theta}{sub m=f}]=0-0.001) and D6S257 (Z{sub max}=3.672-3.6667 at {theta}{sub m=f}=0-0.001), spanning 7 cM, to convulsive seizures and EEG multispike wave complexes. A recombination between D6S276 and D6S273 in one affected member placed the JME locus within or below HLA. Pairwise, multipoint, and recombination analyses in this large family independently proved that a JME gene is located in chromsome 6p, centromeric to HLA. We next screened, with the same chromosome 6p21.2-p11 short tandem-repeat polymorphic markers, seven multiplex pedigrees with classic JME. When lod scores for small multiplex families are added to lod scores of the LA-Belize pedigree, Z{sub max} values for D6S294 and D6S257 are >7 ({theta}{sub m=f}=0.000). Our results prove that in chromosome 6p21.2-p11 an epilepsy locus exists whose phenotype consists of classic JME with convulsions and/or EEG rapid multispike wave complexes. 31 refs., 6 figs., 4 tabs.

  4. Focal cortical dysplasia, microcephaly and epilepsy in a boy with 1q21.1-q21.3 duplication.

    PubMed

    Milone, Roberta; Valetto, Angelo; Battini, Roberta; Bertini, Veronica; Valvo, Giulia; Cioni, Giovanni; Sicca, Federico

    2016-05-01

    The recent advance of new molecular technologies like array - Comparative Genomic Hybridization has fostered the detection of genomic imbalances in subjects with intellectual disability, epilepsy, and/or congenital anomalies. Though some of the rearrangements are relatively frequent, their consequences on phenotypes can be strongly variable. We report on a boy harbouring a de novo 8.3 Mb duplication of chromosome 1q21.1-q21.3 whose complex unusual phenotype deserves attention, due to the presence of focal cortical dysplasia, microcephaly, and epilepsy. Loss-of-function (LOF) effects of genes associated with human disease involved in the rearrangement have been only partially established, and have not been previously associated with brain malformations in several deletion syndromes. Less is known, instead, about the consequences of their duplication on neuronal migration and brain development process. Further advance in neuroimaging and genetic research will help in defining their actual role in neurodevelopment and cerebral cortex malformations. PMID:26975584

  5. Localization of a locus for juvenile myoclonic epilepsy on chromosome 6p11-21.2 and evidence for genetic heterogeneity

    SciTech Connect

    Liu, A.W.; Delgado-Escueta, A.V. |; Alonso, V.M.E.

    1994-09-01

    Juvenile myoclonic epilepsy (JME) is a common form of primary idiopathic generalized epilepsy characterized by myoclonias, tonic-clonic or clonic tonic-clonic convulsions and absences. Ictal electroencephalograms (EEGs) show high amplitude multispikes folowed by slow waves and interictal EEGs manifest 3.5-6 Hz diffuse multispike wave complexes. JME affected about 7-10% of patients with epilepsies and its onset peaks between 13-15 years of age. We recently mapped a JME locus on chromosome 6p21.1-6p11 by linkage analysis of one relatively large JME family from Los Angeles and Belize. Assuming autosomal dominant inheritance with 70% penetrance, pairwise analyses tightly linked JME to D6S257 (Z = 3.67), D6S428 (Z = 3.08) and D6S272 (Z = 3.56) at {theta} = 0, m = f. Recombination and multipoints linkage analysis also suggested a locus is between markers D6S257 and D6S272. We then screened three relatively larger Mexican JME pedigrees with D6S257, D6S272, D6S282, TNF, D6S276, D6S273, D6S105 and F13A1 on chromosome 6p. Assuming autosomal dominant inheritance with incomplete penetrance, linkage to chromosome 6p DNA markers are excluded. Our findings underline the genetic heterogeneity of juvenile myoclonic epilepsy.

  6. Anti-C1q autoantibodies.

    PubMed

    Kallenberg, Cees G M

    2008-09-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this condition. They occur, however, more frequently in (proliferative) lupus nephritis, particularly during active disease. Furthermore, levels of anti-C1q rise, in many cases, prior to a relapse of lupus nephritis, suggesting a pathogenic role for the autoantibodies. Indeed, experimental studies strongly support a pathogenic role for anti-C1q in immune complex-mediated renal disease. In addition, anti-C1q may interfere with the clearance of apoptotic cells, so influencing induction and expression of autoimmunity. PMID:18606253

  7. De Novo Trisomy 1q10q23.3 Mosaicism Causes Microcephaly, Severe Developmental Delay, and Facial Dysmorphic Features but No Cardiac Anomalies

    PubMed Central

    Lo-A-Njoe, Shirley; van der Veken, Lars T.; Rafael-Croes, Louise; Hochstenbach, Ron; Knoers, Nine; van Haelst, Mieke M.

    2016-01-01

    Proximal duplications of chromosome 1q are rare chromosomal abnormalities. Most patients with this condition present with neurological, urogenital, and congenital heart disease and short life expectancy. Mosaicism for trisomy 1q10q23.3 has only been reported once in the literature. Here we discuss a second case: a girl with a postnatal diagnosis of a de novo pure mosaic trisomy 1q1023.3 who has no urogenital or cardiac anomalies. PMID:26942023

  8. The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population

    PubMed Central

    Yu, Wenjun; Guo, Rui; Qu, Xiaoyan; Qiu, Hairong; Li, Jianyong; Zhang, Run; Chen, Lijuan

    2016-01-01

    The prognostic heterogeneity of multiple myeloma (MM) is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21) was found in totally 40 of 86 (46.5%) cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P<0.05). Bortezomib could not significantly improve the overall survival for patients with 1q21 amplification (P>0.05). These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib-based regimens. PMID:26834489

  9. Partial trisomy 1(q42-->qter): a new case with a mild phenotype.

    PubMed Central

    Concolino, D; Cinti, R; Ferraro, L; Moricca, M T; Strisciuglio, P

    1998-01-01

    We report a female patient with a 46,XX,der(8)t(1;8)(q42.1;p23.3) karyotype who had a mild phenotype characterised by a few subtle dysmorphic features and mild developmental retardation, probably resulting from trisomy 1q42-->qter. The deletion on the short arm of the chromosome 8 appeared to be confined to the distal chromosomal segment. Images PMID:9475102

  10. 1q21.1 microduplication in a patient with mental impairment and congenital heart defect.

    PubMed

    Sun, Guowen; Tan, Zhiping; Fan, Liangliang; Wang, Jian; Yang, Yifeng; Zhang, Weizhi

    2015-10-01

    1q21.1 duplication is a rare copy number variant with multiple congenital malformations, including developmental delay, autism spectrum disorder, dysmorphic features and congenital heart anomalies. The present study described a Chinese female patient (age, four years and eight months) with multiple malformations, including congenital heart defect, mental impairment and developmental delay. The parents and the monozygotic twin sister of the patient, however, were physically and psychologically normal. High‑resolution genome‑wide single nucleotide polymorphism array revealed a 1.6‑Mb duplication in chromosome region 1q21.1. This chromosome region contained HFE2, a critical gene involved in hereditary hemochromatosis. However, the parents and monozygotic twin sister of the patient did not carry this genomic lesion. To the best of our knowledge, the present study was the first to report on a 1q21.1 duplication patient in mainland China. PMID:26238956

  11. Proximal microdeletions and microduplications of 1q21.1 contribute to variable abnormal phenotypes

    PubMed Central

    Rosenfeld, Jill A; Traylor, Ryan N; Schaefer, G Bradley; McPherson, Elizabeth W; Ballif, Blake C; Klopocki, Eva; Mundlos, Stefan; Shaffer, Lisa G; Aylsworth, Arthur S

    2012-01-01

    Chromosomal band 1q21.1 can be divided into two distinct regions, proximal and distal, based on segmental duplications that mediate recurrent rearrangements. Microdeletions and microduplications of the distal region within 1q21.1, which are susceptibility factors for a variety of neurodevelopmental phenotypes, have been more extensively studied than proximal microdeletions and microduplications. Proximal microdeletions are known as a susceptibility factor for thrombocytopenia-absent radius (TAR) syndrome, but it is unclear if these proximal microdeletions have other phenotypic consequences. Therefore, to elucidate the clinical significance of rearrangements of the proximal 1q21.1 region, we evaluated the phenotypes in patients identified with 1q21.1 rearrangements after referral for clinical microarray testing. We report clinical information for 55 probands with copy number variations (CNVs) involving proximal 1q21.1: 22 microdeletions and 20 reciprocal microduplications limited to proximal 1q21.1 and 13 microdeletions that include both the proximal and distal regions. Six individuals with proximal microdeletions have TAR syndrome. Three individuals with proximal microdeletions and two individuals with larger microdeletions of proximal and distal 1q21.1 have a ‘partial' TAR phenotype. Furthermore, one subject with TAR syndrome has a smaller, atypical deletion, narrowing the critical deletion region for the syndrome. Otherwise, phenotypic features varied among individuals with these microdeletions and microduplications. The recurrent, proximal 1q21.1 microduplications are enriched in our population undergoing genetic testing compared with control populations. Therefore, CNVs in proximal 1q21.1 can be a contributing factor for the development of abnormal phenotypes in some carriers. PMID:22317977

  12. Molecular cytogenetic determination of a deletion/duplication of 1q that results in a trisomy 18 syndrome-like phenotype

    SciTech Connect

    Mewar, R.; Harrison, W.; Weaver, D.D.; Palmer, C.; Davee, M.A.; Overhauser, J.

    1994-08-15

    We report on an infant who presented at birth with some characteristics of trisomy 18 syndrome, including low birth weight, facial abnormalities, overlapping fingers, and congenital heart defects. On chromosome analysis, no additional chromosome 18 was observed and both chromosome 18 homologues appeared normal. However, a small piece of chromosomal material of unknown origin was detected at the tip of the long arm of chromosome 1. Fluorescence in situ hybridization (FISH) using whole chromosome 18 painting probes disclosed no additional hybridization at the telomere of 1q, suggesting that the material was derived from another chromosome. Further chromosome painting experiments suggested that the telomeric addition was of chromosome 1 origin. To identify subchromosomal regions involved in the rearrangement, additional FISH analyses were performed using single copy and repetitive DNA probes mapping different portions of chromosome 1. The analyses showed that probes mapping to 1q34-43 were duplicated in the derivative chromosome 1. In addition, a DNA probe mapping to 1q44 was found to be deleted from the derivative chromosome 1. Our composite analysis suggests that a deletion and a duplication of chromosome 1q can result in some of the clinical findings usually associated with trisomy 16 syndrome. These results demonstrate the usefulness of FISH analysis when karyotype analysis is not consistent with the clinical description. 23 refs., 3 figs., 2 tabs.

  13. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    PubMed

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties. PMID:26079538

  14. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

    PubMed Central

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T.; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F.; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D.; Moriggl, Richard

    2015-01-01

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent “metastatic founder cells” which have invasive properties. PMID:26079538

  15. Proximal trisomy 1q in a girl with developmental delay and minor anomalies

    SciTech Connect

    Furforo, L. |; Rittler, M.; Slavutsky, I.R.

    1996-09-06

    We report on a girl with developmental delay, macrocephaly, facial asymmetry, small downturned palpebral fissures, high and narrow palate, micrognathia, short neck, a heart defect, and unilateral renal agenesis. Cytogenetic analysis showed a proximal tandem duplication of the long arm of chromosome one (1q12{r_arrow}q21.3). This abnormality was suggested by G-and C-banding but it was specifically characterized by fluorescent in situ hybridization (FISH). Clinical findings in our patient are compared with those of the literature in an attempt to delineate the phenotype in patients with proximal 1q duplication. 12 refs., 4 figs., 1 tab.

  16. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  17. Trisomy 1q32 and monosomy 11q25 associated with congenital heart defect: cytogenomic delineation and patient fourteen years follow-up

    PubMed Central

    2014-01-01

    Background Partial duplication 1q is a rare cytogenetic anomaly frequently associated to deletion of another chromosome, making it difficult to define the precise contribution of the different specific chromosomal segments to the clinical phenotype. Case presentation We report a clinical and cytogenomic study of a patient with multiple congenital anomalies, heart defect, neuromotordevelopment delay, intellectual disability, who presents partial trisomy 1q32 and partial monosomy 11q25 inherited from a paternal balanced translocation identified by chromosome microarray and fluorescence in situ hybridization. Conclusion Compared to patients from the literature, the patient’s phenotype is more compatible to the 1q32 duplication’s clinical phenotype, although some clinical features may also be associated to the deleted segment on chromosome 11. This is the smallest 11q terminal deletion ever reported and the first association between 1q32.3 duplication and 11q25 deletion in the literature. PMID:25184002

  18. Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes.

    PubMed

    Mesquita, Bárbara; Lopes, Paula; Rodrigues, Ana; Pereira, Deolinda; Afonso, Mariana; Leal, Conceição; Henrique, Rui; Lind, Guro E; Jerónimo, Carmen; Lothe, Ragnhild A; Teixeira, Manuel R

    2013-02-01

    Several ETS transcription factors are involved in the pathogenesis of human cancers by different mechanisms. As gene copy number gain/amplification is an alternative mechanism of oncogenic activation and 1q gain is the most common copy number change in breast carcinoma, we investigated how that genomic change impacts in the expression of the three 1q ETS family members ETV3, ELK4, and ELF3. We have first evaluated 141 breast carcinomas for genome-wide copy number changes by chromosomal CGH and showed that 1q21 and 1q32 were the two chromosome bands with most frequent genomic copy number gains. Second, we confirmed by FISH with locus-specific BAC clones that cases showing 1q gain/amplification by CGH showed copy number increase of the ETS genes ETV3 (located in 1q21~23), ELF3, and ELK4 (both in 1q32). Third, gene expression levels of the three 1q ETS genes, as well as their potential targets MYC and CRISP3, were evaluated by quantitative real-time PCR. We here show for the first time that the most common genomic copy number gains in breast cancer, 1q21 and 1q32, are associated with overexpression of the ETS transcription factors ETV3 and ELF3 (but not ELK4) at these loci irrespective of molecular subtypes. Among the three 1q ETS genes, ELF3 has a relevant role in breast carcinogenesis and is also the most likely target of the 1q copy number increase. The basal-like molecular subtype presented the worst prognosis regarding disease-specific survival, but no additional prognostic value was found for 1q copy number status or ELF3 expression. In addition, we show that there is a correlation between the expression of the oncogene MYC, irrespectively of copy number gain at its loci in 8q24, and the expression of both the transcriptional repressor ETV3 and the androgen respondent ELK4. PMID:23329352

  19. Interaction between complement subcomponent C1q and bacterial lipopolysaccharides.

    PubMed

    Zohair, A; Chesne, S; Wade, R H; Colomb, M G

    1989-02-01

    The heptose-less mutant of Escherichia coli, D31m4, bound complement subcomponent C1q and its collagen-like fragments (C1qCLF) with Ka values of 1.4 x 10(8) and 2.0 x 10(8) M-1 respectively. This binding was suppressed by chemical modification of C1q and C1qCLF using diethyl pyrocarbonate (DEPC). To investigate the role of lipopolysaccharides (LPS) in this binding, biosynthetically labelled [14C]LPS were purified from E. coli D31m4 and incorporated into liposomes prepared from phosphatidylcholine (PC) and phosphatidylethanolamine (PE) [PC/PE/LPS, 2:2:1, by wt.]. Binding of C1q or its collagen-like fragments to the liposomes was estimated via a flotation test. These liposomes bound C1q and C1qCLF with Ka values of 8.0 x 10(7) and 2.0 x 10(7) M-1; this binding was totally inhibited after chemical modification of C1q and C1qCLF by DEPC. Liposomes containing LPS purified from the wild-strain E. coli K-12 S also bound C1q and C1qCLF, whereas direct binding of C1q or C1qCLF to the bacteria was negligible. Diamines at concentrations which dissociate C1 into C1q and (C1r, C1s)2, strongly inhibited the interaction of C1q or C1qCLF with LPS. Removal of 3-deoxy-D-manno-octulosonic acid (2-keto-3-deoxyoctonic acid; KDO) from E. coli D31m4 LPS decreases the binding of C1qCLF to the bacteria by 65%. When this purified and modified LPS was incorporated into liposomes, the C1qCLF binding was completely abolished. These results show: (i) the essential role of the collagen-like moiety and probably its histidine residues in the interaction between C1q and the mutant D31m4; (ii) the contribution of LPS, particularly the anionic charges of KDO, to this interaction. PMID:2649081

  20. Chapter 15 Juvenile amyotrophic lateral sclerosis.

    PubMed

    Orban, Paul; Devon, Rebecca S; Hayden, Michael R; Leavitt, Blair R

    2007-01-01

    Several forms of genetically defined juvenile amy-otrophic lateral sclerosis (ALS) have now been charac-terized and discussion of these conditions will form the basis for this chapter. ALS2 is an autosomal recessive form of ALS with a juvenile onset and very slow progression that mapped to chromosome 2q33. Nine different mutations have been identified in the ALS2 gene that result in premature stop codons, suggesting a loss of function in the gene product, alsin. The alsin protein is thought to function as a guanine-nucleotide exchange factor for GTPases and may play a role in vesicle transport or membrane trafficking processes. ALS4 is an autosomal dominant form of juvenile onset ALS associated with slow progression, severe muscle weakness and pyramidal signs, in the absence of bulbar and sensory abnormalities. Mutations in the SETX gene cause ALS4, and the SETX gene product senataxin may have DNA and RNA helicase activity and play a role in the regulation of RNA and/or DNA in the cell. A third form of juvenile-onset ALS (ALS5) is associated with slowly progressing lower motor neuron signs (weak-ness and atrophy) initially of the hands and feet, with eventual bulbar involvement. Progressive upper motor neuron disease becomes more obvious with time. ALS5 has been linked to a 6 cM region of chromosome 15q15.1-q21.1, but the causative gene mutation for ALS5 has yet to be identified. The high degree of clin-ical and genetic heterogeneity in the various forms of juvenile ALS can make differential diagnosis difficult, other genetic disorders that must be considered include: spinal muscular atrophy, hereditary spastic paraplegia, SBMA, GM2 gangliosidosis and the hereditary motor neuronopathies/motor forms of Charcot-Marie-Tooth disease. Acquired disorders that must also be consid-ered include heavy metal intoxications (especially lead), multifocal motor neuropathy, paraneoplastic syndromes, vitamin deficiencies (B12) and infections (HTLV-II, HIV and poliomyelitis). PMID

  1. A family with an inverted tandem duplication 5q22.1q23.2.

    PubMed

    Schmidt, T; Bartels, I; Liehr, T; Burfeind, P; Zoll, B; Shoukier, M

    2013-01-01

    Here, we report a 3-year-old boy with short stature, developmental delay and mild facial dysmorphic signs. Karyotype analysis and array-CGH revealed a pure duplication 5q22.1q23.2 with a length of 14.25 Mb. As demonstrated by multicolor-fluorescence in situ hybridization, the duplicated segment was orientated in an inverted tandem manner. One of the 2 older half-brothers of the index patient was intellectually disabled and showed short stature as well. The mother of the siblings was only 149 cm in height. The affected half-brother as well as the mother of the siblings were tested positive for the same duplication. Duplications of the long arm of chromosome 5 are rare. There are 16 reported cases of different 5q segments with a pure duplication and no additional chromosomal imbalance. In order to refine the 5q-duplication phenotype, reported cases were recently classified in 3 groups on the basis of clinical findings and the involved chromosome segments. However, our case does not fit in any of these groups but is placed in the interjacent chromosomal area between 2 of these groups. Overall, this is the second reported family with a duplication of 5q22.1q23.2 and both families share phenotypic features like short stature, facial dysmorphic signs and speech delay. The reported family provides further information for delineating phenotype-genotype correlations of pure duplications of the 5q region. PMID:23051634

  2. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  3. Anti-C1q in systemic lupus erythematosus.

    PubMed

    Stojan, G; Petri, M

    2016-07-01

    C1q is the first component of the classical complement pathway. Both clinically validated in-house ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays. PMID:27252264

  4. KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers.

    PubMed

    Corson, Timothy W; Huang, Annie; Tsao, Ming-Sound; Gallie, Brenda L

    2005-07-14

    Gain of chromosome 1q31-1q32 is seen in >50% of retinoblastoma and is common in other tumors. To define the minimal 1q region of gain, we determined genomic copy number by quantitative multiplex PCR of 14 sequence tagged sites (STSs) spanning 1q25.3-1q41. The most frequently gained STS at 1q32.1 (71%; 39 of 55 retinoblastoma) defined a 3.06 Mbp minimal region of gain between flanking markers, containing 14 genes. Of these, only KIF14, a putative chromokinesin, was overexpressed in various cancers by real-time RT-PCR. KIF14 mRNA was expressed in 20/22 retinoblastoma samples 100-1000-fold higher than in retina (t-test P=0.00002); cell lines (n=10) had higher levels than tumors (n=12) (P=0.009). KIF14 protein was overexpressed in retinoblastoma tumors and breast cancer cell lines by immunoblot. KIF14 was expressed in 4/4 breast cancer cell lines 31-92-fold higher than in normal breast tissue, in 5/5 medulloblastoma cell lines 22-79-fold higher than in fetal brain, and in 10/22 primary lung tumors 3-34-fold higher than in normal lung. Patients with lung tumors that overexpress KIF14 showed a trend toward decreased survival. KIF14 may thus be important in oncogenesis, and has promise as a prognostic indicator and therapeutic target. PMID:15897902

  5. Three novel C1q domain containing proteins from the disk abalone Haliotis discus discus: Genomic organization and analysis of the transcriptional changes in response to bacterial pathogens.

    PubMed

    Bathige, S D N K; Umasuthan, Navaneethaiyer; Jayasinghe, J D H E; Godahewa, G I; Park, Hae-Chul; Lee, Jehee

    2016-09-01

    The globular C1q (gC1q) domain containing proteins, commonly referred as C1q domain containing (C1qDC) proteins, are an essential family of proteins involved in various innate immune responses. In this study, three novel C1qDC proteins were identified from the disk abalone (Haliotis discus discus) transcriptome database and designated as AbC1qDC1, AbC1qDC2, and AbC1qDC3. The cDNA sequences of AbC1qDC1, AbC1qDC2, and AbC1qDC3 consisted of 807, 1305, and 660 bp open reading frames (ORFs) encoding 269, 435, and 220 amino acids (aa), respectively. Putative signal peptides and the N-terminal gC1q domain were identified in all three AbC1qDC proteins. An additional predicted motif region, known as the coiled coil region (CCR), was identified next to the signal sequence of AbC1qDC2. The genomic organization of the AbC1qDCs was determined using a bacterial artificial chromosome (BAC) library. It was found that the CDS of AbC1qDC1 was distributed among three exons, while the CDSs of AbC1qDC2 and AbC1qDC3 were distributed between two exons. Sequence analysis indicated that the AbC1qDC proteins shared <40% identity with other counterparts from different species. According to the neighbor-joining phylogenetic tree, the proteins were grouped within an invertebrate group with high evolutionary distances, which suggests that they are new members of the C1qDC family. Higher expression of AbC1qDC1 and AbC1qDC2 was detected in hepatopancreas, muscle, and mantle tissues compare to the other tissues analyzed, using reverse transcription, followed by quantitative real-time PCR (qPCR) using SYBR Green, whereas AbC1qDC3 was predominantly expressed in gill tissues, followed by muscles and the hepatopancreas. The temporal expression of AbC1qDC transcripts in gills after bacterial (Vibrio parahaemolyticus and Listeria monocytogenes) and lipopolysaccharide stimulation indicated that AbC1qDCs can be strongly induced by both Gram-negative and Gram-positive bacterial species with different

  6. Fundamental role of C1q in autoimmunity and inflammation

    PubMed Central

    Son, Myoungsun; Santiago-Schwarz, Frances

    2016-01-01

    C1q, historically viewed as the initiating component of the classical complement pathway, also exhibits a variety of complement-independent activities in both innate and acquired immunity. Recent studies focusing on C1q’s suppressive role in the immune system have provided new insight into how abnormal C1q expression and bioactivity may contribute to autoimmunity. In particular, molecular networks involving C1q interactions with cell surface receptors and other ligands are emerging as mechanisms involved in C1q’s modulation of immunity. Here, we discuss the role of C1q in controlling immune cell function, including recently elucidated mechanisms of action, and suggest how these processes are critical for maintaining tissue homeostasis under steady-state conditions and in preventing autoimmunity. PMID:26410546

  7. Genetics Home Reference: 1q21.1 microdeletion

    MedlinePlus

    ... 1 region may also be risk factors for schizophrenia. Some people with a 1q21.1 microdeletion do ... D, Stefansson K. Large recurrent microdeletions associated with schizophrenia. Nature. 2008 Sep 11;455(7210):232-6. ...

  8. Isochromosome 1q as an early genetic event in a child with intracranial ependymoma characterized by molecular cytogenetics.

    PubMed

    Granzow, M; Popp, S; Weber, S; Schoell, B; Holtgreve-Grez, H; Senf, L; Hager, D; Boschert, J; Scheurlen, W; Jauch, A

    2001-10-01

    Data concerning cytogenetic features of childhood ependymoma are rare. In this article, a gain of 1q was identified as the sole alteration in a primary childhood infratentorial ependymoma by comparative genomic hybridization (CGH). A recurrence of this brain tumor was studied using multiplex-fluorescence in situ hybridization (M-FISH) in addition to CGH and G-banding analysis. In accordance with the primary tumor, a gain of 1q corresponding to an isochromosome 1q was observed indicating an early event in the tumor development. Furthermore, M-FISH classified several other rearranged chromosomes including 6q and 17p that have previously been found to be involved in the development and progression of childhood ependymoma. PMID:11672779

  9. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.

    PubMed

    Brunetti-Pierri, Nicola; Berg, Jonathan S; Scaglia, Fernando; Belmont, John; Bacino, Carlos A; Sahoo, Trilochan; Lalani, Seema R; Graham, Brett; Lee, Brendan; Shinawi, Marwan; Shen, Joseph; Kang, Sung-Hae L; Pursley, Amber; Lotze, Timothy; Kennedy, Gail; Lansky-Shafer, Susan; Weaver, Christine; Roeder, Elizabeth R; Grebe, Theresa A; Arnold, Georgianne L; Hutchison, Terry; Reimschisel, Tyler; Amato, Stephen; Geragthy, Michael T; Innis, Jeffrey W; Obersztyn, Ewa; Nowakowska, Beata; Rosengren, Sally S; Bader, Patricia I; Grange, Dorothy K; Naqvi, Sayed; Garnica, Adolfo D; Bernes, Saunder M; Fong, Chin-To; Summers, Anne; Walters, W David; Lupski, James R; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita

    2008-12-01

    Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity. PMID:19029900

  10. A patient with constitutional ring 1 chromosome characterized by SNP array CGH.

    PubMed

    Saliganan, Sheila; Lee, Joanna; Wei, Sainan

    2016-04-01

    We present a male patient with constitutional ring 1 chromosome and subsequent 6 Mb deletion at 1q43q44. The patient displays overlapping clinical features with reported patients with ring 1 chromosome and 1q43q44 microdeletion syndrome. To our knowledge, this is the first patient with ring 1 chromosome characterized by comparative genomic hybridization. PMID:27099748

  11. Emerging and Novel Functions of Complement Protein C1q

    PubMed Central

    Kouser, Lubna; Madhukaran, Shanmuga Priyaa; Shastri, Abhishek; Saraon, Anuvinder; Ferluga, Janez; Al-Mozaini, Maha; Kishore, Uday

    2015-01-01

    Complement protein C1q, the recognition molecule of the classical pathway, performs a diverse range of complement and non-complement functions. It can bind various ligands derived from self, non-self, and altered self and modulate the functions of immune and non-immune cells including dendritic cells and microglia. C1q involvement in the clearance of apoptotic cells and subsequent B cell tolerance is more established now. Recent evidence appears to suggest that C1q plays an important role in pregnancy where its deficiency and dysregulation can have adverse effects, leading to preeclampsia, missed abortion, miscarriage or spontaneous loss, and various infections. C1q is also produced locally in the central nervous system, and has a protective role against pathogens and possible inflammatory functions while interacting with aggregated proteins leading to neurodegenerative diseases. C1q role in synaptic pruning, and thus CNS development, its anti-cancer effects as an immune surveillance molecule, and possibly in aging are currently areas of extensive research. PMID:26175731

  12. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  13. Burkitt-Type Acute Lymphoblastic Leukemia With Precursor B-Cell Immunophenotype and Partial Tetrasomy of 1q: A Case Report.

    PubMed

    Sato, Yuya; Kurosawa, Hidemitsu; Fukushima, Keitaro; Okuya, Mayuko; Arisaka, Osamu

    2016-03-01

    Burkitt-type acute lymphoblastic leukemia (B-ALL) is thought as a variant of Burkitt lymphoma/leukemia and derived from mature B-cell lymphoblast.B-ALL was developed in a 10-year-old girl. Two characteristics were apparent in this case. First, the lymphoblastic cells were positive for CD10, CD19, CD20, and CD22, but negative for terminal deoxynucleotidyl transferase and surface immunoglobulins, indicating a B-cell immunophenotype. The detection of t(8;14)(q24;q32) with a chromosomal analysis is required for a diagnosis of B-ALL. Second, der(1)(pter → q32.1::q32.1 → q21.1::q11 → qter) was detected, in which 1q21.1 to 1q32.1 was inverted and inserted. Finally, partial tetrasomy of 1q was also present. Because B-ALL with abnormal chromosome 1 has been reported poor outcome, the usual chemotherapy for stage 4 Burkitt lymphoma with added rituximab was administered for our patient.We report B-ALL with precursor B-cell immunophenotype and interesting partial tetrasomy of 1q. PMID:26962787

  14. C1q Nephropathy: The Unique Underrecognized Pathological Entity.

    PubMed

    Devasahayam, Joe; Erode-Singaravelu, Gowrishankar; Bhat, Zeenat; Oliver, Tony; Chandran, Arul; Zeng, Xu; Dakshinesh, Paramesh; Pillai, Unni

    2015-01-01

    C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and proliferative glomerulonephritis. Clinical presentation is also diverse, and ranges from asymptomatic hematuria or proteinuria to frank nephritic or nephrotic syndrome in both children and adults. Hypertension and renal insufficiency at the time of diagnosis are common findings. Optimal treatment is not clear and is usually guided by the underlying light microscopic lesion. Corticosteroids are the mainstay of treatment, with immunosuppressive agents reserved for steroid resistant cases. The presence of nephrotic syndrome and FSGS appear to predict adverse outcomes as opposed to favorable outcomes in those with MCD. Further research is needed to establish C1q nephropathy as a universally recognized distinct clinical entity. In this paper, we discuss the current understanding of pathogenesis, histopathology, clinical features, therapeutic options, and outcomes of C1q nephropathy. PMID:26640759

  15. Attenuation (1/Q) estimation in reflection seismic records

    NASA Astrophysics Data System (ADS)

    Raji, Wasiu; Rietbrock, Andreas

    2013-08-01

    Despite its numerous potential applications, the lack of a reliable method for determining attenuation (1/Q) in seismic data is an issue when utilizing attenuation for hydrocarbon exploration. In this paper, a new method for measuring attenuation in reflection seismic data is presented. The inversion process involves two key stages: computation of the centroid frequency for the individual signal using a variable window length and fast Fourier transform; and estimation of the difference in the centroid frequency and travel time for paired incident and transmitted signals. The new method introduces a shape factor and a constant which allows several spectral shapes to be used to represent a real seismic signal without altering the mathematical model. Application of the new method to synthetic data shows that it can provide reliable estimates of Q using any of the spectral shapes commonly assumed for real seismic signals. Tested against two published methods of Q measurement, the new method shows less sensitivity to interference from noise and change of frequency bandwidth. The method is also applied to a 3D data set from the Gullfaks field, North Sea, Norway. The trace length is divided into four intervals: AB, BC, CD, and DE. Results show that interval AB has the lowest 1/Q value, and that interval BC has the highest 1/Q value. The values of 1/Q measured in the CDP stack using the new method are consistent with those measured using the classical spectral ratio method.

  16. A 54 Mb 11qter duplication and 0.9 Mb 1q44 deletion in a child with laryngomalacia and agenesis of corpus callosum

    PubMed Central

    2011-01-01

    Background Partial Trisomy 11q syndrome (or Duplication 11q) has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD). Deletion 1q44 (or Monosomy 1q44) is a well-defined syndrome, but there is controversy about the genes lying in 1q44 region, responsible for agenesis of the corpus callosum. We report a female child with the rare Partial Trisomy 11q syndrome and Deletion 1q44 syndrome. The genomic imbalance in the proband was used for molecular characterization of the critical genes in 1q44 region for agenesis of corpus callosum. Some genes in 11q14q25 may be responsible for laryngomalacia. Results We report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1)t(1;11)(q44;q14)pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11)(q44;q14). SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter. Conclusion Laryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region. PMID:21936942

  17. Characterization of the murine gene of gC1qBP, a novel cell protein that binds the globular heads of C1q, vitronectin, high molecular weight kininogen and factor XII.

    PubMed

    Lim, B L; White, R A; Hummel, G S; Schwaeble, W; Lynch, N J; Peerschke, E I; Reid, K B; Ghebrehiwet, B

    1998-03-16

    gC1qBP is a novel cell protein which was found to interact with the globular heads of C1q, high mol. wt kininogen, factor XII and the heparin-binding, multimeric form of vitronectin. The protein sequence shows no homology to any protein family. This paper describes the genomic organization of mouse gC1qBP and the characterization of its 5' flanking region. The mouse gene consists of six exons separated by five introns, and its total length is approximately 6kb. Exon 1 encodes the putative signal peptide, a long stretch of 70 amino acid residues, and the first four amino acid residues found in the mature gC1qBP. Exons 2-5 encode four very hydrophilic domains, whereas exon 6 encodes a neutral domain. The amino acid sequence responsible for binding to the heparin-binding, multimeric form of vitronectin is located in exon 2. A 1kb DNA fragment upstream of the first initiation codon was sequenced, which contained four potential TATA boxes, seven CAAT boxes, six SP1 sites and various putative transcription factor-binding elements, indicating that the promoter region is in close proximity to the first exon. The mouseC1qbp gene was mapped to chromosome 11, closely linked to D11Mit4 using genomic DNAs from a (C57BL/6J x Mus spretus)F1 x Mus spretus backcross. PMID:9524273

  18. Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

    PubMed Central

    2012-01-01

    Background In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS) after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR), which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Methods Recombinant HmC1q (rHmC1q) was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. Results rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. Conclusions A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal leech. PMID:22356764

  19. Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region

    SciTech Connect

    Elmslie, F.V.; Williamson, M.P.; Rees, M.

    1996-09-01

    Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated {open_quotes}EJM1{close_quotes}), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried out under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score <-2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, {alpha} - that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions. 24 refs., 4 figs., 1 tab.

  20. Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myocloni epilepsy: No evidence for an epilepsy locus in the HLA region

    SciTech Connect

    Whitehouse, W.P.; Rees, M.; Curtis, D.; Sundqvist, A.; Parker, K.; Chung, E.; Baralle, D.; Gardiner, R.M.

    1993-09-01

    Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6889, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype. 39 refs., 4 figs., 2 tabs.

  1. Rieger syndrome with de Novo reciprocal translocation t(1;4) (q23.1;q25)

    SciTech Connect

    Makita, Yoshio; Masuno, Mitsuo; Imaizumi, Kiyoshi

    1995-05-22

    We report on a boy with Rieger syndrome, who had an apparently balanced reciprocal translocation between chromosomes 1 and 4. The clinical manifestations of this patient were characterized by irregular shaped pupils with a prominent Schwalbe line and an umbilical hernia. On cytogenetic studies, he was found to have a de novo reciprocal translocation 46,XY,t(1;4) (q23.1;q25), without visible deletion. His parents had normal chromosomes. A review of both cytogenetic and genetic linkage analyses with Rieger syndrome showed that chromosome 4q was involved. This and other previous reports suggested that the gene for Rieger syndrome is mapped to the 4q25{r_arrow}4q26 segment adjoining the breakpoint. 14 refs., 3 figs., 1 tab.

  2. Trisomy 1q42{r_arrow}qter in a sister and brother: Further delineation of the {open_quotes}trisomy 1q42{r_arrow}qter syndrome{close_quotes}

    SciTech Connect

    Verschuuren-Bemelmans, C.C.; Leegte, B.; Hodenius, T.M.J.

    1995-07-31

    We report on a 22-year-old woman and her 21-year-old brother with mild mental retardation, long face, prominent forehead, retrognathia, and (relative) macrocephaly. At birth they were small for date, their length is now below the 10th centile. Chromosome analysis demonstrated a nearly pure trisomy 1q42{r_arrow}qter in both patients due to unbalanced segregation of a paternal reciprocal balanced translocation 46,XY,t(1;15) (q42;p11). This is the second report of a nearly pure trisomy 1q42{r_arrow}qter. When comparing the manifestations of our patients with those of other reported cases we conclude that the most characteristic clinical manifestations of this syndrome are macrocephaly, prominent forehead, micro/retrognathia, large fontanelle, intrauterine growth retardation, postnatal growth retardation, and mental retardation. 56 refs., 4 figs., 1 tab.

  3. L-C1qDC-1, a novel C1q domain-containing protein from Lethenteron camtschaticum that is involved in the immune response.

    PubMed

    Pei, Guangying; Liu, Ge; Pan, Xiong; Pang, Yue; Li, Qingwei

    2016-01-01

    The C1q domain-containing (C1qDC) proteins are a family of proteins characterized by a globular C1q (gC1q) domain at their C-terminus. These proteins are involved in various processes in vertebrates and are assumed to serve as important pattern recognition receptors in innate immunity in invertebrates. Here, a novel C1qDC protein from Lethenteron camtschaticum was identified and characterized (designated as L-C1qDC-1). After a partial cDNA sequence of L-C1qDC-1 was identified in a L. camtschaticum liver cDNA library, the full-length cDNA was obtained using 3'- and 5'-rapid amplification of cDNA ends (RACE). L-C1qDC-1 encodes 236 amino acids and contains a signal peptide, a collagen-like sequence with Gly-Xaa-Yaa repeats, and a C-terminal gC1q domain. The L-C1qDC-1 protein was primarily distributed in the gut, liver and supraneural body of L. camtschaticum and was also marginally detectable in leukocytes via real-time PCR and immunofluorescence assays. Furthermore, both immunoprecipitation and immunofluorescence results showed that in L. camtschaticum serum, L-C1qDC-1 could interact with variable lymphocyte receptor (VLR) B and displayed strong colocalization with cancer cell immune responses. These results indicated that the L-C1qDC-1 gene encodes a novel C1qDC protein that may play an important role in the immune responses of L. camtschaticum, providing clues for understanding the universal functions of C1qDC proteins in other species and suggesting that these proteins could serve as pattern recognition molecules in immunotherapy. PMID:26342581

  4. Juvenile Arthritis

    MedlinePlus

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

  5. Macrocerebellum, Epilepsy, Intellectual Disability and Gut Malrotation in a Child with a 16q24.1-q24.2 Contiguous Gene Deletion

    PubMed Central

    Seeley, Andrea H.; Durham, Mark A.; Micale, Mark A.; Wesolowski, Jeffrey; Foerster, Bradley R.; Martin, Donna M.

    2014-01-01

    Macrocerebellum is an extremely rare condition characterized by enlargement of the cerebellum with conservation of the overall shape and cytoarchitecture. Here, we report a child with a distinctive constellation of clinical features including macrocerebellum, epilepsy, apparent intellectual disability, dysautonomia, gut malrotation, and poor gut motility. Oligonucleotide chromosome microarray analysis identified a 16q24.1-q24.2 deletion that included four OMIM genes (FBXO31, MAP1LC3B, JPH3, and SLC7A5). Review of prior studies describing individuals with similar or overlapping16q24.1-q24.2 deletions identified no other reports of macrocerebellum. These observations highlight a potential genetic cause of this rare disorder and raise the possibility that one or more gene(s) in the 16q24.1-q24.2 interval regulate cerebellar development. PMID:24719385

  6. [C1Q NEPHROPATHY: CASE REPORTS AND LITERATURE REVIEW].

    PubMed

    Galešić, Krešimir; Horvatić, Ivica; Batinić, Danica; Milošević, Danko; Saraga, Marijan; Durdov, Merica Glavina; Ljubanović, Danica Galešić

    2015-01-01

    C1q nephropathy is considered a form of glomerulonephritis, defined by histological findings of dominant Clq immune deposits in renal biopsy. It is a rare disease, most often manifested in children and young adults. The most common clinical manifestation of the disease is nephrotic syndrome, but other renal syndromes could also be found. The cause of the disease is not known, but the immune pathogenesis could be assumed. Often, resistance to glucocorticoid or other immunosuppressive therapy is present, potentially leading to chronic renal insufficiency. We present ten patients with renal biopsy and clinical findings of Clq nephropathy. None of the patients had clinical or serological manifestations of systemic lupus. All patients had normal findings of C3 and C4 components of complement, as well as normal ANF, anti-dsD-NA and ANCA antibodies. PMID:26749950

  7. Human diploid fibroblasts have receptors for the globular domain of C1Q

    SciTech Connect

    Bordin, S.; Page, R.C.

    1986-03-01

    The authors showed that mass cultures of fibroblasts grown from gingival explants in DB medium with 10% human serum are enriched in a phenotype that binds C1q with an affinity much higher than the rest of the population. Because of potential biologic importance of C1q receptors, the authors studied whether the interaction between C1q and this phenotype was mediated by the globular or collagenous domains of the molecule. Globular fragments were prepared by digesting C1q with collagenase, and collagenous fragments obtained after pepsin treatment. C1q binding on cells in suspension was determined by reaction with /sup 125/I-C1q as reported. Competition experiments were performed under conditions in which intact /sup 125/I-C1q binding saturated all available receptors. The results showed that collagenous fragments inhibited 20% of the /sup 125/I-C1q binding to high affinity receptors, whereas inhibition by globular fragments was 70%. Unlabeled intact C1q and collagen type 1 were used as controls, and inhibited 92% and 17% of C1q binding, respectively. These studies show that C1q interacts with the fibroblast phenotype expressing high affinity receptors through its globular domain. The authors suggest that at sites of trauma, native C1 may bind to the surface of these cells via the globular domain of C1q, and that this unique phenotype may play an important role in tissue repair.

  8. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome.

