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Sample records for chromosome 1q juvenile

  1. Juvenile hemochromatosis locus maps to chromosome 1q in a French Canadian population.

    PubMed

    Rivard, Sylvain R; Lanzara, Carmela; Grimard, Doria; Carella, Massimo; Simard, Hervey; Ficarella, Romina; Simard, Raynald; D'Adamo, Adamo Pio; Férec, Claude; Camaschella, Clara; Mura, Cathrine; Roetto, Antonella; De Braekeleer, Marc; Bechner, Lucien; Gasparini, Paolo

    2003-08-01

    Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder that causes iron overload. In the French Canadian region of Saguenay Lac-Saint-Jean the worldwide largest cohort of JH cases has been identified. Here, we report the mapping of this large cohort of cases to the HFE2 locus on chromosome 1q. A maximum multipoint location score of 7.02 was observed with marker D1S2344. A common ancestral haplotype, showing the presence of a founder effect, was identified. The analysis of recombinants allowed us to confirm the JH candidate region.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. 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.

  9. 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.

  10. 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.

  11. Identification of a locus on chromosome 1q44 for familial cold urticaria.

    PubMed Central

    Hoffman, H M; Wright, F A; Broide, D H; Wanderer, A A; Kolodner, R D

    2000-01-01

    Familial cold urticaria (FCU) is a rare autosomal dominant inflammatory disorder characterized by intermittent episodes of rash with fever, arthralgias, conjunctivitis, and leukocytosis. These symptoms develop after generalized exposure to cold. Some individuals with FCU also develop late-onset reactive renal amyloidosis, which is consistent with Muckle-Wells syndrome. By analyzing individuals with FCU from five families, we identified linkage to chromosome 1q44. Two-point linkage analysis revealed a maximum LOD score (Zmax) of 8.13 (recombination fraction 0) for marker D1S2836; multipoint linkage analysis identified a Zmax of 10. 92 in the same region; and haplotype analysis defined a 10.5-cM region between markers D1S423 and D1S2682. Muckle-Wells syndrome was recently linked to chromosome 1q44, which suggests that the two disorders may be linked to the same locus. PMID:10741953

  12. Chromosome aberrations [dup(1q)] in endometrial cancer: Gene analysis of 54 surgical specimens in Turkey.

    PubMed

    Sever, Erman; Döğer, Emek; Kumbasar, Serkan; Şık, Bulat Aytek; Temur, Muzaffer; Yılmaz, Hasan Taylan; Yılmaz, Özgür; Özbay, Pelin Ozun; Yücesoy, İzzet

    2016-06-01

    We aimed to evaluate the frequency of chromosomal aberrations and mutations in the k-ras or Her-2/neu genes in surgical specimens of endometrial carcinoma and their association with clinicopathological findings. Fifty-four patients who were treated for endometrial cancer between April 2010 and May 2011 at the Kocaeli University Obstetrics and Gynecology Department, Kocaeli, Turkey were enrolled in a prospective study. Clinical and histopathological findings were recorded. Genetic analysis, which included the detection of chromosomal deletions and duplications, as well as k-ras and Her-2/neu mutations, was performed on endometrial samples from surgical specimens. In 70% of cases, tumor size was >2 cm or covered the entire uterine cavity, affecting mostly corpus (76%) and invading less than half of the myometrium (80%). Forty-six cases (86%) had endometrioid-type carcinoma, and early stage (Stage I, 65%) and higher grade (Grade II-III, 66%) tumors were predominant. Lymph node and lymphovascular involvement was positive in 11% and 28% of the patients, respectively. Chromosomal aberrations (deletion or duplication) and Her-2/neu and k-ras mutations were encountered in 44%, 15%, and 13% of surgical specimens, respectively. The most common chromosomal aberration was dup(1q) (n = 16). Oncogenic mutations in Her-2/neu or k-ras had no association with the severity of endometrial cancer, but the presence of chromosomal aberrations, as a whole or dup(1q) alone, were associated with higher tumor size, deeper myometrial invasion, advanced stage or grade, lymphovascular invasion, and lymph node involvement (p < 0.05 for all). Chromosomal aberrations, particularly dup(1q), are related to advanced disease in endometrial cancer. Genetic analysis of cancer tissues may provide important insights in determining disease prognosis. Copyright © 2016. Published by Elsevier B.V.

  13. De novo 911 Kb interstitial deletion on chromosome 1q43 in a boy with mental retardation and short stature.

    PubMed

    Perrone, M D; Rocca, M S; Bruno, I; Faletra, F; Pecile, V; Gasparini, P

    2012-02-01

    Patients with distal deletions of chromosome 1q have a recognizable syndrome that includes microcephaly, hypoplasia or agenesis of the corpus callosum, and psychomotor retardation. Although these symptoms have been attributed to deletions of 1q42-1q44, the minimal chromosomal region involved has not yet defined. In this report, we describe a 7 years old male with mental retardation, cryptorchid testes, short stature and alopecia carrying only an interstitial de novo deletion of 911 Kb in the 1q43 region (239,597,095-240,508,817) encompassing three genes CHRM3, RPS7P5 and FMN2. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  14. Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.

    PubMed

    Schubert, Stephanie A; Ruano, Dina; Elsayed, Fadwa A; Boot, Arnoud; Crobach, Stijn; Sarasqueta, Arantza Farina; Wolffenbuttel, Bruce; van der Klauw, Melanie M; Oosting, Jan; Tops, Carli M; van Eijk, Ronald; Vasen, Hans Fa; Vossen, Rolf Ham; Nielsen, Maartje; Castellví-Bel, Sergi; Ruiz-Ponte, Clara; Tomlinson, Ian; Dunlop, Malcolm G; Vodicka, Pavel; Wijnen, Juul T; Hes, Frederik J; Morreau, Hans; de Miranda, Noel Fcc; Sijmons, Rolf H; van Wezel, Tom

    2017-09-05

    A substantial fraction of familial colorectal cancer (CRC) and polyposis heritability remains unexplained. This study aimed to identify predisposing loci in patients with these disorders. Homozygosity mapping was performed using 222 563 SNPs in 302 index patients with various colorectal neoplasms and 3367 controls. Linkage analysis, exome and whole-genome sequencing were performed in a family affected by microsatellite stable CRCs. Candidate variants were genotyped in 10 554 cases and 21 480 controls. Gene expression was assessed at the mRNA and protein level. Homozygosity mapping revealed a disease-associated region at 1q32.3 which was part of the linkage region 1q32.2-42.2 identified in the CRC family. This includes a region previously associated with risk of CRC. Sequencing identified the p.Asp1432Glu variant in the MIA3 gene (known as TANGO1 or TANGO) and 472 additional rare, shared variants within the linkage region. In both cases and controls the population frequency was 0.02% for this MIA3 variant. The MIA3 mutant allele showed predominant mRNA expression in normal, cancer and precancerous tissues. Furthermore, immunohistochemistry revealed increased expression of MIA3 in adenomatous tissues. Taken together, our two independent strategies associate genetic variations in chromosome 1q loci and predisposition to familial CRC and polyps, which warrants further investigation.

  15. [Prenatal diagnosis of fetal urinary abnormalities and microdeletion on chromosome 1q21.1].

    PubMed

    Fu, Fang; Huang, Yong-hua; Liao, Can; Li, Ru; Feng, Sui-hua; Mai, Qiao-jiao; Li, Wei-kai

    2012-10-01

    To investigate genetic etiology of fetal urinary abnormalities with array-based comparative genomic hycridization(array-CGH). Thirty-two fetuses with variable urinary abnormalities but normal karyotyping by conventional cytogenetic technique were selected. DNA from the fetuses and their parents samples were prepared and hybridization with Affymetrix cytogenetic 2.7M arrays by follwing the manufacture's standard protocol. The data were analyzed by special CHAS software packages. By using array-CGH detection, genomic imbalanced copy number variations (CNVs) were identified in night fetuses(28%), four out of night CNVs were inherited from parental samples; two were indicated to be benign variants(6%) in the database; and the other three CNVs (9%) were all de novo adjacent microdeletions and microduplication mapping on to common chromosome 1q21.1 region, within which was genitourinaty system function associated gene PDZK1. The incidence of genomic unbalanced variations in fetuses with congenital urinary malformations is approximately 28%, including about 9% pathogenic variations. Copy number variations (CNVs) of chromosome 1q21.1 region are associated with congenital urinary malformations which may be due to haploinsufficiency or overexpression of PDZK1 gene.

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

    PubMed Central

    Schumacher, Fredrick R.; Wang, Zhaoming; Skotheim, Rolf I.; Koster, Roelof; Chung, Charles C.; Hildebrandt, Michelle A. T.; Kratz, Christian P.; Bakken, Anne C.; Timothy Bishop, D.; 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; Pablo Lewinger, Juan; 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.

    2013-01-01

    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

  17. 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.

  18. Quantitative trait locus on chromosome 1q influences bone loss in young Mexican American adults

    PubMed Central

    Shaffer, John R.; Kammerer, Candace M.; Bruder, Jan M.; Cole, Shelley A.; Dyer, Thomas D.; Almasy, Laura; MacCluer, Jean W.; Blangero, John; Bauer, Richard L.; Mitchell, Braxton D.

    2009-01-01

    Introduction Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants of the San Antonio Family Osteoporosis Study. Materials and Methods BMD change in 327 Mexican Americans (ages 25–45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h2) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm, and estimate heritability for BMD change of lumbar spine. Results BMD change was significantly heritable for total hip, ultradistal radius and 33% radius (h2 = 0.34, 0.34, 0.27, respectively, p < 0.03 for all), modestly heritable for femoral neck (h2 = 0.22, p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. Conclusions We observed that change in BMD in young adults is heritable, and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests this region may harbor one or more genes involved in regulating early BMD change of the femoral neck. PMID:19067020

  19. Jumping translocations of chromosome 1q in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric heterochromatin.

    PubMed

    Sawyer, J R; Tricot, G; Mattox, S; Jagannath, S; Barlogie, B

    1998-03-01

    Karyotypes in multiple myeloma (MM) are complex and exhibit numerous structural and numerical aberrations. The largest subset of structural chromosome anomalies in clinical specimens and cell lines involves aberrations of chromosome 1. Unbalanced translocations and duplications involving all or part of the whole long arm of chromosome 1 presumably occur as secondary aberrations and are associated with tumor progression and advanced disease. Unfortunately, cytogenetic evidence is scarce as to how these unstable whole-arm rearrangements may take place. We report nonrandom, unbalanced whole-arm translocations of 1q in the cytogenetic evolution of patients with aggressive MM. Whole-arm or "jumping translocations" of 1q were found in 36 of 158 successive patients with abnormal karyotypes. Recurring whole-arm translocations of 1q involved chromosomes 5,8,12,14,15,16,17,19,21, and 22. A newly delineated breakpoint present in three patients involved a whole-arm translocation of 1q to band 5q15. Three recurrent translocations of 1q10 to the short arms of different acrocentric chromosomes have also been identified, including three patients with der(15)t(1;15)(q10;p10) and two patients each with der(21)t(1;21)(q10;p13) and der(22)t(1;22) (q10;p10). Whole-arm translocations of 1q10 to telomeric regions of nonacrocentric chromosomes included der(12)t(1;12) (q10;q24.3) and der(19)t(1;19)(q10;q13.4) in three and two patients, respectively. Recurrent whole-arm translocations of 1q to centromeric regions included der(16)t(1;16)(q10;q10) and der(19)t(1;19)(q10;p10). The mechanisms involved in the 1q instability in MM may be associated with highly decondensed pericentromeric heterochromatin, which may permit recombination and formation of unstable translocations of chromosome 1q. The clonal evolution of cells with extra copies of 1q suggests that this aberration directly or indirectly provides a proliferative advantage.

  20. Role of chromosome 1 pericentric heterochromatin (1q) in pathogenesis of myelodysplastic syndromes: report of 2 new cases.

    PubMed

    Millington, Karmaine; Hudnall, S David; Northup, Jill; Panova, Neli; Velagaleti, Gopalrao

    2008-04-01

    Chromosome 1 pericentromeric heterochromatin (1q) has been shown to play an important role in the pathogenesis of non-Hodgkin lymphoma and multiple myeloma. Myelodysplastic syndrome (MDS) results from marrow failure in two or more cell lineages. Although trisomy 1q has been reported in MDS, it is usually present with additional common abnormalities such as trisomy 8, monosomy 5 or monosomy 7, leading to speculation that 1q abnormalities are mostly secondary events representing clonal evolution. We report two cases of MDS in which consistent involvement of 1q heterochromatin is seen as the primary clonal abnormality. Both patients presented with fatigue and pancytopenia. Based on the published reports and our cases, we propose that the 1q heterochromatin plays a vital role in the pathophysiology of MDS. Abnormalities involving 1q result in aberrant heterochromatin/euchromatin junctions, leading to gene dosage abnormalities. Further studies of 1q abnormalities in MDS might provide specific insights as to the exact role of the excess 1q heterochromatin in the etiology of MDS.

  1. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

    PubMed Central

    Jansen, M.; Mohapatra, G.; Betensky, R.A.; Keohane, C.; Louis, D.N.

    2013-01-01

    Aims Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Postoperative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. PMID:21988727

  2. 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.

  3. Analysis of chromosomal aberrations involving chromosome 1q31-->q53 in a DMBA-induced rat fibrosarcoma cell line: amplification and overexpression of Jak2.

    PubMed

    Sjöling, A; Lindholm, H; Samuelson, E; Yamasaki, Y; Watanabe, T K; Tanigami, A; Levan, G

    2001-01-01

    In a study of DMBA-induced rat fibrosarcomas we repeatedly found deletions and/or amplifications in the long arm of rat chromosome 1 (RNO1). Comparative genome hybridization showed that there was amplification involving RNO1q31-->q53 in one of the DMBA-induced rat fibrosarcoma tumors (LB31) and a cell culture derived from it. To identify the amplified genes we physically mapped rat genes implicated in cancer and analyzed them for signs of amplification. The genes were selected based on their locations in comparative maps between rat and man. The rat proto-oncogenes Ccnd1, Fgf4, and Fgf3 (HSA11q13.3), were mapped to RNO1q43 by fluorescence in situ hybridization (FISH). The Ems1 gene was mapped by radiation hybrid (RH) mapping to the same rat chromosome region and shown to be situated centromeric to Ccnd1 and Fgf4. In addition, the proto-oncogenes Hras (HSA11p15.5) and Igf1r (HSA15q25-->q26) were mapped to RNO1q43 and RNO1q32 by FISH and Omp (HSA11q13.5) was assigned to RNO1q34. PCR probes for the above genes together with PCR probes for the previously mapped rat genes Bax (RNO1q31) and Jak2 (RNO1q51-->q53) were analyzed for signs of amplification by Southern blot hybridization. Low copy number increases of the Omp and Jak2 genes were detected in the LB31 cell culture. Dual color FISH analysis of tumor cells confirmed that chromosome regions containing Omp and Jak2 were amplified and were situated in long marker chromosomes showing an aberrant banding pattern. The configuration of the signals in the marker chromosomes suggested that they had arisen by a break-fusion-bridge (BFB) mechanism. Copyright 2002 S. Karger AG, Basel

  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. Microdeletion of chromosome 1q21.3 in fraternal twins is associated with mental retardation, microcephaly, and epilepsy

    PubMed Central

    Sonmez, Fatma Mujgan; Uctepe, Eyyup; Aktas, Dilek; Alikasifoglu, Mehmet

    2017-01-01

    Summary Reported here are twins, both of whom have a 1q21.3 microdeletion and who exhibit key features common to previously reported cases such as microcephaly and developmental delay. However, some clinical findings and deleted genes differed from those in previously reported cases. The karyotype was normal 46, XX for both of the twins. Array comparative genomic hybridization (CGH) identified a 2.6 Mb deletion on chromosome 1q21.3 (chr1: 153,514,121–156,171,335 bp) in case 1 and a 1.6 Mb deletion on chromosome 1q21.3 (chr1: 154,748,365–156,358,923 bp) in case 2. The deleted region includes DPM3, MUC1, GBA, PKLR, RIT1, and LAMTOR2 in both siblings. To the extent known, this is the second report of a 1q21.3 microdeletion in a family with mental retardation, developmental delay, seizures, and some dysmorphic features, thus expanding the phenotypic spectrum. PMID:28357185

  6. 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.

  7. A 11.7-Mb Paracentric Inversion in Chromosome 1q Detected in Prenatal Diagnosis Associated with Familial Intellectual Disability.

    PubMed

    Rigola, Maria A; Baena, Neus; Català, Vicenç; Lozano, Iris; Gabau, Elisabet; Guitart, Miriam; Fuster, Carmen

    2015-01-01

    Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion.

  8. Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma.

    PubMed

    Kim, Miyoung; Ju, Young Su; Lee, Eun Jin; Kang, Hee Jung; Kim, Han Sung; Cho, Hyoun Chan; Kim, Hyo Jung; Kim, Jung Ah; Lee, Dong Soon; Lee, Young Kyung

    2016-11-01

    We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.

  9. Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma

    PubMed Central

    Kim, Miyoung; Ju, Young-Su; Lee, Eun Jin; Kang, Hee Jung; Kim, Han-Sung; Cho, Hyoun Chan; Kim, Hyo Jung; Kim, Jung-Ah; Lee, Dong Soon

    2016-01-01

    Background We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. Methods The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. Results MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. Conclusions This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis. PMID:27578511

  10. Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African-American pedigrees

    PubMed Central

    Moser, Kathy L.; Neas, Barbara R.; Salmon, Jane E.; Yu, Hua; Gray-McGuire, Courtney; Asundi, Neeraj; Bruner, Gail R.; Fox, Jerome; Kelly, Jennifer; Henshall, Stephanie; Bacino, Debra; Dietz, Myron; Hogue, Robert; Koelsch, Gerald; Nightingale, Lydia; Shaver, Tim; Abdou, Nabih I.; Albert, Daniel A.; Carson, Craig; Petri, Michelle; Treadwell, Edward L.; James, Judith A.; Harley, John B.