    PubMed

    Wisnieski, J J; Naff, G B

    1989-09-01

    Urticaria, angioedema, and arthritis are cardinal features of hypocomplementemic urticarial vasculitis syndrome (HUVS). Considered to be an immune complex-mediated disorder, HUVS has been differentiated from systemic lupus erythematosus (SLE), based on its clinical manifestations and the C1q precipitin (C1q-p) reaction, which is manifested as gel precipitation of C1q by a small percentage of HUVS IgG molecules. This phenomenon has been attributed to an Fc region abnormality, and the responsible IgG molecules are said to possess C1q-p activity. We purified IgG from 4 HUVS patients and confirmed that HUVS IgG contains C1q binding activity. F(ab')2 fragments from these patients also bound to C1q, as measured by 2 different C1q binding methods at physiologic ionic strength; HUVS IgG Fc fragments did not bind to C1q. Preincubation of HUVS F(ab')2 fragments with antibody to human F(ab')2 prevented subsequent binding to C1q. We conclude that IgG antibodies to C1q are present in HUVS serum, and it is likely that these antibodies are C1q-p. Because the clinical manifestations of HUVS and the presence of anti-C1q antibodies have been described in patients with SLE, our findings support the concept that HUVS is an autoimmune syndrome related to SLE. PMID:2528353

  9. A new mosaic der(18)t(1;18)(q32.1;q21.3) with developmental delay and facial dysmorphism.

    PubMed

    Choi, Young-Jin; Shin, Eunsim; Jo, Tae Sik; Moon, Jin-Hwa; Lee, Se-Min; Kim, Joo-Hwa; Oh, Jae-Won; Kim, Chang-Ryul; Seol, In Joon

    2016-02-01

    We report the case of a 22-month-old boy with a new mosaic partial unbalanced translocation of 1q and 18q. The patient was referred to our Pediatric Department for developmental delay. He showed mild facial dysmorphism, physical growth retardation, a hearing disability, and had a history of patent ductus arteriosus. White matter abnormality on brain magnetic resonance images was also noted. His initial routine chromosomal analysis revealed a normal 46,XY karyotype. In a microarray-based comparative genomic hybridization (aCGH) analysis, subtle copy number changes in 1q32.1-q44 (copy gain) and 18q21.33-18q23 (copy loss) suggested an unbalanced translocation of t(1;18). Repeated chromosomal analysis revealed a low-level mosaic translocation karyotype of 46,XY,der(18)t(1;18)(q32.1;q21.3)[12]/46,XY[152]. Because his parents had normal karyotypes, his translocation was considered to be de novo. The abnormalities observed in aCGH were confirmed by metaphase fluorescent in situ hybridization. We report this patient as a new karyotype presenting developmental delay, facial dysmorphism, cerebral dysmyelination, and other abnormalities. PMID:26958068

  10. Juvenile Firesetting.

    PubMed

    Peters, Brittany; Freeman, Bradley

    2016-01-01

    Juvenile firesetting is a significant cause of morbidity and mortality in the United States. Male gender, substance use, history of maltreatment, interest in fire, and psychiatric illness are commonly reported risk factors. Interventions that have been shown to be effective in juveniles who set fires include cognitive behavior therapy and educational interventions, whereas satiation has not been shown to be an effective intervention. Forensic assessments can assist the legal community in adjudicating youth with effective interventions. Future studies should focus on consistent assessment and outcome measures to create more evidence for directing evaluation and treatment of juvenile firesetters. PMID:26593122

  11. Interstitial 1q23.3q24.1 deletion in a patient with renal malformation, congenital heart disease, and mild intellectual disability.

    PubMed

    Mackenroth, Luisa; Hackmann, Karl; Klink, Barbara; Weber, Julia Sara; Mayer, Brigitte; Schröck, Evelin; Tzschach, Andreas

    2016-09-01

    Interstitial deletions including chromosome region 1q23.3q24.1 are rare. Only eight patients with molecularly characterized deletions have been reported to date. Their phenotype included intellectual disability/developmental delay, growth retardation, microcephaly, congenital heart disease, and renal malformations. We report on a female patient with mild developmental delay, congenital heart disease, and bilateral renal hypoplasia in whom an interstitial de novo deletion of approximately 2.7 Mb in 1q23.3q24.1 was detected by array CGH. This is the smallest deletion described in this region so far. Genotype-phenotype comparison with previously published patients allowed us to propose LMX1A and RXRG as potential candidate genes for intellectual disability, PBX1 as a probable candidate gene for renal malformation, and enabled us to narrow down a chromosome region associated with microcephaly. © 2016 Wiley Periodicals, Inc. PMID:27255444

  12. Juvenile Prostitution.

    ERIC Educational Resources Information Center

    Csapo, Marg

    1986-01-01

    Recent research and Canadian government committee reports concerning juvenile prostitution are reviewed. Proposals are made in the realms of law and social policy; and existing programs are described. (DB)

  13. A MOLECULARLY CHARACTERIZED INTERSTITIAL DELETION ENCOMPASSING THE 11q14.1-q23.3 REGION IN A CASE WITH MULTIPLE CONGENITAL ABNORMALITIES.

    PubMed

    Cetin, Z; Altiok-Clark, O; Yakut, S; Guzel-Nur, B; Mihci, E; Berker-Karauzum, S

    2016-01-01

    Interstitial deletion of chromosome 11 long arm is a rare event. In most of the interstitial deletions on the long arm of chromosome 11 both the position and the size of these deletions are heterogeneous making a precise karyotype-phenotype correlation. In only a few of the reported cases has the deletion been molecularly characterized. Our patient was a 13-year-old male presented; mental motor retardation, strabismus, myopia, retinopathy, sensorineural hearing loss, a long and triangular face, a broad forehead, hypotelorism, nasal septal deviation, a beaked nose, hypoplastic ala nasie, bilateral low-set ears, a high arched palate, crowded teeth, retrognathia, thin lips, a long neck, and sloping shoulders, hyperactive behavior, pulmonary stenosis and lumbar scoliosis. Conventional cytogenetic analysis revealed 46,XY,del(11)(q14.1-q23.3) karyotype in the patient. Array-CGH analysis of the patient's DNA revealed an interstitial deletion encompassing 33.2 Mb in the 11q14.1-q23.3 genomic region (chr11: 83,161,443-116,401,751 ; Hg19). In this report, we present a patient with an interstitial deletion on the long arm of chromosome 11 that encompassed the 11q14.1-q23.3 region; and, using array-CGH analysis, we molecularly characterized the deleted region. PMID:27192892

  14. Juvenile idiopathic arthritis

    MedlinePlus

    Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ... The cause of juvenile idiopathic arthritis (JIA) is not known. It ... illness . This means the body attacks and destroys healthy body ...

  15. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  16. Genetic heterogeneity in juvenile NCL

    SciTech Connect

    Hart, Y.M.; Andermann, E.; Mitchison, H.M.

    1994-09-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while the gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.

  17. C1q component of complement binds to fibrinogen and fibrin

    SciTech Connect

    Entwistle, R.A.; Furcht, L.T.

    1988-01-12

    The interaction of complement component C1q with fibrinogen and fibrin was studied by using a solid-phase direct binding assay. Scatchard analysis of radioiodinated fibrinogen binding to C1q indicated at least two high-affinity binding constants (Kd) calculated as 8.5 and 120 nM. In contrast, binding of radioiodinated fibrin to C1q showed only a single class of binding sites with a calculated Kd of 600 nM. Fibrinogen-C1q binding was shown to decrease as a function of increasing salt concentrations, indicating either the presence of charged amino acids in the binding sites or an ionic strength induced conformational dependency of the binding. In direct binding studies using isolated fragments of C1q, both the collagen-like domain of C1q and the globular domains of C1q were shown to bind fibrinogen, indicating at least one binding site for fibrinogen is located in each of the major domains of C1q. Addition of the thrombin-generated peptides of fibrinogen, fibrinopeptides A and B, enhanced C1q-fibrinogen binding, again indicating a complex binding interaction. These results indicate that C1q and fibrinogen are capable of high-affinity interactions that may serve to sequester these complexes in areas of tumors, immune complex deposition, or wounds.

  18. Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

    PubMed Central

    Zhang, Mingxia; Liu, Haiying; Zhang, Guoliang; Deng, Qunyi; Huang, Jian; Gao, Zhiliang; Zhou, Boping; Feng, Carl G.; Chen, Xinchun

    2014-01-01

    Background Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. Methods Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. Results C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. Conclusions C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. PMID:24647646

  19. A 6q14.1-q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain.

    PubMed

    Quintela, Ines; Fernandez-Prieto, Montse; Gomez-Guerrero, Lorena; Resches, Mariela; Eiris, Jesus; Barros, Francisco; Carracedo, Angel

    2015-06-01

    We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1-q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate. PMID:26185640

  20. A 6q14.1-q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

    PubMed Central

    Quintela, Ines; Fernandez-Prieto, Montse; Gomez-Guerrero, Lorena; Resches, Mariela; Eiris, Jesus; Barros, Francisco; Carracedo, Angel

    2015-01-01

    Key Clinical Message We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1-q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate. PMID:26185640

  1. An unusual three-way translocation t(21;8;1)(q22;q22;q32) in a case of acute myeloid leukemia (M2).

    PubMed

    Gmidène, Abir; Sennana, Hlima; Frikha, Rim; Elloumi, Moez; Belaaj, Hatem; Saad, Ali

    2012-01-01

    Variant forms of the classic translocation t(8;21) are uncommon and account approximately 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. These forms involve chromosomes 8, 21, and other chromosomes. Here we report a Tunisian patient with a complex rearrangement t(21;8;1)(q22;q22;q32) revealed by conventional chromosomal study at diagnosis. Fluorescence in situ hybridization study revealed the presence of the AML1-ETO chimeric gene on the derivative chromosome 8. To the best of our knowledge, this is the second case of t(21;8;1) of AML-M2 reported in the literature with the involvement of the same breakpoint at 1q32. This illustrates that this complex translocation is rarely encountered in AML and reinforces the fact that this region may harbour a critical gene candidate that may play an important role in the pathogenesis of AML. More cases are needed to elucidate its clinical features and prognosis. PMID:22484534

  2. Juvenile Spondyloarthritis

    PubMed Central

    Gmuca, Sabrina; Weiss, Pamela F.

    2015-01-01

    Purpose of review To provide a comprehensive update of the pathogenesis, diagnostic imaging, treatments, and disease activity measurements of juvenile spondyloarthritis (JSpA). Recent findings Genetic and microbiome studies have provided new information regarding possible pathogenesis of JSpA. Recent work suggests that children with JSpA have decreased thresholds for pain in comparison to healthy children. Additionally, pain on physical examination and abnormalities on ultrasound of the entheses are not well correlated. Treatment guidelines for juvenile arthritis, including JSpA, were published by the American College of Rheumatology and are based on active joint count and presence of sacroiliitis. Recent studies have established the efficacy of tumor necrosis factor inhibitors in the symptomatic treatment of axial disease, though their efficacy for halting progression of structural damage is less clear. Newly developed disease activity measures for JSpA include the Juvenile Arthritis Disease Activity Score and the JSpA Disease Activity index. In comparison to other categories of juvenile arthritis, children with JSpA are less likely to attain and sustain inactive disease. Summary Further microbiome and genetic research may help elucidate JSpA pathogenesis. More randomized therapeutic trials are needed and the advent of new composite disease activity measurement tools will hopefully allow for the design of these greatly needed trials. PMID:26002028

  3. Four C1q domain-containing proteins involved in the innate immune response in Hyriopsis cumingii.

    PubMed

    Zhao, Ling-Ling; Jin, Min; Li, Xin-Cang; Ren, Qian; Lan, Jiang-Feng

    2016-08-01

    C1q is a key subcomponent of the complement C1 complex. This subcomponent contains a globular C1q (gC1q) domain with remarkable ligand binding properties. C1q domain-containing (C1qDC) proteins are composed of all proteins with a gC1q domain. C1qDC proteins exist in many invertebrates and recognize non-self-ligands. In our study, four C1qDC genes, namely, HcC1qDC1-HcC1qDC4, were identified from Hyriopsis cumingii. HcC1qDC1-HcC1qDC4 encode a protein of 224, 204, 305, and 332 amino acids, respectively. All C1qDC proteins consist of a gC1q domain at the C terminal. In addition to the gC1q domain, a coiled-coil region is found in HcC1qDC4. Multiple alignments and phylogenetic tree analysis revealed that the C1qDC proteins highly differ from one another. Tissue distribution analysis demonstrated that HcC1qDC1-HcC1qDC4 are widely distributed in hemocytes, hepatopancreas, gills, mantle, and foot. These C1qDC genes are regulated by bacteria to varying degrees. These recombinant HcC1qDC proteins exhibit a binding activity against different bacterial species. Our results may suggest the roles of HcC1qDC genes in anti-bacterial immune defense. PMID:27288256

  4. A new mosaic der(18)t(1;18)(q32.1;q21.3) with developmental delay and facial dysmorphism

    PubMed Central

    Choi, Young-Jin; Shin, Eunsim; Jo, Tae Sik; Lee, Se-Min; Kim, Joo-Hwa; Oh, Jae-Won; Kim, Chang-Ryul; Seol, In Joon

    2016-01-01

    We report the case of a 22-month-old boy with a new mosaic partial unbalanced translocation of 1q and 18q. The patient was referred to our Pediatric Department for developmental delay. He showed mild facial dysmorphism, physical growth retardation, a hearing disability, and had a history of patent ductus arteriosus. White matter abnormality on brain magnetic resonance images was also noted. His initial routine chromosomal analysis revealed a normal 46,XY karyotype. In a microarray-based comparative genomic hybridization (aCGH) analysis, subtle copy number changes in 1q32.1–q44 (copy gain) and 18q21.33–18q23 (copy loss) suggested an unbalanced translocation of t(1;18). Repeated chromosomal analysis revealed a low-level mosaic translocation karyotype of 46,XY,der(18)t(1;18)(q32.1;q21.3)[12]/46,XY[152]. Because his parents had normal karyotypes, his translocation was considered to be de novo. The abnormalities observed in aCGH were confirmed by metaphase fluorescent in situ hybridization. We report this patient as a new karyotype presenting developmental delay, facial dysmorphism, cerebral dysmyelination, and other abnormalities. PMID:26958068

  5. Exclusion of linkage between hypokalemic periodic paralysis and a candidate region in 1q31-32 suggests genetic heterogeneity

    SciTech Connect

    Sillen, A.; Wadelius, C.; Gustabson, K.H.

    1994-09-01

    Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disease with attacks of paralysis of varying severity. The attacks occur at intervals of days to years in otherwise healthy people combined with hypokalemia during attacks. The paralysis attacks are precipitated by a number of different factors, like carbohydrate-rich meals, cold, exercise and mental stress. Recently linkage for HOKPP was shown for chromosome 1q31-32 and the disease was mapped between D1S413 and D1S249. The gene for the calcium channel alfa1-subunit (CACNL 1A3) maps to this interval and in two families no recombination was found between a polymorphism in the CACNL 1A3 gene and the disease. This gene is therefore considered to be a candidate for HOKPP. The analysis of a large Danish family excludes linkage to this region and to the CACNL 1A3 gene. In each direction from D1S413, 18.8 cM could be excluded and for D1S249, 14.9 cM. The present study clearly excludes the possibility that the gene causing HOKPP in a large Danish family is located in the region 1q31-32. This result shows that HOKPP is a heterogenous disease, with only one mapped gene so far.

  6. Functional C1q is present in the skin mucus of Siberian sturgeon (Acipenser baerii).

    PubMed

    Fan, Chunxin; Wang, Jian; Zhang, Xuguang; Song, Jiakun

    2015-01-01

    The skin mucus of fish acts as the first line of self-protection against pathogens in the aquatic environment and comprises a number of innate immune components. However, the presence of the critical classical complement component C1q, which links the innate and adaptive immune systems of mammalians, has not been explored in a primitive actinopterygian fish. In this study, we report that C1q is present in the skin mucus of the Siberian sturgeon (Acipenser baerii). The skin mucus was able to inhibit the growth of Escherichia coli. The bacteriostatic activity of the skin mucus was reduced by heating and by pre-incubation with EDTA or mouse anti-human C1q antibody. We also detected C1q protein in skin mucus using the western blot procedure and isolated a cDNA that encodes the Siberian sturgeon C1qC, which had 44.7-51.4% identity with C1qCs in teleosts and tetrapods. A phylogenetic analysis revealed that Siberian sturgeon C1qC lies at the root of the actinopterygian branch and is separate from the tetrapod branch. The C1qC transcript was expressed in many tissues as well as in skin. Our data indicate that C1q is present in the skin mucus of the Siberian sturgeon to protect against water-borne bacteria, and the C1qC found in the sturgeon may represent the primitive form of teleost and tetrapod C1qCs. PMID:24920077

  7. [Langer-Giedion syndrome with 8q23.1-q24.12 deletion diagnosed by comparative genomic hybridization].

    PubMed

    Ruiz-Botero, Felipe; Pachajoa, Harry

    2016-08-01

    The Langer-Giedion syndrome, also known as trichorhinophalangeal syndrome type II, is a hereditary multisystemic disease part of the group of contiguous gene deletion syndromes. The cause of this syndrome is a heterozygous deletion that involves the chromosomal region 8q23.3-q24.11 and mainly affects genes TRPS1, RAD21, and EXT1. This syndrome is characterized by the presence of multiple osteochondromas in limbs, hypertrichosis, and facial phenotype that includes sparse scalp hair, large laterally protruding ears, a long nose with a bulbous tip. We report the case of a Colombian patient with finding of an 8q23.1-q24.12 deletion by comparative genomic hybridization array technique and classical clinical findings, being the first case reported in Colombia. PMID:27399022

  8. Chromosomal Conditions

    MedlinePlus

    ... 150 babies is born with a chromosomal condition. Down syndrome is an example of a chromosomal condition. Because ... all pregnant women be offered prenatal tests for Down syndrome and other chromosomal conditions. A screening test is ...

  9. [Identification of chromosomal aberration in esophageal cancer cells by mixed BAC DNA probes of chromosome arms and regions].

    PubMed

    Jiajie, Hao; Chunli, Wang; Wenyue, Gu; Xiaoyu, Cheng; Yu, Zhang; Xin, Xu; Yan, Cai; Mingrong, Wang

    2014-06-01

    Chromosomal aberration is an important genetic feature of malignant tumor cells. This study aimed to clarify whether BAC DNA could be used to identify chromosome region and arm alterations. For each chromosome region, five to ten 1 Mb BAC DNA clones were selected to construct mixed BAC DNA clones for the particular region. All of the mixed clones from regions which could cover the whole chromosome arm were then mixed to construct mixed BAC DNA clones for the arms. Mixed BAC DNA probes of arms and regions were labeled by degenerate oligonucleotide primed PCR (DOP-PCR) and Nick translation techniques, respectively. The specificities of these probes were validated by fluorescence in situ hybridization (FISH) on the metaphase chromosomes of normal human peripheral blood lymphocytes. FISH with arm-specific mixed BAC DNA probes showed that chromosomal rearrangements and involved chromosome arms were confirmed in several esophageal cancer cells. By using region-specific mixed probes, the breakpoint on 1q from the derivative chromosome t(1q;7q) was identified in 1q32-q41 in esophageal KYSE140 cells. In conclusion, we established an effective labeling method for 1 Mb BAC DNA mixed clone probes, and chromosome arm and region rearrangements could be identified in several esophageal cancer cells by using these probes. Our study provides a more precise method for identification of chromosomal aberration by M-FISH, and the established method may also be applied to the karyotype analysis of hematological malignancies and prenatal diagnosis. PMID:24929514

  10. Cytogenetic effects of radiotherapy. Breakpoint distribution in induced chromosome aberrations

    SciTech Connect

    Barrios, L.; Miro, R.; Caballin, M.R.; Fuster, C.; Guedea, F.; Subias, A.; Egozcue, J. )

    1989-08-01

    A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo. Chromosome arms 1p, 1q, 7q, and 11p were also significantly more affected. Some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected. This band is proposed as a hot point for the clastogenic effect of ionizing radiation. A significant clustering of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpoints was also observed in bands where fragile sites, protooncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominoidea are located.

  11. Isolation and function of a human endothelial cell C1q receptor

    PubMed Central

    Dunn, L.; Berg, R. van den; Lange, Y. Muizert-de; Gerritsen, A.; Es, L. A. van

    1993-01-01

    It has been shown previously that cultured human venous and arterial endothelial cells (EC) bind C1q in a time- and dose-dependent manner. Cultured human endothelial cells express an average number of 5.2 × 105 binding sites/cell. In the present study the putative receptor for C1q (C1qR) was isolated from the membranes of 1–5 × 109 human umbilical cord EC by affinity chromatography on C1q–Sepharose. During isolation, C1qR was detected by its capacity to inhibit the lysis of EAC1q in C1q-deficient serum. The eluate from C1q–Sepharose was concentrated, dialysed and subjected to QAE-A50 chromatography and subsequently to gel filtration on HPLC–TSK 3000. C1qR filtered at an apparent molecular weight of 60 kDa. Purified C1qR exhibited an apparent molecular weight of 55–62 kDa in the unreduced state and a molecular weight of 64–68 kDa in reduced form. Two IgM monoclonal antibodies (mAb) D3 and D5 were raised following immunization of mice with purified receptor preparations. Both monoclonal antibodies increased the binding of 125I-C1q to endothelial cells but F(ab')2 anti-C1qR mAb inhibited the binding of a125I-C1q to EC in a dosedependent manner. The D3 mAb recognized a band of 54–60 kDa in Western blots of membranes of human EC and polymorphonuclear leukocytes. Previously, the authors showed that C1q induces the binding of IgM-containing immune complexes to EC. Therefore, it was hypothesized that during a primary immune response generation of IgM-IC may occur, resulting in binding and activation of C1, dissociation of activated C1 by C1 inhibitor and subsequent interaction of IgM-IC bearing C1q with EC–C1qR. PMID:18475561

  12. Characterization of chromosome 1 abnormalities in malignant melanomas.

    PubMed

    Smedley, D; Sidhar, S; Birdsall, S; Bennett, D; Herlyn, M; Cooper, C; Shipley, J

    2000-05-01

    Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanomas. Specific breakpoints are reported for malignant melanomas throughout the chromosome but especially at 1p36 and at several sites throughout 1p22-q21. In addition, partial deletions and loss of heterozygosity have been found on 1p indicating the possible location of tumor suppressor genes. Here we have characterized the involvement of chromosome 1 in a series of seven malignant melanoma cell lines. Initial chromosome painting studies revealed that six of the cell lines had chromosome 1 rearrangements. Deletions involving 1p10-32, 1q11-44, and 1q25-44 were observed. The other rearrangement breakpoints included three in the 1q10-p11 region with the rest at 1p36, 1p34, 1p32, 1p31, 1p12-13, 1q21, and 1q23. The breaks at 1q10-p11 were investigated further using an alpha-satellite 1 centromere probe and yeast artificial chromosomes (YACs) from the region. Two of the 1q10-p11 breaks mapped in the centromeric region, while the others mapped to variable sites. This suggests that the role of these rearrangements in the pathogenesis of melanomas does not involve the alteration of specific oncogenes in the breakpoint region. During the YAC mapping a previously undetected, small (<1 Mbp) del(1)(p10p11) was identified. This deletion lies within minimal overlapping deleted regions reported in head and neck as well as breast carcinomas and it could therefore facilitate the isolation of a carcinoma-associated tumor suppressor gene. PMID:10738310

  13. Molecular characterization of a novel amplicon at 1q21-q22 frequently observed in human sarcomas.

    PubMed Central

    Forus, A.; Berner, J. M.; Meza-Zepeda, L. A.; Saeter, G.; Mischke, D.; Fodstad, O.; Myklebost, O.

    1998-01-01

    In a recent comparative genomic hybridization (CGH) study of a panel of sarcomas, we detected recurrent amplification of 1q21-q22 in soft tissue and bone tumours. Amplification of this region had not previously been associated with sarcoma development, but occasional amplification of CACY/S100A6 and MUC1 in 1q21 had been reported for melanoma and breast carcinoma respectively. Initial screening by Southern blot analysis showed amplification of S100A6, FLG and SPRR3 in several sarcomas and, in a first attempt to characterize the 1q21-q22 amplicon in more detail, we have now investigated the amplification status of these and 11 other markers in the region in 35 sarcoma samples. FLG was the most frequently amplified gene, and the markers located in the same 4.5-Mb region as FLG showed a higher incidence of amplification than the more distal ones. However, for most of the 14 markers, amplification levels were low, and only APOA2 and the anonymous marker D1S3620 showed high-level amplifications (> tenfold increases) in one sample each. We used fluorescence in situ hybridization (FISH) to determine the amplification patterns of two overlapping yeast artificial chromosomes (YACs) covering the region between D1S3620 and FLG (789f2 and 764a1), as well as two more distally located YACs in nine selected samples. Six samples had amplification of the YAC containing D1S3620 and, in three, 764a1 was also included. Five of these tumours showed normal copies of the more distal YACs; thus, it seems likely that an important gene may be located within 789f2, or very close. Two samples had high copy numbers of the most distal YACs. Taken together, FISH and molecular analyses indicate complex amplification patterns in 1q21-q22 with at least two amplicons: one located near D1S3620/789f2 and one more distal. Images Figure 1 Figure 2 Figure 3 PMID:9716033

  14. Juvenile Spondyloarthropathies.

    PubMed

    Adrovic, Amra; Barut, Kenan; Sahin, Sezgin; Kasapcopur, Ozgur

    2016-08-01

    Juvenile spondyloarthropathies represent a clinical entity separate from the adult disease. Initial clinical signs of juvenile spondyloarthropathies often include lower extremity arthritis and enthesopathy, without axial involvement at the disease onset. Asymmetrical oligoarthritis of lower extremities is typically seen in this type of arthritis. Enthesopathy, which is the hallmark of the disease, is most commonly seen in the Achilles tendon, being manifested by heel pain. Anterior uveitis and HLA-B27 positivity are seen in a proportion of cases. Sacroiliitis is generally asymptomatic in the pediatric population. Ineffective treatment of childhood disease results in disease progression to typical adult form of ankylosing spondylitis. Therefore, early diagnosis and classification remains one of the most relevant questions in pediatric rheumatology. It should be kept in mind that the disease could be misdiagnosed as FMF or Behçet's syndrome in countries with a high incidence of those conditions. This review revises available classification criteria, clinical manifestations and therapeutic options for patients with juvenile spondyloarthropathies. PMID:27402112

  15. Juvenile rheumatoid arthritis

    MedlinePlus

    ... joints. This form of JIA may turn into rheumatoid arthritis. It may involve five or more large and ... no known prevention for JIA. Alternative Names Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ...

  16. Assignment of the human prostaglandin-endoperoxide synthase 2 (PTGS2) gene to 1q25 by fluorescence in situ hybridization

    SciTech Connect

    Tay, A.; Squire, J.A.; Goldberg, H.; Skorecki, K.

    1994-10-01

    A major mechanism for the regulation of prostaglandin synthesis occurs at the level of cyclooxygenase, also known as prostaglandin-endoperoxide synthase (PTGS). Two isoforms of PTGS have been identified: PTGS1, encoded by a 2.8-kb mRNA and a mitogen-inducible form, PTGS2, encoded by a 4.5-kb mRNA. We report here the assignment of the human PTGS2 gene to chromosome 1q25 by fluorescence in situ hybridization (FISH). We note with interest the physical proximity of the PTGS2 gene to that of cytosolic phospholipase A2 (cPLA2), which we have previously mapped to chromosome 1q24-q25. In contrast, the PTGS1 gene has been mapped to chromosome 9. Since cPLA2 and PTGS2 are key enzymes in the synthesis of prostaglandins and thromboxane, the possible implication of this proximity could mean that polymorphic markers already determined for the cPLA2 gene may also prove to be useful as markers for the PTGS2 gene as well. 10 refs., 1 fig.

  17. Transcriptional response of four C1q domain containing protein (C1qDC) genes from Venerupis philippinarum exposed to the water soluble fraction of No.0 diesel oil.

    PubMed

    Zhang, Linbao; Sun, Wei; Cai, Wengui; Zhang, Zhe; Chen, Haigang; Ma, Shengwei; Jia, Xiaoping

    2016-10-01

    As pattern recognitionreceptors, the C1q-domain-containing (C1qDC) proteins play an important role in the pathogen recognition and complement pathway activation. In the present study, four novel C1q domain containing proteins (designated as VpC1qDC1, VpC1qDC2, VpC1qDC3 and VpC1qDC4) were cloned and characterized from clam Venerupis philippinarum. The four VpC1qDCs all possessed the conserved features critical for the fundamental structure and function of the C1q family. The four VpC1qDCs genes showed differential response profiles after exposure to the water soluble fraction of No.0 diesel oil (WSFD). More notably, VpC1qDC1 and VpC1qDC3 were more sensitive to low concentration of WSFD, as their mRNA level changed by higher magnitudes. In addition, VpC1qDC2 and VpC1qDC4 displayed notable increases with larger amplitude to high concentration of WSFD. All these results suggested that the transcriptional response of VpC1qDCs genes were probably a protective mechanism of the cell to oils pollution. The diverse expression patterns of VpC1qDCs demonstrated that VpC1qDC1 and VpC1qDC3 were sensitive responders to environmental stress in V. philippinarum. PMID:27261881

  18. Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation

    PubMed Central

    Sun, Ran; Zhao, Xi; Wang, Zixia; Yang, Jing; Zhao, Limei; Zhan, Bin; Zhu, Xinping

    2015-01-01

    Background Trichinella spiralis expresses paramyosin (Ts-Pmy) as a defense mechanism. Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host’s immune system. In the present study, the binding activity of Ts-Pmy to human complement C1q and its ability to inhibit classical complement activation were investigated. Methods and Findings The binding of recombinant and natural Ts-Pmy to human C1q were determined by ELISA, Far Western blotting and immunoprecipitation, respectively. Binding of recombinant Ts-Pmy (rTs-Pmy) to C1q inhibited C1q binding to IgM and consequently inhibited C3 deposition. The lysis of antibody-sensitized erythrocytes (EAs) elicited by the classical complement pathway was also inhibited in the presence of rTs-Pmy. In addition to inhibiting classical complement activation, rTs-Pmy also suppressed C1q binding to THP-1-derived macrophages, thereby reducing C1q-induced macrophages migration. Conclusion Our results suggest that T. spiralis paramyosin plays an important role in immune evasion by interfering with complement activation through binding to C1q in addition to C8 and C9. PMID:26720603

  19. Why the Y Chromosome?--A Look at Male Lineage and Ancestry

    ERIC Educational Resources Information Center

    Elwess, Nancy L.; Edwards, Felecia; Latourelle, Sandra M.

    2006-01-01

    Up until a short time ago the Y chromosome played the role of the juvenile delinquent within human chromosomes. It was considered to be rich in junk, short on genes, and rapidly degenerating. Now the Y chromosome is growing up by providing a means for investigating human migration. Through the use of genetic markers on the Y chromosomes, students…

  20. Interaction between complement subcomponent C1q and the Klebsiella pneumoniae porin OmpK36.

    PubMed Central

    Albertí, S; Marqués, G; Hernández-Allés, S; Rubires, X; Tomás, J M; Vivanco, F; Benedí, V J

    1996-01-01

    The interaction between C1q, a subcomponent of the complement classical pathway component C1, and OmpK36, a porin protein from Klebsiella pneumoniae, was studied in a solid-phase direct-binding assay, inhibition assays with the purified globular and collagen-like regions of C1q, and cross-linking experiments. We have shown that the binding of C1q to the OmpK36 porin of the serum-sensitive strain K. pneumoniae KT707 occurs in an in vivo situation and that this binding leads to activation of the complement classical pathway and the subsequent deposition of complement components C3b and C5b-9 on the OmpK36 porin. Scatchard analysis of the binding of [125I]C1q to the OmpK36 porin showed two binding sites with dissociation constants of 1.5 and 75 nM. The decrease of [125I]C1q binding to the OmpK36 porin in buffer with increasing salt concentrations and the pIs of the C1q subcomponent (10.3) and OmpK36 porin (4.5) suggest that charged amino acids are involved in the binding phenomenon. In inhibition assays, only the globular regions of C1q inhibited the interaction between C1q and OmpK36 porin, demonstrating that C1q binds to porin through its globular region and not through the collagen-like stalks. PMID:8890231

  1. The C1q Family of Proteins: Insights into the Emerging Non-Traditional Functions

    PubMed Central

    Ghebrehiwet, Berhane; Hosszu, Kinga K.; Valentino, Alisa; Peerschke, Ellinor I. B.

    2012-01-01

    Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage-modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders – including autoimmunity, trophoblast migration, preeclampsia, and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh et al. (2011) showing that pregnant C1q−/− mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q−/− mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al. (2009) which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1) and destabilizing cell adhesion. Downregulation of C1q on the other hand, enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. C1q belongs to a family of structurally and functionally related TNF-α-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the tumor necrosis factor family of proteins, but also explains why C1q has retained some of its ancestral “cytokine-like” activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions. PMID:22536204

  2. A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32.

    PubMed

    Weis, J H; Morton, C C; Bruns, G A; Weis, J J; Klickstein, L B; Wong, W W; Fearon, D T

    1987-01-01

    The alternative or classical pathways for complement system component C3 may be triggered by microorganisms and antigen-antibody complexes. In particular, an activated fragment of C3, C3b, covalently attaches to microorganisms or antigen-antibody complexes, which in turn bind to the C3b receptor, also known as complement receptor 1. The genes encoding the proteins that constitute the C3-activating enzymes have been cloned and mapped to a "complement activation" locus in the major histocompatibility complex, and we demonstrate in this study such a locus on the long arm of chromosome 1 at band 1q32. PMID:3782802

  3. Interstitial deletions 4q21.1q25 and 4q25q27: Phenotypic variability and relation to Rieger anomaly

    SciTech Connect

    Kulharya, A.S.; Schneider, N.R.; Tonk, V.

    1995-01-16

    We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region. 15 refs., 4 figs., 1 tab.

  4. Fighting Juvenile Gun Violence. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Sheppard, David; Grant, Heath; Rowe, Wendy; Jacobs, Nancy

    This bulletin describes the Office of Juvenile Justice and Delinquency Prevention's efforts to fight juvenile gun violence. The Office awarded four community demonstration grants to implement "Partnerships To Reduce Juvenile Gun Violence." Partnership goals include increasing the effectiveness of existing strategies by enhancing and coordinating…

  5. Exclusion of primary congenital glaucoma (PCG) from two candidate regions of chromosomes 1 and 6

    SciTech Connect

    Sarfarazi, M.; Akarsu, A.N.; Barsoum-Homsy, M.

    1994-09-01

    PCG is a genetically heterogeneous condition in which a significant proportion of families inherit in an autosomally recessive fashion. Although association of PCG with chromosomal abnormalities has been repeatedly reported in the literature, the chromosomal location of this condition is still unknown. Therefore, this study is designed to identify the chromosomal location of the PCG locus by positional mapping. We have identified 80 PCG families with a total of 261 potential informative meiosis. A group of 19 pedigrees with a minimum of 2 affected children in each pedigree and consanguinity in most of the parental generation were selected as our initial screening panel. This panel consists of a total of 44 affected and 93 unaffected individuals giving a total of 99 informative meiosis, including 5 phase-known. We used polymerase chain reaction (PCR), denaturing polyacrylamide gels and silver staining to genotype our families. We first screened for markers on 1q21-q31, the reported location for juvenile primary open-angle glaucoma and excluded a region of 30 cM as the likely site for the PCG locus. Association of PCG with both ring chromosome 6 and HLA-B8 has also been reported. Therefore, we genotyped our PCG panel with PCR applicable markers from 6p21. Significant negative lod scores were obtained for D6S105 (Z = -18.70) and D6S306 (Z = -5.99) at {theta}=0.001. HLA class 1 region has also contained one of the tubulin genes (TUBB) which is an obvious candidate for PCG. Study of this gene revealed a significant negative lod score with PCG (Z = -16.74, {theta}=0.001). A multipoint linkage analysis of markers in this and other regions containing the candidate genes will be presented.

  6. Is Collapsing C1q Nephropathy Another MYH9-Associated Kidney Disease? A Case Report

    PubMed Central

    Reeves-Daniel, Amber M.; Iskandar, Samy S.; Bowden, Donald W.; Bostrom, Meredith A.; Hicks, Pamela J.; Comeau, Mary E.; Langefeld, Carl D.; Freedman, Barry I.

    2009-01-01

    C1q nephropathy is a rare kidney disease that can present with nephrotic syndrome and typically has the histological phenotype of either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Disagreement exists as to whether it is a distinct immune complex-mediated glomerulopathy or whether it resides in the spectrum of FSGS-MCD. Two African American patients with C1q nephropathy histologically presenting as the collapsing variant of FSGS (collapsing C1q nephropathy) and rapid loss of kidney function were genotyped for polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9). Both cases were homozygous for the MYH9 E1 risk haplotype; the variant strongly associated with idiopathic FSGS, collapsing FSGS in Human Immunodeficiency Virus-associated nephropathy and focal global glomerulosclerosis (historically attributed to hypertensive nephrosclerosis). Collapsing C1q nephropathy with rapid progression to ESRD appears to reside in the MYH9-associated disease spectrum. PMID:20116156

  7. Maternal complement C1q and increased odds for psychosis in adult offspring

    PubMed Central

    Severance, Emily G.; Gressitt, Kristin L.; Buka, Stephen L.; Cannon, Tyrone D.; Yolken, Robert H.

    2014-01-01

    The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race and gender, with further matching based on mother’s age. IgG markers of C1q, bovine milk casein, egg ovalbumin and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources. PMID:25195065

  8. Transcriptional Factor PU.1 Regulates Decidual C1q Expression in Early Pregnancy in Human.

    PubMed

    Madhukaran, Shanmuga Priyaa; Kishore, Uday; Jamil, Kaiser; Teo, Boon Heng Dennis; Choolani, Mahesh; Lu, Jinhua

    2015-01-01

    C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation. PMID:25762996

  9. Identification of C1q as a Binding Protein for Advanced Glycation End Products.

    PubMed

    Chikazawa, Miho; Shibata, Takahiro; Hatasa, Yukinori; Hirose, Sayumi; Otaki, Natsuki; Nakashima, Fumie; Ito, Mika; Machida, Sachiko; Maruyama, Shoichi; Uchida, Koji

    2016-01-26

    Advanced glycation end products (AGEs) make up a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with the free amino groups of proteins. The abundance of AGEs in a variety of age-related diseases, including diabetic complications and atherosclerosis, and their pathophysiological effects suggest the existence of innate defense mechanisms. Here we examined the presence of serum proteins that are capable of binding glycated bovine serum albumin (AGEs-BSA), prepared upon incubation of BSA with dehydroascorbate, and identified complement component C1q subcomponent subunit A as a novel AGE-binding protein in human serum. A molecular interaction analysis showed the specific binding of C1q to the AGEs-BSA. In addition, we identified DNA-binding regions of C1q, including a collagen-like domain, as the AGE-binding site and established that the amount of positive charge on the binding site was the determining factor. C1q indeed recognized several other modified proteins, including acylated proteins, suggesting that the binding specificity of C1q might be ascribed, at least in part, to the electronegative potential of the ligand proteins. We also observed that C1q was involved in the AGEs-BSA-activated deposition of complement proteins, C3b and C4b. In addition, the AGEs-BSA mediated the proteolytic cleavage of complement protein 5 to release C5a. These findings provide the first evidence of AGEs as a new ligand recognized by C1q, stimulating the C1q-dependent classical complement pathway. PMID:26731343

  10. Function of gC1qR in innate immunity of Chinese mitten crab, Eriocheir sinensis.

    PubMed

    Huang, Ying; Wang, Wen; Ren, Qian

    2016-08-01

    gC1qR is identified as the globular "head" binding protein of the C1q protein and performs an important function in innate immunity. A EsgC1qR gene was identified from the hepatopancreas of Eriocheir sinensis. EsgC1qR encodes a protein with 275 amino acids. Phylogenetic analysis showed that, together with crustaceans gC1qRs, EsgC1qR belongs to one group. EsgC1qR mRNA was detected in hemocytes, intestine, hepatopancreas, gills, eyestalk, heart, muscle, and nerve. The expression of the EsgC1qR transcript in the hepatopancreas could be regulated by lipopolysaccharides (LPS), peptidoglycans (PGN), Staphyloccocus aureus, or Vibrio parahaemolyticus. Recombinant EsgC1qR (rEsgC1qR) protein could bind to various bacteria, LPS, and PGN. rEsgC1qR protein also presents direct bacteria inhibitory activity. rEsgC1qR could interact with EsCnx or EsCrt. Therefore, from the results, we could speculate that EsgC1qR is involved in the innate immunity of Chinese mitten crab, E. sinensis. PMID:26993663

  11. C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation.

    PubMed

    Färber, Katrin; Cheung, Giselle; Mitchell, Daniel; Wallis, Russell; Weihe, Eberhard; Schwaeble, Wilhelm; Kettenmann, Helmut

    2009-02-15

    Microglia, central nervous system (CNS) resident phagocytic cells, persistently police the integrity of CNS tissue and respond to any kind of damage or pathophysiological changes. These cells sense and rapidly respond to danger and inflammatory signals by changing their cell morphology; by release of cytokines, chemokines, or nitric oxide; and by changing their MHC expression profile. We have shown previously that microglial biosynthesis of the complement subcomponent C1q may serve as a reliable marker of microglial activation ranging from undetectable levels of C1q biosynthesis in resting microglia to abundant C1q expression in activated, nonramified microglia. In this study, we demonstrate that cultured microglial cells respond to extrinsic C1q with a marked intracellular Ca(2+) increase. A shift toward proinflammatory microglial activation is indicated by the release of interleukin-6, tumor necrosis factor-alpha, and nitric oxide and the oxidative burst in rat primary microglial cells, an activation and differentiation process similar to the proinflammatory response of microglia to exposure to lipopolysaccharide. Our findings indicate 1) that extrinsic plasma C1q is involved in the initiation of microglial activation in the course of CNS diseases with blood-brain barrier impairment and 2) that C1q synthesized and released by activated microglia is likely to contribute in an autocrine/paracrine way to maintain and balance microglial activation in the diseased CNS tissue. PMID:18831010

  12. Juvenile Justice & Youth Violence.

    ERIC Educational Resources Information Center

    Howell, James C.

    Youth violence and the juvenile justice system in the United States are explored. Part 1 takes stock of the situation. The first chapter discusses the origins and evaluation of the juvenile justice system, and the second considers the contributions of the Federal Juvenile Justice and Delinquency Prevention Act to the existing juvenile justice…

  13. [Juvenile arthritides].

    PubMed

    Horneff, G

    2010-10-01

    Arthritis in children represents a diagnostic and therapeutic challenge. The diagnostic spectrum is broad and a very precise indication for diagnostic and therapeutic procedures, especially in small children, is important. In addition to acute arthritides - viral arthritis, reactive arthritis, Lyme arthritis and septic arthritis - secondary chronic arthritis related to an underlying disease as well as juvenile idiopathic arthritis (JIA), the most common chronic inflammatory systemic disease in children, need to be considered. This overview is a guide to the diagnosis of arthritis in childhood and to evidence-based therapy of JIA in particular. This consists of a combination of nonsteroidal anti-inflammatory drugs, systemic and intraarticular corticosteroids, traditional DMARDs such as sulfasalazine, methotrexate and leflunomide, the TNF inhibitors etanercept, adalimumab and, with restrictions, infliximab, other biopharmaceuticals such as anakinra, canakinumab and rilonacept, and tocilizumab and finally, abatacept. PMID:20798949

  14. 22.5 MB DELETION OF 13q31.1-q34 ASSOCIATED WITH HPE, DWM, AND HSCR: A CASE REPORT AND REDEFINING THE SMALLEST DELETED REGIONS.

    PubMed

    Alp, M Y; Çebi, A H; Seyhan, S; Cansu, A; Aydin, H; Ikbal, M

    2016-01-01

    Partial deletion of the long arm of the chromosome 13, 13q deletion syndrome is a rare chromosomal disorder characterized by severe growth and mental retardation, microcephaly, facial dysmorphism, brain malformations (holoprosencephaly, Dandy-Walker malformation), distal limb defects, eye anomalies, genitourinary and gastrointestinal tract malformations (Hirschsprung's disease). Approximately 1.2 Mb region in 13q32 was suggested as minimal critical region which is responsible for severe mental and growth retardation and brain anomalies. Here we described a male patient with de novo interstitial deletion of 13q31.1-q34 associated with short stature, microcephaly, facial dysmorphism, clinodactyly, cryptorchidism, micropenis, epilepsy, HPE, DWM, and HSCR. According to the literature review, present case indicated that smallest deleted region associated with DWM and HPE might be located at the 13q32.3, limb defects 13q34, anogenital malformations 13q33.3-34, and HSCR 13q31.1-32.1. PMID:27192891

  15. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia

    PubMed Central

    Severance, Emily G.; Gressitt, Kristin; Halling, Meredith; Stallings, Cassie R.; Origoni, Andrea E.; Vaughan, Crystal; Khushalani, Sunil; Alaedini, Armin; Dupont, Didier; Dickerson, Faith B.; Yolken, Robert H.

    2012-01-01

    Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known. Food sensitivities characterized by elevated IgG antibodies to bovine milk caseins and wheat glutens have been reported in individuals with schizophrenia. Here, we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia (n=38), non-recent onset schizophrenia (n=61) and non-psychiatric controls (n=63). C1q seropositivity was significantly associated with both schizophrenia groups (recent onset, odds ratio (OR)=8.02, p≤0.008; non-recent onset, OR=3.15, p≤0.03) compared to controls (logistic regression models corrected for age, sex, race and smoking status). Casein- and/or gluten-IgG binding to C1q was significantly elevated in the non-recent onset group compared to controls (OR=4.36, p≤0.01). Significant amounts of C1q-casein/gluten-related immune complexes and C1q correlations with a marker for gastrointestinal inflammation in non-recent onset schizophrenia suggests a heightened rate of food antigens in the systemic circulation, perhaps via a disease-associated altered intestinal permeability. In individuals who are in the early stages of disease onset, C1q activation may reflect the formation of immune complexes with non-casein- or non-gluten-related antigens, the presence of C1q autoantibodies, and/or a dissociated state of immune complex components. In conclusion, complement activation may be a useful biomarker to diagnose schizophrenia early during the course of the disease. Future prospective studies should evaluate the impacts of casein- and gluten-free diets on C1q activation in schizophrenia. PMID:22801085

  16. Trisomy 1q41-qter and monosomy 3p26.3-pter in a family with a translocation (1;3): further delineation of the syndromes

    PubMed Central

    2014-01-01

    Background Trisomy 1q and monosomy 3p deriving from a t(1;3) is an infrequent event. The clinical characteristics of trisomy 1q41-qter have been described but there is not a delineation of the syndrome. The 3p25.3-pter monosomy syndrome (MIM 613792) characteristics include low birth weight, microcephaly, psychomotor and growth retardation and abnormal facies. Case presentation A 2 years 8 months Mexican mestizo male patient was evaluated due to a trisomy 1q and monosomy 3p derived from a familial t(1;3)(q41;q26.3). Four female carriers of the balanced translocation and one relative that may have been similarly affected as the proband were identified. The implicated chromosomal regions were defined by microarray analysis, the patient had a trisomy 1q41-qter of 30.3 Mb in extension comprising about 240 protein coding genes and a monosomy 3p26.3-pter of 1.7 Mb including only the genes CNTN6 (MIM 607220) and CHL1 (MIM 607416), which have been implicated in dendrite development. Their contribution to the phenotype, regarding the definition of trisomy 1q41-qter and monosomy 3p26.3-pter syndromes are discussed. Conclusion We propose that a trisomy 1q41-qter syndrome should be considered in particular when the following characteristics are present: postnatal growth delay, macrocephaly, wide fontanelle, triangular facies, frontal bossing, thick eye brows, down slanting palpebral fissures, hypertelorism, flat nasal bridge, hypoplasic nostrils, long filtrum, high palate, microretrognathia, ear abnormalities, neural abnormalities (in particular ventricular dilatation), psychomotor developmental delay and mental retardation. Our patient showed most of these clinical characteristics with exception of macrocephaly, possibly due to a compensatory effect by haploinsufficiency of the two genes lost from 3p. The identification of carriers has important implications for genetic counseling as the risk of a new born with either a der(3) or der(1) resulting from an adjacent-1

  17. Receptor-mediated binding of C1 q on pulmonary endothelial cells

    SciTech Connect

    Zhang, S.C.; Schultz, D.; Ryan, U.

    1986-03-01

    Normal undamaged pulmonary endothelial cells (EC) do not express receptors for C3b or the Fc portion of IgG, but both receptors become unmasked after viral infection or exposure to white cell lysates. Here, highly purified human C1q was labeled with /sup 125/I, and the globular subunits were separated from the collagenous portion by collagenase digestion and chromatography. Bovine pulmonary artery EC were cultured without exposure to proteolytic enzymes. Binding assays were carried out at 0/sup 0/C, pH 7.4, ..mu.. = 0.15. Results showed that /sup 125/I-C1q binds to EC, the binding is dose-dependent, and the receptor is saturable. Saturation was approached at a C1q concentration of ca 0.1 ug. By Scatchard analysis, maximum binding was 0.219 pmoles in a volume of 250 ..mu..l for 7 x 10/sup 5/ cells, and the average number of binding sites per cell was 1.88 x 10/sup 5/. Isolated /sup 125/I-C1q heads do not bind, and when native /sup 125/I-C1q was bound to EC radioactivity was eliminated after collagenase treatment for 4 h at 37/sup 0/C. Thus, C1q binds to EC via the collagenous portion. That Fc receptors (globular heads) are exposed was shown by rosette formation with EA and EC bound C1q. Using similar conditions, native C1(C1w x 2C1r x 2C1s) did not bind to EC. These results suggest a mechanism for localizing immune complexes on undamaged pulmonary vessels which may be important for initiation of the inflammatory response.

  18. sghC1q, a novel C1q family member from half-smooth tongue sole (Cynoglossus semilaevis): identification, expression and analysis of antibacterial and antiviral activities.

    PubMed

    Zeng, Yan; Xiang, Jinsong; Lu, Yang; Chen, Yadong; Wang, Tianzi; Gong, Guangye; Wang, Lei; Li, Xihong; Chen, Songlin; Sha, Zhenxia

    2015-01-01

    The C1q family includes many proteins that contain a globular (gC1q) domain, and this family is widely conserved from bacteria to mammals. The family is divided into three subgroups: C1q, C1q-like and ghC1q. In this study, a novel C1q family member, sghC1q, was cloned and identified from Cynoglossus semilaevis (named CssghC1q). The full-length CssghC1q cDNA spans 905 bp, including an open reading frame (ORF) of 768 bp, a 5'-untranslated region (UTR) of 25 bp and a 3'-UTR of 112 bp. The ORF encodes a putative protein of 255 amino acids (aa) with a deduced molecular weight of 28 kDa. The predicted protein contains a signal peptide (aa 1-19), a coiled-coil region (aa 61-102) and a globular C1q (gC1q) domain (aa 117-255). Protein sequence alignment indicated that the C-terminus of CssghC1q is highly conserved across several species. Phylogenetic analysis indicated that CssghC1q is most closely related to Maylandia zebra C1q-like-2-like. The CssghC1q genomic sequence spanned 1562 bp, with three exons and two introns. CssghC1q is constitutively expressed in all evaluated tissues, with the highest expression in the liver and the weakest in the heart. After a challenge with Vibrio anguillarum, CssghC1q transcript levels exhibited distinct time-dependent response patterns in the blood, head kidney, skin, spleen, intestine and liver. Recombinant CssghC1q protein exhibited antimicrobial activities against Gram-negative bacteria, Gram-positive bacteria and viruses. The minimum inhibitory concentration (MIC) values against Vibrio harveyi, Vibrio anguillarum, Pseudomonas aeruginosa and Staphylococcus aureus were 0.043 mg/mL, 0.087 mg/mL, 0.174 mg/mL and 0.025 mg/mL, respectively. A low concentration (0.06 mg/mL) of CssghC1q showed significant antiviral activity in vitro against nervous necrosis virus (NNV). These results suggest that CssghC1q plays a vital role in immune defense against bacteria and viruses. PMID:25312696

  19. A novel multi-domain C1qDC protein from Zhikong scallop Chlamys farreri provides new insights into the function of invertebrate C1qDC proteins.

    PubMed

    Wang, Leilei; Wang, Lingling; Zhang, Daoxiang; Jiang, Qiufen; Sun, Rui; Wang, Hao; Zhang, Huan; Song, Linsheng

    2015-10-01

    The C1q domain containing (C1qDC) proteins are a family of proteins possessing globular C1q (gC1q) domains, and they rely on this domain to recognize various ligands such as PAMPs, immunoglobulins, ligands on apoptotic cell. In the present study, a novel multi-domain C1qDC protein (CfC1qDC-2) was identified from scallop Chlamys farreri, and its full length cDNA was composed of 1648 bp, encoding a signal peptide and three typical gC1q domains. BLAST analysis revealed significant sequence similarity between CfC1qDC-2 and C1qDC proteins from mollusks. Three gC1q domains were predicted in its tertiary structure to form a tightly packed bell-shaped trimer, and each one adopted a typical 10-stranded sandwich fold with a jelly-roll topology and contained six aromatic amino acids forming the hydrophobic core. The mRNA transcripts of CfC1qDC-2 were mainly detected in the tissues of hepatopancreas and gonad of adult scallops, and the expression level was up-regulated in hemocytes after stimulated by LPS, PGN and β-glucan. During the embryonic development of scallop, the mRNA transcripts of CfC1qDC-2 were presented in all the detected stages, and the expression level was up-regulated from D-hinged larvae and reached the highest at eye-spot larvae. The recombinant protein of MBP-CfC1qDC-2 (rCfC1qDC-2) could bind various PAMPs including LPS, PGN, LTA, β-glucan, mannan as well as polyI:C, and different microorganisms including three Gram-negative bacteria, three Gram-positive bacteria and two yeasts, as well as scallop apoptotic cells. Meanwhile, rCfC1qDC-2 could interact with human heat-aggregated IgG and IgM, and inhibit the C1q-dependent hemolysis of rabbit serum. All these results indicated that CfC1qDC-2 could recognize not only PAMPs as a PRR, but also the apoptotic cells. Moreover, the similar structures and functions shared by CfC1qDC-2 and complement C1q provided a new insight into the evolution of C1qDC proteins in complement system. PMID:26049063

  20. Mapping and characterization of the amplicon near APOA2 in 1q23 in human sarcomas by FISH and array CGH

    PubMed Central

    Kresse, Stine H; Berner, Jeanne-Marie; Meza-Zepeda, Leonardo A; Gregory, Simon G; Kuo, Wen-Lin; Gray, Joe W; Forus, Anne; Myklebost, Ola

    2005-01-01

    Background Amplification of the q21-q23 region on chromosome 1 is frequently found in sarcomas and a variety of other solid tumours. Previous analyses of sarcomas have indicated the presence of at least two separate amplicons within this region, one located in 1q21 and one located near the apolipoprotein A-II (APOA2) gene in 1q23. In this study we have mapped and characterized the amplicon in 1q23 in more detail. Results We have used fluorescence in situ hybridisation (FISH) and microarray-based comparative genomic hybridisation (array CGH) to map and define the borders of the amplicon in 10 sarcomas. A subregion of approximately 800 kb was identified as the core of the amplicon. The amplification patterns of nine possible candidate target genes located to this subregion were determined by Southern blot analysis. The genes activating transcription factor 6 (ATF6) and dual specificity phosphatase 12 (DUSP12) showed the highest level of amplification, and they were also shown to be over-expressed by quantitative real-time reverse transcription PCR (RT-PCR). In general, the level of expression reflected the level of amplification in the different tumours. DUSP12 was expressed significantly higher than ATF6 in a subset of the tumours. In addition, two genes known to be transcriptionally activated by ATF6, glucose-regulated protein 78 kDa and -94 kDa (GRP78 and GRP94), were shown to be over-expressed in the tumours that showed over-expression of ATF6. Conclusion ATF6 and DUSP12 seem to be the most likely candidate target genes for the 1q23 amplification in sarcomas. Both genes have possible roles in promoting cell growth, which makes them interesting candidate targets. PMID:16274472

  1. 9q31.1q31.3 deletion in two patients with similar clinical features: a newly recognized microdeletion syndrome?

    PubMed

    Mucciolo, M; Magini, P; Marozza, A; Mongelli, P; Mencarelli, M A; Hayek, G; Tavalazzi, F; Mari, F; Seri, M; Renieri, A; Graziano, C

    2014-03-01

    Interstitial deletions of the long arm of chromosome 9 are rare and most patients have been detected by conventional cytogenetic techniques. Disparities in size and localization are large and no consistent region of overlap has been delineated. We report two similar de novo deletions of 6.3 Mb involving the 9q31.1q31.3 region, identified in two monozygotic twins and one unrelated patient through array-CGH analysis. By cloning the deletion breakpoints, we could show that these deletions are not mediated by segmental duplications. The patients displayed a distinct clinical phenotype characterized by mild intellectual disability, short stature with high body mass index, thick hair, arched eyebrows, flat profile with broad chin and mild prognathism, broad, and slightly overhanging tip of the nose, short neck with cervical gibbus. The twin patients developed a metabolic syndrome (type 2 diabetes, hypercholesterolemia, vascular hypertension) during the third decade of life. Although long-term follow-up and collection of additional patients will be needed to obtain a better definition of the phenotype, our findings characterize a previously undescribed syndromic disorder associated with haploinsufficiency of the chromosome 9q31.1q31.3 region. PMID:24376033

  2. C1q-latex assay for immune complexes. Complexes that react with both C1q and monoclonal rheumatoid factor in lupus erythematosus and lung cancer

    SciTech Connect

    Medof, M.E.

    1982-05-01

    A solid phase radioassay for measurement of ICs in biological fluids is described in which ICs present in test sample bind to C1q immobilized on latex particles and bound complexes are quantitated by reaction with radioiodinated mRF. The radioassay can reproducibly measure 10 ng of aggregated human IgG in serum and differentiate soluble complexes from IC-like materials that precipitate with centrifugation or low temperature or stick to test tube walls. Reagents used in the assay, including C1q-L, can be stored for extended periods of time before use. One hundred four of 171 sera from patients with SLE and 8 of 50 sera from patients with LC, assayed by this method, contained elevated levels of ICs relative to controls . IC levels determined by this method correlated with IC data generated by 125I-C1q-PEG precipitation. Raji cell radioimmune assay, and solid-phase conglutinin assay, in some cases but not other.

  3. Role of complement component C1q in phagocytosis of Listeria monocytogenes by murine macrophage-like cell lines.

    PubMed Central

    Alvarez-Dominguez, C; Carrasco-Marin, E; Leyva-Cobian, F

    1993-01-01

    Listeria monocytogenes is a facultative intracellular pathogen of a great variety of cells. Among them, macrophages constitute the major effector cells of listerial immunity during the course of an infection. Although the molecular bases of L. monocytogenes attachment and entry to phagocytes are not completely understood, it has been demonstrated that C3b significantly increases L. monocytogenes uptake by macrophages via complement receptor type 3. The first component of complement, C1q, is present in organic fluids at a relatively high concentration, and C1q receptor sites in macrophages are also abundant. In the present report, results of studies on the role of C1q in the internalization and infectivity of L. monocytogenes by macrophages are presented. L. monocytogenes uptake is enhanced by prior treatment of bacteria with normal sera. Heated serum or C1q-deficient serum abrogates this enhancement. Purified C1q specifically restored uptake. This effect was blocked by the addition of F(ab')2 anti-C1q antibody but not by an irrelevant matched antibody. Direct binding of C1q to L. monocytogenes was specific, saturable, and dose dependent with both fluorescent and radiolabeled C1q. N-Acetyl-D-alanyl-L-isoglutamine, diaminopimelic acid, and L-rhamnose caused a significant dose-dependent inhibition of C1q binding to bacteria, suggesting that these molecules, at least, are involved in the attachment of C1q to L. monocytogenes cell wall. When C1q binding structures on macrophage-like cells were blocked with saturating concentrations of C1q, the uptake of C1q-opsonized bacteria was less than in untreated cells. These experiments demonstrate that, in addition to other reported mechanisms, L. monocytogenes binds C1q, which mediates enhanced uptake by macrophages through C1q binding structures. Images PMID:8359889

  4. Micro-duplications of 1q32.1 associated with neurodevelopmental delay.

    PubMed

    Olson, H E; Shen, Y; Poduri, A; Gorman, M P; Dies, K A; Robbins, M; Hundley, R; Wu, B; Sahin, M

    2012-02-01

    Distal partial trisomies involving the region 1q32 have been associated with dysmorphic features and developmental delay [1-11]. To further define the critical region for developmental delay and to investigate the genotype-phenotype association of 1q trisomy syndrome, we report two patients with much smaller (3 Mb and 3.5 Mb in size) trisomic regions on 1q32.1. The two micro-duplications largely overlap and both patients exhibited cognitive and motor delays. Case 1 is a 5-year-old boy with global developmental delay, behavioral problems, pervasive developmental disorder not otherwise specified (PDD-NOS), staring spells, headaches, and paresthesias. Case 2 is a 14-year-old girl with seizures, cognitive and motor difficulties, and minor dysmorphic features. These two cases suggest that 1q32.1 region on distal arm of 1q and genes involved are critical to cognitive and motor development in a gene dosage sensitive manner and that other neurological features are variable within this syndrome. PMID:22266072

  5. C1q binding and complement activation by prions and amyloids.

    PubMed

    Sim, Robert B; Kishore, Uday; Villiers, Christian L; Marche, Patrice N; Mitchell, Daniel A

    2007-01-01

    C1q binds to many non-self and altered-self-materials. These include microorganisms, immune complexes, apoptotic and necrotic cells and their breakdown products, and amyloids. C1q binding to amyloid fibrils found as extracellular deposits in tissues, and subsequent complement activation are involved in the pathology of several amyloid diseases, such as Alzheimer's disease. Prion diseases, such as scrapie also involve formation of amyloid by polymerization of the host prion protein (PrP). Complement activation is likely to contribute to neuronal damage in the end stages of prion diseases, but is also thought to participate in the initial infection, dissemination and replication stages. Infectious prion particles are likely to bind C1q and activate the complement system. Bound complement proteins may then influence the uptake and transport of prion particles by dendritic cells (DCs) and their subsequent proliferation at sites such as follicular DCs. PMID:17544820

  6. A Dramatic Increase of C1q Protein in the CNS during Normal Aging

    PubMed Central

    Madison, Daniel V.; Mateos, José María; Fraser, Deborah A.; Lovelett, Emilie A.; Coutellier, Laurence; Kim, Leo; Tsai, Hui-Hsin; Huang, Eric J.; Rowitch, David H.; Berns, Dominic S.; Tenner, Andrea J.; Shamloo, Mehrdad; Barres, Ben A.

    2013-01-01

    The decline of cognitive function has emerged as one of the greatest health threats of old age. Age-related cognitive decline is caused by an impacted neuronal circuitry, yet the molecular mechanisms responsible are unknown. C1q, the initiating protein of the classical complement cascade and powerful effector of the peripheral immune response, mediates synapse elimination in the developing CNS. Here we show that C1q protein levels dramatically increase in the normal aging mouse and human brain, by as much as 300-fold. This increase was predominantly localized in close proximity to synapses and occurred earliest and most dramatically in certain regions of the brain, including some but not all regions known to be selectively vulnerable in neurodegenerative diseases, i.e., the hippocampus, substantia nigra, and piriform cortex. C1q-deficient mice exhibited enhanced synaptic plasticity in the adult and reorganization of the circuitry in the aging hippocampal dentate gyrus. Moreover, aged C1q-deficient mice exhibited significantly less cognitive and memory decline in certain hippocampus-dependent behavior tests compared with their wild-type littermates. Unlike in the developing CNS, the complement cascade effector C3 was only present at very low levels in the adult and aging brain. In addition, the aging-dependent effect of C1q on the hippocampal circuitry was independent of C3 and unaccompanied by detectable synapse loss, providing evidence for a novel, complement- and synapse elimination-independent role for C1q in CNS aging. PMID:23946404

  7. Chromosomal Abnormalities Subdivide Ependymal Tumors into Clinically Relevant Groups

    PubMed Central

    Hirose, Yuichi; Aldape, Kenneth; Bollen, Andrew; James, C. David; Brat, Daniel; Lamborn, Kathleen; Berger, Mitchel; Feuerstein, Burt G.

    2001-01-01

    Ependymoma occurs most frequently within the central nervous system of children and young adults. We determined relative chromosomal copy-number aberrations in 44 ependymomas using comparative genomic hybridization. The study included 24 intracranial and 20 spinal cord tumors from pediatric and adult patients. Frequent chromosomal aberrations in intracranial tumors were gain of 1q and losses on 6q, 9, and 13. Gain of 1q and loss on 9 were preferentially associated with histological grade 3 tumors. On the other hand, gain on chromosome 7 was recognized almost exclusively in spinal cord tumors, and was associated with various other chromosomal aberrations including frequent loss of 22q. We conclude that cytogenetic analysis of ependymomas may help to classify these tumors and provide leads concerning their initiation and progression. The relationship of these aberrations to patient outcome needs to be addressed. PMID:11238062

  8. Juvenile Delinquency: An Introduction

    ERIC Educational Resources Information Center

    Smith, Carolyn A.

    2008-01-01

    Juvenile Delinquency is a term which is often inaccurately used. This article clarifies definitions, looks at prevalence, and explores the relationship between juvenile delinquency and mental health. Throughout, differences between males and females are explored. (Contains 1 table.)

  9. Juvenile Arrests 1996. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    In 1996, law enforcement agencies in the United States made an estimated 2.9 million arrests of persons under the age of 18. According to Federal Bureau of Investigation (FBI) figures, juveniles accounted for 19% of all arrests and 19% of all violent crime in 1996. The substantial growth in juvenile crime that began in the late 1980s peaked in…

  10. Juvenile Arrests, 1999. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This bulletin presents a summary and analysis of national and state juvenile arrest data for 1999. Data come from the FBI's annual "Crime in the United States" report, which offers the estimated number of crimes reported to law enforcement agencies. The 1999 murder rate was the lowest since 1966. Of the nearly 1,800 juveniles murdered in 1999, 33…

  11. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Puzzanchera, Charles

    2009-01-01

    This Bulletin summarizes 2007 juvenile crime and arrest data reported by local law enforcement agencies across the country and cited in the FBI report, "Crime in the United States 2007." The Bulletin describes the extent and nature of juvenile crime that comes to the attention of the justice system. It serves as a baseline for comparison for…

  12. Juvenile Arrests, 2000. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This bulletin examines the national and state juvenile arrest rate in 2000 using data reported annually by local law enforcement agencies nationwide to the FBI's Uniform Crime Reporting program. Results indicate that the murder rate in 2000 was the lowest since 1965; juvenile arrests for violence in 2000 were the lowest since 1988; few juveniles…

  13. Juvenile Arrests, 1998. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This report provides a summary and analysis of national and state juvenile arrest data in the United States. In 1998, law enforcement agencies made an estimated 2.6 million arrests of persons under age 18. Federal Bureau of Investigations statistics indicate that juveniles account for 18% of all arrests, and 17% of all violent crime arrests in…

  14. C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.

    PubMed

    Cai, Yitian; Teo, Boon Heng Dennis; Yeo, Joo Guan; Lu, Jinhua

    2015-09-11

    In infection, complement C1q recognizes pathogen-congregated antibodies and elicits complement activation. Among endogenous ligands, C1q binds to DNA and apoptotic cells, but whether C1q binds to nuclear DNA in apoptotic cells remains to be investigated. With UV irradiation-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 h, binding concentrated in the nuclei to the nucleolus but not the chromatins. When nucleoli were isolated from non-apoptotic cells, C1q also bound to these structures. In vivo, C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. This was inhibited by the C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduces autoimmunity. These findings help us to understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus. PMID:26231209

  15. Juveniles in court.

    PubMed

    Soulier, Matthew F; Scott, Charles L

    2010-01-01

    Nineteenth-century American reformers were concerned about the influence of immaturity and development in juvenile offenses. They responded to their delinquent youths through the creation of juvenile courts. This early American juvenile justice system sought to treat children as different from adults and to rehabilitate wayward youths through the state's assumption of a parental role. Although these rehabilitative goals were never fully realized, the field of American child psychiatry was spawned from these efforts on behalf of delinquent youths. Early child psychiatrists began by caring for juvenile offenders. The function of a child psychiatrist with juvenile delinquents expanded beyond strictly rehabilitation, however, as juvenile courts evolved to resemble criminal adult courts-due to landmark Supreme Court decisions and also juvenile legislation between 1966 and 1975. In response to dramatically increased juvenile violence and delinquency rates in the 1980s, juvenile justice became more retributional, and society was forced to confront issues such as capital punishment for juveniles, their transfer to adult courts, and their competency to stand trial. In the modern juvenile court, child psychiatrists are often asked to participate in the consideration of such issues because of their expertise in development. In that context we review the role of psychiatrists in assisting juvenile courts. PMID:21080770

  16. Concepts Shaping Juvenile Justice

    ERIC Educational Resources Information Center

    White, Rob

    2008-01-01

    Rob White's paper explores ways in which community building can be integrated into the practices of juvenile justice work. He provides a model of what can be called "restorative social justice", one that builds upon the juvenile conferencing model by attempting to fuse social justice concerns with progressive juvenile justice practices.

  17. Juvenile Court Statistics - 1972.

    ERIC Educational Resources Information Center

    Office of Youth Development (DHEW), Washington, DC.

    This report is a statistical study of juvenile court cases in 1972. The data demonstrates how the court is frequently utilized in dealing with juvenile delinquency by the police as well as by other community agencies and parents. Excluded from this report are the ordinary traffic cases handled by juvenile court. The data indicate that: (1) in…

  18. Characterization of a gC1qR from the giant freshwater prawn, Macrobrachium rosenbergii.

    PubMed

    Ye, Ting; Huang, Xin; Wang, Xian-Wei; Shi, Yan-Ru; Hui, Kai-Min; Ren, Qian

    2015-03-01

    gC1qR, as a multicompartmental and a multifunctional protein, plays an important role in innate immunity. In this study, a gC1qR homolog (MrgC1qR) in the giant freshwater prawn, Macrobrachium rosenbergii was identified. MrgC1qR, a 258-amino-acid polypeptide, shares high identities with gC1qR from other species. MrgC1qR gene was expressed in different tissues and was highest expressed in the hepatopancreas. In addition, the MrgC1qR transcript was significantly enhanced after 6 h of white spot syndrome virus (WSSV) infection or post 2 h, 24 h of Vibrio anguillarum challenge compared to appropriate controls. Moreover, recombinant MrgC1qR (rMrgC1qR) had bacterial binding activity, the result also revealed that rMrgC1qR could bind pathogen-associated molecular patterns (PAMPs) such as LPS or PGN, suggesting that MrgC1qRmight function as a pathogen-recognition receptor (PRR). Furthermore, glutathione S-transferase (GST) pull-down assays showed that rMrgC1qR with GST-tag could bind to rMrFicolin1 or rMrFicolin2 with His-tag. Altogether, these results may demonstrate a role for MrgC1qR in innate immunity in the giant freshwater prawns. PMID:25555810

  19. Translocation 10;18 in a patient with juvenile neuronal ceroid-lipofuscinosis (Batten disease)

    SciTech Connect

    Tuck-Muller, C.M.; Li, S.; Chen, H.

    1995-06-05

    We report the first observation of a chromosome abnormality in a patient with typical juvenile ceroid-lipfuscinosis (NCL), who was found to have an apparently balanced translocation between chromosomes 10 and 18 (t(10;18)(q22;q21.1)). Since juvenile NCL was previously mapped to 16p12, this report raises the possibility of heterogeneity in this form of NCL. 22 refs., 2 figs.

  20. Understanding the impact of 1q21.1 copy number variant

    PubMed Central

    2011-01-01

    Background 1q21.1 Copy Number Variant (CNV) is associated with a highly variable phenotype ranging from congenital anomalies, learning deficits/intellectual disability (ID), to a normal phenotype. Hence, the clinical significance of this CNV can be difficult to evaluate. Here we described the consequences of the 1q21.1 CNV on genome-wide gene expression and function of selected candidate genes within 1q21.1 using cell lines from clinically well described subjects. Methods and Results Eight subjects from 3 families were included in the study: six with a 1q21.1 deletion and two with a 1q21.1 duplication. High resolution Affymetrix 2.7M array was used to refine the 1q21.1 CNV breakpoints and exclude the presence of secondary CNVs of pathogenic relevance. Whole genome expression profiling, studied in lymphoblast cell lines (LBCs) from 5 subjects, showed enrichment of genes from 1q21.1 in the top 100 genes ranked based on correlation of expression with 1q21.1 copy number. The function of two top genes from 1q21.1, CHD1L/ALC1 and PRKAB2, was studied in detail in LBCs from a deletion and a duplication carrier. CHD1L/ALC1 is an enzyme with a role in chromatin modification and DNA damage response while PRKAB2 is a member of the AMP kinase complex, which senses and maintains systemic and cellular energy balance. The protein levels for CHD1L/ALC1 and PRKAB2 were changed in concordance with their copy number in both LBCs. A defect in chromatin remodeling was documented based on impaired decatenation (chromatid untangling) checkpoint (DCC) in both LBCs. This defect, reproduced by CHD1L/ALC1 siRNA, identifies a new role of CHD1L/ALC1 in DCC. Both LBCs also showed elevated levels of micronuclei following treatment with a Topoisomerase II inhibitor suggesting increased DNA breaks. AMP kinase function, specifically in the deletion containing LBCs, was attenuated. Conclusion Our studies are unique as they show for the first time that the 1q21.1 CNV not only causes changes in the

  1. Chromosomal Flexibility

    ERIC Educational Resources Information Center

    Journal of College Science Teaching, 2005

    2005-01-01

    Scientists have shown that a genetic element on one chromosome may direct gene activity on another. Howard Hughes Medical Institute (HHMI) researchers report that a multitasking master-control region appears to over-see both a set of its own genes and a related gene on a nearby chromosome. The findings reinforce the growing importance of location…

  2. Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages.

    PubMed

    Thanei, Sophia; Trendelenburg, Marten

    2016-03-01

    Anti-C1q autoantibodies (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE) and correlate with the occurrence of proliferative lupus nephritis. A previous study of anti-C1q in experimental lupus nephritis demonstrated an important role for FcγRs in the pathogenesis of lupus nephritis, suggesting a direct effect on phagocytes. Therefore, we developed an in vitro model to study the effect of SLE patient-derived anti-C1q bound to immobilized C1q (imC1q) on human monocyte-derived macrophages (HMDMs) obtained from healthy donors and SLE patients. HMDMs were investigated by analyzing the cell morphology, LPS-induced cytokine profile, surface marker expression, and phagocytosis rate of apoptotic Jurkat cells. Morphologically, bound anti-C1q induced cell aggregations of HMDMs compared with imC1q or IgG alone. In addition, anti-C1q reversed the effect of imC1q alone, shifting the LPS-induced cytokine release toward a proinflammatory response. FcγR-blocking experiments revealed that the secretion of proinflammatory cytokines was mediated via FcγRII. The anti-C1q-induced inflammatory cytokine profile was accompanied by a downregulation of CD163 and an upregulation of LPS-induced CD80, CD274, and MHC class II. Finally, HMDMs primed on bound anti-C1q versus imC1q alone displayed a significantly lower phagocytosis rate of early and late apoptotic cells accompanied by a reduced Mer tyrosine kinase expression. Interestingly, anti-C1q-dependent secretion of proinflammatory cytokines was similar in SLE patient-derived cells, with the exception that IL-10 was slightly increased. In conclusion, anti-C1q induced a proinflammatory phenotype in HMDMs reversing the effects of imC1q alone. This effect might exacerbate underlying pathogenic mechanisms in lupus nephritis. PMID:26829984

  3. Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations.

    PubMed

    Brisset, Sophie; Capri, Yline; Briand-Suleau, Audrey; Tosca, Lucie; Gras, Domitille; Fauret-Amsellem, Anne-Laure; Pineau, Dominique; Saada, Julien; Ortonne, Valérie; Verloes, Alain; Goossens, Michel; Tachdjian, Gérard; Métay, Corinne

    2015-09-01

    We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype. PMID:26162704

  4. An amphioxus gC1q protein binds human IgG and initiates the classical pathway: Implications for a C1q-mediated complement system in the basal chordate.

    PubMed

    Gao, Zhan; Li, Mengyang; Ma, Jie; Zhang, Shicui

    2014-12-01

    The origin of the classical complement pathway remains open during chordate evolution. A C1q-like member, BjC1q, was identified in the basal chordate amphioxus. It is predominantly expressed in the hepatic caecum, hindgut, and notochord, and is significantly upregulated following challenge with bacteria or lipoteichoic acid and LPS. Recombinant BjC1q and its globular head domain specifically interact with lipoteichoic acid and LPS, but BjC1q displays little lectin activity. Moreover, rBjC1q can assemble to form the high molecular weight oligomers necessary for binding to proteases C1r/C1s and for complement activation, and binds human C1r/C1s/mannan-binding lectin-associated serine protease-2 as well as amphioxus serine proteases involved in the cleavage of C4/C2, and C3 activation. Importantly, rBjC1q binds with human IgG as well as an amphioxus Ig domain containing protein, resulting in the activation of the classical complement pathway. This is the first report showing that a C1q-like protein in invertebrates is able to initiate classical pathway, raising the possibility that amphioxus possesses a C1q-mediated complement system. It also suggests a new scenario for the emergence of the classical complement pathway, in contrast to the proposal that the lectin pathway evolved into the classical pathway. PMID:25174509

  5. Constructions of Optimal (v,{4,5,6},1,Q)-OOCs

    NASA Astrophysics Data System (ADS)

    Li, Xiyang; Fan, Pingzhi; Wu, Dianhua

    Optical code-division multiple-access (OCDMA) is a promising technique for multimedia transmission in fiber-optic local-area networks (LANs). Variable-weight optical orthogonal codes (OOCs) can be used for OCDMA networks supporting multiple quality of services (QoS). Most constructions for optimal variable-weight OOCs have focused on the case where the number of distinct Hamming weights of all codewords is equal to two, and the codewords of weight 3 are normally included. In this letter, four explicit constructions of optimal (v,{4,5,6},1,Q)-OOCs are presented, and more new optimal (v,{4,5,6},1,Q)-OOCs are obtained via recursive constructions. These improve the existing results on optimal variable-weight OOCs with at least three distinct Hamming weights and minimum Hamming weight 4.

  6. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    SciTech Connect

    Tsien, F.; Shapira, E.; Carvalho, T.

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  7. [Allelic disbalance in 1q32 area and microsatellite instability renal papillary adenocarcinoma].

    PubMed

    Moskvinina, L V; Mikhaĭlenko, D S; Andreeva, Iu Iu; Strel'nikov, V V; Zaletaev, D V

    2012-01-01

    Papillary adenocarcinoma is an abundant form of renal cell carcinoma. At present any diagnostic and prognostic molecular markers of papillary adenocarcinoma are absent, however some cytogenetic and molecular-genetic features of disease are known. According to literary data, the 1q32 duplication is associated with progressive deterioration of primary tumor. We have done a genetic typing (D1S2142 and D1S3465 locus) of 39 papillary adenocarcinoma cases, used PCR and fragment analyses of the 1q32 area. Frequency of the allelic disbalance was 36.8%; the microsatellite instability was found out in 48.7% of cases. The association of genetic disturbances with clinic-morphological features of papillary adenocarcinoma wasn't revealed. In some cases genetic heterogeneity of tumor-adjacent renal parenchyma and primary tumors was found out at multifocal renal carcinoma. For the first time we ve demonstrated that the allelic disbalance in 1q32 area and the microsatellite instability are frequent molecular-genetic disturbances in sporadic papillary carcinomas at all stages of the disease. Probably, the microsatellite instability is connected with progressive deterioration of primary tumor at renal papillary adenocarcinoma. PMID:22880406

  8. Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q

    PubMed Central

    Cho, Kyoung Joo; Cheon, So Young; Kim, Gyung Whan

    2016-01-01

    Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been hypothesized to participate in the pathology of neurodegenerative diseases. The systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of selective striatal lesions. However, it remains unclear whether specific neurons are selectively targeted in 3-NP-infused striatal degeneration. Recently, it has been proposed that complement-mediated synapse elimination may be reactivated aberrantly in the pathology of neurodegenerative diseases. We hypothesized that ASK1 is involved in striatal astrocyte reactivation; reactive astrocyte secretes molecules detrimental to neuron; and striatal neurons are more susceptible to these factors. Our results indicate that striatal astrocyte is reactivated and ASK1 level increases after 3-NP general and chronic infusion. Reactive striatal astrocyte increases TGF-beta differentially to cortex and striatum. ASK1 may be involved in regulation of astrocyte TGF-beta and it is linked to the C1q level in spatial and temporal, and moreover in the earlier stage of progressing striatal neuronal loss. Conclusively the present study suggests that ASK1 mediates 3-NP toxicity and regulates C1q level through the astrocyte TGF-beta. And also it may suggest that C1q level may be a surrogate of prediction marker representing neurodegenerative disease progress before developing behavioral impairment. PMID:26728245

  9. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  10. Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein.

    PubMed

    Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M; Di Guilmi, Anne Marie; Frachet, Philippe

    2012-12-14

    C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (K(D) = 0.34-2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response. PMID:23086952

  11. One adaptive synchronization approach for fractional-order chaotic system with fractional-order 1 < q < 2.

    PubMed

    Zhou, Ping; Bai, Rongji

    2014-01-01

    Based on a new stability result of equilibrium point in nonlinear fractional-order systems for fractional-order lying in 1 < q < 2, one adaptive synchronization approach is established. The adaptive synchronization for the fractional-order Lorenz chaotic system with fractional-order 1 < q < 2 is considered. Numerical simulations show the validity and feasibility of the proposed scheme. PMID:25247207

  12. Structural and Functional Characterization of a Single-Chain Form of the Recognition Domain of Complement Protein C1q

    PubMed Central

    Moreau, Christophe; Bally, Isabelle; Chouquet, Anne; Bottazzi, Barbara; Ghebrehiwet, Berhane; Gaboriaud, Christine; Thielens, Nicole

    2016-01-01

    Complement C1q is a soluble pattern recognition molecule comprising six heterotrimeric subunits assembled from three polypeptide chains (A–C). Each heterotrimer forms a collagen-like stem prolonged by a globular recognition domain. These recognition domains sense a wide variety of ligands, including pathogens and altered-self components. Ligand recognition is either direct or mediated by immunoglobulins or pentraxins. Multivalent binding of C1q to its targets triggers immune effector mechanisms mediated via its collagen-like stems. The induced immune response includes activation of the classical complement pathway and enhancement of the phagocytosis of the recognized target. We report here, the first production of a single-chain recombinant form of human C1q globular region (C1q-scGR). The three monomers have been linked in tandem to generate a single continuous polypeptide, based on a strategy previously used for adiponectin, a protein structurally related to C1q. The resulting C1q-scGR protein was produced at high yield in stably transfected 293-F mammalian cells. Recombinant C1q-scGR was correctly folded, as demonstrated by its X-ray crystal structure solved at a resolution of 1.35 Å. Its interaction properties were assessed by surface plasmon resonance analysis using the following physiological C1q ligands: the receptor for C1q globular heads, the long pentraxin PTX3, calreticulin, and heparin. The 3D structure and the binding properties of C1q-scGR were similar to those of the three-chain fragment generated by collagenase digestion of serum-derived C1q. Comparison of the interaction properties of the fragments with those of native C1q provided insights into the avidity component associated with the hexameric assembly of C1q. The interest of this functional recombinant form of the recognition domains of C1q in basic research and its potential biomedical applications are discussed. PMID:26973654

  13. Soluble gC1qR in Blood and Body Fluids: Examination in a Pancreatic Cancer Patient Cohort

    PubMed Central

    Peerschke, Ellinor IB; Brandwijk, Ricardo JMGE; Dembitzer, Francine R; Kinoshita, Yayoi; Ghebrehiwet, Berhane

    2015-01-01

    Background gC1qR is a multifunctional cellular protein that has been linked to inflammation and cancer. gC1qR is highly upregulated in adenocarcinomas as compared to normal tissue counterparts, and soluble gC1qR (sgC1qR) has been detected in vitro in the pericellular milieu of proliferating malignant cells. Aim The present study explored the tissue expression of gC1qR in pancreatic cancer by immunohistochemistry, and the presence of sgC1qR in vivo, by examining blood and malignant effusions from patients with metastatic pancreatic adenocarcinoma. Methods Tissue expression of gC1qR by pancreatic adenocarcinoma was visualized by immunohistochemistry. SgC1qR was quantified in serum from healthy volunteers (n=20) and pancreatic cancer patients (n=34), as well as in malignant pleural (n=23) and peritoneal effusions (n=27), using a newly developed, sensitive immunocapture sandwich ELISA. Results Overexpression of gC1qR was confirmed in pancreatic adenocarcinoma compared to nonmalignant pancreatic tissue. Moreover, increased serum levels of sgC1qR (0.29 ± 0.22 ng/ml) were noted in patients with metastatic pancreatic cancer compared to healthy controls (0.15 ± 0.10 ng/ml) (mean ± S.D.) (p=0.035). In 11 of 16 patients for whom sequential samples were available, serum sgC1qR levels rose with disease progression, and paralleled changes in tumor biomarkers, CEA and CA19.9. In addition to blood, sgC1qR was detected in malignant pleural (0.55 ± 0.47 ng/ml) and peritoneal effusions (0.57 ± 0.38 ng/ml). Conclusion This study provides the first evidence for the presence of sgC1qR in vivo. The ability to detect sgC1qR in blood and body fluids will enable further studies to elucidate its pathophysiology in malignancy. PMID:26973884

  14. Complimentary action: C1q increases ganglion cell survival in an in vitro model of retinal degeneration.

    PubMed

    Taylor, Linnéa; Arnér, Karin; Blom, Anna M; Ghosh, Fredrik

    2016-09-15

    Using a previously described retinal explant culture system as an acute injury model, we here explore the role of C1q, the initiator of the classical complement pathway, in neuronal cell survival and retinal homeostasis. Full-thickness adult rat retinal explants were divided into four groups, receiving the following supplementation: C1q (50nM), C1-inhibitor (C1-inh; Berinert; 500mg/l), C1q+C1-inh, and no supplementation (culture controls). Explants were kept for 12h or 2days after which they were examined morphologically and with a panel of immunohistochemical markers. C1q supplementation protects ganglion cells from degeneration within the explant in vitro system. This effect is correlated to an attenuated endogenous production of C1q, and a quiesced gliotic response. PMID:27609284

  15. Calreticulin contributes to C1q-dependent recruitment of microglia in the leech Hirudo medicinalis following a CNS injury

    PubMed Central

    Le Marrec-Croq, Françoise; Bocquet-Garcon, Annelise; Vizioli, Jacopo; Vancamp, Christelle; Drago, Francesco; Franck, Julien; Wisztorski, Maxence; Salzet, Michel; Sautiere, Pierre-Eric; Lefebvre, Christophe

    2014-01-01

    Background The medicinal leech is considered as a complementary and appropriate model to study immune functions in the central nervous system (CNS). In a context in which an injured leech’s CNS can naturally restore normal synaptic connections, the accumulation of microglia (immune cells of the CNS that are exclusively resident in leeches) has been shown to be essential at the lesion to engage the axonal sprouting. HmC1q (Hm for Hirudo medicinalis) possesses chemotactic properties that are important in the microglial cell recruitment by recognizing at least a C1q binding protein (HmC1qBP alias gC1qR). Material/Methods Recombinant forms of C1q were used in affinity purification and in vitro chemotaxis assays. Anti-calreticulin antibodies were used to neutralize C1q-mediated chemotaxis and locate the production of calreticulin in leech CNS. Results A newly characterized leech calreticulin (HmCalR) has been shown to interact with C1q and participate to the HmC1q-dependent microglia accumulation. HmCalR, which has been detected in only some microglial cells, is consequently a second binding protein for HmC1q, allowing the chemoattraction of resident microglia in the nerve repair process. Conclusions These data give new insight into calreticulin/C1q interaction in an immune function of neuroprotection, suggesting another molecular target to use in investigation of microglia reactivity in a model of CNS injury. PMID:24747831

  16. Immune Complexes in Juvenile Idiopathic Arthritis

    PubMed Central

    Moore, Terry L.

    2016-01-01

    Juvenile idiopathic arthritis (JIA) reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs) and associated complement activation by-products in their sera. Immune complexes (ICs) have been detected in patients’ sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column, C1q solid-phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these ICs has shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF), isotypes of anti-cyclic citrullinated peptide (CCP) antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC) were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of the immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We will further address possible therapeutic modalities that could be instituted as a result of the information gathered by the presence of ICs in JIA. PMID:27242784

  17. Immune Complexes in Juvenile Idiopathic Arthritis.

    PubMed

    Moore, Terry L

    2016-01-01

    Juvenile idiopathic arthritis (JIA) reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs) and associated complement activation by-products in their sera. Immune complexes (ICs) have been detected in patients' sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column, C1q solid-phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these ICs has shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF), isotypes of anti-cyclic citrullinated peptide (CCP) antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC) were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of the immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We will further address possible therapeutic modalities that could be instituted as a result of the information gathered by the presence of ICs in JIA. PMID:27242784

  18. Juvenile Confinement in Context

    ERIC Educational Resources Information Center

    Mendel, Richard A.