    1998-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcγ receptors (FcγR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, λs > 10, purported linkage at 1q41–42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14–23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26–27, and 12p12–11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcγRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects. PMID:9843982

  11. Association of apoptosis-related microsatellite polymorphisms on chromosome 1q in Taiwanese systemic lupus erythematosus patients

    PubMed Central

    Chen, J-Y; Wang, C-M; Lu, S-C; Chou, Y-H; Luo, S-F

    2006-01-01

    Apoptosis is important in the pathogenesis of systemic lupus erythematosus (SLE). Several genome-wide scan studies have suggested chromosome 1q as a genetic susceptibility locus for SLE. This study investigated the association of apoptosis-related genes on chromosome 1q, Fas ligand (FasL), interleukin (IL)-10 and poly(ADP-ribose) polymerase (PARP), promoter microsatellite multi-allelic polymorphisms with SLE susceptibility and clinical characteristics in Taiwan. This study recruited 237 SLE patients and 304 healthy controls. FasL, IL-10 and PARP promoter microsatellite polymorphisms were genotyped employing gene scan. IL-10, located on 1q31–32, emerged as a significant susceptibility gene locus in Taiwanese SLE (T4 statistic = 0·01). IL-10 CA21 allele was the most common allele of 15 identified in Taiwanese, displaying skewed distribution of susceptibility in Taiwanese SLE patients. Conversely, the IL-10 CA20 allele showed a protective effect of SLE susceptibility. Additionally, the IL-10 CA26 allele displayed a negative significant association with ascites and IL-10 CA25 allele increased the occurrence of the anti-cardiolipin IgM antibody. This study identified five alleles of FasL and nine alleles of PARP of microsatellite polymorphisms in Taiwanese patients. FasL and PARP alleles displayed no skewing distribution between Taiwanese SLE patients and controls. However, FasL GT15 and PARP CA17 allele demonstrated a high discoid rash presentation (T4 statistic 0·01 and 0·03, respectively) and PARP CA12 allele displayed a significant association with anti-cardiolipin IgM antibody production (T4 statistic 0·02). IL-10, FasL and PARP microsatellite polymorphisms exhibited significant associations with SLE susceptibility and/or clinical characteristics in Taiwanese patients. Thus, SLE is a complex and multiple genetics determined autoimmune disease. Chromosome 1q23–42 is an important genetic locus for further SLE subphenotype susceptibility study. PMID:16412052

  12. 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.

  13. Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13. 1-q21. 1 and mouse chromosome 5

    SciTech Connect

    Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. ); Altherr, M.R. )

    1994-04-01

    The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. The authors have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with the evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction. 22 refs., 2 figs.

  14. 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

  15. A Sequence-Ready BAC Clone Contig of a 2.2-Mb Segment of Human Chromosome 1q24

    PubMed Central

    Vollrath, Douglas; Jaramillo-Babb, Virna L.

    1999-01-01

    Human chromosomal region 1q24 encodes two cloned disease genes and lies within large genetic inclusion intervals for several disease genes that have yet to be identified. We have constructed a single bacterial artificial chromosome (BAC) clone contig that spans over 2 Mb of 1q24 and consists of 78 clones connected by 100 STSs. The average density of mapped STSs is one of the highest described for a multimegabase region of the human genome. The contig was efficiently constructed by generating STSs from clone ends, followed by library walking. Distance information was added by determining the insert sizes of all clones, and expressed sequence tags (ESTs) and genes were incorporated to create a partial transcript map of the region, providing candidate genes for local disease loci. The gene order and content of the region provide insight into ancient duplication events that have occurred on proximal 1q. The stage is now set for further elucidation of this interesting region through large-scale sequencing. [The sequence data described in this paper have been submitted to GenBank under accession nos. G42259–G42312 and G42330–G42335.] PMID:10022979

  16. Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44.

    PubMed

    Nagamani, Sandesh C Sreenath; Erez, Ayelet; Bay, Carolyn; Pettigrew, Anjana; Lalani, Seema R; Herman, Kristin; Graham, Brett H; Nowaczyk, Malgorzata Jm; Proud, Monica; Craigen, William J; Hopkins, Bobbi; Kozel, Beth; Plunkett, Katie; Hixson, Patricia; Stankiewicz, Pawel; Patel, Ankita; Cheung, Sau Wai

    2012-02-01

    Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.

  17. 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.

  18. Suggestive linkage to chromosome 1q for bone mineral apparent density in Brazilian sister adolescents.

    PubMed

    Fonseca, Romulo Maia Carlos; de França, Nanci Maria; Pereira, Rinaldo Wellerson

    2012-05-01

    To investigate linkage to chromosome 1q and 11q region for lumbar spine, femoral neck and total body BMD and volumetric BMD in Brazilian sister adolescents aged 10-20-year-old and 57 mothers. We evaluated 161 sister pairs (n=329) aged 10-20 years old and 57 of their mothers in this study. Physical traits and lifestyle factors were collected as covariates for lumbar spine (LS), femoral neck (FN) and total body (TB) BMD and bone mineral apparent density (BMAD). We selected nine microsatellite markers in chromosome 1q region (spanning nearly 33cM) and eight in chromosome 11q region (spanning nearly 34cM) to perform linkage analysis. The highest LOD score values obtained from our data were in sister pairs LS BMAD analysis. Their values were: 1.32 (P<0.006), 2.61 (P<0.0002) and 2.44 (P<0.0004) in D1S218, D1S2640 and D1S2623 markers, respectively. No significant LOD score was found with LS and FN BMD/BMAD in chromosome 11q region. Only TB BMD showed significant linkage higher than 1.0 for chromosome 11q region in the markers D11S4191 and D11S937. Our results provided suggestive linkage for LS BMAD at D1S2640 marker in adolescent sister pairs and suggest a possible candidate gene (LHX4) related to adolescent LS BMAD in this region. These results reinforce chromosome 1q21-23 as a candidate region to harbor one or more bone formation/maintenance gene. In the other hand, it did not repeat for chromosome 11q12-13 in our population. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  19. 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.

  20. Terminal (1)(q43) long-arm deletion of chromosome no. 1 in a three-year-old female.

    PubMed

    Mankinen, C B; Sears, J W; Alvarez, V R

    1976-01-01

    A 3-year-old Latin female is reported with a terminal deletion of the No. 1 chromosome, karyotype formula 46, XX, del(1) (q43). Principle clinical features include: Anatomic - microcephaly; bilateral, convergent strabismus; epicanthus; brachycephaly; bulbar nose; sparse hair; partial soft tissue syndactylism between 2nd and 3rd fingers which are slightly tapered; whorls on all 10 fingers; mild prognathism; solitary kidney; vaginal stenosis; vesicoureteral reflux; asymmetric feet; and subluxation of peroneal tendons around the fibula with severe pronation and heal valgus deformity. Neurologic - moderate motor and mental retardation; high-pitched, shrill cry; absent pincer grasp at 3 years; and grand mal seizures documented from 9 months of age.

  1. A neonate with the Pelger-Huët anomaly, cleft lip and palate, and agenesis of the corpus callosum, with a chromosomal microdeletion involving 1q41 to 1q42.12.

    PubMed

    Christensen, R D; Yaish, H M

    2012-03-01

    We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of the corpus callosum, slightly small penis, hypoglycemia, and what initially appeared to be a marked leukocyte 'left shift' on complete blood count, but which was actually a Pelger-Huët anomaly. A chromosomal microdeletion was identified at1q41-42.12.

  2. Prenatal diagnosis of a terminal chromosome 1 (q42-q44) deletion: original case report and review of the literature

    PubMed Central

    Van Linthout, C; Emonard, V; Gatot, JS; Capelle, X; Kridelka, F; Emonts, P; Segghaye, MC

    2016-01-01

    Abstract Terminal chromosome 1q deletion is rarely reported but causes typical malformations that have been well described in childhood. Clinical features include facial dysmorphy, growth and/or psychomotor retardation, brain agenesis or hypoplasia of the corpus callosum, epilepsy and occasional urogenital or cardiac malformations. The diagnosis of this condition is usually made at birth. The rare cases of antenatal diagnosis were based on microcephaly and growth retardation. In the present case, the foetus presented with an hypoplasia of the corpus callosum, a dysmorphic profile and a single umbilical artery. The foetal echocardiography suggested a non- compaction of the left ventricular myocardium. No microcephaly or growth retardation were noted. We compare our antenatal findings to those described in the literature with the aim to better define the antenatal phenotype of the terminal chromosome 1 deletion syndrome. PMID:27909566

  3. 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.

  4. Localization of acyl coenzyme A:cholesterol acyltransferase gene to human chromosome 1q25

    SciTech Connect

    Chang, C.C.Y.; Chang, W.; Chang, T.Y. ); Noll, W.W.; Nutile-McMenemy, N. ); Lindsay, E.A.; Baldini, A. )

    1994-01-01

    Acyl coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes the formation of cholesterol esters from cholesterol and long-chain fatty acyl-coenzyme A. It is believed that ACAT plays a key role in lipoprotein metabolism and atherogenesis. Recently the authors' laboratory succeeded in molecular cloning and functional expression of human macrophage ACAT cDNA. They have now mapped the ACAT gene to chromosome 1, band q25 by using fluorescence in situ hybridization to metaphase chromosomes, and by Southern blotting analysis of human-hamster somatic cell hybrid panels.

  5. 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.

  6. 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

  7. A Locus for an Autosomal Dominant Form of Progressive Renal Failure and Hypertension at Chromosome 1q21

    PubMed Central

    Cohn, Daniel H.; Shohat, Tamy; Yahav, Michal; Ilan, Tsafra; Rechavi, Gidi; King, Lily; Shohat, Mordechai

    2000-01-01

    Linkage studies were performed in a large family with an autosomal dominant phenotype characterized by nephropathy and hypertension. In this family of Iraqi Jewish origin, the nephropathy develops into progressive renal failure. By performing a genomewide linkage search, we localized the disease gene to chromosome 1q21; the highest LOD score was obtained for the marker at locus D1S305, which yielded a maximum LOD score of 4.71 at a recombination fraction of 0. Recombination mapping defined an interval of ∼11.6 cM, between the markers at loci D1S2696 and D1S2635, that contains the disease gene. Localization of the disease-causing gene in this family represents a necessary step toward isolation of the defective gene and toward a deeper understanding of the mechanisms of hypertension and progressive renal failure. PMID:10930359

  8. 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.