    2012-01-01

    For more than a century, the predominant strategy for the treatment and punishment of serious and sometimes not-so-serious juvenile offenders in the United States has been placement into large juvenile corrections institutions, alternatively known as training schools, reformatories, or youth corrections centers. America's heavy reliance on…

  19. Helpful Juvenile Detention.

    ERIC Educational Resources Information Center

    Roush, David W.

    1999-01-01

    Presents a comprehensive, research-based rationale for rejecting "get-tough," punitive approaches to juvenile detention and implementing "helpful programs" in detention settings instead. Offers a review of the information that explains why and how juvenile detention should be a first step in the treatment of young offenders, rather than simply a…

  20. Standards for Juvenile Justice

    ERIC Educational Resources Information Center

    Flicker, Barbara

    1977-01-01

    The Juvenile Justice Standards Project at New York University has proposed a plan to restructure family court procedure. These standards, outlined here by a former project director, cover significant aspects of the relationship of juveniles to social institutions. (Editor/RK)

  1. Juvenile giant fibroadenoma

    PubMed Central

    Yagnik, Vipul D.

    2011-01-01

    Fibroadenomas are benign solid tumor associated with aberration of normal lobular development. Juvenile giant fibroadenoma is usually single and >5 cm in size /or >500 gms in weight. Important differential diagnoses are: phyllodes tumor and juvenile gigantomastia. Simple excision is the treatment of choice. PMID:24765310

  2. Guide to Juvenile Restitution.

    ERIC Educational Resources Information Center

    Schneider, Anne L., Ed.

    This guide is designed to assist programs in developing, expanding, or improving restitution activities for juvenile offenders. The guide is divided into five major sections. Part I focuses on the most fundamental decisions for restitution programs: program philosophy and goals, organizational structure, location within the juvenile justice…

  3. Juvenile Firesetter Intervention Handbook.

    ERIC Educational Resources Information Center

    Gaynor, Jessica

    This handbook is designed to teach communities how to develop an effective juvenile firesetter intervention program. The six chapters of this handbook can be viewed as the six building blocks essential to construct a successful program. The cornerstone of the blueprint is understanding the personality profiles of juvenile firesetters and their…

  4. Juvenile Delinquency in China.

    ERIC Educational Resources Information Center

    Epstein, Irving, Ed.

    1986-01-01

    Contains nine articles which describe the causes and treatment of juvenile delinquency in China. Focuses on the social causes of delinquency, family factors shaping juvenile crimes and mistakes, criminal peer groups, psychological factors related to delinquency, and the role of education in prevention of delinquency. (JDH)

  5. Renewing Juvenile Justice

    ERIC Educational Resources Information Center

    Macallair, Daniel; Males, Mike; Enty, Dinky Manek; Vinakor, Natasha

    2011-01-01

    The Center on Juvenile and Criminal Justice (CJCJ) was commissioned by Sierra Health Foundation to critically examine California's juvenile justice system and consider the potential role of foundations in promoting systemic reform. The information gathered by CJCJ researchers for this report suggests that foundations can perform a key leadership…

  6. Synthetic chromosomes.

    PubMed

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes. PMID:26111960

  7. C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation

    PubMed Central

    Bulla, Roberta; Tripodo, Claudio; Rami, Damiano; Ling, Guang Sheng; Agostinis, Chiara; Guarnotta, Carla; Zorzet, Sonia; Durigutto, Paolo; Botto, Marina; Tedesco, Francesco

    2016-01-01

    Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa−/−) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa−/− mice. Bone marrow (BM) chimeras between C1qa−/− and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth. PMID:26831747

  8. Chromosome and cell genetics

    SciTech Connect

    Sharma, A.K.; Sharma, A.

    1985-01-01

    This book contains 11 chapters. Some of the titles are: Chromosomes in differentiation; Chromosome axis; Nuclear and organelle split genes; Chemical mutagenesis; and Chromosome architecture and additional elements.

  9. Complement protein C1q modulates neurite outgrowth in vitro and spinal cord axon regeneration in vivo.

    PubMed

    Peterson, Sheri L; Nguyen, Hal X; Mendez, Oscar A; Anderson, Aileen J

    2015-03-11

    Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons to regenerate and results in lifelong functional deficits. The inflammatory response to CNS trauma is mediated by a diverse set of cells and proteins with varied, overlapping, and opposing effects on histological and behavioral recovery. Importantly, the contribution of individual inflammatory complement proteins to spinal cord injury (SCI) pathology is not well understood. Although the presence of complement components increases after SCI in association with axons and myelin, it is unknown whether complement proteins affect axon growth or regeneration. We report a novel role for complement C1q in neurite outgrowth in vitro and axon regrowth after SCI. In culture, C1q increased neurite length on myelin. Protein and molecular assays revealed that C1q interacts directly with myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth-enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons, complement C1q blocked both the growth inhibitory and repulsive turning effects of MAG in vitro. Furthermore, C1q KO mice demonstrated increased sensory axon turning within the spinal cord lesion after SCI with peripheral conditioning injury, consistent with C1q-mediated neutralization of MAG. Finally, we present data that extend the role for C1q in axon growth and guidance to include the sprouting patterns of descending corticospinal tract axons into spinal gray matter after dorsal column transection SCI. PMID:25762679

  10. Complement Protein C1q Modulates Neurite Outgrowth In Vitro and Spinal Cord Axon Regeneration In Vivo

    PubMed Central

    Peterson, Sheri L.; Nguyen, Hal X.; Mendez, Oscar A.

    2015-01-01

    Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons to regenerate and results in lifelong functional deficits. The inflammatory response to CNS trauma is mediated by a diverse set of cells and proteins with varied, overlapping, and opposing effects on histological and behavioral recovery. Importantly, the contribution of individual inflammatory complement proteins to spinal cord injury (SCI) pathology is not well understood. Although the presence of complement components increases after SCI in association with axons and myelin, it is unknown whether complement proteins affect axon growth or regeneration. We report a novel role for complement C1q in neurite outgrowth in vitro and axon regrowth after SCI. In culture, C1q increased neurite length on myelin. Protein and molecular assays revealed that C1q interacts directly with myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth-enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons, complement C1q blocked both the growth inhibitory and repulsive turning effects of MAG in vitro. Furthermore, C1q KO mice demonstrated increased sensory axon turning within the spinal cord lesion after SCI with peripheral conditioning injury, consistent with C1q-mediated neutralization of MAG. Finally, we present data that extend the role for C1q in axon growth and guidance to include the sprouting patterns of descending corticospinal tract axons into spinal gray matter after dorsal column transection SCI. PMID:25762679

  11. Deletions in 14q24.1q24.3 are associated with congenital heart defects, brachydactyly, and mild intellectual disability.

    PubMed

    Oehl-Jaschkowitz, Barbara; Vanakker, Olivier M; De Paepe, Anne; Menten, Björn; Martin, Thomas; Weber, Georg; Christmann, Alexander; Krier, Romain; Scheid, Simone; McNerlan, Susan E; McKee, Shane; Tzschach, Andreas

    2014-03-01

    Interstitial deletions of chromosome band 14q24.1q24.3 are apparently very rare. We report on three unrelated patients with overlapping de novo deletions of sizes 5.4, 2.8, and 2.3 Mb in this region. While some clinical problems such as intestinal malrotation, cryptorchidism, and ectopic kidney were only observed in single patients, all three patients had mild intellectual disability, congenital heart defects (truncus arteriosus, pulmonary atresia, atrial septal defect, and/or ventricular septal defect), brachydactyly, hypertelorism, broad nasal bridge, and thin upper lips. Likely haploinsufficiency of one or several of the 19 genes in the common deleted interval (ACTN1, DCAF5, EXD2, GALNTL1, ERH, SLC39A9, PLEKHD1, CCDC177, KIAA0247, LOC100289511, SRSF5, SLC10A1, SMOC1, SLC8A3, ADAM21P1, COX16, SYNJ2BP, SYNJ2BP-COX16, ADAM21) was responsible for these manifestations, but apart from SMOC1, mutations in which cause autosomal recessive Waardenburg anophthalmia syndrome, and ACTN1, mutations in which are associated with congenital macrothrombocytopenia, no disease associations have so far been reported for the other genes. Functional studies and a systematic search for mutations or chromosome aberrations in this region will elucidate the role of individual genes in the clinical manifestations and will provide insight into the underlying biological mechanisms. PMID:24357125

  12. Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular "heads" of C1q (gC1q-R).

    PubMed Central

    Joseph, K; Ghebrehiwet, B; Peerschke, E I; Reid, K B; Kaplan, A P

    1996-01-01

    High molecular weight kininogen (HK) and factor XII are known to bind to human umbilical vein endothelial cells (HUVEC) in a zinc-dependent and saturable manner indicating that HUVEC express specific binding site(s) for those proteins. However, identification and immunochemical characterization of the putative receptor site(s) has not been previously accomplished. In this report, we have identified a cell surface glycoprotein that is a likely candidate for the HK binding site on HUVECs. When solubilized HUVEC membranes were subjected to an HK-affinity column in the presence or absence of 50 microM ZnCl2 and the bound membrane proteins eluted, a single major protein peak was obtained only in the presence of zinc. SDS/PAGE analysis and silver staining of the protein peak revealed this protein to be 33 kDa and partial sequence analysis matched the NH2 terminus of gC1q-R, a membrane glycoprotein that binds to the globular "heads" of C1q. Two other minor proteins of approximately 70 kDa and 45 kDa were also obtained. Upon analysis by Western blotting, the 33-kDa band was found to react with several monoclonal antibodies (mAbs) recognizing different epitopes on gC1q-R. Ligand and dot blot analyses revealed zinc-dependent binding of biotinylated HK as well as biotinylated factor XII to the isolated 33-kDa HUVEC molecule as well as recombinant gC1q-R. In addition, binding of 125I-HK to HUVEC cells was inhibited by selected monoclonal anti-gC1q-R antibodies. C1q, however, did not inhibit 125I-HK binding to HUVEC nor did those monoclonals known to inhibit C1q binding to gC1q-R. Taken together, the data suggest that HK (and factor XII) bind to HUVECs via a 33-kDa cell surface glycoprotein that appears to be identical to gC1q-R but interact with a site on gC1q-R distinct from that which binds C1q. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8710908

  13. Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.

    PubMed

    Matsuda, Keiko; Budisantoso, Timotheus; Mitakidis, Nikolaos; Sugaya, Yuki; Miura, Eriko; Kakegawa, Wataru; Yamasaki, Miwako; Konno, Kohtarou; Uchigashima, Motokazu; Abe, Manabu; Watanabe, Izumi; Kano, Masanobu; Watanabe, Masahiko; Sakimura, Kenji; Aricescu, A Radu; Yuzaki, Michisuke

    2016-05-18

    Postsynaptic kainate-type glutamate receptors (KARs) regulate synaptic network activity through their slow channel kinetics, most prominently at mossy fiber (MF)-CA3 synapses in the hippocampus. Nevertheless, how KARs cluster and function at these synapses has been unclear. Here, we show that C1q-like proteins C1ql2 and C1ql3, produced by MFs, serve as extracellular organizers to recruit functional postsynaptic KAR complexes to the CA3 pyramidal neurons. C1ql2 and C1ql3 specifically bound the amino-terminal domains of postsynaptic GluK2 and GluK4 KAR subunits and the presynaptic neurexin 3 containing a specific sequence in vitro. In C1ql2/3 double-null mice, CA3 synaptic responses lost the slow, KAR-mediated components. Furthermore, despite induction of MF sprouting in a temporal lobe epilepsy model, KARs were not recruited to postsynaptic sites in C1ql2/3 double-null mice, leading to reduced recurrent circuit activities. C1q family proteins, broadly expressed, are likely to modulate KAR function throughout the brain and represent promising antiepileptic targets. PMID:27133466

  14. Juvenile Justice in California, 1983.

    ERIC Educational Resources Information Center

    California State Dept. of Justice, Sacramento. Bureau of Criminal Statistics and Special Services.

    This publication provides an overview of the processing of juvenile delinquency cases through the California juvenile justice system; provides information to aid administrators, planners, and researchers in the administration of juvenile justice; and maintains baseline data for further studies of the system. Information on juvenile arrests and…

  15. Determination of the effective strong coupling constant $\\alpha_{s,g_1}(Q^2)$ from CLAS spin structure function data

    SciTech Connect

    Deur, Alexandre; Burkert, Volker; Chen, Jian-Ping; Korsch, Wolfgang

    2008-07-01

    We present a new extraction of the effective strong coupling constant $\\alpha_{s,g_1}(Q^2)$. The result agrees with a previous determination and extends the measurement of the low and high $Q^2$ behavior of $\\alpha_{s,g_1}(Q^2)$ that was previously deduced from sum rules. In particular, it experimentally verifies the lack of $Q^2$-dependence of $\\alpha_{s,g_1}(Q^2)$ in the low $Q^2$ limit. This fact is necessary for application of the AdS/CFT correspondence to QCD calculations. We provide a physics motivated parameterization of $\\alpha_{s,g_1}(Q^2)$ that can equivalently be used to parameterize the $Q^2$-dependence of the generalized Gerasimov-Drell-Hearn and Bjorken sums.

  16. Common variants of SLAMF1 and ITLN1 on 1q21 are associated with type 2 diabetes in Indian population.

    PubMed

    Tabassum, Rubina; Mahajan, Anubha; Dwivedi, Om Prakash; Chauhan, Ganesh; Spurgeon, Charles J; Kumar, M V Kranthi; Ghosh, Saurabh; Madhu, S V; Mathur, Sandeep K; Chandak, Giriraj R; Tandon, Nikhil; Bharadwaj, Dwaipayan

    2012-03-01

    Though multiple studies link chromosomal regions 1q21-q23 and 20q13 with type 2 diabetes, fine mapping of these regions is yet to confirm gene(s) explaining the linkages. These candidate regions remain unexplored in Indians, which is a high-risk population for type 2 diabetes. Hypothesizing regulatory regions to have a more important role in complex disorders, we examined association of 207 common variants in proximal promoter and untranslated regions of genes on 1q21-23 and 20q13 with type 2 diabetes in 2115 North Indians. Further, top signals were replicated in an independent group of 2085 North Indians. Variants-rs11265455-SLAMF1 (odds ratios (OR)=1.32, P=1.1 × 10(-3)), rs1062827-F11R (OR=1.36, P=1.7 × 10(-3)) and rs12565932-F11R (OR=1.35, P=1.8 × 10(-3)) were top signals for association with type 2 diabetes whereas rs1333062-ITLN1 (OR=1.28, P=3.4 × 10(-3)) showed strongest association in body mass index-stratified analysis. Replication of these four variants confirmed associations of rs11265455-SLAMF1 (OR=1.27, P=9.1 × 10(-3)) and rs1333062-ITLN1 (OR=1.25, P=1.1 × 10(-3)) with type 2 diabetes. Meta-analysis further corroborated the association of rs11265455-SLAMF1 (OR random effect=1.29, P random effect=3.9 × 10(-5)) and rs1333062-ITLN1 (OR random effect=1.19, P random effect=1.8 × 10(-4)). In conclusion, the study demonstrates that variants of SLAMF1 and ITLN1, both implicated in inflammation, are associated with type 2 diabetes in Indians. PMID:22277902

  17. Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.

    PubMed

    Aissani, Brahim; Zhang, Kui; Mensenkamp, Arjen R; Menko, Fred H; Wiener, Howard W

    2015-08-01

    Mutations in fumarate hydratase (FH) on chromosome 1q43 cause a rare cancer syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), but are rare in nonsyndromic and common uterine leiomyoma (UL) or fibroids. Studies suggested that variants in FH or in a linked gene may also predispose to UL. We re-sequenced 2.3 Mb of DNA spanning FH in 96 UL cases and controls from the multiethnic NIEHS-uterine fibroid study, and in 18 HLRCC-associated UL probands from European families then selected 221 informative SNPs for follow-up genotyping. We report promising susceptibility associations with UL peaking at rs78220092 (P=7.0×10(-5)) in the RGS7-FH interval in African Americans. In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10(-4)). We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control. Our fine association mapping and integration of existing gene profiling data showing upregulated expression of the lncRNA and downregulation of PLD5 in fibroids, as compared to matched myometrium, suggest a potential role of this genomic region in UL pathogenesis. While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation. PMID:26113603

  18. Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval

    PubMed Central

    Aissani, Brahim; Zhang, Kui; Mensenkamp, Arjen R; Menko, Fred H; Wiener, Howard W

    2015-01-01

    Mutations in fumarate hydratase (FH) on chromosome 1q43 cause a rare cancer syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), but are rare in nonsyndromic and common uterine leiomyoma (UL) or fibroids. Studies suggested that variants in FH or in a linked gene may also predispose to UL. We re-sequenced 2.3 Mb of DNA spanning FH in 96 UL cases and controls from the multiethnic NIEHS-uterine fibroid study, and in 18 HLRCC-associated UL probands from European families then selected 221 informative SNPs for follow-up genotyping. We report promising susceptibility associations with UL peaking at rs78220092 (P=7.0×10−5) in the RGS7-FH interval in African Americans. In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10−4). We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control. Our fine association mapping and integration of existing gene profiling data showing upregulated expression of the lncRNA and downregulation of PLD5 in fibroids, as compared to matched myometrium, suggest a potential role of this genomic region in UL pathogenesis. While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation. PMID:26113603

  19. Juvenile Sex Offenders.

    PubMed

    Ryan, Eileen P; Otonichar, Joseph M

    2016-07-01

    Sexual offending by juveniles accounts for a sizable percentage of sexual offenses, especially against young children. In this article, recent research on female juvenile sex offenders (JSOs), risk factors for offending in juveniles, treatment, and the ways in which these youth may differ from general delinquents will be reviewed. Most JSOs do not go on to develop paraphilic disorders or to commit sex offenses during adulthood, and as a group, they are more similar to nonsexual offending juvenile delinquents than to adult sex offenders. Recent research has elucidated some differences between youth who commit sex offenses and general delinquents in the areas of atypical sexual interests, the use of pornography, and early sexual victimization during childhood. PMID:27222141

  20. Polyneuropathy in juvenile dermatomyositis.

    PubMed

    Vogelgesang, S A; Gutierrez, J; Klipple, G L; Katona, I M

    1995-07-01

    We describe 2 patients in whom juvenile dermatomyositis (DM) was associated with well defined clinical polyneuropathies, and review the clinical and serological data. Light and electron microscopy were used to study muscle and nerve tissues from one patient. Neuropathy in our patients was associated with ulcerative skin lesions and elevated serum levels of factor VIII related antigen. Light microscopic studies of muscle revealed perifascicular atrophy and microinfarcts consistent with juvenile DM. Light microscopy of the affected sural nerve showed axonal degeneration. Electron microscopy of the same nerve demonstrated capillary endothelial inclusions characteristic of those observed as manifestations of early endothelial injury in juvenile DM muscle tissue. Polyneuropathy in patients with juvenile DM is a rare complication and is likely due to ischemia secondary to endothelial damage. PMID:7562774

  1. Chromosome Microarray.

    PubMed

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  2. Chromosome Analysis

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  3. Challenging behaviour in a patient with schizophrenia and a 1q21.1 duplication

    PubMed Central

    Gulati, Gautam; Behrman, Sophie; Khosla, Vivek; Murphy, Valerie

    2014-01-01

    We report the case of a 42-year-old man with a 22-year history of schizophrenia, necessitating frequent detentions under the Mental Health Act for relapses in his mental state and challenging behaviour which has also brought him into contact with the law. His illness has proven resistant to treatment with conventional strategies and he developed serious priapism with clozapine. His challenging behaviour, some of which is not felt to be associated with schizophrenia, complicates any discharge planning from his current detention. Based on a history of childhood cardiac disease, and mildly atypical facies, a genetic screen was requested which showed a 1q21.1 duplication, likely causal in his schizophrenic illness. A review of proteins coded by the locus of the duplication did not reveal any specific targets for pharmacotherapy. PMID:24973346

  4. Complement C1q Reduces Early Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

    PubMed Central

    Bhatia, Vinay K.; Yun, Sheng; Leung, Viola; Grimsditch, David C.; Benson, G. Martin; Botto, Marina B.; Boyle, Joseph J.; Haskard, Dorian O.

    2007-01-01

    We explored the role of the classic complement pathway in atherogenesis by intercrossing C1q-deficient mice (C1qa−/−) with low-density lipoprotein receptor knockout mice (Ldlr−/−). Mice were fed a normal rodent diet until 22 weeks of age. Aortic root lesions were threefold larger in C1qa−/−/Ldlr−/− mice compared with Ldlr−/− mice (3.72 ± 1.0% aortic root versus 1.1 ± 0.4%; mean ± SEM, P < 0.001). Furthermore, the cellular composition of lesions in C1qa−/−/Ldlr−/− was more complex, with an increase in vascular smooth muscle cells. The greater aortic root lesion size in C1qa−/−/Ldlr−/− mice occurred despite a significant reduction in C5b-9 deposition per lesion unit area, suggesting the critical importance of proximal pathway activity. Apoptotic cells were readily detectable by cleaved caspase-3 staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and electron microscopy in C1qa−/−/Ldlr−/−, whereas apoptotic cells were not detected in Ldlr−/− mice. This is the first direct demonstration of a role for the classic complement pathway in atherogenesis. The greater lesion size in C1qa−/−/Ldlr−/− mice is consistent with the emerging homeostatic role for C1q in the disposal of dying cells. This study suggests the importance of effective apoptotic cell removal for containing the size and complexity of early lesions in atherosclerosis. PMID:17200212

  5. Integrated Genomic and Transcriptional Profiling Identifies Chromosomal Loci with Altered Gene Expression in Cervical Cancer

    PubMed Central

    Wilting, Saskia M.; de Wilde, Jillian; Meijer, Chris J. L. M.; Berkhof, Johannes; Yi, Yajun; van Wieringen, Wessel N.; Braakhuis, Boudewijn J. M.; Meijer, Gerrit A.; Ylstra, Bauke; Snijders, Peter J. F.; Steenbergen, Renske D. M.

    2009-01-01

    For a better understanding of the consequences of recurrent chromosomal alterations in cervical carcinomas, we integrated genome-wide chromosomal and transcriptional profiles of 10 squamous cell carcinomas (SCCs), 5 adenocarcinomas (AdCAs) and 6 normal controls. Previous genomic profiling showed that gains at chromosome arms 1q, 3q, and 20q as well as losses at 8q, 10q, 11q, and 13q were common in cervical carcinomas. Altered regions spanned multiple megabases, and the extent to which expression of genes located there is affected remains unclear. Expression analysis of these previously chromosomally profiled carcinomas yielded 83 genes with significantly differential expression between carcinomas and normal epithelium. Application of differential gene locus mapping (DIGMAP) analysis and the array CGH expression integration tool (ACE-it) identified hotspots within large chromosomal alterations in which gene expression was altered as well. Chromosomal gains of the long arms of chromosome 1, 3, and 20 resulted in increased expression of genes located at 1q32.1-32.2, 3q13.32-23, 3q26.32-27.3, and 20q11.21-13.33, whereas a chromosomal loss of 11q22.3-25 was related to decreased expression of genes located in this region. Overexpression of DTX3L, PIK3R4, ATP2C1, and SLC25A36, all located at 3q21.1-23 and identified by DIGMAP, ACE-it or both, was confirmed in an independent validation sample set consisting of 12 SCCs and 13 normal ectocervical samples. In conclusion, integrated chromosomal and transcriptional profiling identified chromosomal hotspots at 1q, 3q, 11q, and 20q with altered gene expression within large commonly altered chromosomal regions in cervical cancer. PMID:18618715

  6. Microglial activation and increased synthesis of complement component C1q precedes blood-brain barrier dysfunction in rats.

    PubMed

    Lynch, Nicholas J; Willis, Colin L; Nolan, Christopher C; Roscher, Silke; Fowler, Maxine J; Weihe, Eberhard; Ray, David E; Schwaeble, Wilhelm J

    2004-01-01

    A reliable way to visualise the state of microglial activation is to monitor the microglial gene expression profile. Microglia are the only CNS resident cells that synthesise C1q, the recognition sub-component of the classical complement pathway, in vivo. C1q biosynthesis in resting ramified microglia is often low, but it increases dramatically in activated microglia. In this study, the expression of C1q was used to monitor microglial activation at all stages of 3-chloropropanediol-induced neurotoxicity, a new model of blood-brain barrier (BBB) breakdown. In rats, 3-chloropropanediol produces very focused lesions in the brain, characterised by early astrocyte swelling and loss, followed by neuronal death and barrier dysfunction. Using in situ hybridisation, immunohistochemistry, and real-time RT-PCR, we found that increased C1q biosynthesis and microglial activation precede BBB dysfunction by at least 18 and peak 48 h after injection of 3-chloropropanediol, which coincides with the onset of active haemorrhage. Microglial activation is biphasic; an early phase of global activation is followed by a later phase in which microglial activation becomes increasingly focused in the lesions. During the early phase, expression of the pro-inflammatory mediators interleukin-1beta (IL1beta), tumour necrosis factor alpha (TNFalpha) and early growth response-1 (Egr-1) increased in parallel with C1q, but was restricted to the lesions. Expression of C1q (but not IL1beta, TNFalpha or Egr-1) remains high after BBB function is restored, and is accompanied by late up-regulation of the C1q-associated serine proteases, C1r and C1s, suggesting that microglial biosynthesis of the activation complex of the classical pathway may support the removal of cell debris by activation of complement. PMID:14644096

  7. Genetics Home Reference: juvenile polyposis syndrome

    MedlinePlus

    ... In the third type, known as juvenile polyposis coli, affected individuals develop polyps only in their colon. People with generalized juvenile polyposis and juvenile polyposis coli typically develop polyps during childhood. Most juvenile polyps ...

  8. C1q binding and activation of the complement classical pathway by Klebsiella pneumoniae outer membrane proteins.

    PubMed Central

    Albertí, S; Marqués, G; Camprubí, S; Merino, S; Tomás, J M; Vivanco, F; Benedí, V J

    1993-01-01

    The mechanisms of killing of Klebsiella pneumoniae serum-sensitive strains in nonimmune serum by the complement classical pathway have been studied. The bacterial cell surface components that bind C1q more efficiently were identified as two major outer membrane proteins, presumably the porins of this bacterial species. These two outer membrane proteins were isolated from a representative serum-sensitive strain. We have demonstrated that in their purified form, they bind C1q and activate the classical pathway in an antibody-independent manner, with the subsequent consumption of C4 and reduction of the serum total hemolytic activity. Activation of the classical pathway has been observed in human nonimmune serum and agammaglobulinemic serum (both depleted in factor D). Binding of C1q to other components of the bacterial outer membrane, in particular the rough lipopolysaccharide, could not be demonstrated. Activation of the classical pathway by this lipopolysaccharide was also much less efficient than activation by the two outer membrane proteins. The antibody-independent binding of C1q to serum-sensitive strains was independent of the presence of capsular polysaccharide, while strains possessing lipopolysaccharide O antigen bind less C1q and are resistant to complement-mediated killing. Images PMID:8432605

  9. Juvenile Incarceration and Health.

    PubMed

    Barnert, Elizabeth S; Perry, Raymond; Morris, Robert E

    2016-03-01

    Addressing the health status and needs of incarcerated youth represents an issue at the nexus of juvenile justice reform and health care reform. Incarcerated youth face disproportionately higher morbidity and higher mortality compared to the general adolescent population. Dental health, reproductive health, and mental health needs are particularly high, likely as a result of lower access to care, engagement in high-risk behaviors, and underlying health disparities. Violence exposure and injury also contribute to the health disparities seen in this population. Further, juvenile incarceration itself is an important determinant of health. Juvenile incarceration likely correlates with worse health and social functioning across the life course. Correctional health care facilities allow time for providers to address the unmet physical and mental health needs seen in this population. Yet substantial challenges to care delivery in detention facilities exist and quality of care in detention facilities varies widely. Community-based pediatricians can serve a vital role in ensuring continuity of care in the postdetention period and linking youth to services that can potentially prevent juvenile offending. Pediatricians who succeed in understanding and addressing the underlying social contexts of their patients' lives can have tremendous impact in improving the life trajectories of these vulnerable youth. Opportunities exist in clinical care, research, medical education, policy, and advocacy for pediatricians to lead change and improve the health status of youth involved in the juvenile justice system. PMID:26548359

  10. Epidemiology of juvenile violence.

    PubMed

    Farrington, D P; Loeber, R

    2000-10-01

    It is difficult to review the epidemiology of juvenile violence because few studies focus specifically on this topic as opposed to childhood aggression or delinquency in general. More research is needed specifically on juvenile violence, which is generally measured using official records or self-reports. Self-report research shows that a substantial fraction of the male juvenile population commits violence, and that very few violent acts are followed by arrests or convictions. Racial differences in violence may be explainable by reference to racial differences in community contexts. There is a great deal of versatility in juvenile violence. Juveniles who commit one type of violent offense also tend to commit other types and nonviolent offenses. Violent offenders tend to be persistent or frequent offenders, and there is little difference between violent offenders and nonviolent but equally frequent offenders. Nevertheless, there is some degree of specialization in violence. More research is needed to investigate whether risk factors exist for violence that are not risk factors for serious nonviolent delinquency (e.g., biologic factors). Violent juveniles tend to have co-occurring problems such as victimization, substance abuse, and school failure. Often, they might be described as multiple-problem youth. There is considerable continuity from childhood aggression to juvenile violence. An early age of onset of violence predicts a large number of violent offenses. The major long-term risk factors for juvenile violence are individual (high impulsiveness and low intelligence, possibly linked to the executive functions of the brain), family (poor supervision, harsh discipline, child physical abuse, a violent parent, large family size, poverty, a broken family), peer delinquency, gang membership, urban residence, and living in a high-crime neighborhood (characterized by gangs, guns, and drugs in the United States). More research is needed on interactions among risk factors

  11. Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling*

    PubMed Central

    Miao, Haofei; Jia, Yingying; Xie, Sichun; Wang, Xin; Zhao, Jianfei; Chu, Youjun; Zhou, Zhilei; Shi, Zhubing; Song, Xiaomin; Li, Lin

    2014-01-01

    Previously, we have identified Caprin-2 as a new regulator in canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation; moreover, we found that its C-terminal C1q-related domain (Cap2_CRD) is required for this process. Here, we determined the crystal structures of Cap2_CRD from human and zebrafish, which both associate as a homotrimer with calcium located at the symmetric center. Surprisingly, the calcium binding-deficient mutant exists as a more stable trimer than its wild-type counterpart. Further studies showed that this Caprin-2 mutant disabled in binding calcium maintains the activity of promoting LRP5/6 phosphorylation, whereas the mutations disrupting Cap2_CRD homotrimer did impair such activity. Together, our findings suggested that the C-terminal CRD domain of Caprin-2 forms a flexible homotrimer mediated by calcium and that such trimeric assembly is required for Caprin-2 to regulate canonical Wnt signaling. PMID:25331957

  12. Juvenile Sex Offenders.

    PubMed

    Ryan, Eileen P

    2016-01-01

    Public policy has tended to treat juvenile sex offenders (JSOs) as adult sex offenders in waiting, despite research that contradicts this notion. Although as a group, JSOs are more similar to general delinquents than to adult sex offenders, atypical sexual interests and sexual victimization during childhood may be a pathway for sexual offending that differentiates some JSOs from their nonsexually delinquent peers. Developmental considerations must be considered in risk assessment evaluations of these youth. This article reviews theories of sexual offending in youth, risk factors for juvenile offending and reoffending, psychopathology in JSOs, risk assessment, and treatment. PMID:26593121

  13. Relationships between chromosome structure and chromosomal aberrations

    NASA Astrophysics Data System (ADS)

    Eidelman, Yuri; Andreev, Sergey

    An interphase nucleus of human lymphocyte was simulated by the novel Monte Carlo tech-nique. The main features of interphase chromosome structure and packaging were taken into account: different levels of chromatin organisation; nonrandom localisation of chromosomes within a nucleus; chromosome loci dynamics. All chromosomes in a nucleus were modelled as polymer globules. A dynamic pattern of intra/interchromosomal contacts was simulated. The detailed information about chromosomal contacts, such as distribution of intrachromoso-mal contacts over the length of each chromosome and dependence of contact probability on genomic separation between chromosome loci, were calculated and compared to the new exper-imental data obtained by the Hi-C technique. Types and frequencies of simple and complex radiation-induced chromosomal exchange aberrations (CA) induced by X-rays were predicted with taking formation and decay of chromosomal contacts into account. Distance dependence of exchange formation probability was calculated directly. mFISH data for human lymphocytes were analysed. The calculated frequencies of simple CA agreed with the experimental data. Complex CA were underestimated despite the dense packaging of chromosome territories within a nucleus. Possible influence of chromosome-nucleus structural organisation on the frequency and spectrum of radiation-induced chromosome aberrations is discussed.

  14. Juvenile Battens Disease.

    ERIC Educational Resources Information Center

    Gayton, Romayne

    1987-01-01

    Ten children diagnosed with juvenile Battens disease were tested over a three-year period in general intelligence, memory, listening and speech, motor skills, and general learning. Results showed that the patients followed a predetermined pattern but that the time span for development of memory, communication, and behavior problems varied greatly.…

  15. Treating the Juvenile Offender

    ERIC Educational Resources Information Center

    Hoge, Robert D., Ed.; Guerra, Nancy G., Ed.; Boxer, Paul, Ed.

    2008-01-01

    This authoritative, highly readable reference and text is grounded in the latest knowledge on how antisocial and criminal behavior develops in youth and how it can effectively be treated. Contributors describe proven ways to reduce juvenile delinquency by targeting specific risk factors and strengthening young people's personal, family, and…

  16. Scrapie pathogenesis: the role of complement C1q in scrapie agent uptake by conventional dendritic cells.

    PubMed

    Flores-Langarica, Adriana; Sebti, Yasmine; Mitchell, Daniel A; Sim, Robert B; MacPherson, Gordon G

    2009-02-01

    Mice lacking complement components show delayed development of prion disease following peripheral inoculation. The delay could relate to reduced scrapie prion protein (PrP(Sc)) accumulation on follicular dendritic cells (DCs). However conventional DCs (cDCs) play a crucial role in the early pathogenesis of prion diseases and complement deficiency could result in decreased PrP(Sc) uptake by cDCs in the periphery. To explore this possibility, we cultured murine splenic or gut-associated lymph node cDCs with scrapie-infected whole brain homogenate in the presence or absence of complement. Uptake decreased significantly if the serum in the cultures was heat-inactivated. Because heat inactivation primarily denatures C1q, we used serum from C1q(-/-) mice and showed that PrP(Sc) uptake was markedly decreased. PrP(Sc) internalization was saturable and temperature-dependent, suggesting receptor-mediated uptake. Furthermore, uptake characteristics differed from fluid-phase endocytosis. Immunofluorescence showed colocalization of C1q and PrP(Sc), suggesting interaction between these molecules. We evaluated the expression of several complement receptors on cDCs and confirmed that cDCs that take up PrP(Sc) express one of the C1q receptors, calreticulin. Our results show that C1q participates in PrP(Sc) uptake by cDCs, revealing a critical role for cDCs in initial prion capture, an event that takes place before the PrP(Sc) accumulation within the follicular DC network. PMID:19155476

  17. Chromosome alterations in breast carcinomas: frequent involvement of DNA losses including chromosomes 4q and 21q.

    PubMed Central

    Schwendel, A.; Richard, F.; Langreck, H.; Kaufmann, O.; Lage, H.; Winzer, K. J.; Petersen, I.; Dietel, M.

    1998-01-01

    Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated tumours were associated with gains on 1q and 11q12-13 along with losses on 1p21-22, 4q, 13q, 11q21-ter. Undifferentiated breast carcinomas were characterized by additional DNA imbalances, i.e. deletions of 5q13-23, all of chromosome 9, the centromeric part of chromosome 13 including band 13q14 and the overrepresentation of chromosome X. We speculate that these changes are associated with tumour progression of invasive ductal breast cancer. Images Figure 2 Figure 3 PMID:9743305

  18. Complement Component C1q Programs a Pro-Efferocytic Phenotype while Limiting TNFα Production in Primary Mouse and Human Macrophages

    PubMed Central

    Hulsebus, Holly J.; O’Conner, Sean D.; Smith, Emily M.; Jie, Chunfa; Bohlson, Suzanne S.

    2016-01-01

    Deficiency in complement component C1q is associated with an inability to clear apoptotic cells (efferocytosis) and aberrant inflammation in lupus, and identification of the pathways involved in these processes should reveal important regulatory mechanisms in lupus and other autoimmune or inflammatory diseases. In this study, C1q-dependent regulation of TNFα/IL-6 expression and efferocytosis was investigated using primary mouse bone marrow-derived macrophages and human monocyte-derived macrophages. C1q downregulated LPS-dependent TNFα production in mouse and human macrophages. While prolonged stimulation with C1q (18 h) was required to elicit a dampening of TNFα production from mouse macrophages, the human macrophages responded to C1q with immediate downregulation of TNFα. IL-6 production was unchanged in mouse and upregulated by human macrophages following prolonged stimulation with C1q. Our previous studies indicated that C1q programmed enhanced efferocytosis in mouse macrophages by enhancing expression of Mer tyrosine kinase and its ligand Gas6, a receptor–ligand pair that also inhibits proinflammatory signaling. Here, we demonstrated that C1q-dependent programming of human macrophage efferocytosis required protein synthesis; however, neither Mer nor the related receptor Axl was upregulated in human cells. In addition, while the C1q-collagen-like tails are sufficient for promoting C1q-dependent phagocytosis of antibody-coated targets, the C1q-tails failed to program enhanced efferocytosis or dampen TNFα production. These data further elucidate the mechanisms by which C1q regulates proinflammatory signaling and efferocytosis in macrophages, functions that are likely to influence the progression of autoimmunity and chronic inflammation. PMID:27379094

  19. Constitutive heterochromatin of chromosome 1 and Duffy blood group alleles in schizophrenia

    SciTech Connect

    Kosower, N.S.; Gerad, L.; Goldstein, M.; Parasol, N.

    1995-04-24

    Cytogenetic analysis was carried out in unrelated schizophrenic patients, unrelated controls and patients and family members in multiplex families. The size-distribution of chromosome 1 heterochromatic region (1qH, C-band variants) among 21 unrelated schizophrenic patients was different from that found in a group of 46 controls. The patient group had 1qH variants of smaller size than the control group (P < 0.01). Incubation of phytohemagglutinin-treated blood lymphocytes with 5-azacytidine (which causes decondensation and extension of the heterochromatin) led to a lesser degree of heterochromatin decondensation in a group of patients than in the controls (7 schizophrenic, 9 controls, P < 0.01). The distribution of phenotypes of Duffy blood group system (whose locus is linked to the 1qH region) among 28 schizophrenic patients was also different from that in the general population. Cosegregation of schizophrenia with a 1qH (C-band) variant and Duffy blood group allele was observed in one of six multiplex families. The overall results suggest that alterations within the Duffy/1qH region are involved in schizophrenia in some cases. This region contains the locus of D5 dopamine receptor pseudogene 2 (1q21.1), which is transcribed in normal lymphocytes. 33 refs., 1 fig., 2 tabs.

  20. Chromosomal rearrangements underlying karyotype differences between Chinese pangolin (Manis pentadactyla) and Malayan pangolin (Manis javanica) revealed by chromosome painting.

    PubMed

    Nie, Wenhui; Wang, Jinhuan; Su, Weiting; Wang, Yingxiang; Yang, Fengtang

    2009-01-01

    The Chinese pangolin (Manis pentadactyla), a representative species of the order Pholidota, has been enlisted in the mammalian whole-genome sequencing project mainly because of its phylogenetic importance. Previous studies showed that the diploid number of M. pentadactyla could vary from 2n = 36 to 42. To further characterize the genome organization of M. pentadactyla and to elucidate chromosomal mechanism underlying the karyotype diversity of Pholidota, we flow-sorted the chromosomes of 2n = 40 M. pentadactyla, and generated a set of chromosome-specific probes by DOP-PCR amplification of flow-sorted chromosomes. A comparative chromosome map between M. pentadactyla and the Malayan pangolin (Manis javanica, 2n = 38), as well as between human and M. pentadactyla, was established by chromosome painting for the first time. Our results demonstrate that seven Robertsonian rearrangements, together with considerable variations in the quantity of heterochromatin and in the number of nucleolar organizer regions (NORs) differentiate the karyotypes of 2n = 38 M. javanica and 2n = 40 M. pentadactyla. Moreover, we confirm that the M. javanica Y chromosome bears one NOR. Comparison of human homologous segment associations found in the genomes of M. javanica and M. pentadactyla revealed seven shared associations (HSA 1q/11, 2p/5, 2q/10q, 4p+q/20, 5/13, 6/19p and 8q/10p) that could constitute the potential Pholidota-specific signature rearrangements. PMID:19283495

  1. Comparison of autoantibodies to the collagen-like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus.

    PubMed

    Wisnieski, J J; Jones, S M

    1992-03-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an apparent autoimmune disorder that resembles SLE. We previously showed that C1q precipitins in HUVS sera are IgG autoantibody to human C1q. We have compared HUVS anti-C1q autoantibody to a similar autoantibody in the serum of some patients with SLE. As with anti-C1q autoantibody in SLE sera, the HUVS autoantibody binds only to the collagen-like region (CLR) of C1q. In both HUVS and SLE, IgG2 is the predominant subclass of IgG autoantibody and IgM autoantibody to C1q is uncommon. In both diseases, anti-C1q autoantibodies bind preferentially to surface-adsorbed C1q or CLR fragments compared to these antigens in solution. Finally, when HUVS or SLE autoantibodies were added to CLR-coated wells already bound, respectively, by SLE or HUVS autoantibodies, no increases in CLR binding were observed, suggesting that HUVS and SLE autoantibodies to C1q bind to the same CLR epitope(s). PMID:1538123

  2. [Pauciarticular juvenile chronic arthritis].

    PubMed

    Hertzberger-ten Cate, R; Fiselier, T

    1991-10-01

    On basis of clinical and immunogenetic factors most children with pauciarticular juvenile chronic arthritis can be included in one of the subtypes: type 1 and type 2 pauciarticular JCA. Type 1 occurs in young children, mainly girls, with involvement of knees, ankles or elbows. In the majority of children antinuclear antibodies can be detected. The presence of these autoantibodies is associated with chronic anterior uveitis. Type 2 or the juvenile spondylarthropathies include morbus Bechterew, the reactive arthritides and arthritis associated with psoriasis and inflammatory bowel diseases. Large joints of the lower extremities are involved, back pain is unusual at onset, but enthesitis is frequently present. There is a strong association with HLA-B27. Treatment of both subsets consists of non-steroidal anti-inflammatory drugs, application of intra-articular steroids, physio- and hydrotherapy and splinting. In children with a polyarticular course of type 1, or a prolonged course of type 2 disease modifying drugs are often needed. PMID:1957301

  3. [Juvenile psoriatic arthritis].

    PubMed

    Lu, Shan; Zhou, Wei; Zhang, Qian; Yu, Xin-Ying; Liu, Dong-Ming; Liu, Xiang-Yuan

    2007-08-01

    A case of juvenile psoriatic arthritis in a 12 year-old boy was reported. The patient had a history of one and half a year of bilateral heel pain, followed by pain in the right knee and ankle and right hip joint. He developed psoriatic lesions affecting his nails and skin. He had increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) contents. Human leukocyte antigen (HLA) B27 was detected but serum rheumatoid factor was not in the patient. A skin biopsy revealed psoriasis and ultrasonography demonstrated synovitis in right knee and ankle. Juvenile psoriatic arthritis was diagnosed based on his physical, laboratory and skin biopsy findings. A treatment with nonsteroidal anti-inflammatory drugs and sulfasalazine produced no effect. Leflunomide in conjunction with anti-TNF biologic agents (Etanercept) was administered, followed by symptomatic improvement 2 weeks later. PMID:17706035

  4. gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection

    SciTech Connect

    Yao Zhiqang; Shata, Mohamed Tarek; Tricoche, Nancy; Shan, M.M.; Brotman, Betsy; Pfahler, Wolfram; Hahn, Young S. . E-mail: ysh5e@virginia.edu; Prince, Alfred M.