  9. 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.

  10. Familial Isolated Clubfoot Is Associated with Recurrent Chromosome 17q23.1q23.2 Microduplications Containing TBX4

    PubMed Central

    Alvarado, David M.; Aferol, Hyuliya; McCall, Kevin; Huang, Jason B.; Techy, Matthew; Buchan, Jillian; Cady, Janet; Gonzales, Patrick R.; Dobbs, Matthew B.; Gurnett, Christina A.

    2010-01-01

    Clubfoot is a common musculoskeletal birth defect for which few causative genes have been identified. To identify the genes responsible for isolated clubfoot, we screened for genomic copy-number variants with the Affymetrix Genome-wide Human SNP Array 6.0. A recurrent chromosome 17q23.1q23.2 microduplication was identified in 3 of 66 probands with familial isolated clubfoot. The chromosome 17q23.1q23.2 microduplication segregated with autosomal-dominant clubfoot in all three families but with reduced penetrance. Mild short stature was common and one female had developmental hip dysplasia. Subtle skeletal abnormalities consisted of broad and shortened metatarsals and calcanei, small distal tibial epiphyses, and thickened ischia. Several skeletal features were opposite to those described in the reciprocal chromosome 17q23.1q23.2 microdeletion syndrome associated with developmental delay and cardiac and limb abnormalities. Of note, during our study, we also identified a microdeletion at the locus in a sibling pair with isolated clubfoot. The chromosome 17q23.1q23.2 region contains the T-box transcription factor TBX4, a likely target of the bicoid-related transcription factor PITX1 previously implicated in clubfoot etiology. Our result suggests that this chromosome 17q23.1q23.2 microduplication is a relatively common cause of familial isolated clubfoot and provides strong evidence linking clubfoot etiology to abnormal early limb development. PMID:20598276

  11. The CAPN2/CAPN8 Locus on Chromosome 1q Is Associated with Variation in Serum Alpha-Carotene Concentrations.

    PubMed

    D'Adamo, Christopher R; Dawson, Valerie J; Ryan, Kathleen A; Yerges-Armstrong, Laura M; Semba, Richard D; Steinle, Nanette I; Mitchell, Braxton D; Shuldiner, Alan R; McArdle, Patrick F

    2016-01-01

    Alpha-carotene is a provitamin A carotenoid present in fruits and vegetables. Higher serum concentrations of α-carotene have been associated with lower risk of cancer and all-cause mortality. Previous studies have suggested that genetic variants influence serum concentrations of provitamin A carotenoids, but to date no variants have been robustly associated with serum α-carotene concentrations. The aim of this study was to identify genetic associations with serum α-carotene concentrations using the genome-wide association study (GWAS) approach. A GWAS of serum α-carotene concentrations was conducted in 433 Old Order Amish adults who had consumed a 6-day controlled diet. Linear regression models adjusting for age, gender, and family structure were utilized to evaluate associations between genetic variants and serum α-carotene concentrations. Genome-wide significant associations with α-carotene concentrations were observed for loci on chromosome 1q41 between the genes CAPN2 and CAPN8 (rs12137025, p = 3.55 × 10-8), chromosome 2p21 in PRKCE (rs2594495, p = 1.01 × 10-8), and chromosome 4q34 (rs17830069, p = 2.89 × 10-8). We identified 3 novel loci associated with serum α-carotene concentrations among a population that consumed a controlled diet. While replication is necessary, the CAPN2/CAPN8 locus provides compelling evidence for an association with serum α-carotene concentrations and may suggest a relationship with the development and progression of cancers. © 2016 S. Karger AG, Basel.

  12. A prenatally ascertained de novo terminal deletion of chromosomal bands 1q43q44 associated with multiple congenital abnormalities in a female fetus.

    PubMed

    Sismani, Carolina; Christopoulou, Georgia; Alexandrou, Angelos; Evangelidou, Paola; Donoghue, Jacqueline; Konstantinidou, Anastasia E; Velissariou, Voula

    2015-01-01

    Terminal deletions in the long arm of chromosome 1 result in a postnatally recognizable disorder described as 1q43q44 deletion syndrome. The size of the deletions and the resulting phenotype varies among patients. However, some features are common among patients as the chromosomal regions included in the deletions. In the present case, ultrasonography at 22 weeks of gestation revealed choroid plexus cysts (CPCs) and a single umbilical artery (SUA) and therefore amniocentesis was performed. Chromosomal analysis revealed a possible terminal deletion in 1q and high resolution array CGH confirmed the terminal 1q43q44 deletion and estimated the size to be approximately 8 Mb. Following termination of pregnancy, performance of fetopsy allowed further clinical characterization. We report here a prenatal case with the smallest pure terminal 1q43q44 deletion, that has been molecularly and phenotypically characterized. In addition, to our knowledge this is the first prenatal case reported with 1q13q44 terminal deletion and Pierre-Robin sequence (PRS). Our findings combined with review data from the literature show the complexity of the genetic basis of the associated syndrome.

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

    PubMed

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

    2015-03-01

    To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. 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. 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. 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.

  14. 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

  15. Chromosome 1q loss of heterozygosity frequently occurs in sporadic insulinomas and is associated with tumor malignancy.

    PubMed

    Yang, Ying-Mai; Liu, Tong-Hua; Chen, Yuan-Jia; Jiang, Wei-Jun; Qian, Jia-Ming; Lu, Xin; Gao, Jie; Wu, Sha-Fei; Sang, Xin-Ting; Chen, Jie

    2005-11-01

    The pathogenesis of sporadic insulinomas is not clear, and there are no reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor. It was reported that 1q LOH might contribute to pathogenesis in gastrinomas and was correlated with tumor progression. However, little data are available on 1q LOH in sporadic insulinomas. In our study, we determine whether 1q LOH occurs in sporadic insulinomas and is associated with tumor malignancy by performing 1q allelotyping with 17 markers in 40 tumors and pair normal DNA. Thirty-five (88%) insulinomas had 1q LOH. Of the 35 insulinomas with 1q LOH, 14 (40%) had 1q21.3-23.2 LOH over a 7.5 cM region (SRO-1), whereas LOH in 21 tumors (60%) occurred at 1q31.3 over an 11.4 cM area (SRO-2). Of 24 tumors without MEN1 LOH, 20 had either SRO-1 or SRO-2 LOH (83%), whereas in 16 tumors with MEN1 LOH, 9 were shown to have LOH at either SRO-1 or SRO-2 (56%) (p = 0.065). This result suggests that LOH at 2 SRO might be MEN1 gene independent and may contribute to the pathogenesis in a subset of insulinomas without MEN1 gene LOH. The presence of 1q21.3-23.2 LOH is significantly associated with malignancy of insulinomas (p = 0.014). The high frequency of LOH at 1q 21.3-23.2 and 1q31.3 suggests these 2 areas may harbor putative tumor suppressor genes that may play an important role in the tumorigenesis of a subset of insulinomas. LOH at 1q21.3-23.2, which was associated with tumor malignancy, could be one of the genetic markers for identifying malignancy in sporadic insulinomas.

  16. FISH-Based Analysis of Clonally Derived CHO Cell Populations Reveals High Probability for Transgene Integration in a Terminal Region of Chromosome 1 (1q13)

    PubMed Central

    Li, Shengwei; Gao, Xiaoping; Peng, Rui; Zhang, Sheng; Fu, Wei

    2016-01-01

    A basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. Here, we constructed engineered Chinese hamster ovary cell lines (CHO-S) with a pCHO-hVR1 vector that carried an extracellular domain of a VEGF receptor (VR) fusion gene. Forty-five clones with high hVR1 expression were selected for karyotype analysis. Using fluorescence in situ hybridization (FISH) and G-banding, we found that pCHO-hVR1 was integrated into three chromosomes, including chromosomes 1, Z3 and Z4. Four clones were selected to evaluate their productivity under non-fed, non-optimized shake flask conditions. The results showed that clones 1 and 2 with integration sites on chromosome 1 revealed high levels of hVR1 products (shake flask of approximately 800 mg/L), whereas clones 3 and 4 with integration sites on chromosomes Z3 or Z4 had lower levels of hVR1 products. Furthermore, clones 1 and 2 maintained their productivity stabilities over a continuous period of 80 generations, and clones 3 and 4 showed significant declines in their productivities in the presence of selection pressure. Finally, pCHO-hVR1 localized to the same region at chromosome 1q13, the telomere region of normal chromosome 1. In this study, these results demonstrate that the integration of exogenous hVR1 gene on chromosome 1, band q13, may create a high protein-producing CHO-S cell line, suggesting that chromosome 1q13 may contain a useful target site for the high expression of exogenous protein. This study shows that the integration into the target site of chromosome 1q13 may avoid the problems of random integration that cause gene silencing or also overcome position effects, facilitating exogenous gene expression in CHO-S cells. PMID:27684722

  17. FISH-Based Analysis of Clonally Derived CHO Cell Populations Reveals High Probability for Transgene Integration in a Terminal Region of Chromosome 1 (1q13).