    2006-03-15

    Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence.

  5. Soluble gC1qR Is an Autocrine Signal That Induces B1R Expression on Endothelial Cells

    PubMed Central

    Ji, Yan; Valentino, Alisa; Pednekar, Lina; Ramadass, Mahalakshmi; Habiel, David; Kew, Richard R.; Hosszu, Kinga H.; Galanakis, Dennis K.; Kishore, Uday; Peerschke, Ellinor I. B.

    2014-01-01

    Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein–coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β. The C1q receptor, receptor for the globular heads of C1q (gC1qR), which plays a role in BK generation, is expressed on activated ECs and is also secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we hypothesized that it may also serve as an autocrine/paracrine signal for the induction of B1R expression. In this study, we show that gC1qR binds to ECs via a highly conserved domain consisting of residues 174–180, as assessed by solid-phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs (24 h, 37°C) with sgC1qR resulted in enhancement of B1R expression, whereas incubation with gC1qR lacking aa 174–180 and 154–162 had a diminished effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R expression through de novo synthesis, as well as rapid translocation of preformed B1R. PMID:24319267

  6. The Precarious Prokaryotic Chromosome

    PubMed Central

    2014-01-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the two distinct ways to organize chromosomes are driven by the differences between the global-consecutive chromosome cycle of eukaryotes and the local-concurrent chromosome cycle of prokaryotes. Specifically, progressive chromosome segregation in prokaryotes demands a single duplicon per chromosome, while other “precarious” features of the prokaryotic chromosomes can be viewed as compensations for this severe restriction. PMID:24633873

  7. The precarious prokaryotic chromosome.

    PubMed

    Kuzminov, Andrei

    2014-05-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the two distinct ways to organize chromosomes are driven by the differences between the global-consecutive chromosome cycle of eukaryotes and the local-concurrent chromosome cycle of prokaryotes. Specifically, progressive chromosome segregation in prokaryotes demands a single duplicon per chromosome, while other "precarious" features of the prokaryotic chromosomes can be viewed as compensations for this severe restriction. PMID:24633873

  8. B-chromosome evolution.

    PubMed Central

    Camacho, J P; Sharbel, T F; Beukeboom, L W

    2000-01-01

    B chromosomes are extra chromosomes to the standard complement that occur in many organisms. They can originate in a number of ways including derivation from autosomes and sex chromosomes in intra- and interspecies crosses. Their subsequent molecular evolution resembles that of univalent sex chromosomes, which involves gene silencing, heterochromatinization and the accumulation of repetitive DNA and transposons. B-chromosome frequencies in populations result from a balance between their transmission rates and their effects on host fitness. Their long-term evolution is considered to be the outcome of selection on the host genome to eliminate B chromosomes or suppress their effects and on the B chromosome's ability to escape through the generation of new variants. Because B chromosomes interact with the standard chromosomes, they can play an important role in genome evolution and may be useful for studying molecular evolutionary processes. PMID:10724453

  9. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer

    PubMed Central

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G. William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand–receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  10. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer.

    PubMed

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand-receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  11. Solid-phase C1q-directed bacterial capture followed by PCR for detection of Chlamydia trachomatis in clinical specimens.

    PubMed Central

    Herbrink, P; van den Munckhof, H A; Niesters, H G; Goessens, W H; Stolz, E; Quint, W G

    1995-01-01

    An antigen capture system based on the binding of bacteria to solid-phase immobilized complement C1q followed by PCR for detection of Chlamydia trachomatis in clinical samples was developed and clinically evaluated. Comparison of C1q-directed antigen capture PCR with cell culture and direct PCR on 71 consecutive clinical specimens revealed an identical sensitivity. In this group, all 11 cell culture-positive samples were positive by direct PCR and C1q-directed antigen capture PCR. In addition, two samples found negative by cell culture were found positive by both direct PCR and C1q-directed antigen capture PCR. To further assess the sensitivity of C1q-directed antigen capture PCR, 20 clinical samples with one to five inclusions in cell culture and 20 clinical samples with 6 to 20 inclusions in cell culture were tested. Results obtained showed sensitivities of 95 and 90% for clinical samples with 6 to 20 and 1 to 5 inclusions in cell culture, respectively. Using C1q-coated solid phases, C1q-binding Chlamydia particles can be concentrated from large volumes with concomitant removal of inhibitors of PCR, allowing the use of large volumes of clinical samples for clinical testing. Since C1q has been shown to bind to a range of gram-negative bacteria, the newly developed technique has utility for a broad range of bacteria. PMID:7714179

  12. Juvenile Mentoring Program: A Progress Review. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Novotney, Laurence C.; Mertinko, Elizabeth; Lange, James; Baker, Tara Kelley

    The greatest support offered by the Office of Juvenile Justice and Delinquency Prevention for youth mentoring has been through the Juvenile Mentoring Program (JUMP), which provides one-to-one mentoring for youth at risk of delinquency, gang involvement, educational failure, or dropping out of school. Information on JUMP has been collected through…

  13. Mapping of aldose reductase gene sequences to human chromosomes 1, 3, 7, 9, 11, and 13

    SciTech Connect

    Bateman, J.B.; Kojis, T. UCLA School of Medicine, Los Angeles, CA ); Heinzmann, C.; Sparkes, R.S.; Klisak, I.; Diep, A. ); Carper, D. ); Nishimura, Chihiro ); Mohandas, T. )

    1993-09-01

    Aldose reductase (alditol:NAD(P)+ 1-oxidoreductase; EC 1.1.1.21) (AR) catalyzes the reduction of several aldehydes, including that of glucose, to the corresponding sugar alcohol. Using a complementary DNA clone encoding human AR, the authors mapped the gene sequences to human chromosomes 1, 3, 7, 9, 11, 13, 14, and 18 by somatic cell hybridization. By in situ hybridization analysis, sequences were localized to human chromosomes 1q32-q43, 3p12, 7q31-q35, 9q22, 11p14-p15, and 13q14-q21. As a putative functional AR gene has been mapped to chromosome 7 and a putative pseudogene to chromosome 3, the sequences on the other seven chromosomes may represent other active genes, non-aldose reductase homologous sequences, or pseudogenes. 24 refs., 3 figs., 2 tabs.

  14. Mapping quantitative trait loci for heat tolerance at anthesis in rice using chromosomal segment substitution lines

    PubMed Central

    Zhao, Lei; Lei, Jianguo; Huang, Yingjin; Zhu, Shan; Chen, Hongping; Huang, Renliang; Peng, Zhiqin; Tu, Qinghua; Shen, Xianhua; Yan, Song

    2016-01-01

    To study the genetic basis of heat tolerance at anthesis, a set of chromosome segment substitution lines (CSSLs) derived from Sasanishiki (japonica ssp. heat susceptible) and Habataki (indica spp. heat tolerant) were used for analysis across three high temperature environments. Spikelet fertility (SF), daily flowering time (DFT) and pollen shedding level (PSL) under high temperature (HT) were assessed. Eleven related QTLs were detected, of which, two QTLs qSFht2 and qSFht4.2 for spikelet fertility were identified on chromosomes 2 and 4. Four QTLs qDFT3, qDFT8, qDFT10.1 and qDFT11 for daily flowering time were detected on chromosomes 3, 8, 10 and 11. The other five QTLs qPSLht1, qPSLht4.1, qPSLht5, qPSLht7 and qPSLht10.2 on chromosomes 1, 4, 5, 7 and 10, respectively, were found had effects both on spikelet fertility and pollen shedding level. Of the 11 QTLs, 8 were overlapped with QTLs reported by others, 3 QTLs qPSLht4.1, qPSLht7 and qPSLht10.2 identified in this study were novel. The stability of qPSLht4.1 was further verified at different temperatures, which could be used to improve the pollen shedding and pollen growth on stigma for rice heat-tolerance breeding. PMID:27436945

  15. A hantavirus causing hemorrhagic fever with renal syndrome requires gC1qR/p32 for efficient cell binding and infection

    SciTech Connect

    Choi, Yun; Kwon, Young-Chan; Kim, Soo-In; Park, Jung-Min; Lee, Kyung-Hee; Ahn, Byung-Yoon

    2008-11-25

    Hantaan virus (HTNV) is a pathogenic hantavirus that causes hemorrhagic fever with renal syndrome (HFRS). HTNV infection is mediated by {alpha}v{beta}3 integrin. We used protein blots of Vero E6 cell homogenates to demonstrate that radiolabeled HTNV virions bind to gC1qR/p32, the acidic 32-kDa protein known as the receptor for the globular head domain of complement C1q. RNAi-mediated suppression of gC1qR/p32 markedly reduced HTNV binding and infection in human lung epithelial A549 cells. Conversely, transient expression of either simian or human gC1qR/p32 rendered non-permissive CHO cells susceptible to HTNV infection. These results suggest an important role for gC1qR/p32 in HTNV infection and pathogenesis.

  16. Assignment of a human homolog of the mouse Htr3 receptor gene to chromosome 11q23.1-q23.2

    SciTech Connect

    Weiss, B.; Mertz, A.; Rappold, G.

    1995-09-01

    Serotonin or 5-hydroxytryptamine (5-HT) represents a family of neurotransmitters acting through the 5-HT neuroreceptors. One of these receptors, HTR3, belongs to the family of ligand gated ion channels. Activation of the HTR3 receptor mediates a variety of physiological effects in central and peripheral neurons such as cytotoxic drug-evoked emesis and nociception and is believed to influence behavior relevant to anxiety and cognitive disorders. 16 refs., 1 fig.

  17. Juvenile psittacine environmental enrichment.

    PubMed

    Simone-Freilicher, Elisabeth; Rupley, Agnes E

    2015-05-01

    Environmental enrichment is of great import to the emotional, intellectual, and physical development of the juvenile psittacine and their success in the human home environment. Five major types of enrichment include social, occupational, physical, sensory, and nutritional. Occupational enrichment includes exercise and psychological enrichment. Physical enrichment includes the cage and accessories and the external home environment. Sensory enrichment may be visual, auditory, tactile, olfactory, or taste oriented. Nutritional enrichment includes variations in appearance, type, and frequency of diet, and treats, novelty, and foraging. Two phases of the preadult period deserve special enrichment considerations: the development of autonomy and puberty. PMID:25902270

  18. Chromosome abnormality rate among Iranian patients with idiopathic mental retardation from consanguineous marriages

    PubMed Central

    Behjati, Farkhondeh; Ghasemi Firouzabadi, Saghar; Kahrizi, Kimia; Kariminejad, Roxana; Bagherizadeh, Iman; Ansari, Javad; Fallah, Masoumeh; Mojtahedi, Forough; Darvish, Hossein; Bahrami Monajemi, Gholamreza; Abedini, S. Sedigheh; Jamali, Payman; Mojahedi, Faezeh; Zadeh-Vakili, Azita; Najmabadi, Hossein

    2011-01-01

    Introduction Mental retardation (MR) has heterogeneous aetiology mostly with genetic causes. Chromosomal aberrations are one of the most common causes of MR. Reports on chromosome abnormality rate among consanguineous families are sparse. In order to identify the chromosome abnormality rate in idiopathic mental retardation from consanguineous marriages, a total of 322 Iranian families with positive family history for MR were investigated in the Genetics Research Center. Material and methods In the majority of families (92%) at least two sibs were affected with MR and none had specific chromosomal syndromes such as Down syndrome. Standard cytogenetic techniques using high resolution GTG banding were carried out on all the patients. Results The overall chromosome abnormality rate contributing to mental retardation was 1.24% (4 cases), which comprised 46,XY,der(18)t(4;18)(q31.1;q23)mat; 45,XY,-21,-22,+der(22)t(21;22)(q21.1;q13.33)mat; 46,XY,rec(2)dup(2p)inv(2)(p25.1q37.3)pat, and 46,XY,der(11)t(10;11)(q25.2;q25)pat. Conclusions Although the most likely genetic cause of mental retardation in patients with consanguineous parents is autosomal recessive, the fact that 1.24% of our patients had chromosomal abnormalities emphasizes the importance of cytogenetic investigation as the first laboratory genetic tests for all MR patients. To our knowledge, this is the first report on the rate of chromosome abnormality among patients with idiopathic mental retardation from consanguineous marriages. PMID:22291774

  19. Juvenile Justice in Rural America.

    ERIC Educational Resources Information Center

    Jankovic, Joanne, Ed.; And Others

    Producing a much-needed organized body of literature about rural juvenile justice, 14 papers (largely from the 1979 National Symposium on Rural Justice) are organized to identify current issues, identify forces causing changes in current systems, review programs responding to rural juvenile justice problems, and provide planning models to aid…

  20. Psychopathology in Female Juvenile Offenders

    ERIC Educational Resources Information Center

    Dixon, Angela; Howie, Pauline; Starling, Jean

    2004-01-01

    Background: The aim was to document the spectrum of present and lifetime psychological disorders in female juvenile offenders, and to examine the relations between mental health status and socio-demographic, family and trauma variables. Method: One hundred juvenile offenders were matched with a comparison group of 100 females on age and…

  1. Iatrogenic Effect of Juvenile Justice

    ERIC Educational Resources Information Center

    Gatti, Uberto; Tremblay, Richard E.; Vitaro, Frank

    2009-01-01

    Background: The present study uses data from a community sample of 779 low-SES boys to investigate whether intervention by the juvenile justice system is determined, at least in part, by particular individual, familial and social conditions, and whether intervention by the juvenile courts during adolescence increases involvement in adult crime.…

  2. Juvenile Crime. Opposing Viewpoints Series.

    ERIC Educational Resources Information Center

    Sadler, A. E., Ed.

    Books in the Opposing Viewpoints Series present debates about current issues that can be used to teach critical reading and thinking skills. The variety of opinions expressed in this collection of articles and book excerpts explores many aspects of juvenile crime. It is a commonly held view that the number of crimes committed by juveniles is…

  3. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  4. Chromosomal Disorders and Autism.

    ERIC Educational Resources Information Center

    Gillberg, Christopher

    1998-01-01

    This paper reviews the literature on chromosomal aberrations in autism, especially possible gene markers. It notes that Chromosome 15 and numerical and structural abnormalities of the sex chromosomes have been most frequently reported as related to the genesis of autism. (Author/DB)

  5. Chromosomal development of cancer

    SciTech Connect

    1993-12-31

    Chapter 30, describes the chromosomal development of cancer. It has been established through cytological research that the number of chromosomes in cancer cells often deviates greatly from the usual number in healthy cells of the host organism. This chapter includes discussions on chromosome studies in ascites tumors, stemline and tumor development, mitotic aberrations in cancer, and selection and tumor progression. 25 refs., 2 figs.

  6. Mental Illness and Juvenile Offenders

    PubMed Central

    Underwood, Lee A.; Washington, Aryssa

    2016-01-01

    Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided. PMID:26901213

  7. Mental Illness and Juvenile Offenders.

    PubMed

    Underwood, Lee A; Washington, Aryssa

    2016-02-01

    Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided. PMID:26901213

  8. Mapping strategies: Chromosome 16 workshop

    SciTech Connect

    Not Available

    1989-01-01

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

  9. Stroke-Like Presentation Following Febrile Seizure in a Patient with 1q43q44 Deletion Syndrome

    PubMed Central

    Robinson, J. Elliott; Wolfe, Stephanie M.; Kaiser-Rogers, Kathleen; Greenwood, Robert S.

    2016-01-01

    Hemiconvulsion–hemiplegia–epilepsy syndrome (HHE) is a rare outcome of prolonged hemiconvulsion that is followed by diffuse unilateral hemispheric edema, hemiplegia, and ultimately hemiatrophy of the affected hemisphere and epilepsy. Here, we describe the case of a 3-year-old male with a 1;3 translocation leading to a terminal 1q43q44 deletion and a terminal 3p26.1p26.3 duplication that developed HHE after a prolonged febrile seizure and discuss the pathogenesis of HHE in the context of the patient’s complex genetic background. PMID:27199890

  10. Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa.

    PubMed

    Takizawa, Y; Pulkkinen, L; Shimizu, H; Lin, L; Hagiwara, S; Nishikawa, T; Uitto, J

    1998-05-01

    Herlitz junctional epidermolysis bullosa (OMIM#226700) is a lethal, autosomal recessive blistering disorder caused by mutations in one of the three genes LAMA3, LAMB3, or LAMC2, encoding the constitutive polypeptide subunits of laminin 5. In this study, we describe a patient homozygous for a novel nonsense mutation Q936X in exon 19 of LAMB3, which has been mapped to chromosome 1q32. The patient was born with extensive blistering and demonstrated negative immunofluorescence staining for laminin 5, and transmission electron microscopy revealed tissue separation within lamina lucida of the dermal-epidermal junction, diagnostic of Herlitz junctional epidermolysis bullosa. The mother of the proband was found to be a heterozygous carrier for this mutation, whereas the father demonstrated the wild-type LAMB3 allele only. Nonpaternity was excluded by 13 microsatellite markers in six different chromosomes. Genotype analysis using 28 microsatellite markers spanning chromosome 1 revealed that the patient had maternal primary heterodisomy, as well as meroisodisomy within two regions of chromosome 1, one on 1p and the other one on 1q, the latter region containing the maternal LAMB3 mutation. These results suggest that Herlitz junctional epidermolysis bullosa in this patient developed as a result of reduction to homozygosity of the maternal LAMB3 mutation on chromosome 1q32. PMID:9579554

  11. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    PubMed

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. PMID:26918856

  12. Miranda Rights: Implications for Juveniles with Disabilities

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Barrett, David E.; Losinski, Mickey L.

    2011-01-01

    Juvenile delinquency in the United States has been a persistent concern for decades. Consequently, because more juveniles have been referred to juvenile court and the arrest rate of preteen offenders has increased to almost three times that of older youth, the persistent and often controversial issue of the capacity of juvenile offenders to waive…

  13. Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q

    SciTech Connect

    Scherer, S.W.; Heng, H.H.Q.; Lap-Chee Tsui

    1996-01-15

    Metabotropic glutamate receptors (GRMs) are neutrotransmitter receptors that respond to glutamate stimulations by activating GTP-binding proteins and modulating second-messenger cascades. Eight related GRMs have been identified to date. In this study, we have mapped GRM3 and GRM8 to human chromosome 7q21.1-q21.2 and 7q31.3-q32.1, respectively, using somatic cell hybrid and fluorescence in situ hybridization analysis. A yeast artificial chromosome contig was constructed surrounding the genes, allowing their location to be integrated into the genetic and physical map of chromosome 7. 20 refs., 2 figs.

  14. De Novo Interstitial Microdeletion at 1q32.1 in a 10-Year-Old Boy with Developmental Delay and Dysmorphism

    PubMed Central

    Carter, Jennifer; Zombor, Melinda; Máté, Adrienn; Sztriha, László; Waters, Jonathan J.

    2016-01-01

    A 10-year-old boy was referred with developmental delay and dysmorphism. Genomewide aCGH microarray analysis detected a de novo 3.7 Mb deletion at 1q32.1: arr 1q32.1(199,985,888-203,690,832)x1 dn [build HG19]. This first report of a deletion in this region implies a critical role for dosage-sensitive genes within 1q32.1 in neurological development. This is consistent with previously reported duplications of this region in patients with a similar phenotype. PMID:26955491

  15. De Novo Interstitial Microdeletion at 1q32.1 in a 10-Year-Old Boy with Developmental Delay and Dysmorphism.

    PubMed

    Carter, Jennifer; Zombor, Melinda; Máté, Adrienn; Sztriha, László; Waters, Jonathan J

    2016-01-01

    A 10-year-old boy was referred with developmental delay and dysmorphism. Genomewide aCGH microarray analysis detected a de novo 3.7 Mb deletion at 1q32.1: arr 1q32.1(199,985,888-203,690,832)x1 dn [build HG19]. This first report of a deletion in this region implies a critical role for dosage-sensitive genes within 1q32.1 in neurological development. This is consistent with previously reported duplications of this region in patients with a similar phenotype. PMID:26955491

  16. Detection of chromosome imbalances in retinoblastoma by parallel karyotype and CGH analyses.

    PubMed

    Mairal, A; Pinglier, E; Gilbert, E; Peter, M; Validire, P; Desjardins, L; Doz, F; Aurias, A; Couturier, J

    2000-08-01

    We have studied a series of 20 primary retinoblastomas by karyotypic analysis and comparative genomic hybridization (CGH), to perform an exhaustive evaluation of chromosome imbalances in this tumor. In addition, 4 tumors were studied by CGH only. On the whole, CGH results were largely in agreement with those of karyotypic analysis and with known cytogenetic data. The most frequent imbalances were +6p (13/24 cases), +1q (12/24), -16/-16q (11/24), and +2p (9/24). Recurrent high-level amplifications were observed in 2p23-25 and 1q21. Amplification of 2p23-25, present in 4 cases among which 3 showed double-minute chromosomes, was related to MYCN amplification, as demonstrated by FISH and PCR. No evident correlation was found in this small series between any of the imbalances identified and either the differentiation or the histoprognostic risk. PMID:10862045

  17. Chromosomes, conflict, and epigenetics: chromosomal speciation revisited.

    PubMed

    Brown, Judith D; O'Neill, Rachel J

    2010-01-01

    Since Darwin first noted that the process of speciation was indeed the "mystery of mysteries," scientists have tried to develop testable models for the development of reproductive incompatibilities-the first step in the formation of a new species. Early theorists proposed that chromosome rearrangements were implicated in the process of reproductive isolation; however, the chromosomal speciation model has recently been questioned. In addition, recent data from hybrid model systems indicates that simple epistatic interactions, the Dobzhansky-Muller incompatibilities, are more complex. In fact, incompatibilities are quite broad, including interactions among heterochromatin, small RNAs, and distinct, epigenetically defined genomic regions such as the centromere. In this review, we will examine both classical and current models of chromosomal speciation and describe the "evolving" theory of genetic conflict, epigenetics, and chromosomal speciation. PMID:20438362

  18. The Ah receptor nuclear translocator gene (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3

    SciTech Connect

    Johnson, B.; Brooks, B.A.; Heinzmann, C. ); Mohandas, T. )

    1993-09-01

    The authors have mapped the Ah (aryl hydrocarbon) receptor nuclear translocator (ARNT) gene to a conserved linkage group located on mouse chromosome 3 and human chromosome 1. EcoRi-digested DNA from a panel of 17 human x mouse somatic cell hybrids was probed with a cDNA fragment of the human ARNT gene. Six of the 17 independent mouse x human hybrids were positive for human bands. Human chromosome 1 showed complete cosegregation with the gene, whereas discordant segregation was observed for all other human chromosomes. The human gene was localized to 1q21 by using DNA from mouse x human hybrid clones that retain translocations involving human chromosome 1, by segregation analysis in nine informative CEPH families, and by in situ hybridization. The mouse homologue was mapped to mouse chromosome 3 using a panel of 16 hamster x mouse somatic cell hybrids. Six of 16 mouse x hamster hybrids were positive for mouse bands, showing complete concordance with mouse chromosome 3. The mouse Arnt gene was regionally mapped on chromosome 3, using linkage analysis in an interspecific backcross. The results indicate that the mouse gene resides about 40 cM from the centromere and about 10 cM proximal to Cf-3, the gene for tissue factor. 41 refs., 4 figs., 5 tabs.

  19. gC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection.

    PubMed

    Ghebrehiwet, B; Lim, B L; Kumar, R; Feng, X; Peerschke, E I

    2001-04-01

    Human gC1q-R (p33, p32, C1qBP, TAP) is a ubiquitously expressed, multiligand-binding, multicompartmental cellular protein involved in various ligand-mediated cellular responses. Although expressed on the surface of cells, an intriguing feature of the membrane-associated form of gC1q-R is that its translated amino acid sequence does not predict the presence of either a sequence motif compatible with a transmembrane segment or a consensus site for a glycosylphosphatidylinositol anchor. Moreover, the N-terminal sequence of the pre-pro-protein gC1q-R contains a motif that targets the molecule to the mitochondria and as such was deemed unlikely to be expressed on the surface. However, several lines of experimental evidence clearly show that gC1q-R is present in all compartments of the cell, including the extracellular cell surface. First, surface labeling of B lymphocytes with the membrane-impermeable reagent sulfosuccinimidyl 6-(biotinamido)hexanoate shows specific biotin incorporation into the surface-expressed but not the intracellular form of gC1q-R. Second, FACS and confocal laser scanning microscopic analyses using anti-gC1q-R IgG mAb 60.11 or 74.5.2, and the fluorophore Alexa 488-conjugated F(ab')2 goat anti-mouse IgG as a probe, demonstrated specific staining of Raji cells (>95% viable). Three-dimensional analyses of the same cells by confocal microscopy showed staining distribution that was consistent with surface expression. Third, endothelial gC1q-R, which is associated with the urokinase plasminogen activator receptor, and cytokeratin 1 bind 125I-high molecular weight kininogen in a specific manner, and the binding is inhibited dose-dependently by mAb 74.5.2 recognizing gC1q-R residues 204-218. Fourth, native gC1q-R purified from Raji cell membranes but not intracellular gC1q-R is glycosylated, as evidenced by a positive periodic acid Schiff stain as well as sensitivity to digestion with endoglycosidase H and F. Finally, cross-linking experiments using C1q

  20. A Tiling Microarray Expression Analysis of Rice Chromosome 4 Suggests a Chromosome-Level Regulation of TranscriptionW⃞

    PubMed Central

    Jiao, Yuling; Jia, Peixin; Wang, Xiangfeng; Su, Ning; Yu, Shuliang; Zhang, Dongfen; Ma, Ligeng; Feng, Qi; Jin, Zhaoqing; Li, Lei; Xue, Yongbiao; Cheng, Zhukuan; Zhao, Hongyu; Han, Bin; Deng, Xing Wang

    2005-01-01

    The complete genome sequence of cultivated rice (Oryza sativa) provides an unprecedented opportunity to understand the biology of this model cereal. An essential and necessary step in this effort is the determination of the coding information and expression patterns of each sequenced chromosome. Here, we report an analysis of the transcriptional activity of rice chromosome 4 using a tiling path microarray based on PCR-generated genomic DNA fragments. Six representative rice organ types were examined using this microarray to catalog the transcribed regions of rice chromosome 4 and to reveal organ- and developmental stage–specific transcription patterns. This analysis provided expression support for 82% of the gene models in the chromosome. Transcriptional activities in 1643 nonannotated regions were also detected. Comparison with cytologically defined chromatin features indicated that in juvenile-stage rice the euchromatic region is more actively transcribed than is the transposon-rich heterochromatic portion of the chromosome. Interestingly, increased transcription of transposon-related gene models in certain heterochromatic regions was observed in mature-stage rice organs and in suspension-cultured cells. These results suggest a close correlation between transcriptional activity and chromosome organization and the developmental regulation of transcription activity at the chromosome level. PMID:15863518

  1. Juvenile nasopharyngeal angiofibroma.

    PubMed

    Makhasana, Jashika Adil Shroff; Kulkarni, Meena A; Vaze, Suhas; Shroff, Adil Sarosh

    2016-01-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor arising predominantly in the nasopharynx of adolescent males. It is an aggressive neoplasm and shows a propensity for destructive local spread often extending to the base of the skull and into the cranium. Clinically, however, it is obscure with painless, progressive unilateral nasal obstruction being the common presenting symptom with or without epistaxis and rhinorrhea. Diagnosis of JNA is made by complete history, clinical examination, radiography, nasal endoscopy and by using specialized imaging techniques such as arteriography, computer tomography and magnetic resonance imaging. Histopathology reveals a fibrocellular stroma with spindle cells and haphazard arrangement of collagen interspersed with an irregular vascular pattern. A case report of JNA with rare intra-oral manifestation in a 17-year-old male patient is presented in the article. JNA being an aggressive tumor may recur posttreatment. Thus, early diagnosis, accurate staging, and adequate treatment are essential in the management of this lesion. PMID:27601836

  2. Juvenile nasopharyngeal angiofibroma

    PubMed Central

    Makhasana, Jashika Adil Shroff; Kulkarni, Meena A; Vaze, Suhas; Shroff, Adil Sarosh

    2016-01-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor arising predominantly in the nasopharynx of adolescent males. It is an aggressive neoplasm and shows a propensity for destructive local spread often extending to the base of the skull and into the cranium. Clinically, however, it is obscure with painless, progressive unilateral nasal obstruction being the common presenting symptom with or without epistaxis and rhinorrhea. Diagnosis of JNA is made by complete history, clinical examination, radiography, nasal endoscopy and by using specialized imaging techniques such as arteriography, computer tomography and magnetic resonance imaging. Histopathology reveals a fibrocellular stroma with spindle cells and haphazard arrangement of collagen interspersed with an irregular vascular pattern. A case report of JNA with rare intra-oral manifestation in a 17-year-old male patient is presented in the article. JNA being an aggressive tumor may recur posttreatment. Thus, early diagnosis, accurate staging, and adequate treatment are essential in the management of this lesion. PMID:27601836

  3. Juvenile idiopathic arthritis

    PubMed Central

    Bhatt, Krupa H; Karjodkar, Freny R; Sansare, Kaustubh; Patil, Darshana

    2014-01-01

    Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential. PMID:24808703

  4. Inferring Planet Occurrence Rates With a Q1-Q16 Kepler Planet Candidate Catalog Produced by a Machine Learning Classifier

    NASA Astrophysics Data System (ADS)

    Catanzarite, Joseph; Jenkins, Jon Michael; Burke, Christopher J.; McCauliff, Sean D.; Kepler Science Operations Center

    2015-01-01

    NASA's Kepler Space Telescope monitored the photometric variations of over 170,000 stars within a ~100 square degree field in the constellation Cygnus, at half-hour cadence, over its four year prime mission. The Kepler SOC (Science Operations Center) pipeline calibrates the pixels of the target apertures for each star, corrects light curves for systematic error, and detects TCEs (threshold-crossing events) that may be due to transiting planets. Finally the pipeline estimates planet parameters for all TCEs and computes quantitative diagnostics that are used by the TCERT (Threshold Crossing Event Review Team) to produce a catalog containing KOIs (Kepler Objects of Interest). KOIs are TCEs that are determined to be either likely transiting planets or astrophysical false positives such as background eclipsing binary stars. Using examples from the Q1-Q16 TCERT KOI catalog as a training set, we created a machine-learning classifier that dispositions the TCEs into categories of PC (planet candidate), AFP (astrophysical false positive) and NTP (non-transiting phenomenon). The classifier uniformly and consistently applies heuristics developed by TCERT as well as other diagnostics to the Q1-Q16 TCEs to produce a more robust and reliable catalog of planet candidates than is possible with only human classification. In this work, we estimate planet occurrence rates, based on the machine-learning-produced catalog of Kepler planet candidates. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  5. Juvenile Angiofibroma: Evolution of Management

    PubMed Central

    Nicolai, Piero; Schreiber, Alberto; Bolzoni Villaret, Andrea

    2012-01-01

    Juvenile angiofibroma is a rare benign lesion originating from the pterygopalatine fossa with distinctive epidemiologic features and growth patterns. The typical patient is an adolescent male with a clinical history of recurrent epistaxis and nasal obstruction. Although the use of nonsurgical therapies is described in the literature, surgery is currently considered the ideal treatment for juvenile angiofibroma. Refinement in preoperative embolization has provided significant reduction of complications and intraoperative bleeding with minimal risk of residual disease. During the last decade, an endoscopic technique has been extensively adopted as a valid alternative to external approaches in the management of small-intermediate size juvenile angiofibromas. Herein, we review the evolution in the management of juvenile angiofibroma with particular reference to recent advances in diagnosis and treatment. PMID:22164185

  6. In Silico and In Vitro Studies on the Protein-Protein Interactions between Brugia malayi Immunomodulatory Protein Calreticulin and Human C1q

    PubMed Central

    Yadav, Sunita; Gupta, Smita; Selvaraj, Chandrabose; Doharey, Pawan Kumar; Verma, Anita; Singh, Sanjeev Kumar; Saxena, Jitendra Kumar

    2014-01-01

    Filarial parasites modulate effective immune response of their host by releasing a variety of immunomodulatory molecules, which help in the long persistence of the parasite within the host. The present study was aimed to characterize an immunomodulatory protein of Brugia malayi and its interaction with the host immune component at the structural and functional level. Our findings showed that Brugia malayi Calreticulin (BmCRT) is responsible for the prevention of classical complement pathway activation via its interaction with the first component C1q of the human host. This was confirmed by inhibition of C1q dependent lysis of immunoglobulin-sensitized Red Blood Cells (S-RBCs). This is possibly the first report which predicts CRT-C1q interaction on the structural content of proteins to explain how BmCRT inhibits this pathway. The molecular docking of BmCRT-C1q complex indicated that C1qB chain (IgG/M and CRP binding sites on C1q) played a major role in the interaction with conserved and non-conserved regions of N and P domain of BmCRT. Out of 37 amino acids of BmCRT involved in the interaction, nine amino acids (Pro126, Glu132, His147, Arg151, His153, Met154, Lys156, Ala196 and Lys212) are absent in human CRT. Both ELISA and in silico analysis showed the significant role of Ca+2 in BmCRT-HuC1q complex formation and deactivation of C1r2–C1s2. Molecular dynamics studies of BmCRT-HuC1q complex showed a deviation from ∼0.4 nm to ∼1.0 nm. CD analyses indicated that BmCRT is composed of 49.6% α helix, 9.6% β sheet and 43.6% random coil. These findings provided valuable information on the architecture and chemistry of BmCRT-C1q interaction and supported the hypothesis that BmCRT binds with huC1q at their targets (IgG/M, CRP) binding sites. This interaction enables the parasite to interfere with the initial stage of host complement activation, which might be helpful in parasites establishment. These results might be utilized for help in blocking the C1q

  7. A rare mosaic interstitial deletion of 7q, 46,XX/46,XX,del(7)(q22.1q31.33), results in a mild clinical phenotype

    SciTech Connect

    Shapira, S.K.; Kochanek, S.; Shaffer, L.G.

    1994-09-01

    Constitutional mosaic structural rearrangements, including deletions, are extremely rare in the population. We present a case of mosaicism for a deletion of chromosome 7q. The patient`s phenotype is much milder than that of non-mosaic patients with a similar deletion of 7q. A 6 and 9/12-year-old Caucasian girl was evaluated because of attention deficit disorder and speech delay. She was born at 38 weeks gestation to her 37 year old G2P2 mother. Her birth weight was 2.2 kg (3rd centile), length was 47 cm (10th-25th centile), and OFC was 30.5 cm (<10th centile). Her motor development was normal. Her speech development was profoundly delayed with her first words spoken at 3 years, and 2-3 word sentences spoken at 5-6 years. At 6 and 9/12 years, she manifested mild mental retardation and profound speech delay, but only mildly dysmorphic features (protuberant ears with under-developed antihelices, flattened forehead, moderate micro-retrognathia). Height, weight, and OFC were at the 10th centile. Chromosomal analysis showed the presence of two cell lines, with 66% of the lymphocytes having a 46,XX pattern and 33% having a 46,XX,del(7)(q22.1q31.33) karyotype. Less than 20 cases of interstitial 7q deletions extending from bands 7q21 or 7q22 to 7q31 or 7q32 have been reported. Our patient represents the first documented case with a mosaic interstitial deletion of chromosome 7q. Furthermore, the deletion resulted in a relatively mild phenotype when compared to reported non-mosaic interstitial 7q deletions, and thus expands the range of clinical heterogeneity that can be anticipated in interstitial deletion patients.

  8. A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2.

    PubMed Central

    Thierfelder, L; MacRae, C; Watkins, H; Tomfohrde, J; Williams, M; McKenna, W; Bohm, K; Noeske, G; Schlepper, M; Bowcock, A

    1993-01-01

    We report that a gene responsible for familial hypertrophic cardiomyopathy (FHC) in a kindred with a mild degree of cardiac hypertrophy maps to chromosome 15q2. The gene encoding cardiac actin, located on chromosome 15q, was analyzed and excluded as a candidate for FHC at this locus. Two additional families with typical FHC were studied and the disorder in one also maps to the chromosome 15q2 locus. The maximum combined multipoint logarithm of odds score in the two linked families is 6.02. Although these two kindreds reside in the same country, we believe that their disorder is caused by independent mutations in the 15q2 locus because of the clinical and genotypic differences between affected individuals. Mutations in at least four loci can cause FHC: chromosomes 14q1 (beta cardiac myosin heavy chain gene), 1q3, and 15q2 and another unidentified locus, suggesting substantial genetic heterogeneity. PMID:8327508

  9. Rapid speciation and chromosomal evolution in mammals.

    PubMed Central

    Bush, G L; Case, S M; Wilson, A C; Patton, J L

    1977-01-01

    To test the hypothesis that population subdivision into small demes promotes both rapid speciation and evolutionary changes in gene arrangement by inbreeding and drift, we estimated rates of speciation and rates of chromosomal evolution in 225 genera of vertebrates. Rates of speciation were estimated by considering the number of living species in each genus and the fossil record of each genus as well as information about extinction rates. Speciation rate was strongly correlated with rate of chromosomal evolution and average rates of speciation in lower vertebrate genera were one-fifth those in mammalian genera. Genera with high karyotypic diversity and rapid speciation rates may generally have small effective population size (Ne), whereas large Ne values may be associated with karyotypically uniform genera and slow rates of speciation. Speciation and chromosomal evolution seem fastest in those genera with species organized into clans or harems (e.g., some primates and horses) or with limited adult vagility and juvenile dispersal, patchy distribution, and strong individual territoriality (e.g., some rodents). This is consistent with the above hypothesis regarding the evolutionary importance of demes. PMID:269445

  10. Genetic variants at 1q32.1, 10q11.2 and 19q13.41 are associated with prostate-specific antigen for prostate cancer screening in two Korean population-based cohort studies.

    PubMed

    Kim, Soriul; Shin, Chol; Jee, Sun Ha

    2015-02-10

    Prostate-specific antigen (PSA) levels are affected by non-cancerous conditions such as benign prostatic hyperplasia, inflammations, and inherited factors. To search for genetic variants associated with PSA levels, we conducted a genome-wide association study (GWAS) using a two-stage design. A total of 554 men from the Korean Cancer Prevention Study-II were used as a discovery stage and 1575 men collected by the Korean Genome Epidemiology Study were used as a replication stage. Analysis by Genome-wide Human single-nucleotide polymorphism (SNP) array 5.0 was performed by using DNAs derived from venous blood. We analyzed the association between genetic variants and PSA levels using multivariate linear regression models, including age as a covariate. We detected 12 genome-wide significant signals on chromosome 1q32.1, 10q11.2, and 19q13.41 between PSA levels and SNPs. The top SNP associated with log PSA levels was rs2153904 in SLC45A3 (p values, 5.24×10(-9) to 2.00×10(-6)). We also investigated GWAS using 754 subjects from KCPS-II cohort whether our genome-wide significant loci were associated with a risk of prostate cancer (PCa) (200 PCa cases and 554 controls). Three of the SNPs on 10q11.2, rs7077830, rs2611489, and rs4631830, were associated with a risk of PCa. However, two loci, 1q32.1 and 19q13, were not significantly associated with a PCa risk. We suggest that our results for some but not all PCa risk SNPs to be associated with PSA levels could be used as an evidence for the advance of individual PCa screening strategies, such as applying a personalized cutoff value for PSA. PMID:25434496

  11. Glycyrrhizic acid prevents astrocyte death by neuromyelitis optica-specific IgG via inhibition of C1q binding.

    PubMed

    Kim, Ji-Sun; Cheon, Soyoung; Kim, Seung Woo; Kim, Boram; Kim, Heejaung; Park, Ki Duk; Kim, Sung-Min

    2016-09-16

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is mediated by complement-dependent cytotoxicity (CDC) of NMO-specific immunoglobulin G (IgG) antibodies (NMO-IgG). Glycyrrhizic acid (GA) has numerous pharmacological effects including inhibition of the complement pathway. We aimed to study the influence of GA on NMO-IgG-induced CDC. NMO-IgG samples from 7 patients with NMO, together with human complement, induced CDC in an aquaporin 4 M23-overexpressing glial cell line, an in vitro NMO model. GA attenuated NMO-IgG-induced CDC in a dose-dependent manner. The mechanism of the GA-related CDC inhibition was sequentially dissected and found to involve inhibition of C1q binding to NMO-IgG. Consequently, GA attenuates NMO-IgG-induced CDC and may be a promising novel therapeutic agent against NMO. PMID:27462020

  12. Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade

    PubMed Central

    Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

    2014-01-01

    In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it’s plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it’s current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation aggregation. We discuss our findings in the context of tick feeding physiology. PMID:25454607

  13. Membrane-associated CD93 regulates leukocyte migration and C1q-hemolytic activity during murine peritonitis1

    PubMed Central

    Greenlee-Wacker, Mallary C.; Briseño, Carlos; Galvan, Manuel; Moriel, Gabriela; Velázquez, Peter; Bohlson, Suzanne S.

    2011-01-01

    CD93 is emerging as a novel regulator of inflammation; however, its molecular function is unknown. CD93 exists as a membrane-associated glycoprotein on the surface of cells involved in the inflammatory cascade, including endothelial and myeloid cells. A soluble form (sCD93) is detectable in blood and is elevated with inflammation. Here we demonstrate heightened susceptibility to thioglycollate-induced peritonitis in CD93−/− mice. CD93−/− mice showed a 1.6 to 1.8-fold increase in leukocyte infiltration during thioglycollate-induced peritonitis between 3 and 24 hours that returned to wildtype levels by 96 hours. Impaired vascular integrity in CD93−/− mice during peritonitis was demonstrated using fluorescence multi-photon intravital microscopy; however, no differences in cytokine or chemokine levels were detected by Luminex Multiplex or ELISA analysis. C1q-hemolytic activity in CD93−/− mice was decreased by 22% at time zero and by 46% 3 hours post thioglycollate injection suggesting a defect in the classical complement pathway. Leukocyte recruitment and C1q-hemolytic activity was restored to wildtype levels when CD93 was expressed on either hematopoietic cells or non-hematopoietic cells in bone marrow chimeric mice. However, elevated levels of sCD93 in inflammatory fluid were observed only when CD93 was expressed on non-hematopoietic cells. Since cell-associated CD93 was sufficient to restore a normal inflammatory response, these data suggest that cell-associated CD93, and not sCD93, regulates leukocyte recruitment and complement activation during murine peritonitis. PMID:21849679

  14. Membrane-associated CD93 regulates leukocyte migration and C1q-hemolytic activity during murine peritonitis.

    PubMed

    Greenlee-Wacker, Mallary C; Briseño, Carlos; Galvan, Manuel; Moriel, Gabriela; Velázquez, Peter; Bohlson, Suzanne S

    2011-09-15

    CD93 is emerging as a novel regulator of inflammation; however, its molecular function is unknown. CD93 exists as a membrane-associated glycoprotein on the surface of cells involved in the inflammatory cascade, including endothelial and myeloid cells. A soluble form (sCD93) is detectable in blood and is elevated with inflammation. In this study, we demonstrate heightened susceptibility to thioglycollate-induced peritonitis in CD93(-/-) mice. CD93(-/-) mice showed a 1.6-1.8-fold increase in leukocyte infiltration during thioglycollate-induced peritonitis between 3 and 24 h that returned to wild type levels by 96 h. Impaired vascular integrity in CD93(-/-) mice during peritonitis was demonstrated using fluorescence multiphoton intravital microscopy; however, no differences in cytokine or chemokine levels were detected with Luminex Multiplex or ELISA analysis. C1q-hemolytic activity in CD93(-/-) mice was decreased by 22% at time zero and by 46% 3 h after thioglycollate injection, suggesting a defect in the classical complement pathway. Leukocyte recruitment and C1q-hemolytic activity was restored to wild type levels when CD93 was expressed on either hematopoietic cells or nonhematopoietic cells in bone marrow chimeric mice. However, elevated levels of sCD93 in inflammatory fluid were observed only when CD93 was expressed on nonhematopoietic cells. Because cell-associated CD93 was sufficient to restore a normal inflammatory response, these data suggest that cell-associated CD93, and not sCD93, regulates leukocyte recruitment and complement activation during murine peritonitis. PMID:21849679

  15. Managing juvenile Huntington's disease.

    PubMed

    Quarrell, Oliver W J; Nance, Martha A; Nopoulos, Peggy; Paulsen, Jane S; Smith, Jonathan A; Squitieri, Ferdinando

    2013-06-01

    Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience. PMID:24416077

  16. Chromosomal localization of the human fibromodulin gene

    SciTech Connect

    Roughley, P.J.; Sztrolovics, R.; Grover, J.