    PubMed

    Li, Shengwei; Gao, Xiaoping; Peng, Rui; Zhang, Sheng; Fu, Wei; Zou, Fangdong

    A basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. Here, we constructed engineered Chinese hamster ovary cell lines (CHO-S) with a pCHO-hVR1 vector that carried an extracellular domain of a VEGF receptor (VR) fusion gene. Forty-five clones with high hVR1 expression were selected for karyotype analysis. Using fluorescence in situ hybridization (FISH) and G-banding, we found that pCHO-hVR1 was integrated into three chromosomes, including chromosomes 1, Z3 and Z4. Four clones were selected to evaluate their productivity under non-fed, non-optimized shake flask conditions. The results showed that clones 1 and 2 with integration sites on chromosome 1 revealed high levels of hVR1 products (shake flask of approximately 800 mg/L), whereas clones 3 and 4 with integration sites on chromosomes Z3 or Z4 had lower levels of hVR1 products. Furthermore, clones 1 and 2 maintained their productivity stabilities over a continuous period of 80 generations, and clones 3 and 4 showed significant declines in their productivities in the presence of selection pressure. Finally, pCHO-hVR1 localized to the same region at chromosome 1q13, the telomere region of normal chromosome 1. In this study, these results demonstrate that the integration of exogenous hVR1 gene on chromosome 1, band q13, may create a high protein-producing CHO-S cell line, suggesting that chromosome 1q13 may contain a useful target site for the high expression of exogenous protein. This study shows that the integration into the target site of chromosome 1q13 may avoid the problems of random integration that cause gene silencing or also overcome position effects, facilitating exogenous gene expression in CHO-S cells.

  18. Mosaic trisomy 1q: a recurring chromosome anomaly that is a diagnostic challenge and is associated with a Fryns-like phenotype.

    PubMed

    Bone, Kathleen M; Chernos, Judy E; Perrier, Renee; Innes, A Micheil; Bernier, Francois P; McLeod, Ross; Thomas, Mary Ann

    2017-06-01

    Trisomy of the long arm of chromosome 1 is a very rare cytogenetic anomaly that is difficult to diagnose because of tissue-limited mosaicism. This study aimed to further characterize the prenatal and post-natal findings associated with this anomaly, including the first reported chromosomal microarray finding. This is a retrospective study of six cases of mos 46,X,der(Y)t(Y;1)(q12;q21)/46,XY, diagnosed both prenatally and post-natally. Detailed clinical features and pregnancy outcome were documented. Recurrent prenatal and post-natal features of our case series, as well as the previously reported cases, were described, suggesting a Fryns-like phenotype. A diagnosis of mosaic trisomy 1q is difficult to confirm post-natally in some cases because of the tissue provided for analysis, emphasizing the need to study multiple tissue types in cases of fetal loss with a suspected underlying chromosomal imbalance. The overlap of clinical features between mosaic trisomy 1q and Fryns syndrome emphasizes the need to obtain appropriate samples for genetic analysis. The present cases and a review of the literature suggest that partial trisomy of the long arm of chromosome 1 is a distinct de novo clinical entity with low recurrence risk. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

  19. 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma

    PubMed Central

    Fournier, Alexandra; McLeer-Florin, Anne; Lefebvre, Christine; Duley, Samuel; Barki, Leila; Ribeyron, Juliana; Kassambara, Alboukadel; Hamaidia, Sieme; Granjon, Aurélie; Gressin, Rémy; Lajmanovich, Alicia; Bonnefoix, Thierry; Chauvelier, Stéphanie; Debernardi, Alexandra; Rousseaux, Sophie; de Fraipont, Florence; Figeac, Martin; Kerckaert, Jean-Pierre; De Vos, John; Usson, Yves; Delaval, Katia; Grichine, Alexei; Vourc'h, Claire; Khochbin, Saadi; Feil, Robert; Leroux, Dominique; Callanan, Mary B

    2010-01-01

    Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence that a distinct category of chromosomal translocations observed in human tumours—those targeting 1q12 satellite DNA—can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localized to the nuclear periphery and to arise as a consequence of long range ‘pairing’ between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localization and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in diffuse large B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression via long range epigenetic mechanisms. PMID:20432501

  20. Significance of complement components C1q and C4 bound to circulating immune complexes in juvenile idiopathic arthritis: support for classical complement pathway activation.

    PubMed

    Gilliam, Brooke E; Reed, Melinda R; Chauhan, Anil K; Dehlendorf, Amanda B; Moore, Terry L

    2011-01-01

    Immune complexes (ICs) from sera of juvenile idiopathic arthritis (JIA) patients show increased complement opsonisation; however, a definitive role for involvement of the classical or alternative pathway is not entirely clear. To delineate the role of these pathways, we measured activated complement products bound to circulating IC (CICs) in the sera of JIA patients. Sera from 100 JIA patients and 22 healthy children were collected. C1q, C4, C3, C3d, and membrane attack complex (MAC) bound to CICs were measured by enzyme-linked immunosorbent assay. Data was compared to IgM rheumatoid factor (RF), IgG anti-cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels. Mean levels of C1q, C4, and MAC bound to CICs were significantly elevated in JIA patients compared to healthy children. C1q correlated significantly with C4 and MAC bound to CICs and C4 and MAC also demonstrated significant correlation. No significant differences were noted in complement components bound to CICs when evaluating IgM RF, anti-CCP antibody, and CRP positivity. A significant correlation was noted between MAC bound to CICs and ESR. C1q and MAC bound to CICs mean levels were significantly higher in patients with an elevated ESR compared to those with a normal ESR level. JIA patients have elevated levels of complement components bound to CICs, particularly from the classical pathway. Moreover, classical pathway components were associated with ESR, a marker of disease activity. MAC bound to CICs also correlated significantly with ESR, further supporting the notion of complement-mediated tissue injury that is triggered by IC-mediated classical pathway activation.

  1. Linkage Analyses at the Chromosome 1 Loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in Families with Hereditary Prostate Cancer

    PubMed Central

    Berry, Rebecca; Schaid, Daniel J.; Smith, Jeffrey R.; French, Amy J.; Schroeder, Jennifer J.; McDonnell, Shannon K.; Peterson, Brett J.; Wang, Zheng-Yuan; Carpten, John D.; Roberts, Steven G.; Tester, David J.; Blute, Michael L.; Trent, Jeffrey M.; Thibodeau, Stephen N.

    2000-01-01

    Summary Recent studies suggest that hereditary prostate cancer (PRCA) is a complex disease, involving multiple susceptibility genes and variable phenotypic expression. Through linkage analysis, potential prostate cancer susceptibility loci have been mapped to 3 regions on chromosome 1. To investigate the reported linkage to these regions, we conducted linkage studies on 144 PRCA families by using microsatellite markers in regions 1q24-25 (HPC1) and 1q42.2-43 (PCAP). We also examined the 1p36 (CAPB) region in 13 PRCA families with at least one case of brain cancer. No significant evidence of linkage to the HPC1 or PCAP region was found when the entire data set was analyzed. However, weak evidence for linkage to HPC1 was observed in the subset of families with male-to-male transmission (n=102; maximum multipoint nonparametric linkage [NPL] 1.99, P=.03). Weak evidence for linkage with heterogeneity within this subset was also observed (HLOD 1.21, P=.02), with ∼20% of families linked. Although not statistically significant, suggestive evidence for linkage to PCAP was observed for the families (n=21) that met the three criteria of male-to-male transmission, average age of diagnosis <66 years, and ⩾5 affected individuals (maximum multipoint NPL 1.45, P=.08). There was no evidence for linkage to CAPB in the brain cancer–prostate cancer subset. These results strengthen the argument that prostate cancer is a heterogeneous disease and that multiple genetic and environmental factors may be important for its etiology. PMID:10677314

  2. 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.

  3. Characterization of two ectrodactyly-associated translocation breakpoints separated by 2.5 Mb on chromosome 2q14.1-q14.2.

    PubMed

    David, Dezso; Marques, Bárbara; Ferreira, Cristina; Vieira, Paula; Corona-Rivera, Alfredo; Ferreira, José Carlos; van Bokhoven, Hans

    2009-08-01

    Split hand-split foot malformation or ectrodactyly is a heterogeneous congenital defect of digit formation. The aim of this study is the mapping of the breakpoints and a detailed molecular characterization of the candidate genes for an isolated and syndromic form of ectrodactyly, both associated with de novo apparently balanced chromosome translocations involving the same chromosome 2 band, [t(2;11)(q14.2;q14.2)] and [t(2;4)(q14.1;q35)], respectively. Breakpoints were mapped by fluorescence in situ hybridization using bacterial artificial chromosome clones. Where possible, these breakpoints were further delimited. Candidate genes were screened for pathogenic mutations and the expression levels of two of them analysed. The isolated bilateral split foot malformation-associated chromosome 2 breakpoint was localized at 120.9 Mb, between the two main candidate genes, encoding GLI-Kruppel family member GLI2 and inhibin-betaB. The second breakpoint associated with holoprosencephaly, hypertelorism and ectrodactyly syndrome was mapped 2.5 Mb proximal at 118.4 Mb and the candidate genes identified from this region were the insulin-induced protein 2 and the homeobox protein engrailed-1. No clear pathogenic mutations were identified in any of these genes. The breakpoint between INHBB and GLI2 coincides with a previously identified translocation breakpoint associated with ectrodactyly. We propose a mechanism by which translocations in the 2q14.1-q14.2 region disrupt the specific arrangement of long-range regulatory elements that control the tight quantitative spatiotemporal expression of one or more genes from the breakpoint region.

  4. 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

  5. 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.

  6. Chlorambucil induced chromosome damage in juvenile chronic arthritis.

    PubMed Central

    Palmer, R G; Varonos, S; Doré, C J; Denman, A M; Ansell, B M

    1985-01-01

    Sister chromatid exchanges, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 23 patients with juvenile chronic arthritis receiving long term, low dose chlorambucil treatment. Thirty five patients with juvenile chronic arthritis who had not been treated with cytotoxic drugs served as controls. All of the treated patients have cells with abnormal sister chromatid exchange frequencies. Damage is related to the daily dose and may, in part, be determined by the duration of treatment. Sister chromatid exchanges from nine patients who had received chlorambucil at some time in the past remained high for at least five months after stopping the drug. Long term follow up will determine whether sister chromatid exchange analysis can help predict those most at risk of drug induced malignancies. Images Fig. 1 PMID:4073932

  7. 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.

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

    PubMed

    Belmouden, A; Adam, M F; Dupont de Dinechin, S; Brézin, A P; Rigault, P; Chumakov, I; Bach, J F; Garchon, H J

    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 (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene.

  9. Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer.

    PubMed Central

    Gibbs, M; Chakrabarti, L; Stanford, J L; Goode, E L; Kolb, S; Schuster, E F; Buckley, V A; Shook, M; Hood, L; Jarvik, G P; Ostrander, E A

    1999-01-01

    One hundred fifty-two families with prostate cancer were analyzed for linkage to markers spanning a 20-cM region of 1q42.2-43, the location of a putative prostate cancer-susceptibility locus (PCAP). No significant evidence for linkage was found, by use of both parametric and nonparametric tests, in our total data set, which included 522 genotyped affected men. Rejection of linkage may reflect locus heterogeneity or the confounding effects of sporadic disease in older-onset cases; therefore, pedigrees were stratified into homogeneous subsets based on mean age at diagnosis of prostate cancer and number of affected men. Analyses of these subsets also detected no significant evidence for linkage, although LOD scores were positive at higher recombination fractions, which is consistent with the presence of a small proportion of families with linkage. The most suggestive evidence of linkage was in families with at least five affected men (nonparametric linkage score of 1.2; P=.1). If heterogeneity is assumed, an estimated 4%-9% of these 152 families may show linkage in this region. We conclude that the putative PCAP locus does not account for a large proportion of these families with prostate cancer, although the linkage of a small subset is compatible with these data. PMID:10090894

  10. Duplication at chromosome 2q31.1-q31.2 in a family presenting syndactyly and nystagmus.

    PubMed

    Ghoumid, Jamal; Andrieux, Joris; Sablonnière, Bernard; Odent, Sylvie; Philippe, Nathalie; Zanlonghi, Xavier; Saugier-Veber, Pascale; Bardyn, Thomas; Manouvrier-Hanu, Sylvie; Holder-Espinasse, Muriel

    2011-11-01

    HOXD genes encode transcription factors involved in the antero-posterior patterning of the limb bud and in the specification of fingers. During the embryo development, HOXD genes are expressed, following a spatio-temporal colinearity that involves at least three regions, centrometric and telomeric to this cluster. Here, we describe a father and a daughter presenting a 3-4 hand bilateral syndactyly associated with a nystagmus. Array-comparative genomic hybridisation showed a 3.8 Mb duplication at 2q31.1-q31.2, comprising 27 genes including the entire HOXD cluster. We performed expression studies in lymphoblasts by reverse transcription-PCR and observed an HOXD13 and HOXD10 overexpression, whereas the HOXD12 expression was decreased. HOXD13 and HOXD10 overexpression, associated with a misregulation of at least HOXD12, may therefore induce the syndactyly. Deletions of the HOXD cluster and its regulatory sequences induce hand malformations and, particularly, finger anomalies. Recently, smaller duplications of the same region have been reported in association with a mesomelic dysplasia, type Kantaputra. We discuss the variable phenotypes associated with such 2q duplications.

  11. Distribution of T1, Q, Pegasus and mariner transposable elements on the polytene chromosomes of PEST, a standard strain of Anopheles gambiae.

    PubMed

    Mukabayire, O; Besansky, N J

    1996-06-01

    The chromosomal locations of four families of transposable elements, T1, Q, Pegasus and mariner, have been determined by in situ hybridization to polytene chromosomes of ovarian nurse cells of the mosquito Anopheles gambiae. As part of this effort, we have developed a vigorous pink-eyed laboratory strain of A. gambiae (PEST), rendered homozygous standard for chromosomal inversions on all autosomes. Ten different individuals of this strain were studied with each transposable element probe. The average number of hybridization sites per genome was 83.9 for T1, 63.4 for Q, 31.5 for Pegasus and 64.7 for mariner, excluding pericentric and centromeric regions. However, some degree of polymorphism was observed within each family such that, considering all ten individuals, 94 different sites were detected for T1, 82 sites for Q, 45 sites for Pegasus and 71 sites for mariner. The mean occupancy per site varied from 0.70 (Pegasus) to 0.91 (mariner), which, while significantly higher than that seen for transposable elements in natural populations of Drosophila melanogaster, is comparable to that seen in established laboratory stocks. In addition, these element families were not randomly distributed. All but Pegasus were concentrated in centromeric heterochromatin and centromere-proximal euchromatin, most showed a deficit of hybridization sites in the distal section of chromosomes, and a significant proportion of sites were coincident between families. These results provide the first detailed examination of the cytogenetic location of transposable elements in a nondrosophilid insect, and, through comparison with the behavior of transposable elements in Drosophila, may provide insight into the interaction between elements and host. The mapped elements are also expected to serve as landmarks useful in integrating the developing physical map of the PEST strain with the chromosomal banding pattern.

  12. Calsquestrin 1 (CASQ1) gene polymorphisms under chromosome 1q21 linkage peak are associated with type 2 diabetes in Northern European Caucasians.

    PubMed

    Das, Swapan Kumar; Chu, Winston; Zhang, Zhengxian; Hasstedt, Sandra J; Elbein, Steven C

    2004-12-01

    Genome-wide scans in multiple populations have identified chromosome 1q21-q24 as one susceptibility region for type 2 diabetes. To map the susceptibility genes, we first placed a dense single nucleotide polymorphism (SNP) map across the linked region. We identified two SNPs that showed strong associations, and both mapped to within intron 2 of the calsequestrin 1 (CASQ1) gene. We tested the hypothesis that sequence variation in or near CASQ1 contributed to type 2 diabetes susceptibility in Northern European Caucasians by identifying additional SNPs from the public database and by screening the CASQ1 gene for additional variation. In addition to 15 known SNPs in this region, we found 8 new SNPs, 3 of which were in exons. A single rare nonsynonymous SNP in exon 11 (A348V) was not associated with type 2 diabetes. The associated SNPs were localized to the region between -1,404 in the 5' flanking region and 2,949 in intron 2 (P = 0.002 to P = 0.034). No SNP 3' to intron 2, including the adjacent gene PEA15, showed an association. The strongest associations were restricted to individuals of Northern European ancestry ascertained in Utah. A six-marker haplotype was also associated with type 2 diabetes (P = 0.008), but neither transmission disequilibrium test nor family-based association studies were significant for the most strongly associated SNP in intron 2 (SNP CASQ2312). An independent association of SNPs in introns 2 and 4 with type 2 diabetes is reported in Amish families with linkage to chromosome 1q21-q24. Our findings suggest that noncoding SNPs in CASQ1 alter diabetes susceptibility, either by a direct effect on CASQ1 gene expression or perhaps by regulating a nearby gene such as PEA15.

  13. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

    PubMed Central

    Zhang, Mingfeng; Wang, Zhaoming; Obazee, Ofure; Jia, Jinping; Childs, Erica J.; Hoskins, Jason; Figlioli, Gisella; Mocci, Evelina; Collins, Irene; Chung, Charles C.; Hautman, Christopher; Arslan, Alan A.; Beane-Freeman, Laura; Bracci, Paige M.; Buring, Julie; Duell, Eric J.; Gallinger, Steven; Giles, Graham G.; Goodman, Gary E.; Goodman, Phyllis J.; Kamineni, Aruna; Kolonel, Laurence N.; Kulke, Matthew H.; Malats, Núria; Olson, Sara H.; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Zheng, Wei; Abnet, Christian C.; Albanes, Demetrius; Andreotti, Gabriella; Brais, Lauren; Bueno-de-Mesquita, H. Bas; Basso, Daniela; Berndt, Sonja I.; Boutron-Ruault, Marie-Christine; Bijlsma, Maarten F.; Brenner, Hermann; Burdette, Laurie; Campa, Daniele; Caporaso, Neil E.; Capurso, Gabriele; Cavestro, Giulia Martina; Cotterchio, Michelle; Costello, Eithne; Elena, Joanne; Boggi, Ugo; Gaziano, J. Michael; Gazouli, Maria; Giovannucci, Edward L.; Goggins, Michael; Gross, Myron; Haiman, Christopher A.; Hassan, Manal; Helzlsouer, Kathy J.; Hu, Nan; Hunter, David J.; Iskierka-Jazdzewska, Elzbieta; Jenab, Mazda; Kaaks, Rudolf; Key, Timothy J.; Khaw, Kay-Tee; Klein, Eric A.; Kogevinas, Manolis; Krogh, Vittorio; Kupcinskas, Juozas; Kurtz, Robert C.; Landi, Maria T.; Landi, Stefano; Marchand, Le Loic; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L.; Neale, Rachel E.; Oberg, Ann L.; Panico, Salvatore; Patel, Alpa V.; Peeters, Petra H. M.; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Purdue, Mark; Quiros, J. Ramón; Riboli, Elio; Rothman, Nathaniel; Scarpa, Aldo; Scelo, Ghislaine; Shu, Xiao-Ou; Silverman, Debra T.; Soucek, Pavel; Strobel, Oliver; Sund, Malin; Małecka-Panas, Ewa; Taylor, Philip R.; Tavano, Francesca; Travis, Ruth C.; Thornquist, Mark; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Vashist, Yogesh; Vodicka, Pavel; Wactawski-Wende, Jean; Wentzensen, Nicolas; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Kooperberg, Charles; Risch, Harvey A.; Jacobs, Eric J.; Li, Donghui; Fuchs, Charles; Hoover, Robert; Hartge, Patricia; Chanock, Stephen J.; Petersen, Gloria M.; Stolzenberg-Solomon, Rachael S.; Wolpin, Brian M.; Kraft, Peter; Klein, Alison P.; Canzian, Federico; Amundadottir, Laufey T.