    1994-09-01

    The identification and mapping of genes is a fundamental step in understanding inherited diseases. This study reports the chromosomal localization of the human gene encoding fibromodulin, a collagen-binding proteoglycan which exhibits a wide distribution in connective tissue extracellular matrices. Attempts to localize the gene utilizing a probe covering the published coding region of the human fibromodulin cDNA were unsuccessful. Thus, in order to obtain an alternate probe, the 3{prime}-untranslated region of the cDNA was cloned utilizing the 3{prime}-RACE protocol. Southern blot analysis of human genomic DNA with probes covering either the coding sequence or the 3{prime}-untranslated region revealed simple patterns, indicative of a single-copy gene. Fluorescence in situ hybridization analysis with the 3{prime}-untranslated region probe resulted in hybridization at two chromosomal regions. The majority of signals were observed at 1q32, but some signals were also observed at 9q34.1. The localization of the fibromodulin gene to chromosome 1 was confirmed by the polymerase chain reaction analysis of genomic DNA from a panel of somatic cell hybrid lines. In addition to allowing the gene localization, cloning of the 3{prime}-untranslated region demonstrates that the human fibromodulin cDNA possesses an insert of approximately 160 base pairs which is not present in the published bovine sequence. The human sequence also possesses a single polyadenylation signal, yielding a 3 kb mRNA which was observed in Northern blotting experiments. These results now provide the necessary information to evaluate the potential role of fibromodulin in genetic disorders of connective tissues.

  17. Diversity of breakpoints of variant Philadelphia chromosomes in chronic myeloid leukemia in Brazilian patients

    PubMed Central

    Chauffaille, Maria de Lourdes Lopes Ferrari; Bandeira, Ana Carolina de Almeida; da Silva, Aline Schiavoni Guarnieri

    2014-01-01

    Background Chronic myeloid leukemia is a myeloproliferative disorder characterized by the Philadelphia chromosome or t(9;22)(q34.1;q11.2), resulting in the break-point cluster region-Abelson tyrosine kinase fusion gene, which encodes a constitutively active tyrosine kinase protein. The Philadelphia chromosome is detected by karyotyping in around 90% of chronic myeloid leukemia patients, but 5–10% may have variant types. Variant Philadelphia chromosomes are characterized by the involvement of another chromosome in addition to chromosome 9 or 22. It can be a simple type of variant when one other chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. Few studies have reported the incidence of variant Philadelphia chromosomes or the breakpoints involved among Brazilian chronic myeloid leukemia patients. Objective The aim of this report is to describe the diversity of the variant Philadelphia chromosomes found and highlight some interesting breakpoint candidates for further studies. Methods the Cytogenetics Section Database was searched for all cases with diagnoses of chronic myeloid leukemia during a 12-year period and all the variant Philadelphia chromosomes were listed. Results Fifty (5.17%) cases out of 1071 Philadelphia-positive chronic myeloid leukemia were variants. The most frequently involved chromosome was 17, followed by chromosomes: 1, 20, 6, 11, 2, 10, 12 and 15. Conclusion Among all the breakpoints seen in this survey, six had previously been described: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 and 17q21. The fact that some regions get more frequently involved in such rare rearrangements calls attention to possible predisposition that should be further studied. Nevertheless, the pathological implication of these variants remains unclear. PMID:25638762

  18. C1q Modulates the Response to TLR7 Stimulation by Pristane-Primed Macrophages: Implications for Pristane-Induced Lupus.

    PubMed

    Carlucci, Francesco; Ishaque, Attia; Ling, Guang Sheng; Szajna, Marta; Sandison, Ann; Donatien, Philippe; Cook, H Terence; Botto, Marina

    2016-02-15

    The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b(+) Ly6C(high) inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa(-/-) mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b(+) Ly6C(high) inflammatory monocytes in C1qa(-/-) mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model. PMID:26773156

  19. Plant sex chromosome evolution.

    PubMed

    Charlesworth, Deborah

    2013-01-01

    It is now well established that plants have an important place in studies of sex chromosome evolution because of the repeated independent evolution of separate sexes and sex chromosomes. There has been considerable recent progress in studying plant sex chromosomes. In this review, I focus on how these recent studies have helped clarify or answer several important questions about sex chromosome evolution, and I shall also try to clarify some common misconceptions. I also outline future work that will be needed to make further progress, including testing some important ideas by genetic, molecular, and developmental approaches. Systems with different ages can clearly help show the time course of events during changes from an ancestral co-sexual state (hermaphroditism or monoecy), and I will also explain how different questions can be studied in lineages whose dioecy or sex chromosomes evolved at different times in the past. PMID:23125359

  20. Capturing Chromosome Conformation

    NASA Astrophysics Data System (ADS)

    Dekker, Job; Rippe, Karsten; Dekker, Martijn; Kleckner, Nancy

    2002-02-01

    We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.

  1. Genetics Home Reference: juvenile Paget disease

    MedlinePlus

    ... juvenile Paget disease: Genetic Testing Registry: Hyperphosphatasemia with bone disease These resources from MedlinePlus offer information about the ... familial osteoectasia hyperostosis corticalis deformans juvenilis hyperphosphatasemia ... idiopathic idiopathic hyperphosphatasia JPD juvenile Paget's ...

  2. New Treatments Helping Kids with Juvenile Arthritis

    MedlinePlus

    ... 159984.html New Treatments Helping Kids With Juvenile Arthritis Several biologics have been approved by the FDA ... 20, 2016 (HealthDay News) -- New treatments for juvenile arthritis offer hope to children with the chronic autoimmune ...

  3. Roles of two-component system AfsQ1/Q2 in regulating biosynthesis of the yellow-pigmented coelimycin P2 in Streptomyces coelicolor.

    PubMed

    Chen, Shuangshuang; Zheng, Guosong; Zhu, Hong; He, Huiqi; Chen, Lei; Zhang, Weiwen; Jiang, Weihong; Lu, Yinhua

    2016-08-01

    We previously demonstrated that in Streptomyces coelicolor two-component system AfsQ1/Q2 activates the production of the yellow-colored coelimycin P2 (also named as yCPK) on glutamate-supplemented minimal medium, and the response regulator AfsQ1 could specifically bind to the intergenic region between two structural genes, cpkA and cpkD Here, a more in-depth investigation was performed to elucidate the mechanism underlying the role of AfsQ1/Q2 in regulating coelimycin P2 biosynthesis. Deletion of afsQ1/Q2 resulted in markedly decreased expression of the whole coelimycin P2 biosynthetic gene cluster. Electrophoretic mobility shift assays revealed that AfsQ1 bound only to the target site identified previously, but not to any other promoters in the gene cluster. Mutations of AfsQ1-binding motif only resulted in drastically reduced transcription of the cpkA/B/C operon (encoding three type I polyketide synthases) and intriguingly, led to enhanced expression of some coelimcyin P2 genes, particularly accA1 and scF These results suggested the direct role of AfsQ1/Q2 in regulating coelimycin production, which is directly mediated by the structural genes, but not the cluster-situated regulatory genes, and also implied that other unknown mechanisms may be involved in AfsQ1/Q2-mediated regulation of coelimycin P2 biosynthesis. PMID:27313101

  4. Characteristics of adopted juvenile delinquents.

    PubMed

    Kim, W J; Zrull, J P; Davenport, C W; Weaver, M

    1992-05-01

    There have been many reports describing the uniqueness of adopted children and adolescents' delinquent behaviors in terms of both their delinquent characteristics and courts' treatment of them. A total of 43 adopted juveniles, 32 extrafamilial (1.0%) and 11 intrafamilial (0.3%) adoptions were initially identified out of 3,280 juvenile delinquents. The adopted subjects were then compared with the demographically matched and offense matched nonadopted subjects. The family variables, such as marital and employment status of parents, were significantly different. However, there were only a few discernible trends, and in general there were no significant differences between the adopted and nonadopted juveniles in terms of their offense characteristics and dispositions. PMID:1592787

  5. Comparative bacteriology of juvenile periodontitis.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Palcanis, K G; Ranney, R R

    1985-01-01

    Statistical comparisons of the floras associated with juvenile periodontitis, severe periodontitis, and moderate periodontitis indicated that differences in the bacterial compositions of affected sites in these populations were not statistically significant. The subgingival flora of affected juvenile periodontitis sites was statistically significantly different from the adjacent supragingival flora and from the subgingival floras of people with healthy gingiva and of children with developing (experimental) gingivitis. However, the subgingival flora of affected juvenile periodontitis sites was not significantly different from the flora of sites with gingival index scores of 1 or 2 in adults with developing (experimental) gingivitis. Of 357 bacterial taxa among over 18,000 isolates, 54 non-treponemal species, 2 treponemal species, and mycoplasma were most associated with diseased periodontal sulci. These species comprised an increasing proportion of the flora during developing gingivitis and constituted over half of the cultivable flora of diseased sites. PMID:3988344

  6. Sequential cloning of chromosomes

    DOEpatents

    Lacks, Sanford A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  7. Sequential cloning of chromosomes

    DOEpatents

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  8. Sequential cloning of chromosomes

    SciTech Connect

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  9. Inferring Planet Occurrence Rates With a Q1-Q17 Kepler Planet Candidate Catalog Produced by a Machine Learning Classifier

    NASA Astrophysics Data System (ADS)

    Catanzarite, Joseph; Jenkins, Jon Michael; McCauliff, Sean D.; Burke, Christopher; Bryson, Steve; Batalha, Natalie; Coughlin, Jeffrey; Rowe, Jason; mullally, fergal; thompson, susan; Seader, Shawn; Twicken, Joseph; Li, Jie; morris, robert; smith, jeffrey; haas, michael; christiansen, jessie; Clarke, Bruce

    2015-08-01

    NASA’s Kepler Space Telescope monitored the photometric variations of over 170,000 stars, at half-hour cadence, over its four-year prime mission. The Kepler pipeline calibrates the pixels of the target apertures for each star, produces light curves with simple aperture photometry, corrects for systematic error, and detects threshold-crossing events (TCEs) that may be due to transiting planets. The pipeline estimates planet parameters for all TCEs and computes diagnostics used by the Threshold Crossing Event Review Team (TCERT) to produce a catalog of objects that are deemed either likely transiting planet candidates or false positives.We created a training set from the Q1-Q12 and Q1-Q16 TCERT catalogs and an ensemble of synthetic transiting planets that were injected at the pixel level into all 17 quarters of data, and used it to train a random forest classifier. The classifier uniformly and consistently applies diagnostics developed by the Transiting Planet Search and Data Validation pipeline components and by TCERT to produce a robust catalog of planet candidates.The characteristics of the planet candidates detected by Kepler (planet radius and period) do not reflect the intrinsic planet population. Detection efficiency is a function of SNR, so the set of detected planet candidates is incomplete. Transit detection preferentially finds close-in planets with nearly edge-on orbits and misses planets whose orbital geometry precludes transits. Reliability of the planet candidates must also be considered, as they may be false positives. Errors in detected planet radius and in assumed star properties can also bias inference of intrinsic planet population characteristics.In this work we infer the intrinsic planet population, starting with the catalog of detected planet candidates produced by our random forest classifier, and accounting for detection biases and reliabilities as well as for radius errors in the detected population.Kepler was selected as the 10th mission

  10. Nonrandom chromosomal aberrations and cytogenetic heterogeneity in gallbladder carcinomas.

    PubMed

    Gorunova, L; Parada, L A; Limon, J; Jin, Y; Hallén, M; Hägerstrand, I; Iliszko, M; Wajda, Z; Johansson, B

    1999-12-01

    Chromosome banding analysis of 11 short-term cultured gallbladder carcinomas revealed acquired clonal aberrations in seven tumors (five primary and two metastases). Three of these had one clone, whereas the remaining four were cytogenetically heterogeneous, displaying two to seven aberrant clones. Of a total of 21 abnormal clones, 18 had highly complex karyotypes and three exhibited simple numerical deviations. Double minutes and homogeneously staining regions were observed in one and two carcinomas, respectively. To characterize the karyotypic profile of gallbladder cancer more precisely, we have combined the present findings with our three previously reported cases, thereby providing the largest cytogenetic database on this tumor type to date. A total of 287 chromosomal breakpoints were identified, 251 of which were found in the present study. Chromosome 7 was rearranged most frequently, followed by chromosomes 1, 3, 11, 6, 5, and 8. The bands preferentially involved were 1p32, 1p36, 1q32, 3p21, 6p21, 7p13, 7q11, 7q32, 19p13, 19q13, and 22q13. Nine recurrent abnormalities could, for the first time, be identified in gallbladder carcinoma: del(3)(p13), i(5)(p10), del(6)(q13), del(9)(p13), del(16)(q22), del(17)(p11), i(17)(q10), del(19)(p13), and i(21)(q10). The most common partial or whole-arm gains involved 3q, 5p, 7p, 7q, 8q, 11q, 13q, and 17q, and the most frequent partial or whole-arm losses affected 3p, 4q, 5q, 9p, 10p, 10q, 11p, 14p, 14q, 15p, 17p, 19p, 21p, 21q, and Xp. These chromosomal aberrations and imbalances provide some starting points for molecular analyses of genomic regions that may harbor genes of pathogenetic importance in gallbladder carcinogenesis. Genes Chromosomes Cancer 26:312-321, 1999. PMID:10534766

  11. Consistent chromosome abnormalities including double minutes (dms) in adenocarcinoma of the pancreas

    SciTech Connect

    Griffin, C.A.; Morsberger, L.; Ellingham, T.

    1994-09-01

    Little is known about the somatic genetic changes which characterize pancreatic adenocarcinoma (PA), and identification of acquired genomic alterations would further our understanding of the biology of this neoplasm. We have studied 62 primary specimens of PA using classical and FISH methods. Clonally abnormal karyotypes were observed in 44 neoplasms. Karyotypes were generally complex (greater than 3 abnormalities) including both numerical and structural chromosome changes. Many tumors contained at least one marker chromosome. The most frequent whole chromosomal gains were chromosomes 20 (7 tumors) and 7 (5 tumors). Losses were much more frequent: chromosome 18 was lost in 22 tumors, followed by chromosomes 13 (15 tumors), 12 (13 tumors), and 6 (12 tumors). Structural abnormalities were common. 200 chromosome breakpoints were identified. Excluding Robertsonian translocations, chromosomal arms most frequently involved were 6q (12 chromosomes), 1p and 3p (10 each), 11p and 17p (9 each), 1q (8), 8p and 19q (7 each). Of particular interest, we found dms in 6 cases. These represent the first PAs with cytogenetic evidence of gene amplification, and are under investigation using chromosome microdissection. To begin to define the smallest region of 6q which is deleted, 5 tumors with 6q deletions were hybridized with a biotin-labeled probe, made by microdissection of 6q24-qter. Loss of one copy of this region was verified in 4/5 tumors; additional probes are being made. Our results are similar to those of 34 other reported PAs, and the combined data suggest that gains of chromosomes 7 and 20 and deletions and rearrangements of 1p and 6q may be particularly important in the biology of adenocarcinoma of the pancreas.

  12. Families, Juvenile Justice and Children's Mental Health.

    ERIC Educational Resources Information Center

    McManus, Marilyn C., Ed.

    1997-01-01

    The theme issue of this bulletin is a discussion of youth with emotional disturbances who are in the juvenile justice system and how to meet their needs. Articles include: (1) "Responding to the Mental Health Needs of Youth in the Juvenile Justice System" (Susan Rotenberg); (2) "Prevalence of Mental Disorders among Youth in the Juvenile Justice…

  13. Sex Differences in Attributions of Juvenile Delinquency.

    ERIC Educational Resources Information Center

    Sagatun, Inger J.

    This paper is an application of attribution theory to the processing of juvenile delinquents in an attempt to understand the differential treatment of female and male offenders within the juvenile justice system. The paper explores the attributions of juvenile delinquency both by male and female minors, by male and female parents, and by male and…

  14. Guidelines for Juvenile Information Sharing. OJJDP Report

    ERIC Educational Resources Information Center

    Mankey, Jennifer; Baca, Patricia; Rondenell, Stephanie; Webb, Marilyn; McHugh, Denise

    2006-01-01

    The juvenile information sharing (JIS) guidelines were prepared by the Center for Network Development (CND) for the Office of Juvenile Justice and Delinquency Prevention (OJJDP). The guidelines suggest a course of action for key agency and organization stakeholders involved in a state or local effort to implement and sustain juvenile information…

  15. On the Prevention of Juvenile Crime

    ERIC Educational Resources Information Center

    Lelekov, V. A.; Kosheleva, E. V.

    2008-01-01

    Crimes committed by juveniles are among the most urgent social problems. Juvenile crime is as prevalent as crime itself is, and it has not been solved completely in any society and cannot be solved through law enforcement measures alone. In this article, the authors discuss the dynamics and structure of juvenile crime in Russia and present data…

  16. Reforming Our Expectations about Juvenile Justice

    ERIC Educational Resources Information Center

    Rodriguez, Pamela F.; Baille, Daphne M.

    2010-01-01

    Typing the term "juvenile justice reform" into a Google[TM] search will result in 60 pages of entries. But what is meant by juvenile justice reform? What does it look like? How will one know when it is achieved? This article defines juvenile justice reform, discusses the principles of effective reform, and describes the practice of juvenile…

  17. Do Juveniles Bully More than Young Offenders?

    ERIC Educational Resources Information Center

    Ireland, Jane L.

    2002-01-01

    Study compares bullying behavior among juvenile and young offenders. Ninety-five male juvenile and 196 male young offenders completed two questionnaires, measuring bullying directly and behaviors indicative of "being bullied" or of "bullying others". Juveniles perceived a higher extent of bullying and reported significantly more physical,…

  18. Intensive Reading Instruction in Juvenile Correctional Settings

    ERIC Educational Resources Information Center

    Williams, Jacob L.; Wexler, Jade; Roberts, Greg; Carpenter, Clint

    2011-01-01

    Despite 60 years of evidence linking juvenile illiteracy and delinquency, practitioners and policymakers have been painfully slow in the implementation of evidence-based reading interventions for incarcerated juveniles. We will present the Texas Juvenile Justice Tiered Instructional Model, an evidence-based reading program model created…

  19. A new chromosome was born: comparative chromosome painting in Boechera.

    PubMed

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  20. Mobilizing Communities To Prevent Juvenile Crime. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Bownes, Donna; Ingersoll, Sarah

    Through Title V Incentive Grants for Local Delinquency Prevention Programs (Community Prevention Grants), the Office of Juvenile Justice and Delinquency Prevention (OJJDP) allocated $20 million in fiscal year 1997 to states to complement law enforcement and justice system efforts by helping local communities foster strong families and nurture…

  1. Special Education and the Juvenile Justice System. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Burrell, Sue; Warboys, Loren

    This bulletin summarizes provisions of federal law as they pertain to special education and juvenile justice. It discusses provisions of the Individuals with Disabilities Education Act 1997 including: the definition of disability; free appropriate public education; identification, referral, and evaluation; the individualized education program…

  2. Race as a Factor in Juvenile Arrests. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Pope, Carl E.; Snyder, Howard E.

    This bulletin examines the effect of race on police decisions to take juvenile offenders into custody. Analysis of 1997 and 1998 data on 17 states from the Federal Bureau of Investigation's National Incident-Based Reporting System indicates that there is no evidence to support the hypothesis that police are more likely to arrest nonwhite juvenile…

  3. Prevention of Serious and Violent Juvenile Offending. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Wasserman, Gail A.; Miller, Laurie S.; Cothern, Lynn

    This bulletin explores the proximal risk factors for juvenile offending, reviews the early developmental precursors to violent offending, and summarizes approaches to prevention. It also discusses components of intervention programs, limitations of single-focus prevention, examples of multi systemic interventions, and limitations of prevention…

  4. Mapping of the receptor protein-tyrosine kinase 10 to human chromosome 1q21-q23 and mouse chromosome 1H1-5 by fluorescence in situ hybridization

    SciTech Connect

    Edelhoff, S.; Disteche, C.M.; Lai, C.

    1995-01-01

    Receptor protein-tyrosine kinases (PTKs) play a critical role in the transduction of signals important to cell growth, differentiation, and survival. Mutations affecting the expression of receptor PTK genes have been associated with a number of vertebrate and invertebrate developmental abnormalities, and the aberrant regulation of tyrosine phosphorylation is implicated in a variety of neoplasias. One estimate suggests that approximately 100 receptor PTK genes exist in the mammalian genome, about half of which have been identified. The tyro-10 receptor protein-tyrosine kinase, first identified in a PCR-based survey for novel tyrosine kinases in the rat nervous system, defines a new subfamily of PTKs. It exhibits a catalytic domain most closely related to those found in the trk PTK receptor subfamily, which transduces signals for nerve growth factor and the related molecules brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4 (NT-3 and NT-4). Trk and the related PTK receptors trkB and trkC play a critical role in the neurotrophin-dependent survival of subsets of sensory and motor neurons. The predicted tyro-10 extracellular region is, however, distinct from that of the trk subfamily and is unique except for a domain shared with the blood coagulation factors V and VIII, thought to be involved in phospholipid binding. Although tyro-10 RNA is most abundant in heart and skeletal muscle in the adult rat, it is expressed in a wide variety of tissues, including the developing and mature brain. Tyro-10 appears identical to the murine TKT sequence reported by Karn et al. and exhibits a high degree of similarity with the CaK, DDR, and Nep PTKs. A ligand for tyro-10 has not yet been identified. 10 refs., 1 fig.

  5. Circular-dichroism and electron-microscopy studies of human subcomponent C1q before and after limited proteolysis by pepsin.

    PubMed Central

    Brodsky-Doyle, B; Leonard, K R; Reid, K B

    1976-01-01

    1. A fragment of human subcomponent C1q was prepared by limited proteolysis with pepsin at 37 degrees C for 20 h, and at pH4.4, followed by gel filtration on Sephadex G-200. This fragment was shown to contain all the collagen-like features known to be present in the intact molecule [Reid (1976) Biochem. J. 155, 5-17]. 2. Circular-dichroism studies showed the presence of positive bands at 230 and 223 nm in the intact subcomponent C1q and pepsin fragment respectively, compared with a positive band at 220 nm obtained for lathyritic rat skin collagen. These bands were abolished by collagenase treatment, which suggested that there may some collagen-like triple-helical structure in subcomponent C1q and that this structure resides in the pepsin-resistant portion of the molecule. However, the 230 and 223 nm bands had a substantially lower magnitude than that obtained for the unaggregated single fibres of totally triple-helical collagen. 3. Thermal-transition temperatures obtained for subcomponent C1q, the pepsin fragment and the reduced and alkylated pepsin fragment were 48 degrees, 48 degrees and 39 degrees C respectively, compared with a value of 38 degrees C obtained for lathyritic rat skin collagen. 4. Only the unreduced pepsin fragment regained significant amounts (up to 60%) of collagen-like structure, after heat denaturation and cooling, as estimated by circular-dichroism measurements. 5. Electron-microscopy studies of subcomponent C1q and the collagen-like pepsin-resistant fragment of subcomponent C1q showed that the six peripheral globular regions of the molecule were fragmented by pepsin leaving the six collagen-like connecting strands and fibril-like central portion intact. Images PLATE 1 PLATE 2 PMID:187173

  6. Evaluation of Endothelial Cell Adhesion Molecules and Anti-C1q Antibody in Discriminating between Active and Non-Active Systemic Lupus Erythematosus

    PubMed Central

    Mahayidin, Hasni; Yahya, Nurul Khaiza; Wan Ghazali, Wan Syamimee; Mohd Ismail, Asmahan; Wan Ab Hamid, Wan Zuraida

    2016-01-01

    Background Detecting the active state of systemic lupus erythematosus (SLE) is important but challenging. This study aimed to determine the diagnostic accuracy of serum endothelial cell adhesion molecules (ICAM-1 and VCAM-1) and anti-C1q antibody in discriminating between active and non-active SLE. Methods Using SELENA-SLE disease activity index (SLEDAI), 95 SLE patients (45 active and 50 non-active) were assessed. A score above five was considered indicative of active SLE. The blood samples were tested for serum ICAM-1, VCAM-1 and anti-C1q antibody using enzyme-linked immunosorbent assay (ELISA). Results The levels of serum VCAM-1 and anti-C1q antibody were significantly higher in active SLE patients. Both VCAM-1 and anti-C1q were able to discriminate between active and non-active SLE (p-value < 0.001 and 0.005, respectively). From the receiver operating characteristic curves (ROCs) constructed, the optimal cut-off values for VCAM-1 and anti-C1q antibody in discriminating between active and non-active SLE were 30.5 ng/mL (69.0% sensitivity, 60.0% specificity, PPV 58.5%, NPV 66.7%) and 7.86 U/mL (75.6% sensitivity, 80% specificity, PPV 77.3%, NPV 78.4%), respectively. However, serum ICAM-1 level was unable to discriminate between the two groups (p-value = 0.193). Conclusion Anti-C1q antibody demonstrated the best diagnostic accuracy in discriminating between active and non-active SLE patients. PMID:27418866

  7. The Exosporium of B.cereus Contains a Binding Site for gC1qR/p33: Implication in Spore Attachment and/or Entry.

    SciTech Connect

    GHEBREHIWET,B.; TANTRAL, L.; TITMUS, M.A.; PANESSA-WARREN, B.J.; TORTORA, G.T.; WONG, S.S.; WARREN, J.B.

    2008-01-01

    B. cereus, is a member of a genus of aerobic, gram-positive, spore-forming rod-like bacilli, which includes the deadly, B. anthracis. Preliminary experiments have shown that gC1qR binds to B.cereus spores that have been attached to microtiter plates. The present studies were therefore undertaken, to examine if cell surface gC1qR plays a role in B.cereus spore attachment and/or entry. Monolayers of human colon carcinoma (Caco-2) and lung cells were grown to confluency on 6 mm coverslips in shell vials with gentle swirling in a shaker incubator. Then, 2 {micro}l of a suspension of strain SB460 B.cereus spores (3x10{sup 8}/ml, in sterile water), were added and incubated (1-4 h; 36{sup 0} C) in the presence or absence of anti-gC1qR mAb-carbon nanoloops. Examination of these cells by EM revealed that: (1) When B. cereus endospores contacted the apical Caco-2 cell surface, or lung cells, gClqR was simultaneously detectable, indicating upregulation of the molecule. (2) In areas showing spore contact with the cell surface, gClqR expression was often adjacent to the spores in association with microvilli (Caco-2 cells) or cytoskeletal projections (lung cells). (3) Furthermore, the exosporia of the activated and germinating spores were often decorated with mAb-nanoloops. These observations were further corroborated by experiments in which B.cereus spores were readily taken up by monocytes and neutrophils, and this uptake was partially inhibited by mAb 60.11, which recognizes the C1q binding site on gC1qR. Taken together, the data suggest a role, for gC1qR at least in the initial stages of spore attachment and/or entry.

  8. VizieR Online Data Catalog: Transit metric for Q1-Q17 Kepler candidates (Thompson+, 2015)

    NASA Astrophysics Data System (ADS)

    Thompson, S. E.; Mullally, F.; Coughlin, J.; Christiansen, J. L.; Henze, C. E.; Haas, M. R.; Burke, C. J.

    2016-02-01

    We describe a new metric that uses machine learning to determine if a periodic signal found in a photometric time series appears to be shaped like the signature of a transiting exoplanet. This metric uses dimensionality reduction and k-nearest neighbors to determine whether a given signal is sufficiently similar to known transits in the same data set. This metric is being used by the Kepler Robovetter to determine which signals should be part of the Q1-Q17 DR24 catalog of planetary candidates. The Kepler Mission reports roughly 20000 potential transiting signals with each run of its pipeline, yet only a few thousand appear to be sufficiently transit shaped to be part of the catalog. The other signals tend to be variable stars and instrumental noise. With this metric, we are able to remove more than 90% of the non-transiting signals while retaining more than 99% of the known planet candidates. When tested with injected transits, less than 1% are lost. This metric will enable the Kepler mission and future missions looking for transiting planets to rapidly and consistently find the best planetary candidates for follow-up and cataloging. (1 data file).

  9. HYDRAULIC CONDUCTIVITY OF SALTSTONE FORMULATED USING 1Q11, 2Q11 AND 3Q11 TANK 50 SLURRY SAMPLES

    SciTech Connect

    Reigel, M.; Nichols, R.

    2012-06-27

    As part of the Saltstone formulation work requested by Waste Solidification Engineering (WSE), Savannah River National Laboratory (SRNL) was tasked with preparing Saltstone samples for fresh property analysis and hydraulic conductivity measurements using actual Tank 50 salt solution rather than simulated salt solution. Samples of low level waste salt solution collected from Tank 50H during the first, second, and third quarters of 2011 were used to formulate the Saltstone samples. The salt solution was mixed with premix (45 wt % slag, 45 wt % fly ash, and 10 wt % cement), in a ratio consistent with facility operating conditions during the quarter of interest. The fresh properties (gel, set, bleed) of each mix were evaluated and compared to the recommended acceptance criteria for the Saltstone Production Facility. ASTM D5084-03, Method C was used to measure the hydraulic conductivity of the Saltstone samples. The hydraulic conductivity of Saltstone samples prepared from 1Q11 and 2Q11 samples of Tank 50H is 4.2E-9 cm/sec and 2.6E-9 cm/sec, respectively. Two additional 2Q11 and one 3Q11 sample were not successfully tested due to the inability to achieve stable readings during saturation and testing. The hydraulic conductivity of the samples made from Tank 50H salt solution compare well to samples prepared with simulated salt solution and cured under similar conditions (1.4E-9 - 4.9E-8 cm/sec).

  10. Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants.

    PubMed

    Martínez-Quintana, Efrén; Medina-Gil, José M; Rodríguez-González, Fayna; Garay-Sánchez, Paloma; Limiñana, José M; Saavedra, Pedro; Tugores, Antonio

    2014-08-01

    There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant. PMID:24504666

  11. Ets-2 is involved in transcriptional regulation of C1qTNF-related protein 5 in muscle cells.

    PubMed

    Park, Eun-Ju; Kim, Mi-Jin; Lee, Wan; Park, Seung-Yoon

    2012-10-01

    It was recently reported that C1qTNF-related protein 5 (CTRP5) regulates glucose and lipid metabolism in muscle cells. However, the molecular mechanism of CTRP5 expression has not been fully investigated. In this study we demonstrate the mechanism regulating the transcription of the CTRP5 gene in muscle cells. We found that potential binding sites for transcription factors were conserved in proximal region of CTRP5 promoters in human, mouse and rat. Among these factors, Ets-2 was found to increase the promoter activity of the CTRP5 gene in C2C12 cells. Deletion of -166 to -80 in the CTRP5 promoter region significantly decreased Ets-2-induced CTRP5 promoter activity. Mutagenesis evaluation indicated that two putative Ets-2-binding sites in the CTRP5 promoter are important in CTRP5 activation. Promoter enzyme immunoassay showed that Ets-2 binds directly to two Ets-2-responsive elements at regions -166/-80 of the CTRP5 promoter. Taken together, these results suggest that Ets-2 play a key role in transcriptional regulation of CTRP5 in muscle cells. PMID:22740135

  12. Genetic markers on chromosome 7.

    PubMed Central

    Tsui, L C

    1988-01-01

    Chromosome 7 is frequently associated with chromosome aberrations, rearrangements, and deletions. It also contains many important genes, gene families, and disease loci. This brief review attempts to summarise these and other interesting aspects of chromosome 7. With the rapid accumulation of cloned genes and polymorphic DNA fragments, this chromosome has become an excellent substrate for molecular genetic studies. PMID:3290488

  13. Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13

    SciTech Connect

    Lundberg, C.; Skoog, L.; Cavenee, W.K.; Nordenskjoeld, M.

    1987-04-01

    The genotypes at chromosomal loci defined by recombinant DNA probes revealing restriction fragment length polymorphisms were determined in constitutional and tumor tissue from 10 cases of ductal breast cancer: eight premenopausal females and two males. Somatic loss of constitutional heterozygosity was observed at loci on chromosome 13 in primary tumor tissue from three females and one male. In two cases, specific loss of heterozygosity at three distinct genetic loci along the length of the chromosome was observed. In another case, concurrent loss of alleles at loci on chromosomes 2, 13, 14, and 20 was detected, whereas a fourth case showed loss of heterozygosity for chromosomes 5 and 13. In each instance, the data were consistent with loss of one of the homologous chromosomes by mitotic nondisjunction. Analysis of loci on several other chromosomes showed retention of constitutional heterozygosity suggesting the relative specificity of the events. In contrast, similar analyses of other breast cancers, including comedocarcinoma, medullary carcinoma, and juvenile secretory carcinoma, showed no loss of alleles at loci on chromosome 13. These data indicate that the pathogenesis of ductal breast cancer may, in a substantial proportion of cases, involve unmasking of a recessive locus on chromosome 13 and suggest the involvement of such a locus in heritable forms of this disease.

  14. Incidence of Chromosome Disorders

    PubMed Central

    Valentine, G. H.

    1979-01-01

    A minority of conceptions result in live births. Of recognized conceptions, 15% result in spontaneous abortions, up to 60% of which are due to chromosome abnormalities. The incidence of the different disorders is given. Of live births, one in 200 suffers a chromosome abnormality. The common abnormalities are described with their incidence. The effect of maternal age on this incidence is pronounced, but even so must be kept in proportion for counselling purposes.

  15. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  16. Pure chromosome-specific PCR libraries from single sorted chromosomes.

    PubMed Central

    VanDevanter, D R; Choongkittaworn, N M; Dyer, K A; Aten, J; Otto, P; Behler, C; Bryant, E M; Rabinovitch, P S

    1994-01-01

    Chromosome-specific DNA libraries can be very useful in molecular and cytogenetic genome mapping studies. We have developed a rapid and simple method for the generation of chromosome-specific DNA sequences that relies on polymerase chain reaction (PCR) amplification of a single flow-sorted chromosome or chromosome fragment. Previously reported methods for the development of chromosome libraries require larger numbers of chromosomes, with preparation of pure chromosomes sorted by flow cytometry, generation of somatic cell hybrids containing targeted chromosomes, or a combination of both procedures. These procedures are labor intensive, especially when hybrid cell lines are not already available, and this has limited the generation of chromosome-specific DNA libraries from nonhuman species. In contrast, a single sorted chromosome is a pure source of DNA for library production even when flow cytometric resolution of chromosome populations is poor. Furthermore, any sorting cytometer may be used with this technique. Using this approach, we demonstrate the generation of PCR libraries suitable for both molecular and fluorescence in situ hybridization studies from individual baboon and canine chromosomes, separate human homologues, and a rearranged marker chromosome from a transformed cell line. PCR libraries specific to subchromosomal regions have also been produced by sorting a small chromosome fragment. This simple and rapid technique will allow generation of nonhuman linkage maps and probes for fluorescence in situ hybridization and the characterization of marker chromosomes from solid tumors. In addition, allele-specific libraries generated by this strategy may also be useful for mapping genetic diseases. Images PMID:8016078

  17. Factors affecting attitudes toward juvenile sex offenders.

    PubMed

    Sahlstrom, Kimberly J; Jeglic, Elizabeth L

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment amenability were negative. No differences in attitudes toward juvenile sex offenders were found between those who had been victims of sexual abuse and those that had not. Sex offenses committed by juvenile female sex offenders were viewed to be more serious and require more intervention than those committed by juvenile male sex offenders. PMID:19042245

  18. Transfer of Juvenile Cases to Criminal Court.

    PubMed

    Lee, Soo Jung; Kraus, Louis J

    2016-01-01

    The first juvenile court was founded in 1899 with the focus on rehabilitation of a juvenile offender as opposed to punishment in adult court. Determining culpability and disposition for adolescents has become a source of much discussion. With serious crimes, juvenile delinquents may be transferred from juvenile court to adult criminal court; this practice became more prevalent in the past century. However, growing knowledge of adolescent development has mitigated the culpability of youth offenders and resulted in judicial decisions influential to juvenile dispositions. PMID:26593117

  19. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  20. [Sex-linked juvenile retinoschisis].

    PubMed

    François, P; Turut, P; Soltysik, C; Hache, J C

    1976-02-01

    About 13 observations of sexe linked juvenile retinoschisis, the authors describe the ophthalmoscopic, fluorographic and functional aspects of the disease whose caracteristics are:--its sexe linked recessive heredity; --its clinical characterestics associating: a microcystic macular degeneration, peripheral retinal lesions, vitreous body alterations, --an electroretinogram of the negative type. PMID:132916

  1. Juvenile Court: Today and Tomorrow.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Discusses whether juveniles who commit criminal law violations should be tried in the same courts as adults. Addresses the issue of transfers that is a legal mechanism used to move youth to criminal court. Considers alternative proposals for handling youth brought to the judicial system and the role of the federal government. (CMK)

  2. Juvenile Criminals: Who Are They?

    ERIC Educational Resources Information Center

    Antonov, A. I.; Lebed, O. L.

    2005-01-01

    Many adolescents who were born in the late 1970s and 1980s in Russia became juvenile criminals due to the change in the social structure, the proclamation of the values of the comfortable way of life, the institution of property ownership and so forth. Many young people have to help relatives who are in need, and this as well often causes them to…

  3. Juvenile Justice and Substance Use

    ERIC Educational Resources Information Center

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad…

  4. Juvenile Diabetes and Rehabilitation Counseling.

    ERIC Educational Resources Information Center

    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  5. Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

    PubMed Central

    Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

    1994-01-01

    Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

  6. The expression level of gC1qR is down regulated at the early time of infection with porcine circovirus of type 2 (PCV-2) and gC1qR interacts differently with the Cap proteins of porcine circoviruses.

    PubMed

    Kouokam Fotso, Guy Baudry; Bernard, Cécilia; Bigault, Lionel; de Boisséson, Claire; Mankertz, Annette; Jestin, André; Grasland, Béatrice

    2016-07-15

    Porcine circoviruses (PCV) are small, non-enveloped single-stranded DNA-viruses. Porcine circovirus type 2 (PCV-2) is the causal agent of post-weaning multisystemic wasting syndrome (PMWS) whereas porcine circovirus of type 1 (PCV-1) is non- pathogenic. gC1qR is a membrane-located receptor of the complement protein subunit C1q and interacts with PCV capsid proteins. The mechanisms associated with the triggering of PMWS are not well known and gC1qR may have a role in the life cycle and eventually in the pathogenicity of PCV. The objectives of this study were to determine the level of expression of gC1qR during early PCV-2 infection, to determine the region of PCV-2 capsid protein (Cap) required for the interaction with gC1qR and to evaluate the interaction of gC1qR with Cap proteins of different PCV strains. The results indicate that gC1qR transcripts are downregulated in the tonsils and the tracheo-bronchial lymph nodes of piglets infected by PCV-2 at the early time of the infection. The N-terminal amino acids (a.a. 1-59) of PCV-2b Cap, an arginine rich region, are involved in the interaction with gC1qR. Porcine gC1qR interacts with Cap proteins of two pathogenic viral strains, PCV-2a and PCV-2b, while interaction has been observed with only one Cap protein of two investigated strains of PCV-1. The amino acids 30 and 49 of PCV-1Cap, solely, were not responsible of the difference of interaction observed. We have also shown that gC1qR interacts strongly with PCV-2Caps and PCV-1 GER Cap. This result suggests that the different interaction of gC1qR with PCV Cap proteins may have an impact on the pathogenicity of the PCV. PMID:27063333

  7. Micromechanics of human mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Sun, Mingxuan; Kawamura, Ryo; Marko, John F.

    2011-02-01

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed.

  8. Type I bipolar disorder associated with a fragile site on chromosome 1

    SciTech Connect

    Turecki, G.; Mari, J.J.; M. de Smith, A.C.

    1995-06-19

    The objective of this paper is to study the association between chromosomal fragile sites and type I bipolar disorder. This case-control study compares bipolar patients with normal controls. Ten cases of type I bipolar disorder diagnosed according to DSM-III-R criteria and the Composite International Diagnostic Interview (CIDI) were selected from the Escola Paulista affective disorders outpatient clinic and 10 healthy controls (CIDI negative for psychiatric diagnoses) matched for sex and age were drawn from the otorhinolaryngologic outpatient clinic of the same hospital. The cytogenetic analysis was carried out with blood lymphocytes, which were cultured in a folic acid-free medium. A total of 100 mitoses per subject were blindly analyzed to the psychiatric diagnostic assignment, and fragile sites were identified according to a minimum expected frequency of events per band in conformity with a Poisson distribution. A higher frequency of chromosomal lesions for cases than controls was found for the following bands: 1q32, 5q31, and 11q23, the 1q32 being considered a fragile site. Although no evident neuropsychiatric etiological component has been mapped to the 1q32 region so far, this finding may lead to further investigation of a possible linkage between genetic markers of this region and bipolar disorder. 40 refs., 2 tabs.

  9. Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval.

    PubMed

    Allamand, V; Broux, O; Richard, I; Fougerousse, F; Chiannilkulchai, N; Bourg, N; Brenguier, L; Devaud, C; Pasturaud, P; Pereira de Souza, A

    1995-06-01

    A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to approximately 3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Réunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Réunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population. PMID:7762565

  10. Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval

    SciTech Connect

    Allamand, V.; Broux, O.; Richard, I.

    1995-06-01

    A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to {approximately}3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Reunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Reunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population. 40 refs., 4 figs., 4 tabs.

  11. Juvenile social status predicts primary sex allocation in a sex changing fish.

    PubMed

    Solomon-Lane, Tessa K; Shvidkaya, Polina; Thomas, Alma; Williams, Megan M; Rhyne, Andrew; Rogers, Lock; Grober, Matthew S

    2016-07-01

    Both individual sex and population sex ratio can affect lifetime reproductive success. As a result, multiple mechanisms have evolved to regulate sexual phenotype, including adult sex change in fishes. While adult sex change is typically socially regulated, few studies focus on the non-chromosomal mechanisms regulating primary sex allocation. We investigated primary sex determination in the bluebanded goby (Lythrypnus dalli), a bidirectionally sex-changing fish. Of the studies investigating primary sex determination in species with adult sex change, this is the first to incorporate the roles of social status and size, key factors for determining adult sex allocation. For L. dalli, adult sex is regulated by social status: dominants are male; subordinates are female. In social groups of laboratory-reared juveniles, we demonstrate that status also predicts primary sex. Dominant juveniles developed male-typical genitalia, and their gonads contained significantly less ovarian tissue than subordinates, which developed female-typical genitalia. To better understand natural development, we quantified the distribution of juveniles and adults on the reef and analyzed genital papilla and gonad morphology in a sample of wild-caught juveniles. Juveniles were observed in various social environments, and most grouped with other juveniles and/or adults. The majority of field-caught juveniles had female-typical genitalia and bisexual, female-biased gonads. These data are consistent with a single mechanism that regulates sexual phenotype throughout life. Social status could first cause and then maintain through adulthood a female-biased population, allowing individuals to regulate sex based on local conditions, which is important for optimizing lifetime reproductive success. PMID:27402570

  12. Mapping quantitative trait loci for heat tolerance at anthesis in rice using chromosomal segment substitution lines.

    PubMed

    Zhao, Lei; Lei, Jianguo; Huang, Yingjin; Zhu, Shan; Chen, Hongping; Huang, Renliang; Peng, Zhiqin; Tu, Qinghua; Shen, Xianhua; Yan, Song

    2016-06-01

    To study the genetic basis of heat tolerance at anthesis, a set of chromosome segment substitution lines (CSSLs) derived from Sasanishiki (japonica ssp. heat susceptible) and Habataki (indica spp. heat tolerant) were used for analysis across three high temperature environments. Spikelet fertility (SF), daily flowering time (DFT) and pollen shedding level (PSL) under high temperature (HT) were assessed. Eleven related QTLs were detected, of which, two QTLs qSF (ht) 2 and qSF (ht) 4.2 for spikelet fertility were identified on chromosomes 2 and 4. Four QTLs qDFT3, qDFT8, qDFT10.1 and qDFT11 for daily flowering time were detected on chromosomes 3, 8, 10 and 11. The other five QTLs qPSL (ht) 1, qPSL (ht) 4.1, qPSL (ht) 5, qPSL (ht) 7 and qPSL (ht) 10.2 on chromosomes 1, 4, 5, 7 and 10, respectively, were found had effects both on spikelet fertility and pollen shedding level. Of the 11 QTLs, 8 were overlapped with QTLs reported by others, 3 QTLs qPSL (ht) 4.1, qPSL (ht) 7 and qPSL (ht) 10.2 identified in this study were novel. The stability of qPSL (ht) 4.1 was further verified at different temperatures, which could be used to improve the pollen shedding and pollen growth on stigma for rice heat-tolerance breeding. PMID:27436945

  13. High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma

    PubMed Central

    Toujani, Saloua; Dessen, Philippe; Ithzar, Nathalie; Danglot, Gisèle; Richon, Catherine; Vassetzky, Yegor; Robert, Thomas; Lazar, Vladimir; Bosq, Jacques; Da Costa, Lydie; Pérot, Christine; Ribrag, Vincent; Patte, Catherine; Wiels, Jöelle; Bernheim, Alain

    2009-01-01

    Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58–96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96–61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43–60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies. PMID:19759907

  14. Structure and chromosomal localization of the gene encoding the human myelin protein zero (MPZ)

    SciTech Connect

    Hayasaka, Kiyoshi; Himoro, Masato; Takada, Goro ); Wang, Yimin; Takata, Mizuho; Minoshima, Shinsei; Shimizu, Nobuyoshi; Miura, Masayuki; Uyemura, Keiichi )

    1993-09-01

    The authors describe the cloning, characterization, and chromosomal mapping of the human myelin protein zero (MPZ) gene (a structural protein of myelin and an adhesive glycoprotein of the immunoglobulin superfamily). The gene is about 7 kb long and consists of six exons corresponding of the functional domains. All exon-intron junction sequences conform to the GT/AG rule. The 5[prime]-flanking region of the gene has a TA-rich element (TATA-like box), two CAAT boxes, and a single defined transcription initiation site detected by the primer extension method. The gene for human MPZ was assigned to chromosome 1q22-q23 by spot blot hybridization of flow-sorted human chromosomes and fluorescence in situ hybridization. The localization of the MPZ gene coincides with the locus for Charcot-Marie-Tooth disease type 1B, determined by linkage analysis. 20 refs., 3 figs., 1 tab.

  15. Juvenile Crime, Juvenile Justice. Panel on Juvenile Crime: Prevention, Treatment, and Control.

    ERIC Educational Resources Information Center

    McCord, Joan, Ed.; Widom, Cathy Spatz, Ed.; Crowell, Nancy A., Ed.

    This book discusses patterns and trends in crimes committed by children and adolescents, analyzing youth crime as a subset of general crime and studying the impact of race and gender. It evaluates different approaches to forecasting future crime rates. Data come from a national panel that examined what is known about juvenile crime and its…

  16. Linkage mapping in Papio baboons: Conservation of a syntenic group of six markers on human chromosome 1

    SciTech Connect

    Rogers, J.; Witte, S.M.; Kammerer, C.M.; Hixson, J.E.; MacCluer, J.W.

    1995-07-20

    We have established multipoint genetic linkage among six loci in baboons (Papio hamadryas). Published PCR primers designed to amplify five human microsatellite loci were used to amplify homologous loci in 229 pedigreed baboons. Southern blotting was used to type two RFLPs in a functional gene (anti-thrombin III) in a subset of those animals. All six loci are known to map to human chromosome 1q, a region of the genome predicted by karyotype studies to be conserved in baboons. Pairwise recombination frequencies and lod scores indicate that the six loci are also linked in baboons. Recombination distances among the loci are similar to those reported for humans. Like humans, the baboons exhibit higher rates of recombination in females than in males. This study demonstrates that (1) microsatellite loci first described and characterized in the human genome can be effectively used for genetic linkage mapping in nonhuman primates, (2) a group of genetic loci known to be linked on human chromosome 1q are also linked in the baboon genome, and (3) sex differences in recombination frequencies among loci on human chromosome 1q are also observe din the genome of this Old World monkey. This constitutes the first reported multipoint linkage map in any nonhuman primate. 26 refs., 1 fig., 3 tabs.

  17. Sustained Systemic Glucocerebrosidase Inhibition Induces Brain α-Synuclein Aggregation, Microglia and Complement C1q Activation in Mice

    PubMed Central

    Rocha, Emily M.; Smith, Gaynor A.; Park, Eric; Cao, Hongmei; Graham, Anne-Renee; Brown, Eilish; McLean, Jesse R.; Hayes, Melissa A.; Beagan, Jonathan; Izen, Sarah C.; Perez-Torres, Eduardo

    2015-01-01

    Abstract Aims: Loss-of-function mutations in GBA1, which cause the autosomal recessive lysosomal storage disease, Gaucher disease (GD), are also a key genetic risk factor for the α-synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies. GBA1 encodes for the lysosomal hydrolase glucocerebrosidase and reductions in this enzyme result in the accumulation of the glycolipid substrates glucosylceramide and glucosylsphingosine. Deficits in autophagy and lysosomal degradation pathways likely contribute to the pathological accumulation of α-synuclein in PD. In this report we used conduritol-β-epoxide (CBE), a potent selective irreversible competitive inhibitor of glucocerebrosidase, to model reduced glucocerebrosidase activity in vivo, and tested whether sustained glucocerebrosidase inhibition in mice could induce neuropathological abnormalities including α-synucleinopathy, and neurodegeneration. Results: Our data demonstrate that daily systemic CBE treatment over 28 days caused accumulation of insoluble α-synuclein aggregates in the substantia nigra, and altered levels of proteins involved in the autophagy lysosomal system. These neuropathological changes were paralleled by widespread neuroinflammation, upregulation of complement C1q, abnormalities in synaptic, axonal transport and cytoskeletal proteins, and neurodegeneration. Innovation: A reduction in brain GCase activity has been linked to sporadic PD and normal aging, and may contribute to the susceptibility of vulnerable neurons to degeneration. This report demonstrates that systemic reduction of GCase activity using chemical inhibition, leads to neuropathological changes in the brain reminiscent of α-synucleinopathy. Conclusions: These data reveal a link between reduced glucocerebrosidase and the development of α-synucleinopathy and pathophysiological abnormalities in mice, and support the development of GCase therapeutics to reduce α-synucleinopathy in PD and related disorders

  18. Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

    SciTech Connect

    Sjoewall, Christopher; Askendal, Agneta; Almroth, Gunnel

    2007-01-05

    C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fc{gamma} receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups.

  19. Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression

    PubMed Central

    Yabumoto, Chizuru; Akazawa, Hiroshi; Yamamoto, Rie; Yano, Masamichi; Kudo-Sakamoto, Yoko; Sumida, Tomokazu; Kamo, Takehiro; Yagi, Hiroki; Shimizu, Yu; Saga-Kamo, Akiko; Naito, Atsuhiko T.; Oka, Toru; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Uejima, Etsuko; Komuro, Issei

    2015-01-01

    Disruption of angiotensin II type 1 (AT1) receptor prolonged life span in mice. Since aging-related decline in skeletal muscle function was retarded in Atgr1a−/− mice, we examined the role of AT1 receptor in muscle regeneration after injury. Administration of AT1 receptor blocker irbesartan increased the size of regenerating myofibers, decreased fibrosis, and enhanced functional muscle recovery after cryoinjury. We recently reported that complement C1q, secreted by macrophages, activated Wnt/β-catenin signaling and promoted aging-related decline in regenerative capacity of skeletal muscle. Notably, irbesartan induced M2 polarization of macrophages, but reduced C1q expression in cryoinjured muscles and in cultured macrophage cells. Irbesartan inhibited up-regulation of Axin2, a downstream gene of Wnt/β-catenin pathway, in cryoinjured muscles. In addition, topical administration of C1q reversed beneficial effects of irbesartan on skeletal muscle regeneration after injury. These results suggest that AT1 receptor blockade improves muscle repair and regeneration through down-regulation of the aging-promoting C1q-Wnt/β-catenin signaling pathway. PMID:26571361

  20. Potent inhibition of the classical pathway of complement by a novel C1q-binding peptide derived from the human astrovirus coat protein.

    PubMed

    Gronemus, Jenny Q; Hair, Pamela S; Crawford, Katrina B; Nyalwidhe, Julius O; Cunnion, Kenji M; Krishna, Neel K

    2010-01-01

    Previous work from our laboratories has demonstrated that purified, recombinant human astrovirus coat protein (HAstV CP) binds C1q and mannose-binding lectin (MBL) inhibiting activation of the classical and lectin pathways of complement, respectively. Analysis of the 787 amino acid CP molecule revealed that residues 79-139 share limited sequence homology with human neutrophil defensin-1 (HNP-1), a molecule previously demonstrated to bind C1q and MBL, inhibiting activation of the classical and lectin pathways of complement, respectively. A 30 amino acid peptide derived from this region of the CP molecule competitively inhibited the binding of wild-type CP to C1q. The parent peptide and various derivatives were subsequently assayed for C1q binding, inhibition of C1 and C4 activation as well as suppression of complement activation in hemolytic assays. The parent peptide and several derivatives inhibited complement activation in these functional assays to varying degrees. One peptide derivative in particular (E23A) displayed superior inhibition of complement activation in multiple assays of classical complement pathway activation. Further analysis revealed homology to a plant defensin allowing development of a proposed structural model for E23A. Based upon these findings, we hypothesize that further rationale optimization of E23A may result in a promising therapeutic inhibitor for the treatment of inflammatory and autoimmune diseases in which dysregulated activation of the classical and lectin pathways of complement contribute to pathogenesis. PMID:20728940

  1. Viral induction of site-specific chromosome damage.

    PubMed

    Fortunato, Elizabeth A; Spector, Deborah H

    2003-01-01

    The advent of advanced cell culture and cytogenetics techniques in the 1950s opened a new avenue for research on the pathogenic interactions between animal viruses and their hosts. Studies of many viruses revealed their ability to nonspecifically induce cytogenetic damage to their host cell's chromosomes. However, only three viruses, the oncogenic adenoviruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV), have been found to cause non-random, site-specific chromosomal damage. Adenovirus (Ad) type 12 induces fragility at four distinct loci (RNU1, RNU2, RN5S and PSU1) in many different types of human cells. A common feature of these loci is that they contain a repeated array of transcriptionally active genes encoding small structural RNAs. Site-specific induction of breaks also requires the virally encoded E1B protein of M(r) 55000 and the C-terminus of the cellular p53 protein. Analysis of the induction of damage by HSV and HCMV necessitates consideration of several factors, including the strain of virus used, the timing of infection, the type of cell used, and the multiplicity of infection. Both HSV strains 1 and 2 are cytotoxic, although the former seems to be more proficient at inducing damage. At early times post infection, HSV induces breaks and specific uncoiling of the centromeres of chromosomes 1, 9 and 16. This is followed at later times by a more complete severing of all of the chromosomes, termed pulverisation. Damage by HSV requires viral entry and de novo viral protein synthesis, with immediate early viral proteins responsible for the induction of breaks and uncoiling and early gene products (most likely nucleases) involved in the extensive pulverisation seen later. HCMV has been studied primarily in permissive human fibroblasts. Its ability to induce specific damage in chromosome 1 at two loci, 1q21 and 1q42, was only recently revealed as the cells must be in S-phase when they are infected for the breaks to be observed. In contrast to

  2. A Practical Approach to Juvenile Dermatomyositis and Juvenile Scleroderma.

    PubMed

    McCann, Liza J; Pain, Clare E

    2016-02-01

    Juvenile dermatomyositis and juvenile scleroderma are rare multisystem autoimmune disorders. Although they share some pathognomonic hallmarks with adult onset myositis or scleroderma, there are significant differences in presentation, characteristics and associated features when the diseases present in childhood. In view of this, and the rarity of the conditions, it is important for care to be led by teams with expertise in pediatric rheumatology conditions. Prognosis has improved significantly in the West; likely due to early diagnosis and aggressive treatment with immunosuppressive medications. However, this trend is not replicated in the developing world. Early recognition of these diseases is crucial to achieve rapid and sustained remission and prevent disease or medication associated complications. This article aims to provide a practical overview for recognition, diagnosis and treatment of these conditions. PMID:26489640

  3. Chromosomes of kinetoplastida.

    PubMed Central

    Van der Ploeg, L H; Cornelissen, A W; Barry, J D; Borst, P

    1984-01-01

    We have compared chromosome-sized DNA molecules (molecular karyotypes) of five genera (nine species) of kinetoplastida after cell lysis and deproteinization of DNA in agarose blocks and size fractionation of the intact DNA molecules by pulsed field gradient (PFG) gel electrophoresis. With the possible exception of Trypanosoma vivax and Crithidia fasciculata, all species have at least 20 chromosomes. There are large differences between species in molecular karyotype and in the chromosomal distribution of the genes for alpha- and beta-tubulin, rRNA and the common mini-exon sequence of kinetoplastid mRNAs. In all cases, the rRNA genes are in DNA that is larger than 500 kb. Whereas T. brucei has approximately 100 mini-chromosomes of 50-150 kb, only few are found in T. equiperdum; T. vivax has no DNA smaller than 2000 kb. As all three species exhibit antigenic variation, small chromosomes with telomeric variant surface glycoprotein genes cannot be vital to the mechanism of antigenic variation. The apparent plasticity of kinetoplastid genome composition makes PFG gel electrophoresis a potentially useful tool for taxonomic studies. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:6526012

  4. Juvenile glaucoma linked to GLCIA in a Panamanian family.

    PubMed Central

    Lichter, P R; Richards, J E; Boehnke, M; Othman, M; Cameron, B D; Stringham, H M; Downs, C A; Lewis, S B; Boyd, B F

    1996-01-01

    PURPOSE: To carry out clinical and genetic characterization of juvenile-onset primary open-angle glaucoma (POAG) inherited as an autosomal dominant trait in a Panamanian family. METHODS: Twenty-two members of a six-generation Panamanian family underwent an ophthalmologic evaluation. Blood samples were collected from 20 of these individuals for preparation of DNA for use in screening of microsatellite repeat genetic markers via polymerase chain reaction. RESULTS: Eleven living family members covering 4 generations were diagnosed as affected with open-angle glaucoma of primarily juvenile onset. Four of 6 other at-risk individuals examined and enrolled were characterized as unaffected and two as indeterminate. Two additional individuals were not included in this study because they were too young to characterize or to provide a blood sample. Three spouses of affected family members were also examined and found not to have glaucoma. Of clinical importance was the finding of markedly elevated intraocular pressure (IOP) in 2 affected brothers, both of whom were advised to have urgent filtration surgery; the finding of elevated IOP in the only seeing eye of the mother of these brothers, causing us to advise her to pursue more aggressive treatment; and the finding of early signs of glaucoma in a previously undiagnosed 9-year-old family member. Linkage analysis using selected microsatellite repeat markers in the 1q21-q31 region revealed strong evidence for linkage to the GLC1A gene with a maximum lod score of 3.75 for marker D1S431 at a recombination fraction of 0.00. CONCLUSIONS: The most likely interpretation of our data is that a mutation in the GLC1A gene is responsible for juvenile-onset POAG in this Panamanian family, thus expanding the countries of origin where this gene has been found to exist. The numbers of families with GLC1A glaucoma now reported from only a few centers worldwide raise questions about whether this disease may be more common than once thought

  5. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

    SciTech Connect

    Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron D.; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.; Furlong, Clement E.

    2005-08-01

    The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

  6. Plant Sex Chromosomes.

    PubMed

    Charlesworth, Deborah

    2016-04-29

    Although individuals in most flowering plant species, and in many haploid plants, have both sex functions, dioecious species-in which individuals have either male or female functions only-are scattered across many taxonomic groups, and many species have genetic sex determination. Among these, some have visibly heteromorphic sex chromosomes, and molecular genetic studies are starting to uncover sex-linked markers in others, showing that they too have fully sex-linked regions that are either too small or are located in chromosomes that are too small to be cytologically detectable from lack of pairing, lack of visible crossovers, or accumulation of heterochromatin. Detailed study is revealing that, like animal sex chromosomes, plant sex-linked regions show evidence for accumulation of repetitive sequences and genetic degeneration. Estimating when recombination stopped confirms the view that many plants have young sex-linked regions, making plants of great interest for studying the timescale of these changes. PMID:26653795

  7. Sex chromosome drive.

    PubMed

    Helleu, Quentin; Gérard, Pierre R; Montchamp-Moreau, Catherine

    2015-02-01

    Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species. PMID:25524548

  8. Segregation analysis of juvenile myoclonic epilepsy

    SciTech Connect

    Weissbecker, K.A.; Delgado-Escueta, A.V.; Medina, M.T.

    1994-09-01

    Juvenile myoclonic epilepsy (JME) is a non-progressive epilepsy characterized by involuntary jerks and an adolescent age of onset. There conflicting reports regarding the mode of inheritance of JME - polygenic, autosomal recessive, and two-locus models have all been proposed. We performed a segregation analysis of 53 nuclear families of JME probands using the Elston and Stewart algorithm (S.A.G.E version 2.1). Relatives of the proband were classified as affected if they had a confirmed history of JME, absence or grand mal epilepsy, or if they were clinically asymptomatic but had 3.5-6 Hz multispike wave complexes on electroencephalography. Using these criteria, 40 relatives were affected in addition to the 53 probands. All Mendelian models were rejected when compared to the unrestricted model which estimated transmission probabilities. The environmental models were also rejected. Of the Mendelian modes, the most parsimonious model was the autosomal recessive model with 53% penetrance and a rate of sporadic cases of 0.0039. We conclude that although there is evidence for a genetic component contributing to the familiality of JME, this component can not be explained by a single major gene. These results, along with contradictory reports regarding the linkage of JME to the short arm of chromosome 6, suggest the presence of genetic heterogeneity and/or a more complex mode of inheritance, such as a two-locus model. Since lod score linkage analyses are dependent on the assumption of a single major gene mode, these findings emphasize the necessity of performing non-parametric linkage analyses when studying JME.

  9. Chromosomes and clinical anatomy.

    PubMed

    Gardner, Robert James McKinlay

    2016-07-01

    Chromosome abnormalities may cast light on the nature of mechanisms whereby normal anatomy evolves, and abnormal anatomy arises. Correlating genotype to phenotype is an exercise in which the geneticist and the anatomist can collaborate. The increasing power of the new genetic methodologies is enabling an increasing precision in the delineation of chromosome imbalances, even to the nucleotide level; but the classical skills of careful observation and recording remain as crucial as they always have been. Clin. Anat. 29:540-546, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990310

  10. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    PubMed Central

    Pinton, Alain; Ducos, Alain; Yerle, Martine

    2003-01-01

    A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+) translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5) were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2) from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases. PMID:14604515

  11. Chromosomal changes in aggressive breast cancers with basal-like features

    PubMed Central

    Yu, Wayne; Kanaan, Yasmine; Bae, Young-Kyung; Gabrielson, Edward

    2009-01-01

    Using high-resolution oligonucleotide CGH arrays, we evaluated chromosomal copy number changes in a series of 16 breast cancers, selected on the basis of highly similar pathological and molecular features characteristic of the “basal-like” phenotype. Each of these cancers showed numerous gains and losses, reflecting multiple chromosomal rearrangements during the development of these high-grade cancers. Chromosomal losses were particularly prevalent on chromosomal arms 5q, 8p, 9q, 12q, 17p, 19p, and Xq, and gains were commonly seen on chromosomal arms 1q, 8q, and 17q. Particularly remarkable were regions of high-level amplification (> 8-fold copy number change) on 4q12, 8q23.3, 19p12, and 19q13.2. These regions included candidate oncogenes cKIT, JUND, and AKT2., and immunohistochemistry confirmed that these particular genes were highly expressed in the cancers harboring the specific amplifications. However, each of these amplifications was observed only in individual cases, and no particular chromosomal alteration appeared to generally characterize this group of cancers. Thus, genomic changes among breast cancers with basal-like features appear to be very heterogeneous. Distinct high-level amplifications may provide new targets for treating some of these cancers, but copy number changes do not reveal a distinctive genomic fingerprint for this proposed class of breast cancers. PMID:19602461

  12. A unique case of female pseudohermaphroditism with 21-hydroxylase deficiency and small supernumerary marker chromosome 7.

    PubMed

    Al-Achkar, Walid; Wafa, Abdulsamad; Assaad, Manar; Ehlers, Christian; Liehr, Thomas

    2013-05-01

    Small supernumerary marker chromosomes (sSMCs) are present in ~2.6x10⁶ individuals worldwide. Concerning their clinical consequences as well as their chromosomal origin and shape, sSMCs are a heterogeneous group of derivative chromosomes; 70% of sSMC carriers are clinically normal. In the present study, we report on a female with mosaicism (45%) of a de novo sSMC derived from chromosome 7, in which the observed clinical signs do not correspond to comparable cases in the literature. She is clinically normal apart from problems in gender determination, a uterus without ovaries and an external penis, pointing overall towards an adrenogenital syndrome (AGS). 21-Hydroxylase deficiency (21-OHD) is the most common cause of AGS. A corresponding analysis for underlying mutations in the CYP21A2 gene revealed a homozygous mutation c.518T>A (p.Ile173Asn) inherited from both non-related parents. Overall, in this study, we report a unique case of female pseudohermaphroditism, classified as a simple virilization form of 21-OHD having an additional minute-shaped chromosome 7 [min(7)(:p11.1->q11.23:)]. Notably, AGS was due to a mutation in the CYP21A2 gene located on chromosome 6. This is a further example that detection of an sSMC does not always resolve the clinical case. PMID:23450434

  13. Deletion of chromosome 21 in a girl with congenital hypothyroidism and mild mental retardation

    SciTech Connect

    Ahlbom, B.E.; Anneren, G.; Sidenvall, R.

    1996-08-23

    We report on a girl with a large interstitial deletion of the long arm of chromosome 21 and with mild mental retardation, congenital hypothyroidism, and hyperopia. The deletion [del(21)(q11.1-q22.1)] extends molecularly from marker D21S215 to D21S213. The distal breakpoint is not clearly defined but is situated between markers D21S213 and IFNAR. This patient has the largest deletion of chromosome 21 known without having severe mental retardation or malformations. The deletion does not involve the {open_quotes}Down syndrome chromosome{close_quotes} region, the region of chromosome 21 which in trisomy causes most of the manifestations of Down syndrome. Apparently, the proximal part of the long arm of chromosome 21 does not include genes that are responsible for severe clinical effects in the event of either deletion or duplication, since several reported patients with either trisomy or deletion of this region have mild phenotypic abnormalities. Congenital hypothyroidism is much more common in Down syndrome than in the average population. Thus, the congenital hypothyroidism of the present patient might indicate that there is one or several genes on the proximal part of chromosome 21, which might be of importance for the thyroid function. 24 refs., 4 figs., 2 tabs.

  14. Juvenile morphology in baleen whale phylogeny

    NASA Astrophysics Data System (ADS)

    Tsai, Cheng-Hsiu; Fordyce, R. Ewan

    2014-09-01

    Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

  15. Juvenile morphology in baleen whale phylogeny

    NASA Astrophysics Data System (ADS)

    Tsai, Cheng-Hsiu; Fordyce, R. Ewan

    2014-08-01

    Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

  16. Characterization of chromosomal architecture in Arabidopsis by chromosome conformation capture

    PubMed Central

    2013-01-01

    Background The packaging of long chromatin fibers in the nucleus poses a major challenge, as it must fulfill both physical and functional requirements. Until recently, insights into the chromosomal architecture of plants were mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation capture technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalized description of nuclear organization. Results Employing circular chromosome conformation capture, this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organization of chromosomes is reflected in the genome-wide interactome. In addition, we study the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 maintains a pericentromere-like interaction profile and interactome despite its euchromatic surrounding. Conclusion Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: heterochromatin and euchromatin represent two distinct interactomes; interactions between chromosomes correlate with the linear position on the chromosome arm; and distal chromosome regions have a higher potential to interact with other chromosomes. PMID:24267747

  17. Cloning, sequencing, and analysis of inv8 chromosome breakpoints associated with recombinant 8 syndrome.

    PubMed

    Graw, S L; Sample, T; Bleskan, J; Sujansky, E; Patterson, D

    2000-03-01

    Rec8 syndrome (also known as "recombinant 8 syndrome" and "San Luis Valley syndrome") is a chromosomal disorder found in individuals of Hispanic descent with ancestry from the San Luis Valley of southern Colorado and northern New Mexico. Affected individuals typically have mental retardation, congenital heart defects, seizures, a characteristic facial appearance, and other manifestations. The recombinant chromosome is rec(8)dup(8q)inv(8)(p23.1q22.1), and is derived from a parental pericentric inversion, inv(8)(p23.1q22.1). Here we report on the cloning, sequencing, and characterization of the 8p23.1 and 8q22 breakpoints from the inversion 8 chromosome associated with Rec8 syndrome. Analysis of the breakpoint regions indicates that they are highly repetitive. Of 6 kb surrounding the 8p23.1 breakpoint, 75% consists of repetitive gene family members-including Alu, LINE, and LTR elements-and the inversion took place in a small single-copy region flanked by repetitive elements. Analysis of 3.7 kb surrounding the 8q22 breakpoint region reveals that it is 99% repetitive and contains multiple LTR elements, and that the 8q inversion site is within one of the LTR elements. PMID:10712224

  18. Chromosome Variations And Human Behavior

    ERIC Educational Resources Information Center

    Soudek, D.

    1974-01-01

    Article focused on the science of cytogenetics, which studied the transmission of the units of heredity called chromosomes, and considered the advantage of proper diagnosis of genetic diseases, treated on the chromosomal level. (Author/RK)

  19. JUVENILE DELINQUENCY AND YOUTH CRIME, TASK FORCE REPORT, REPORT ON JUVENILE JUSTICE AND CONSULTANTS PAPERS.

    ERIC Educational Resources Information Center

    President's Commission on Law Enforcement and Administration of Justice, Washington, DC.

    THIS REPORT CONSISTS OF A DETAILED DISCUSSION OF THE JUVENILE COURT SYSTEM AND THE PREVENTION OF DELINQUENCY. THE COMMISSION'S RECOMMENDATIONS ON JUVENILE DELINQUENCY INCLUDE THE AREAS OF THE JUVENILE JUSTICE SYSTEM, HOUSING AND RECREATION, FAMILIES, INVOLVING YOUTHS IN COMMUNITY LIFE, SCHOOLS, AND EMPLOYMENT. THE APPENDIXES, WHICH CONSTITUTE THE…

  20. The JDAI Story: Building a Better Juvenile Detention System. Pathways to Juvenile Detention Reform. Overview.

    ERIC Educational Resources Information Center

    Stanfield, Rochelle

    This monograph describes the work of five Juvenile Detention Alternatives Initiative (JDAI) sites designed to streamline and rationalize local juvenile detention systems and to reduce overcrowding in juvenile detention centers, thus improving conditions and saving jurisdictions money in overtime and additional staff and millions of dollars to…

  1. Black Juveniles in the Juvenile Justice System: A Cause for Alarm.

    ERIC Educational Resources Information Center

    LeFlore, Larry

    This report examines the representation of black youth in the juvenile justice system, describes changes in juvenile justice philosophy, and discusses policy implications. Black youth are overrepresented at all stages of the juvenile justice system compared to white youth. Positivist theories explain this overrepresentation as the result of…

  2. A Juvenile Justice System for the 21st Century. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Bilchik, Shay

    This bulletin describes the objectives and elements of an effective juvenile justice system and suggests legislative and administrative strategies for its implementation. An effective juvenile justice system must meet the three objectives of holding the juvenile offender accountable, enabling the offender to become a capable and productive…

  3. National Implications in Juvenile Justice: The Influence of Juvenile Mentoring Programs on At Risk Youth.

    ERIC Educational Resources Information Center

    Belshaw, Scott H.; Kritsonis, William Allan

    2007-01-01

    In 1972 the federal government created the Juvenile Justice Delinquency Prevention Act that procured funding for various governmental programs to combat the sudden increase in juvenile crime. A provision of this Act set out the creation of mentoring programs to help decrease the juvenile crime rate and dropout rates in secondary schools. This…

  4. Runaway Juvenile Crime? The Context of Juvenile Arrests in America. Research in Brief.

    ERIC Educational Resources Information Center

    Ziedenberg, Jason; Schiraldi, Vincent

    The Violent and Repeat Juvenile Offender Act of 1997 (S-10) was to be debated in the Senate in spring 1998. This bill would blur the distinction between juvenile and adult criminal systems, making it easier to imprison children as young as 14. Supporters of S-10 were citing statistics to indicate that juvenile crime was on the rise. In fact, the…

  5. A Handbook for Juveniles and Parents on Maine's Juvenile Justice System.

    ERIC Educational Resources Information Center

    Mehnert, Irene

    This guide explains Maine's juvenile justice system so that juveniles and/or their parents can know what to expect or what to do in a situation involving juveniles, public officials and the law. Although it is geographically specific, it could serve as a model to other states. The booklet can serve as a checklist to make sure law enforcement…

  6. Why Chromosome Palindromes?

    PubMed Central

    Betrán, Esther; Demuth, Jeffery P.; Williford, Anna

    2012-01-01

    We look at sex-limited chromosome (Y or W) evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the “palindromes as protectors” view: (1) genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2) under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes. PMID:22844637

  7. The Y Chromosome

    ERIC Educational Resources Information Center

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  8. Why chromosome palindromes?

    PubMed

    Betrán, Esther; Demuth, Jeffery P; Williford, Anna

    2012-01-01

    We look at sex-limited chromosome (Y or W) evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the "palindromes as protectors" view: (1) genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2) under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes. PMID:22844637

  9. A unique complex translocation involving six different chromosomes in a case of childhood acute lymphoblastic leukemia with the Philadelphia chromosome and adverse prognosis.

    PubMed

    Achkar, Walid Al; Wafa, Abdulsamad; Mkrtchyan, Hasmik; Moassass, Faten; Liehr, Thomas

    2010-09-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Approximately 84% of cases of ALL are classified as B-precursor ALL, 14% of cases are T-cell and 2% of cases are B-cell (B-)ALL. About one third of B-ALL cases show an abnormal karyotype. Combining data obtained by immunophenotyping, karyotyping and molecular cytogenetic analyses allows for a better understanding of this heterogeneous disease. This study reports an exceptional B-ALL case with a poor prognosis and unique complex chromosomal aberrations not previously observed, i.e., a translocation involving the six chromosomal regions 1q42, 4q21, 4q24, 4q35 (twice), 8q22 and 10p15.3 besides 9q34 and 22q11.2. PMID:22966383

  10. Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

    PubMed Central

    Hidalgo, Alfredo; Monroy, Alberto; Arana, Rosa Ma; Taja, Lucía; Vázquez, Guelaguetza; Salcedo, Mauricio

    2003-01-01

    Background Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation. Methods We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients. Results All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Conclusions Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma. PMID:12659655

  11. Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: complement component C1q and Prnp polymorphisms

    USGS Publications Warehouse

    Blanchong, Julie A.; Heisey, Dennis M.; Scribner, Kim T.; Libants, Scot V.; Johnson, Chad; Aiken, Judd M.; Langenberg, Julia A.; Samuel, Michael D.

    2009-01-01

    The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p < 0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.

  12. [Chromosomal organization of the genomes of small-chromosome plants].

    PubMed

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species. PMID:20058798

  13. Intrachromosomal rearrangements in two representatives of the genus Saltator (Thraupidae, Passeriformes) and the occurrence of heteromorphic Z chromosomes.

    PubMed

    dos Santos, Michelly da Silva; Kretschmer, Rafael; Silva, Fabio Augusto Oliveira; Ledesma, Mario Angel; O'Brien, Patricia C M; Ferguson-Smith, Malcolm A; Del Valle Garnero, Analía; de Oliveira, Edivaldo Herculano Corrêa; Gunski, Ricardo José

    2015-10-01

    Saltator is a genus within family Thraupidae, the second largest family of Passeriformes, with more than 370 species found exclusively in the New World. Despite this, only a few species have had their karyotypes analyzed, most of them only with conventional staining. The diploid number is close to 80, and chromosome morphology is similar to the usual avian karyotype. Recent studies using cross-species chromosome painting have shown that, although the chromosomal morphology and number are similar to many species of birds, Passeriformes exhibit a complex pattern of paracentric and pericentric inversions in the chromosome homologous to GGA1q in two different suborders, Oscines and Suboscines. Hence, considering the importance and species richness of Thraupidae, this study aims to analyze two species of genus Saltator, the golden-billed saltator (S. aurantiirostris) and the green-winged saltator (S. similis) by means of classical cytogenetics and cross-species chromosome painting using Gallus gallus and Leucopternis albicollis probes, and also 5S and 18S rDNA and telomeric sequences. The results show that the karyotypes of these species are similar to other species of Passeriformes. Interestingly, the Z chromosome appears heteromorphic in S. similis, varying in morphology from acrocentric to metacentric. 5S and 18S probes hybridize to one pair of microchromosomes each, and telomeric sequences produce signals only in the terminal regions of chromosomes. FISH results are very similar to the Passeriformes already analyzed by means of molecular cytogenetics (Turdus species and Elaenia spectabilis). However, the paracentric and pericentric inversions observed in Saltator are different from those detected in these species, an observation that helps to explain the probable sequence of rearrangements. As these rearrangements are found in both suborders of Passeriformes (Oscines and Suboscines), we propose that the fission of GGA1 and inversions in GGA1q have occurred very

  14. Brief Report: A Case of Autism Associated with del(2)(q32.1q32.2) or (q32.2q32.3).

    ERIC Educational Resources Information Center

    Gallagher, Louise; Becker, Kristin; Kearney, Geraldine; Dunlop, Adam; Stallings, Ray; Green, Andrew; Fitzgerald, Michael; Gill, Michael

    2003-01-01

    This paper reports a clinical case of autism with a deletion on chromosome 2 in a young male with high functioning autism. The deletion seems to correspond with regions emerging from linkage studies. The paper proposes this chromosomal region as a possible candidate region in the search for autism genes. (Contains references.) (Author/DB)

  15. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

    Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

  16. Biologic agents in juvenile spondyloarthropathies.

    PubMed

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  17. Juvenile justice and substance use.

    PubMed

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad range of negative effects, such as smoking, risky sexual behavior, violence, and poor educational, occupational, and psychological outcomes. The high rates of substance use problems among young offenders, says Chassin, suggest a large need for treatment. Although young offenders are usually screened for substance use disorders, Chassin notes the need to improve screening methods and to ensure that screening takes place early enough to allow youths to be diverted out of the justice system into community-based programs when appropriate. Cautioning that no single treatment approach has been proven most effective, Chassin describes current standards of "best practices" in treating substance use disorders, examines the extent to which they are implemented in the juvenile justice system, and describes some promising models of care. She highlights several treatment challenges, including the need for better methods of engaging adolescents and their families in treatment and the need to better address environmental risk factors, such as family substance use and deviant peer networks, and co-occurring conditions, such as learning disabilities and other mental health disorders. Chassin advocates policies that encourage wider use of empirically validated therapies and of documented best practices for treating substance use disorders. High relapse rates among youths successfully treated for substance use disorders also point to a greater need for aftercare services and for managing these disorders as chronic illnesses characterized by relapse and remission. A shortage of aftercare services and a lack of service coordination in the

  18. Juvenile xanthogranuloma: unusual intraoral finding.

    PubMed

    Collins, L; Banks, R; Robinson, M

    2015-01-01

    Juvenile xanthogranuloma is a rare non-Langerhans cell histiocytosis that usually presents as a self-limiting dermatological condition in young children. Rarely, extracutaneous sites may also be involved. We report a case in a 3-year-old girl that presented intraorally as a solitary, well-defined, soft, purple palatal swelling. Patients with these rare intraoral lesions may present to dentists and subsequently to oral and maxillofacial surgeons. Diagnosis requires histopathological analysis and immunohistochemical staining. Further investigation from other specialties is required to rule out involvement of other organ systems. PMID:25300889

  19. Juvenile Competency to Stand Trial.

    PubMed

    Stepanyan, Sofia T; Sidhu, Shawn S; Bath, Eraka

    2016-01-01

    Competency to stand trial is interpreted as a protected due process right for all defendants and is defined as a defendant's fundamental knowledge and understanding of the criminal charges being filed, roles and procedures within the courtroom, and a general ability to work with the defense counsel. Questions of competency are most often raised by the judge, defense, or the prosecution, and competency evaluations are most often completed by psychiatrists or psychologists with forensic training or work experience. Mental illness, intellectual disability, developmental disorders, and developmental immaturity are the 4 main factors considered in most juvenile competency evaluations. PMID:26593118

  20. The chromosome cycle of prokaryotes

    PubMed Central

    Kuzminov, Andrei

    2013-01-01

    Summary In both eukaryotes and prokaryotes, chromosomal DNA undergoes replication, condensation-decondensation and segregation, sequentially, in some fixed order. Other conditions, like sister-chromatid cohesion (SCC), may span several chromosomal events. One set of these chromosomal transactions within a single cell cycle constitutes the “chromosome cycle”. For many years it was generally assumed that the prokaryotic chromosome cycle follows major phases of the eukaryotic one: -replication-condensation-segregation-(cell division)-decondensation-, with SCC of unspecified length. Eventually it became evident that, in contrast to the strictly consecutive chromosome cycle of eukaryotes, all stages of the prokaryotic chromosome cycle run concurrently. Thus, prokaryotes practice “progressive” chromosome segregation separated from replication by a brief SCC, and all three transactions move along the chromosome at the same fast rate. In other words, in addition to replication forks, there are “segregation forks” in prokaryotic chromosomes. Moreover, the bulk of prokaryotic DNA outside the replication-segregation transition stays compacted. I consider possible origins of this concurrent replication-segregation and outline the “nucleoid administration” system that organizes the dynamic part of the prokaryotic chromosome cycle. PMID:23962352

  1. Sex chromosome aneuploidy and aging.

    PubMed

    Stone, J F; Sandberg, A A

    1995-10-01

    Loss of an X chromosome in females and of the Y chromosome in males are phenomena associated with aging. X chromosome loss occurs in and may be limited to PHA stimulated peripheral lymphocytes. In males, the loss of the Y is most evident in bone marrow cells, but also occurs to a lesser extent in PHA stimulated peripheral lymphocytes. X chromosome loss is associated with premature centromere division leading to anaphase lag and elimination in micronuclei. The mechanism of Y chromosome loss has not been elucidated. No pathological consequence of either X or Y chromosome loss has been convincingly demonstrated. With the advent of FISH technology, measurement of sex chromosome aneuploidy may prove to be a convenient assay for cellular senecence and aging. PMID:7565866

  2. Juvenile Obesity, Physical Activity, and Lifestyle Changes.

    ERIC Educational Resources Information Center

    Bar-Or, Oded

    2000-01-01

    Because many obese children become obese adults, the recent rapid increase in juvenile obesity poses a major public health challenge. Enhanced physical activity is a cornerstone in a multidisciplinary approach to preventing and treating juvenile obesity. Giving exercise recommendations focused for obese youth is critical. Cutting down on sedentary…

  3. Special Education in Wisconsin's Juvenile Detention System

    ERIC Educational Resources Information Center

    Zenz, Tamara; Langelett, George

    2004-01-01

    This study looks at incarcerated youth in the public juvenile detention facilities of Wisconsin. State percentages of youth in Wisconsin public schools with Emotional, Learning, Cognitive, and/or Low Incidence Disabilities are compared to percentages reported from the state and county operated juvenile detention facilities. The study investigates…

  4. Juvenile Justice in Indiana: Facing the Issues.

    ERIC Educational Resources Information Center

    Smith, Doreen L.

    The Indiana juvenile justice system is charged with intervening on behalf of youthful offenders for the purposes of providing care, treatment, protection, or rehabilitation. This report provides an overview of the state's juvenile justice system, which has fallen under widespread criticism for many years. The following issues are identified: data…

  5. Role Socialization of Juvenile Court Probation Officers.

    ERIC Educational Resources Information Center

    Petronio, Richard J.

    1982-01-01

    Tested the degree of association between probation officers' sent and received roles and role behavior in four juvenile courts. Found the role communicated to probation officers by their superiors was predictive of the role the probation officers perceived but not of the role as enacted with juveniles. (Author)

  6. Juvenile dispersal in Calomys venustus (Muridae: Sigmodontinae)

    NASA Astrophysics Data System (ADS)

    Priotto, José; Steinmann, Andrea; Provensal, Cecilia; Polop, Jaime

    2004-05-01

    Both spacing behaviour and dispersal movement are viewed as hierarchical processes in which the effects may be expressed at spatial scale. This research was carried out to examine the hypothesis that the presence of parents promotes the dispersal of juveniles from their natal nest and their father or mother home-range, in Calomys venustus.The study was carried out in four 0.25 ha fences (two controls and two experimentals), in a natural pasture. This study had two periods: Father Removal (FR) (August and December 1997; year one) and Mother Removal (MR) (August 1998 and January 1999; year two). For the FR treatment fathers were removed after juveniles were born, but in the MR treatment mothers were removed after the juveniles were weaned. The effect of parents on the dispersal distance of juveniles was analysed with respect to their natal nest and their mother and father home-range. Dispersal distance from the nest of C. venustus was independent of either male or female parent. Juveniles were more dispersing in relation to the centre of activity of their mothers than to that of their fathers, and females were more dispersing than males. Female juveniles overlap their home-range with their parents less than male juveniles do. The differences observed between female and male juveniles would be related to their different sexual maturation times, as well as to the female territoriality.

  7. Juveniles' Motivations for Remaining in Prostitution

    ERIC Educational Resources Information Center

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

  8. Juvenile Offender Comprehensive Reentry Substance Abuse Treatment

    ERIC Educational Resources Information Center

    Watson, Donnie W.

    2004-01-01

    The literature provides ample evidence of the relationship of substance abuse to crime. Research over the last 20 years has established a strong correlation between substance abuse and juvenile delinquency (held, 1998). Currently, there are more than 350,000 juveniles on probation and in continuing care programs in the U.S. who have substance…

  9. Peer Relationships Among Institutionalized Juvenile Boys

    ERIC Educational Resources Information Center

    Preveaux, Neal E.; Ray, Glen E.; LoBello, Steven G.; Mehta, Sheila

    2004-01-01

    This study examined peer relationships (sociometric status and friendship) of institutionalized juvenile males ages 12 to 18. Results replicated previous studies using "normal" nondelinquent samples demonstrating that sociometrically popular status juveniles were evaluated higher on sociability and leadership than were average- or rejected-status…

  10. Genetic and clinical evaluation of juvenile retinoschisis.

    PubMed

    Kim, Judy E; Ruttum, Mark S; Koeberl, Matthew J; Hassemer, Eryn L; Sidjanin, D J

    2009-04-01

    Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.(1) Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants. PMID:19393523

  11. Genetic and clinical evaluation of juvenile retinoschisis

    PubMed Central

    Kim, Judy E.; Ruttum, Mark S.; Koeberl, Matthew J.; Hassemer, Eryn L.; Sidjanin, D. J.