    2016-01-01

    Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10−15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10−9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10−8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10−8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10−4-2.0×10−3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology. PMID:27579533

  14. Human cardiac troponin T: Identification of fetal isoforms and assignment of the TNNT2 locus to chromosome 1q

    SciTech Connect

    Townsend, P.J.; Farza, H.; Yacoub, M.H.; Barton, P.J.R. ); MacGeoch, C.; Spurr, N.K. ); Wade, R. ); Gahlmann, R. )

    1994-05-15

    The troponin complex is located on the thin filament of striated muscle and is composed of three component polypeptides: Troponin T, troponin I, and troponin C. Three troponin T genes have been described on the basis of molecular cloning in humans and other vertebrates. These are expressed in a tissue-specific manner and encode the troponin T isoforms expressed in cardiac muscle, slow skeletal muscle, and fast skeletal muscle, respectively. Each of these genes is subject to alternative splicing, resulting in the production of multiple tissue-specific isoforms. The authors have cloned cDNAs encoding human cardiac troponin T from adult heart and have used these to demonstrate that multiple cardiac troponin T mRNAs are present in the human fetal heart, resulting from alternative splicing in the 5[prime] coding region of the gene. Hybridization of the cloned cDNAs to genomic DNA identifies a single-copy gene, and using somatic cell hybrid analysis, the authors have mapped the corresponding gene locus (designated TNNT2) to the long arm of chromosome 1 (1cen-qter). 52 refs., 2 figs., 1 tab.

  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. Genome-wide scan for hypertension linkage to chromosome 12q23.1 - q23.3 in a Chinese family.

    PubMed

    Dong, Yan; Yang, Lin; Fang, Fang; Zhang, Jing; Jiang, Gengru; Xu, Shijie

    2013-05-01

    Essential hypertension is a multifactorial disorder with a complex phenotype. Here we report a susceptibility locus for the hypertension mapped by a genome-wide microsatellite scanning in an affected Chinese family, in which 11 members had hypertension before the age of 40. A total of 22 individuals from a single family from Shanghai, PR China, were genotyped on more than 400 microsatellite markers with a spacing gap of less than 10 cm for nearly the entire scanned genome. Linkage analysis suggested that an affected disorder is linked to a locus in the chromosome interval 12q23.1 to 12q23.3; two-point parametric analysis showed a logarithm of odds (LOD) score of 2.97 for the marker D12S346 (12q23.1) and 1.40 for the marker D12S78 (12q23.3). Fine mapping and haplotype analysis subsequently confirmed that eight continuous markers (D12Sac023161, D12S1706, D12S346, D12S1588, D12S1607, D12Sac010202, D12S78, D12Sac084356) had positive LOD with a maximum two-point LOD score of 3.34 for the marker D12S1706 and a maximum multi-point LOD score was 2.4002 for D12Sac010202, their NPL scores were 10.9091 for D12S1706 and 10.9114 for D12Sac010202. A novel locus for essential hypertension was identified on chromosome 12q23.1 - q23.3. This finding implies that the region 12q23.1 to 12q23.3 might encompass a susceptible gene that caused hypertension in this Chinese family.

  17. Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21

    SciTech Connect

    McKinley-Grant, L.J.; Idler, W.W.; Bernstein, I.A.; Parry, D.A.D.; Cannizzaro, L.; Croce, C.M.; Huebner, K.; Lessin, S.R.; Steinert, P.M. )

    1989-07-01

    Filaggrins are an important class of intermediate filament-associated proteins that interact with keratin intermediate filaments of terminally differentiating mammalian epidermis. They show wide species variations and their aberrant expression has been implicated in a number of keratinizing disorders. The authors have isolated a cDNA clone encoding human filaggrin and used this to demonstrate that the human gene encodes a polyprotein precursor containing numerous tandem filaggrin repeats. This structure is similar to that of mouse; however, the human filaggrin repeat is much longer (972 base pairs; 324 amino acids) and shows little sequence homology to the mouse protein. Also, data presented here reveal that the human filaggrin repeats show considerable sequence variations; such polymorphism is not found in the mouse. Furthermore, chromosomal mapping data revealed that the human gene is located at 1q21, indicating that the polymorphism is confined to a single locus. By peptide mapping, they define a short linker sequence within the human filaggrin repeat that is excised by proteolysis to yield functional molecules. Finally, they show by in situ hybridization that human filaggrin precursor gene expression is tightly regulated at the transcriptional level in terminally differentiating epidermis and that this represents a useful system in which to study intermediate filament-intermediate filament-associated protein interactions as well as disorders of keratinization.

  18. Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort.

    PubMed

    Azad, Taif A; Edward, Nikhil B; Kondkar, Altaf A; Kalantan, Hatem; Altuwaijri, Saleh; Sultan, Tahira; Al-Mobarak, Faisal A; Al-Obeidan, Saleh A; Abu-Amero, Khaled K

    2017-06-26

    To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG). Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin. Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor "A" allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases. Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.

  19. 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.

  20. FISH analysis of 1cen-1q12 breakage, chromosome 1 numerical abnormalities and centromeric content of micronuclei in buccal cells from thyroid cancer and hyperthyroidism patients treated with radioactive iodine.

    PubMed

    Ramírez, M J; Surrallés, J; Galofré, P; Creus, A; Marcos, R

    1999-01-01

    One of the health consequences of the Chernobyl nuclear power plant accident was a radioactive iodine-related increase in the incidence of thyroid cancer in exposed children. This radioisotope is used in the treatment of thyroid cancer and hyperthyroidism patients providing a convenient opportunity to study cytogenetic damage induced by known doses of radioactive iodine in treated patients. We used pancentromeric FISH on micronuclei and chromosome 1 tandem labelling FISH to monitor overall chromosome breakage and loss, 1q12 breakage and decondensation and chromosome 1 numerical abnormalities in buccal cells from 31 radioactive iodine-exposed hyperthyroidism and thyroid cancer patients. The overall outcome of the study, with 250,000 buccal cells analysed, is that there was no radioactive iodine-related increase in the frequency of micronuclei, 1q12 breakage, 1q12 decondensation or chromosome 1 numerical abnormalities. In addition, neither age nor gender, health status nor radioactive iodine dose modulated the frequency of the above cytogenetic end points. Although several uncertainties of these emerging molecular cytogenetic methodologies will require further experimentation, we conclude that, at the reported exposure levels, radioactive iodine did not induce detectable chromosome damage in buccal cells from treated patients.

  1. The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type IIa (USH2A) gene in 1q41

    SciTech Connect

    Sumegi, Janos; Wang, Ji-Yi; Zhen, Dong-Kai

    1996-07-01

    The gene for Usher syndrome type II (USH2A), and autosomal recessive syndromic deafness, has been mapped to a region of 1q41 flanked proximally by D1S217 and distally by D1S439. Using sequence-tagged sites (STSs) within the region, a total of 21 yeast artificial chromosome (YAC) clones were isolated and ordered into a single contig that spans approximately 11.0 Mb. The order of microsatellite and STS markers in this region was established as D1S505-D1S425-DXS217-D1S556-D1S237-D1S474-EB1-KB6-AFM144XF2-KB1-KB4-D1S229-D1S490-D1S227-TGF{beta}2-D1S439. Analysis of newly positioned polymorphic markers in recombinant individuals in two Usher syndrome type IIa families has enabled us to identify DXS474 and AFM144XF2 as two flanking markers for the Usher type IIa locus. The physical distance between the two markers is 1.0 Mb. This region is covered by eight YACs from the CEPH library: 945f7, 867g9, 762a6, 919h3, 794b8, 785h4, 848b9, and 841g2. A long range physical map of the Usher type IIa critical region, using MluI, BssHII, NotI, EagI, and SacII, has been developed. 41 refs., 5 figs.