    2014-01-01

    Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.1 Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants. PMID:19393523

  12. Juvenile Anorexia Nervosa: Family Therapy's Natural Niche

    ERIC Educational Resources Information Center

    Fishman, H. Charles

    2006-01-01

    Juvenile Anorexia Nervosa (AN) is a severe problem both in terms of presenting symptomatology and its tendency toward chronicity. Researchers have consistently shown that family-based approaches are superior to individual approaches for the treatment of juvenile AN. This article addresses the capacity deficit of trained family therapists to treat…

  13. Moral Development of Solo Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Van Vugt, Eveline; Stams, Geert Jan; Dekovic, Maja; Brugman, Daan; Rutten, Esther; Hendriks, Jan

    2008-01-01

    This study compared the moral development of solo juvenile male sex offenders (n = 20) and juvenile male non-offenders (n = 76), aged 13-19 years, from lower socioeconomic and educational backgrounds. The Moral Orientation Measure (MOM) was used to assess punishment- and victim-based moral orientation in sexual and non-sexual situations. Moral…

  14. Juvenile Offenders and Victims: 2006 National Report

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    2006-01-01

    This report presents comprehensive information on juvenile crime, violence, and victimization and on the juvenile justice system. This report brings together the latest available statistics from a variety of sources and includes numerous tables, graphs, and maps, accompanied by analyses in clear, nontechnical language. The report offers Congress,…

  15. Juvenile Offenders and Victims: 1999 National Report.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    This report offers the Congress, state legislators, and other state and local policymakers, professors and teachers, juvenile justice professionals, and concerned citizens solid answers to the most frequently asked questions about the nature of juvenile crime and victimization and about the justice system's response. Citing FBI and other data…

  16. Factors Affecting Attitudes toward Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Sahlstrom, Kimberly J.; Jeglic, Elizabeth L.

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment…

  17. Psychiatric Disorder in a Juvenile Assessment Center

    ERIC Educational Resources Information Center

    McReynolds, Larkin S.; Wasserman, Gail A.; DeComo, Robert E.; John, Reni; Keating, Joseph M.; Nolen, Scott

    2008-01-01

    Juvenile assessment centers (JACs) were developed to address service fragmentation and promote the sharing of information among agencies providing services to youth involved with the juvenile justice system. To date, there are no reports that describe the diagnostic profiles of the youth served by such centers. The authors hypothesize that the…

  18. Juvenile Delinquency: Research, Theory, and Comment.

    ERIC Educational Resources Information Center

    Moore, Bernice Milburn

    While this booklet on juvenile delinquency does not attempt a full review of the literature, it has been designed to further an understanding and appreciation of the social-psychological problems of deviant behavior. The booklet briefly covers the publicity which juvenile delinquency has been given in recent years, as well as the difficulties…

  19. Literacy Levels of Male Juvenile Justice Detainees

    ERIC Educational Resources Information Center

    Wheldall, Kevin; Watkins, Renae

    2004-01-01

    The assessment records detailing the reading and spelling performance of a group of male juvenile justice detainees admitted over a 3-month period were examined in an attempt to quantify the basic literacy levels of juvenile offenders. Results of student self-ratings of their reading ability were also analysed. The participants comprised 68 males…

  20. Chromosome 19 International Workshop

    SciTech Connect

    Pericak-Vance, M.A. . Medical Center); Ropers, H.H. . Dept. of Human Genetics); Carrano, A.J. )

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  1. Comparative genomic hybridisation divides retinoblastomas into a high and a low level chromosomal instability group

    PubMed Central

    van der Wal, J E; Hermsen, M A J A; Gille, H J P; Schouten-Van Meeteren, N Y N; Moll, A C; Imhof, S M; Meijer, G A; Baak, J P A; van der Valk, P

    2003-01-01

    Background: Retinoblastoma is the most common intraocular malignancy in childhood and is responsible for approximately 1% of all deaths caused by childhood cancer. Aims/methods: Comparative genomic hybridisation was performed on 13 consecutive, histologically confirmed retinoblastomas to analyse patterns of chromosomal changes and correlate these to clinicopathological variables. Six cases were hereditary and seven cases were sporadic. Results: In 11 of the 13 tumours chromosomal abnormalities were detected, most frequently gains. Frequent chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q, and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%). High level copy number gains were found at 5p15 and 6p11–12. A loss at 13q14 occurred in three cases only. Relatively few events occurred in the hereditary cases (27) compared with the non-hereditary cases (70 events). The number of chromosomal aberrations in these 13 retinoblastomas showed a bimodal distribution. Seven tumours showed less than four chromosomal aberrations, falling into a low level chromosomal instability (CIN) group, and six tumours showed at least eight aberrations, falling into a high level CIN group. In the low level CIN group the mean age was half that seen in the high level CIN group, there were less male patients, and there were more hereditary and bilateral cases. Microsatellite instability was not detected in either of the two groups. Conclusion: Despite the complex pattern of genetic changes in retinoblastomas, certain chromosomal regions appear to be affected preferentially. On the basis of the number of genetic events, retinoblastomas can be divided in low and a high level chromosomal instability groups, which have striking differences in clinical presentation. PMID:12499428

  2. Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion

    SciTech Connect

    Shashi, V.; Golden, W.L.; Allinson, P.S.

    1996-06-01

    It has been demonstrated in animal studies that, in animals heterozygous for pericentric chromosomal inversions, loop formation is greatly reduced during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the inversion. A recent study in yeast has shown that telomeres, rather than centromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analysis and DNA polymorphisms the nature of meiotic recombination in a three-generation family with a large pericentric X chromosome inversion, inv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegregating with the inversion. On DNA analysis there was no evidence of meiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that the X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result in reduction of recombination between the normal and inverted X chromosomes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by the pericentric inversion. 50 refs., 7 figs., 1 tab.

  3. Interpreting Chromosome Aberration Spectra

    NASA Technical Reports Server (NTRS)

    Levy, Dan; Reeder, Christopher; Loucas, Bradford; Hlatky, Lynn; Chen, Allen; Cornforth, Michael; Sachs, Rainer

    2007-01-01

    Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

  4. New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene

    PubMed Central

    2014-01-01

    Background Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have been reported. A deregulated expression of TRPS1 has been hypothesised as cause of the TRPS phenotype of these patients. Case presentation We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting TRPS1 or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of TRPS1, and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA LINC00536, at approximately 300 kb from the TRPS1 5’ end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325 kb from the TRPS1 promoter. Conclusions We suggest that the disruption of the genomic architecture of cis regulatory elements downstream the TRPS1 5′ region, combined with the translocation of a novel enhancer element nearby TRPS1, might be the

  5. Juvenile delinquency and adolescent fatherhood.

    PubMed

    Khurana, Atika; Gavazzi, Stephen M

    2011-08-01

    This study examined ecological risk factors associated with teen paternity in a sample of 2,931 male adolescents coming to the attention of juvenile courts across five midwestern counties. In contrast to previous studies documenting significantly higher rates of teen paternity among African American youth, we found that the European American court-involved youth in our sample were as likely to be teen fathers as their African American counterparts. However, an in-depth examination of the social ecologies of these court-involved youth revealed significant racial differences (regardless of the paternity status), with African American males reporting more prior offenses, delinquent peer associations, traumatic pasts, risky sexual behaviors, and educational risks as compared to European American youth, who reported greater involvement in substance use. Furthermore, logistic regression analyses revealed that after controlling for age and racial background, youth who reported greater exposure to trauma and prior offenses had significantly greater odds of having fathered a child. Surprisingly, youth who were teen fathers reported lower rates of behavioral problems as compared to their nonfathering peers. Given the cross-sectional nature of our data, interpretation of this result is limited. Overall, our findings underscore the need for developing a comprehensive understanding of the ecological risk and protective factors present in the lives of teen fathers coming in contact with the juvenile justice system, as an essential first step in designing effective and relevant intervention programs and services for this at-risk population. PMID:20508087

  6. Family transitions and juvenile delinquency.

    PubMed

    Schroeder, Ryan D; Osgood, Aurea K; Oghia, Michael J

    2010-01-01

    There is a large body of research that shows children from non-intact homes show higher rates of juvenile delinquency than children from intact homes, partially due to weaker parental control and supervision in non-intact homes. What has not been adequately addressed in the research is the influence of changes in family structure among individual adolescents over time on delinquent offending. Using the first and third waves of the National Youth Study, we assess the effect of family structure changes on changes in delinquent offending between waves through the intermediate process of changes in family time and parental attachment. Although prior research has documented adolescents in broken homes are more delinquent than youth in intact homes, the process of family dissolution is not associated with concurrent increases in offending. In contrast, family formation through marriage or cohabitation is associated with simultaneous increases in offending. Changes in family time and parental attachment account for a portion of the family formation effect on delinquency, and prior parental attachment and juvenile offending significantly condition the effect of family formation on offending. PMID:20879178

  7. Juvenile Gaucher disease simulating osteomyelitis

    SciTech Connect

    Miller, J.H.; Ortega, J.A.; Heisel, M.A.

    1981-10-01

    A case in which several imaging procedures suggested juvenile Gaucher disease in a child who presented with symptomatology of osteomyelitis is discussed. The 20-month girl was given a Technetium-99m radionuclide skeletal examination which revealed intense uptake of tracer agents along the shaft of the right femur. It was also found that the liver and spleen were dramatically Ga-67 avid. The bone pain symptomatology suggested an osteomyelitis of the femur, but skeletal scintigraphy with Tc-99m-labeled bone tracer demonstrated photopenic areas involving the femur, suggesting that the bone pain may have been due to marrow packed with Gaucher cells. This overexpansion of the marrow may lead to microfractures with remodeling seen radiographically as periosteal new bone and scintigraphically as increased periosteal deposition of tracer agent. The radiogallium study was useful to exclude an underlying osteomyelitis in the involved femurs. Although juvenile Gaucher disease is unusual, it should be considered in any child who presents with the constellation of hepatosplenomegaly and bone pain simulating osteomyelitis.

  8. Refinement of the cone-rod retinal dystrophy locus on chromosome 19q

    SciTech Connect

    Gregory, C.Y.; Evans, K.; Bhattacharya, S.S.; Whittaker, J.L.; Fryer, A.; Weissenbach, J.

    1994-11-01

    Cone-rod dystrophy (CRD) is a severe example of an inherited retinal dystrophy: ophthalmic diseases that as a group constitute the commonest causes of blindness in children in the developed world and account for a significant proportion of visual handicap in adults. Two case reports suggested loci for CRD-causing genes on chromosomes 18q and chromosome 17q. Recently, we reported the results of a total genome search that localized an autosomal dominant form of CRD to chromosome 19q in the region 19q13.1-q13.2. Since then, using data from a short tandem repeat-polymorphism linkage map of chromosome 19 and recently developed microsatellite markers in this region, we have been able to further refine the localization of the chromosome 19q CRD-causing gene. Seven new microsatellite markers were used to genotype 34 affected subjects, 22 unaffected subjects, and 15 spouses. Two-point, multipoint, and FASTMAP analyses were performed. 11 refs., 1 tab.

  9. Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism

    PubMed Central

    Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

    2010-01-01

    We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism. PMID:20684015

  10. The IgG Fc receptor, FcγRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma

    PubMed Central

    Callanan, Mary B.; Le Baccon, Patricia; Mossuz, Pascal; Duley, Samuel; Bastard, Christian; Hamoudi, Rifat; Dyer, Martin J.; Klobeck, Gustav; Rimokh, Ruth; Sotto, Jean Jacques; Leroux, Dominique

    2000-01-01

    Rearrangement of chromosomal bands 1q21–23 is one of the most frequent chromosomal aberrations observed in hematological malignancy. The genes affected by these rearrangements remain poorly characterized. Typically, 1q21–23 rearrangements arise during tumor evolution and accompany disease-specific chromosomal rearrangements such as t(14;18) (BCL2) and t(8;14) (MYC), where they are thus thought to play an important role in tumor progression. The pathogenetic basis of this 1q21–23-associated disease progression is currently unknown. In this setting, we surveyed our series of follicular lymphoma for evidence of recurring 1q21–23 breaks and identified three cases in which a t(14;18)(q32;q21) was accompanied by a novel balanced t(1;22)(q22;q11). Molecular cloning of the t(1;22) in a cell line (B593) derived from one of these cases and detailed fluorescent in situ hybridization mapping in the two remaining cases identified the FCGR2B gene, which encodes the immunoreceptor tyrosine-based inhibition motif-bearing IgG Fc receptor, FcγRIIB, as the target gene of the t(1;22)(q22;q11). We demonstrate deregulation of FCGR2B leading to hyperexpression of FcγRIIb2 as the principal consequence of the t(1;22). This is evidence that IgG Fc receptors can be targets for deregulation through chromosomal translocation in lymphoma. It suggests that dysregulation of FCGR2B may play a role in tumor progression in follicular lymphoma. PMID:10618414

  11. Chromosome band 16q24 is frequently deleted in human gastric cancer.

    PubMed

    Mori, Y; Matsunaga, M; Abe, T; Fukushige, S; Miura, K; Sunamura, M; Shiiba, K; Sato, M; Nukiwa, T; Horii, A

    1999-05-01

    We have analysed the loss of heterozygosity (LOH) on chromosome bands 16q22-q24 in 24 primary gastric cancer tissues and found three regions of frequent allelic loss (16q22, 16q24.1-q24.3 and 16q24.3). The region for the most frequent allelic loss (63%) was in 16q24.1-q24.3. LOH of this region had no relationship with histological subtype, but a significant association between LOH and microscopic lymphangial invasion was observed. Although not significant, vascular and gastric wall invasions are also associated with LOH. The region includes the locus for the H-cadherin gene. Therefore we examined the genetic and epigenetic alterations of this gene. Markedly reduced expression was observed in gastric cancer cell lines compared with that of normal gastric mucosa. However, no mutation was found in this gene in any of the gastric cancer tissues or the gastric cancer cell lines. Furthermore, we analysed the methylation status of the 5'-flanking region of the gene, but no significant association was found. We suggest that some other tumour suppressor gene(s) in 16q24.1-q24.3 may be responsible for gastric carcinogenesis. PMID:10408866

  12. Challenging the Myths: 1999 National Report Series. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    This bulletin, extracted from "Juvenile Offenders and Victims: 1999 National Report," examines juvenile crime statistics, demonstrating that the predictions in the early 1990s of the emergence of juvenile superpredators (juveniles for whom violence is a way of life) is not supported by current data. Research indicates that levels of predatory…

  13. 8 CFR 236.3 - Detention and release of juveniles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Detention and release of juveniles. 236.3 Section 236.3 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION... Aliens Prior to Order of Removal § 236.3 Detention and release of juveniles. (a) Juveniles. A juvenile...

  14. Juvenile Offenders with Mental Health Needs: Reducing Recidivism Using Wraparound

    ERIC Educational Resources Information Center

    Pullmann, Michael D.; Kerbs, Jodi; Koroloff, Nancy; Veach-White, Ernie; Gaylor, Rita; Sieler, Dede

    2006-01-01

    The rate of youth with mental health needs is disproportionately high in juvenile justice. Wraparound planning involves families and providers in coordinating juvenile justice, mental health, and other services and supports. This study compares data from two groups of juvenile offenders with mental health problems: 106 youth in a juvenile justice…

  15. Structure and chromosomal localization of the human homeobox gene Prox 1

    SciTech Connect

    Zinovieva, R.D.; Duncan, M.K.; Johnson, T.R.

    1996-08-01

    The genomic organization and nucleotide sequence of the human homeobox gene Prox 1 as well as its chromosomal localization have been determined. This gene spans more than 40 kb, consists of at least 5 exons, and encodes an 83-kDa protein. It shows 89% identity with the chicken sequence at the nucleotide level in the coding region, while the human and chicken proteins are 94% identical. Among the embryonic tissues analyzed (lens, brain, lung, liver, and kidney), the human Prox 1 gene is most actively expressed i the developing lens, similar to the expression pattern of the chicken Prox 1 gene. The Prox 1 gene was mapped to human chromosome 1q32.2-q32.3. 26 refs., 6 figs.

  16. Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21

    SciTech Connect

    Shugart, Yin Y.; Banerjee, P.; Knowles, J.A.

    1995-08-01

    The inherited retinal degenerations known as retinitis pigmentosa (RP) can be caused by mutations at many different loci and can be inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait. Two forms of autosomal recessive (arRP) have been reported to cosegregate with mutations in the rhodopsin gene and the beta-subunit of rod phosphodiesterase on chromosome 4p. Genetic linkage has been reported on chromosomes 6p and 1q. In a large Dominican family, we reported an arRp gene near the region of the peripherin/RDS gene. Four recombinations were detected between the disease locus and an intragenic marker derived from peripherin/RDS. 26 refs., 2 figs., 1 tab.

  17. Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation

    SciTech Connect

    Scott, J.A.; Wenger, S.L.; Chakravarti, A.

    1995-03-13

    A 9-year-old, mildly mentally retarded girl presented with phenotypic manifestations of Down syndrome. G-banded chromosomal analyses of peripheral blood lymphocytes from the patient and her parents, and skin fibroblasts from the patient, did not detect any abnormality. Molecular analysis of 15 highly polymorphic chromosome 21 dinucleotide repeat markers demonstrated a partial duplication of the Down syndrome critical region (D21S55, subband 21q22.2) of maternal origin in the patient. The segmental trisomy was confirmed by FISH analysis using the cosmid probe D21S55. Further analysis demonstrated that the trisomy was due to segregation of an apparently balanced cryptic translocation from the mother. The patient`s karyotype is 46,XX,-12,tder(12)t(12;21)(p13.1;q22.2)mat. 21 refs., 3 figs., 1 tab.

  18. Maternal uniparental disomy of chromosome 1 with reduction to homozygosity of the LAMB3 locus in a patient with Herlitz junctional epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Bullrich, F; Czarnecki, P; Weiss, L; Uitto, J

    1997-09-01

    Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder characterized by blister formation at the level of the lamina lucida within the cutaneous basement-membrane zone. Classic lethal JEB (Herlitz type [H-JEB]; OMIM 226700) is frequently associated with premature-termination-codon mutations in both alleles of one of the three genes (LAMA3, LAMC2, or LAMB3) encoding the subunit polypeptides (alpha3, beta3, and gamma2) of laminin 5. In this study, we describe a unique patient with H-JEB, who was homozygous for a nonsense mutation, Q243X, in the LAMB3 gene on chromosome 1 and who had normal karyotype 46,XY. The mother was found to be a carrier of the Q243X mutation, whereas the father had two normal LAMB3 alleles. Nonpaternity was excluded by use of 11 microsatellite markers from six different chromosomes. The use of 17 partly or fully informative microsatellite markers spanning the entire chromosome 1 revealed that the patient had both maternal uniparental meroisodisomy of a 35-cM region on 1q containing the maternal LAMB3 mutation and maternal uniparental heterodisomy of other regions of chromosome 1. Thus, the results suggested that reduction to homozygosity of the 1q region containing the maternal LAMB3 mutation caused the H-JEB phenotype. The patient was normally developed at term and did not show overt dysmorphisms or malformations. This is the first description of uniparental disomy of human chromosome 1. PMID:9326326

  19. Juvenile curfews: are they an effective and constitutional means of combating juvenile violence?

    PubMed

    Fried, C S

    2001-01-01

    Curfew ordinances have become a popular way to attempt to combat juvenile crime and victimization. Although the Supreme Court has yet to hear a curfew case, several constitutional challenges have been brought in lower federal courts. The cases are replete with psychological assumptions for which there is limited empirical evidence. In applying the "strict scrutiny" standard, several courts have also questioned whether juvenile curfews are narrowly tailored to further the State's interest in reducing juvenile crime and victimization. While public opinion and reports from several police jurisdictions support the utility of juvenile curfews, recent empirical studies indicate that curfews are not effective at reducing juvenile offending or victimization. This paper argues that the emerging evidence does not support the use of juvenile curfews and urges policy makers and the courts to examine the efficacy of curfew legislation. Directions for future research that could be helpful to the courts in applying the Bellotti factors to curfew cases are also suggested. PMID:11241685

  20. Law & psychiatry: punishing juveniles who kill.

    PubMed

    Appelbaum, Paul S

    2012-10-01

    Punishment of juvenile murderers forces policy makers to weigh the developmental immaturity of adolescents against the heinousness of their crimes. The U.S. Supreme Court has progressively limited the severity of punishments that can be imposed on juveniles, holding that their impulsivity, susceptibility to peer pressure, and more fluid character render them less culpable for their actions. Having eliminated the death penalty as a punishment, the Court recently struck down mandatory life sentences without prospect of parole. The decision is interesting for its emphasis on rehabilitation, opening the door to further restrictions on punitive sentences for juveniles-and perhaps for adults too. PMID:23032673

  1. C1q-tumour necrosis factor-related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells.

    PubMed

    Glogowska, Aleksandra; Kunanuvat, Usakorn; Stetefeld, Jörg; Patel, Trushar R; Thanasupawat, Thatchawan; Krcek, Jerry; Weber, Ekkehard; Wong, G William; Del Bigio, Marc R; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2013-12-01

    We report a novel ligand-receptor system composed of the leucine-rich G-protein-coupled relaxin receptor, RXFP1, and the C1q-tumour necrosis factor-related protein 8 (CTRP8) in human primary brain cancer, a tumour entity devoid of the classical RXFP1 ligands, RLN1-3. In structural homology studies and computational docking experiments we delineated the N-terminal region of the globular C1q region of CTRP8 and the leucine-rich repeat units 7 and 8 of RXFP1 to mediate this new ligand-receptor interaction. CTRP8 secreted from HEK293T cells, recombinant human (rh) CTRP8, and short synthetic peptides derived from the C1q globular domain of human CTRP8 caused the activation of RXFP1 as determined by elevated intracellular cAMP levels and the induction of a marked pro-migratory phenotype in established glioblastoma (GB) cell lines and primary cells from GB patients. Employing a small competitor peptide, we were able to disrupt the CTRP8-RXFP1-induced increased GB motility. The CTRP8-RXFP1-mediated migration in GB cells involves the activation of PI3K and specific protein kinase C pathways and the increased production/secretion of the potent lysosomal protease cathepsin B (cathB), a known prognostic marker of GB. Specific inhibition of CTRP8-induced cathB activity effectively blocked the ability of primary GB to invade laminin matrices. Finally, co-immunoprecipitation studies revealed the direct interaction of human CTRP8 with RXFP1. Our results support a therapeutic approach in GB aimed at targeting multiple steps of the CTRP8-RXFP1 signalling pathway by a combined inhibitor and peptide-based strategy to block GB dissemination within the brain. PMID:24014093

  2. PON1Q192R genetic polymorphism modifies organophosphorous pesticide effects on semen quality and DNA integrity in agricultural workers from southern Mexico

    SciTech Connect

    Perez-Herrera, N.; Polanco-Minaya, H. |; Salazar-Arredondo, E. |; Solis-Heredia, M.J.; Hernandez-Ochoa, I.; Rojas-Garcia, E.; Alvarado-Mejia, J.; Borja-Aburto, V.H.; Quintanilla-Vega, B.

    2008-07-15

    Pesticide exposure, including organophosphorous (OP) insecticides, has been associated with poor semen quality, and paraoxonase (PON1), an enzyme involved in OP deactivation, may have a role on their susceptibility, due to PON1 polymorphisms. Our objective was to evaluate the role of PON1Q192R polymorphism on the susceptibility to OP toxicity on semen quality and DNA integrity in agricultural workers. A cross-sectional study was conducted in farmers with Mayan ascendancy from southeastern Mexico chronically exposed to pesticides; mostly OP. Fifty four agricultural workers (18-55 years old) were included, who provided semen and blood samples. Semen quality was evaluated according to WHO, sperm DNA damage by in situ-nick translation (NT-positive cells), PON1Q192R polymorphism by real-time PCR and serum PON1 activity by using phenylacetate and paraoxon. Two OP exposure indexes were created: at the month of sampling and during 3 months before sampling, representing the exposure to spermatids-spermatozoa and to cells at one spermatogenic cycle, respectively. PON1 192R and 192Q allele frequencies were 0.54 and 0.46, respectively. Significant associations were found between OP exposure at the month of sampling and NT-positive cells and sperm viability in homozygote 192RR subjects, and dose-effect relationships were observed between OP exposure during 3 months before sampling and sperm quality parameters and NT-positive cells in homozygote 192RR farmers. This suggests that cells at all stages of spermatogenesis are target of OP, and that there exists an interaction between OP exposure and PON1Q192R polymorphism on these effects; farmers featuring the 192RR genotype were more susceptible to develop reproductive toxic effects by OP exposure.

  3. The 4q25, 1q21, and 16q22 polymorphisms and recurrence of atrial fibrillation after pulmonary vein isolation

    PubMed Central

    Kozluk, Edward; Franaszczyk, Maria; Lodzinski, Piotr; Piatkowska, Agnieszka; Ploski, Rafal; Opolski, Grzegorz

    2016-01-01

    Introduction The efficacy of pulmonary vein isolation (PVI) in atrial fibrillation (AF) is well documented. Several single nucleotide polymorphisms (SNPs) are associated with AF, mainly in the 4q25 locus, but also in 16q22 and 1q21. The aim of our study was to test the association between those SNPs and short- and long-term results of PVI. Material and methods Patients with AF who underwent PVI between 2006 and 2009 were included in the study. Pulmonary vein isolation was performed using a 4-mm non-irrigated ablation catheter, circular mapping catheter, and the LocaLisa system. All patients were genotyped for the 4q25, 16q22, and 1q21 SNPs. Results Two-hundred and thirty-eight patients were included. The median follow-up was 45 months. Six-month efficacy was 59.7%. None of the polymorphisms was linked with the risk of AF recurrence after 6 months in univariate analysis. In multivariate analysis rs2200733 in the recessive model was linked significantly with AF recurrence (odds ratio 1.87, p = 0.008). None of the polymorphisms predicted AF recurrence in long-term follow-up. Conclusions There is a trend in the relationship between TT genotype of the rs2200733 polymorphism and increased rate of AF recurrence after PVI in short-term (6 months) follow-up. None of the tested SNPs 4q25, 16q22, and 1q21 correlated with the results of a single AF ablation in long-term follow-up. PMID:26925117

  4. Juvenile Huntington disease in Argentina.

    PubMed

    Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis; Sanguinetti, Ana; Cordi, Lorena; Binelli, Adrian; Persi, Gabriel; Squitieri, Ferdinando

    2016-01-01

    We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors. PMID:26602194

  5. Sociologic perspectives on juvenile violence.

    PubMed

    Currie, E

    2000-10-01

    In sum, there are four sets of social factors that help us understand why juvenile violence appears when, and where, it does, and why some communities and entire societies are persistently wracked by youth violence whereas others are largely spared its worst expressions. When it comes to the first three factors in particular--deprivation, disorganization, and brutalization--the evidence for these links is as strong as anything in social science, and that evidence is supported by a variety of sources and a variety of methods of investigation. Such investigation includes the knowledge we gain through social intervention. Some of the most effective violence prevention programs are successful precisely because they confront and deflect the social forces that otherwise often lead to violence. Consider, for example, the home-visiting programs that work with poor parents in disorganized communities to lower the risks of child abuse; and some of the more "holistic" or "multisystemic" efforts to work with violent juvenile offenders. The best of these programs work by tackling the problems of social isolation and lack of supports in the community, as well as immediate issues of economic survival for vulnerable families and children. More generally, we know that the availability of steady and rewarding work in the future, of the kind that can reliably sustain a family, is one of the most important factors allowing some youths to "desist" from violence as they mature. These conclusions give us much to be encouraged about, and much to be alarmed about. On the one hand, understanding that youth violence often is rooted in a set of adverse social conditions that are identifiable, and potentially modifiable, is a fundamentally optimistic message. It reminds us that the level of juvenile violence we suffer in America today is neither fated nor inevitable. Other societies that are in many respects much like us suffer far less of it; so could we, and we increasingly understand some

  6. The chromosome periphery during mitosis.

    PubMed

    Hernandez-Verdun, D; Gautier, T

    1994-03-01

    A complex structure, visible by electron microscopy, surrounds each chromosome during mitosis. The organization of this structure is distinct from that of the chromosomes and the cytoplasm. It forms a perichromosomal layer that can be isolated together with the chromosomes. This layer covers the chromosomes except in centromeric regions. The perichromosomal layer includes nuclear and nucleolar proteins as well as ribonucleoproteins (RNPs). The list of proteins and RNAs identified includes nuclear matrix proteins (perichromin, peripherin), nucleolar proteins (perichro-monucleolin, Ki-67 antigen, B23 protein, fibrillarin, p103, p52), ribosomal proteins (S1) and snRNAs (U3 RNAs). Only limited information is available about how and when the perichromosomal layer is formed. During early prophase, the proteins extend from the nucleoli towards the periphery of the nucleus. Thin cordon-like structures reach the nuclear envelope delimiting areas in which chromosomes condense. At telophase, the proteins are associated with the part of the chromosomes remaining condensed and accumulate in newly formed nucleoli in regions where chromatin is already decondensed. The perichromosomal layer contains several different classes of proteins and RNPs and it has been attributed various roles: (1) in chromosome organization, (2) as a barrier around the chromosomes, (3) involvement in compartmentation of the cells in prophase and telophase and (4) a binding site for chromosomal passenger proteins necessary to the early process of nuclear assembly. PMID:8166671

  7. Complex chromosomal rearrangement and associated counseling issues in a family with Pelizaeus-Merzbacher disease.

    PubMed

    Woodward, Karen; Cundall, Maria; Palmer, Rodger; Surtees, Robert; Winter, Robin M; Malcolm, Sue

    2003-04-01

    We report cytogenetic and molecular findings in a family in which Pelizaeus-Merzbacher disease has arisen by a sub-microscopic duplication of the proteolipid protein (PLP1) gene involving the insertion of approximately 600 kb from Xq22 into Xq26.3. The duplication arose in an asymptomatic mother on a paternally derived X chromosome and was inherited by her son, the proband, who is affected with Pelizaeus-Merzbacher disease. The mother also carries a large interstitial deletion of approximately 70 Mb extending from Xq21.1 to Xq27.3, which is present in a mosaic form. In lymphocytes, the mother has no normal cells, having one population with three copies of the PLP1gene (one normal X and one duplication X chromosome) and the other population having only one copy of the PLP1 gene (one normal X and one deleted X chromosome). Her karyotype is 46,XX.ish dup (X) (Xpter --> Xq26.3::Xq22 --> Xq22::Xq26.3 --> Xqter)(PLP++)/46,X,del(X)(q21.1q27.3).ish del(X)(q21.1q27.3)(PLP-). Both ends of the deletion have been mapped by fluorescence in situ hybridization using selected DNA clones and neither involves the PLP1 gene or are in the vicinity of the duplication breakpoints. Prenatal diagnosis was carried out in a recent pregnancy and the complex counseling issues associated with these chromosomal rearrangements are discussed. PMID:12605435

  8. Social reward among juvenile mice

    PubMed Central

    Panksepp, J B; Lahvis, G P

    2007-01-01

    Mammalian social relationships, such as mother–offspring attachments and pair bonds, can directly affect reproductive output. However, conspecifics approach one another in a comparatively broad range of contexts, so conceivably there are motivations for social congregation other than those underlying reproduction, parental care or territoriality. Here, we show that reward mediated by social contact is a fundamental aspect of juvenile mouse sociality. Employing a novel social conditioned place preference (SCPP) procedure, we demonstrate that social proximity is rewarding for juvenile mice from three inbred strains (A/J, C57BL/6J and DBA/2J), while mice from a fourth strain (BALB/cJ) are much less responsive to social contact. Importantly, this strain-dependent difference was not related to phenotypic variability in exploratory behavior or contextual learning nor influenced by the genetic background associated with maternal care or social conditioning. Furthermore, the SCPP phenotype was expressed early in development (postnatal day 25) and did not require a specific sex composition within the conditioning group. Finally, SCPP responses resulted from an interaction between two specifiable processes: one component of the interaction facilitated approach toward environments that were associated with social salience, whereas a second component mediated avoidance of environmental cues that predicted social isolation. We have thus identified a genetically prescribed process that can attribute value onto conditions predicting a general form of social contact. To our knowledge, this is the first definitive evidence to show that genetic variation can influence a form of social valuation not directly related to a reproductive behavior. PMID:17212648

  9. Autoantibodies against protective molecules--C1q, C-reactive protein, serum amyloid P, mannose-binding lectin, and apolipoprotein A1: prevalence in systemic lupus erythematosus.

    PubMed

    Shoenfeld, Yehuda; Szyper-Kravitz, Martine; Witte, Torsten; Doria, Andrea; Tsutsumi, Akito; Tatsuya, Abe; Dayer, Jean-Michel; Roux-Lombard, Pascale; Fontao, Lionel; Kallenberg, Cees G M; Bijl, Marc; Matthias, Torsten; Fraser, Abigail; Zandman-Goddard, Gisele; Blank, Miri; Gilburd, Boris; Meroni, Pier Luigi

    2007-06-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of several autoantibodies. Among the multiple factors involved in SLE development, apoptotic defects and impaired clearance of cellular debris have gained considerable interest, as they contribute to autoantigen overload. Several molecules of the innate immunity, also participate in the removal of damaged and apoptotic cells. Among them are C1q, C-reactive protein (CRP), serum amyloid P protein (SAP), mannose-binding lectin (MBL), and apolipoprotein A1 (APO A1). To evaluate the prevalence of autoantibodies against CRP, SAP, MBL, APO A1, and C1q among SLE patients, and their relationship with disease activity, a total of 150 SLE patients were screened for the presence of elevated antibody titers against C1q, CRP, SAP, MBL, and APO A1, utilizing the enzyme-linked immunosorbent assay (ELISA) method. Disease activity was assessed using the ECLAM or SLEDAI scores. The study population comprised two groups of patients: 100 patients with quiescent disease (median ECLAM score 2) comprised the first group, and 50 patients with active disease (median SLEDAI score 16) comprised group 2. Elevated titers of anti-CRP antibodies were significantly elevated only in group 1 (10% versus 4% of controls). Antibodies against SAP were evaluated only among patients in group 1, and were found at a significant high prevalence (20%). Elevated titers of anti-MBL antibodies were significantly elevated only in group 1 (15% versus 3.6%); and antibodies directed against APO A1 were significantly elevated in 21% of group 1, and 50% of group 2 patients. Elevated titers of anti-C1q were evaluated only in group 2, and were found at a significant prevalence of 66%. Significant correlation with disease activity was found only for anti-APO A1 antibodies, and only in group 1. Several patients harbored more than one of the autoantibodies tested. In patients with SLE, autoantibodies directed against protective

  10. Chromosome Connections: Compelling Clues to Common Ancestry

    ERIC Educational Resources Information Center

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  11. Comprehensive molecular cytogenetic investigation of chromosomal abnormalities in human medulloblastoma cell lines and xenograft.

    PubMed Central

    Aldosari, Naji; Wiltshire, Rodney N.; Dutra, Amalia; Schrock, Evelin; McLendon, Roger E.; Friedman, Henry S.; Bigner, Darell D.; Bigner, Sandra H.

    2002-01-01

    Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors. Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridization to study 4 medulloblastoma cell lines and 1 xenograft. Cell line D-425 Med had a relatively simple karyotype, with a terminal deletion of 10q and amplification of MYC in double-minutes (dmins). FISH demonstrated that an apparent isochromosome (17q) by routine karyotyping was actually an unbalanced translocation between 2 copies of chromosome 17. Cell line D-556 Med also had a simple near-diploid stemline with an unbalanced 1;13 translocation resulting in a gain of 1q, an isochromosome (17q), and dmins. These findings were initially described using routine G-banded preparations, and FISH showed that the dmins were an amplification of MYC and the i(17q) was an isodicentric 17q chromosome. The other finding was confirmed by FISH, SKY, and comparative genomic hybridization. Cell lines D-721 Med and D-581 Med had complex karyotypic patterns that could be completely characterized only when FISH and SKY were used. Xenograft D-690 Med also had a complex pattern that FISH and SKY were helpful in completely elucidating. Interestingly, balanced reciprocal translocations were seen as well as complicated unbalanced translocations and marker chromosomes. Comparative genomic hybridization demonstrated only a deletion of 10q22-10q24, supporting the idea that despite the complexity of the chromosomal rearrangements, minimal alterations in the overall chromosomal content had occurred. This study demonstrates that routine cytogenetic preparations are adequate to describe chromosomal abnormalities in occasional medulloblastoma samples, but a broader spectrum of molecular cytogenetic methods is required to completely analyze most of these tumor samples. PMID:11916498

  12. The XXXXY Chromosome Anomaly

    PubMed Central

    Zaleski, Witold A.; Houston, C. Stuart; Pozsonyi, J.; Ying, K. L.

    1966-01-01

    The majority of abnormal sex chromosome complexes in the male have been considered to be variants of Klinefelter's syndrome but an exception should probably be made in the case of the XXXXY individual who has distinctive phenotypic features. Clinical, radiological and cytological data on three new cases of XXXXY syndrome are presented and 30 cases from the literature are reviewed. In many cases the published clinical and radiological data were supplemented and re-evaluated. Mental retardation, usually severe, was present in all cases. Typical facies was observed in many; clinodactyly of the fifth finger was seen in nearly all. Radiological examination revealed abnormalities in the elbows and wrists in all the 19 personally evaluated cases, and other skeletal anomalies were very frequent. Cryptorchism is very common and absence of Leydig's cells may differentiate the XXXXY chromosome anomaly from polysomic variants of Klinefelter's syndrome. The relationship of this syndrome to Klinefelter's syndrome and to Down's syndrome is discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15 PMID:4222822

  13. X-chromosome workshop.

    PubMed

    Paterson, A D

    1998-01-01

    Researchers presented results of ongoing research to the X-chromosome workshop of the Fifth World Congress on Psychiatric Genetics, covering a wide range of disorders: X-linked infantile spasms; a complex phenotype associated with deletions of Xp11; male homosexuality; degree of handedness; bipolar affective disorder; schizophrenia; childhood onset psychosis; and autism. This report summarizes the presentations, as well as reviewing previous studies. The focus of this report is on linkage findings for schizophrenia and bipolar disorder from a number of groups. For schizophrenia, low positive lod scores were obtained for markers DXS991 and DXS993 from two studies, although the sharing of alleles was greatest from brother-brother pairs in one study, and sister-sister in the other. Data from the Irish schizophrenia study was also submitted, with no strong evidence for linkage on the X chromosome. For bipolar disease, following the report of a Finnish family linked to Xq24-q27, the Columbia group reported some positive results for this region from 57 families, however, another group found no evidence for linkage to this region. Of interest, is the clustering of low positive linkage results that point to regions for possible further study. PMID:9686435

  14. Single chromosome transcriptional profiling reveals chromosome-level regulation of gene expression

    PubMed Central

    Levesque, Marshall J.; Raj, Arjun

    2013-01-01

    Here we report iceFISH, a multiplex imaging method for measuring gene expression and chromosome structure simultaneously on single chromosomes. We demonstrate that chromosomal translocations can alter transcription chromosome-wide, finding substantial differences in transcriptional frequency between genes located on a translocated chromosome in comparison to the normal chromosome in the same cell. Examination of correlations between genes on a single chromosome revealed a cis chromosome-level transcriptional interaction spanning 14.3 megabases. PMID:23416756

  15. Identification of a 1.1-Mb region for a carcass weight QTL onbovine Chromosome 14.

    PubMed

    Mizoshita, Kazunori; Takano, Atsushi; Watanabe, Toshio; Takasuga, Akiko; Sugimoto, Yoshikazu

    2005-07-01

    We previously mapped a quantitative trait locus for carcass weight, designated Carcass Weight-1 (CW-1), to bovine Chromosome 14 using a purebred Wagyu pedigree based on progeny design analysis. To refine the critical region within 8.1 cM flanked by microsatellites BMS1941 and INRA094, we constructed a bacterial artificial chromosome (BAC) contig composed of 60 tiled BAC clones and prepared a high-density physical map including 80 microsatellites, of which 55 were developed in this study. We conducted linkage disequilibrium (LD) mapping in the CW-1 region with 47 microsatellites using paternal half-sib pedigrees whose sires exhibited homozygous CW-1 Q alleles in the region. The LD mapping study significantly narrowed the CW-1 locus to the 1.1-Mb region between microsatellites DIK7012 and DIK7020. Finally, we surveyed the 1.1-Mb-region genotypes of 1700 steers from 11 bulls having -/-, Q/-, or Q/Q alleles in the region, and we examined the effect of the CW-1 Q allele on carcass weight. The presence of the first Q increased carcass weight by 23.6 kg (95% confidence interval [CI], 17.6-29.5 kg), and the second Q increased carcass weight an additional 15.2 kg (95% CI, 10.7-19.7 kg). These results indicate the presence of a gene responsible for carcass weight within the 1.1-Mb region. PMID:16151698

  16. Heritability and heteromorphic distributions of AluI chromosome banding variants in twins

    SciTech Connect

    Huang, B.; Meyer, J.M.; Jackson-Cook, C.K.

    1995-07-03

    The heritability and heteromorphic appearance of chromosomal banding patterns induced through in situ digestion with the restriction enzyme AluI were studied by analyzing the chromosomes of 25 monozygotic and 25 dizygotic twin pairs selected at random from a juvenile twin registry. A total of 19 AluI banding variants were found to be heteromorphic, with the pericentromeric region of chromosome 3 and the satellites of chromosome 22 being most and least heteromorphic, respectively. As expected, the correlations of the semi-quantitative scores for each of the chromosomal variants were significantly higher between MZ twin pairs (ranging from 0.48 to 0.95) than DZ twin pairs (ranging from -0.02 to 0.69), suggesting that genetic factors play an important role in their appearance. This finding was confirmed in a model fitting analysis in which the heritabilities of the AluI-induced chromosome variants were found to range from 70 to 96% for 12/13 heteromorphisms studied. These consistent findings are significant in that these variants may be useful for family studies in clinical genetics. 23 refs., 6 figs., 3 tabs.

  17. Juvenile rheumatoid arthritis with cardiac tamponade.

    PubMed Central

    Majeed, H A; Kvasnicka, J

    1978-01-01

    A 4-year-old girl with seronegative systemic juvenile rheumatoid arthritis developed acute cardiac tamponade. Pericardiocentesis and systemic corticosteroids resulted in complete recovery of the pericardial involvement. This was followed by complete remission of rheumatoid disease. Images PMID:686861

  18. Juvenile Arthritis: Discoveries Lead to Newer Treatments

    MedlinePlus

    ... Consumers Home For Consumers Consumer Updates Juvenile Arthritis: Discoveries Lead to Newer Treatments Share Tweet Linkedin Pin ... better for different subgroups of the disease. In recent years, FDA has approved several of these treatments. ...

  19. Screening Incarcerated Juveniles Using the MAYSI-2.

    PubMed

    Gilbert, Amy L; Grande, Todd L; Hallman, Janelle; Underwood, Lee A

    2015-01-01

    The high prevalence of mental health disorders among incarcerated juveniles is a matter of national and global concern. Juvenile justice personnel need accurate screening measures that identify youth requiring immediate mental health services. The purpose of this study was threefold: (a) to examine the utility of the Massachusetts Youth Screening Instrument, Version 2 (MAYSI-2) in identifying juveniles with mental health concerns in a large sample of juveniles (N = 4,009), (b) to provide data regarding rates of identified mental health needs in incarcerated youth, and (c) to provide descriptive comparisons to other studies using the MAYSI-2. Mean scores of subscales were compared with the MAYSI-2 normative samples and other recent studies. Results indicated that this population has a high occurrence of mental health symptoms and there is high variability in the severity of the symptoms. In addition, a multivariate analysis of variance test found significant differences in mental health problems across ethnic groups. PMID:25431437

  20. Genetics Home Reference: juvenile primary osteoporosis

    MedlinePlus

    ... caused by a shortage of calcium and other minerals in bones (decreased bone mineral density), which makes the bones brittle and prone ... protein is involved in the regulation of bone mineral density. LRP5 gene mutations that cause juvenile primary ...