  2. Connexin 50 gene on human chromosome 1q21 is associated with schizophrenia in matched case–control and family‐based studies

    PubMed Central

    Ni, Xingqun; Valente, Jose; Azevedo, Maria H; Pato, Michelle T; Pato, Carlos N; Kennedy, James L

    2007-01-01

    Background The gap junction subunit connexin permits direct intercellular exchange of ions and molecules including glutamate, and plays an important role in the central nervous system. The connexin 40 (Cx40) and connexin 50 (Cx50) genes are located on chromosome 1q21.1, a region strongly linked with schizophrenia. These lines of evidence suggest that Cx40 and Cx50 may play a role in schizophrenia. Methods Using an allele‐specific PCR assay, four polymorphisms each were genotyped for Cx40 and Cx50 in 190 Caucasian patients with schizophrenia and 190 controls matched for sex, age and ethnicity. Following up, Cx50 rs989192 and rs4950495 were investigated in 99 Canadian and 163 Portuguese trios and nuclear families with schizophrenia probands. Hardy–Weinberg equilibrium and linkage disequilibrium (LD) block identification was carried out with HaploView, and association analysis for alleles and haplotypes with a permutation test of 10 000 simulations was carried out using the UNPHASED software program. Results Distributions of genotype frequencies of all markers were in Hardy–Weinberg equilibrium in Caucasian patients, controls and families. One rs989192‐rs4950495 LD block was found in patients but not in controls. We found a significant association between the Cx50 rs989192‐rs4950495 haplotype and schizophreniay (χ2 = 29.55, p<0.01). The A‐C haplotype had a higher frequency in patients (χ2 = 7.153, p<0.01). Family studies also showed that the A‐C haplotype was transmitted more often to patients with schizophrenia (χ2 = 8.43, p<0.01). No association of Cx40 with schizophrenia was found for allele, genotype or haplotype analyses. Conclusions Our matched case–control and family study indicate that Cx50, but not Cx40, may play a role in the genetic susceptibility to schizophrenia. PMID:17412882

  3. Evidence for a novel autosomal dominant retinitis pigmentosa linked to chromosome 1p22.1-q12 in a Chinese family.

    PubMed

    Yuan, Yuan; Zhou, Xin; Wang, Fei; Yan, Min; Ding, Feng

    2011-02-01

    To identify the causative genetic locus in a Chinese autosomal dominant retinitis pigmentosa (adRP) family that contained seven affected members in three generations. After clinical diagnosis and exclusion of all mapped genes and loci, the SLINK program was used to simulate the maximum logarithm of the likelihood ratio (LOD) score for a linkage study in this small family. A genome-wide scan was performed using microsatellite markers at 10 cM intervals. Two-point and multipoint LOD scores were calculated, and haplotypes were constructed. The H11 family clinical presentation included an early onset of night blindness, a progressive loss of the peripheral visual field, typical retinitis pigmentosa (RP) fundus changes, and a cataract complication. A maximum two-point LOD score of 2.54 (θ = 0) was found at markers D1S2739, D1S457, D1S187, D1S189, and D1S305, and multipoint linkage analysis yielded a maximum LOD score of 2.54 for marker D1S187. These LOD scores were the closest to the maximum simulated LOD score. Haplotype analysis revealed that this form of adRP segregates with a 38.25 cM region that spanned 50 Mb on chromosome 1p22.1-q12. Although this locus overlaps the RP19 locus caused by mutations in ABCA4 and the RP32 locus, both are inherited in an autosomal recessive mode rather than the autosomal dominant mode of inheritance found in the H11 family. The identification of this potential new locus for adRP further confirms the high level of heterogeneity for RP.

  4. 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.

  5. 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).

    PubMed Central

    Fukai, K.; Oh, J.; Karim, M. A.; Moore, K. J.; Kandil, H. H.; Ito, H.; Bürger, J.; Spritz, R. A.

    1996-01-01

    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. PMID:8751863

  6. Chromosomal micro-aberration in a Saudi family with Juvenile myoclonic epilepsy.

    PubMed

    Naseer, Muhammad Imran; Chaudhary, Adeel G; Sogaty, Sameera; Rasool, Mahmood; Karim, Sajjad; Schulten, Hans-Juergen; Bibi, Fehmida; Pushparaj, Peter Natesan; Algahtani, Hussein A; Al-Qahtani, Mohammad H

    2017-07-31

    Epilepsy is genetically complex neurological disorder affecting millions of people of the world. Juvenile myoclonic epilepsy (JME) is a most common epilepsy syndromes that starts in the teen age group commonly between ages 12 and 18, and lasts into adulthood. Out of 14 people with epilepsy one suffer with JME. Myoclonic seizures and muscle twitching or uncontrolled jerking are the most common type of seizure in the people suffering with JME. To observe the novel CNVs involved in JME we investigated a Saudi family with nine siblings with one male and one female affected members. In this study we used high density whole genome Agilent sure print G3 Hmn CGH 2x 400K array-CGH chips. Our results showed CNVs including the amplifications and deletions in different chromosomal regions in the patients as compared to the normal members of the family. Amplifications were observed in the chromosome 22 cytoband 22q11.23 with LDL receptor related protein 5 like (LRP5L), Immunoglobulin Lambda-Like Polypeptide 3 (IGLL3) and crystallin beta B2 pseudogene (CRYBB2P) genes respectively whereas the deletions were observed in the chromosomal regions 4q22.2 with Glutamate receptor, ionotropic, delta 2 (GRID2) as potential gene cytoband 1p31.1 with potential Neuronal Growth Regulator 1 gene (NEGR1) gene in this region and NME/NM23 family member (NME7) gene cytoband 1q24. Moreover, the array CGH results deletions and duplication were also validated by using primer for simple PCR or also by using quantitative real time PCR analysis. We found deletions and duplication in JME patients in our study for the first time in Saudi population. Our results suggest that array-CGH should be considered as a first line genetic test for epilepsy unless there is a strong evidence for a specific monogenic syndrome. The use of high throughput technique in this study will help to identify novel mechanisms underlying epileptic disorder in order to lowering the burden of epilepsy in Saudi Arabia. Copyright

  7. 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.

  8. Linkage and association mapping of a chromosome 1q21-q24 type 2 diabetes susceptibility locus in northern European Caucasians.

    PubMed

    Das, Swapan Kumar; Hasstedt, Sandra J; Zhang, Zhengxian; Elbein, Steven C

    2004-02-01

    We have identified a region on chromosome 1q21-q24 that was significantly linked to type 2 diabetes in multiplex families of Northern European ancestry and also in Pima Indians, Amish families, and families from France and England. We sought to narrow and map this locus using a combination of linkage and association approaches by typing microsatellite markers at 1.2 and 0.5 cM densities, respectively, over a region of 37 cM (23.5 Mb). We tested linkage by parametric and nonparametric approaches and association using both case-control and family-based methods. In the 40 multiplex families that provided the previous evidence for linkage, the highest parametric, recessive logarithm of odds (LOD) score was 5.29 at marker D1S484 (168.5 cM, 157.5 Mb) without heterogeneity. Nonparametric linkage (NPL) statistics (P = 0.00009), SimWalk2 Statistic A (P = 0.0002), and sib-pair analyses (maximum likelihood score = 6.07) all mapped to the same location. The one LOD CI was narrowed to 156.8-158.9 Mb. Under recessive, two-point linkage analysis, adjacent markers D1S2675 (171.5 cM, 158.9 Mb) and D1S1679 (172 cM, 159.1 Mb) showed LOD scores >3.0. Nonparametric analyses revealed a second linkage peak at 180 cM near marker D1S1158 (163.3 Mb, NPL score 3.88, P = 0.0001), which was also supported by case-control (marker D1S194, 178 cM, 162.1 Mb; P = 0.003) and family-based (marker ATA38A05, 179 cM, 162.5 Mb; P = 0.002) association studies. We propose that the replicated linkage findings actually encompass at least two closely spaced regions, with a second susceptibility region located telomeric at 162.5-164.7 Mb.

  9. Allelic expression imbalance screening of genes in chromosome 1q21-24 region to identify functional variants for Type 2 diabetes susceptibility.

    PubMed

    Mondal, Ashis K; Sharma, Neeraj K; Elbein, Steven C; Das, Swapan K

    2013-07-02

    Type 2 diabetes (T2D)-associated SNPs are more likely to be expression quantitative trait loci (eQTLs). The allelic expression imbalance (AEI) analysis is the measure of relative expression between two allelic transcripts and is the most sensitive measurement to detect cis-regulatory effects. We performed AEI screening to detect cis-regulators for genes expressed in transformed lymphocytes of 190 Caucasian (CA) and African American (AA) subjects to identify functional variants for T2D susceptibility in the chromosome 1q21-24 region of linkage. Among transcribed SNPs studied in 115 genes, significant AEI (P < 0.001) occurred in 28 and 30 genes in CA and AA subjects, respectively. Analysis of the effect of selected AEI-SNPs (≥10% mean AEI) on total gene expression further established the cis-eQTLs in thioesterase superfamily member-4 (THEM4) (rs13320, P = 0.027), and IGSF8 (rs1131891, P = 0.02). Examination of published genome-wide association data identified significant associations (P < 0.01) of three AEI-SNPs with T2D in the DIAGRAM-v3 dataset. Six AEI single nucleotide polymorphisms, including rs13320 (P = 1.35E-04) in THEM4, were associated with glucose homeostasis traits in the MAGIC dataset. Evaluation of AEI-SNPs for association with glucose homeostasis traits in 611 nondiabetic subjects showed lower AIRG (P = 0.005) in those with TT/TC genotype for rs13320. THEM4 expression in adipose was higher (P = 0.005) in subjects carrying the T allele; in vitro analysis with luciferase construct confirmed the higher expression of the T allele. Resequencing of THEM4 exons in 192 CA subjects revealed four coding nonsynonymous variants, but did not explain transmission of T2D in 718 subjects from 67 Caucasian pedigrees. Our study indicates the role of a cis-regulatory SNP in THEM4 that may influence T2D predisposition by modulating glucose homeostasis.

  10. Allelic expression imbalance screening of genes in chromosome 1q21–24 region to identify functional variants for Type 2 diabetes susceptibility

    PubMed Central

    Mondal, Ashis K.; Sharma, Neeraj K.; Elbein, Steven C.

    2013-01-01

    Type 2 diabetes (T2D)-associated SNPs are more likely to be expression quantitative trait loci (eQTLs). The allelic expression imbalance (AEI) analysis is the measure of relative expression between two allelic transcripts and is the most sensitive measurement to detect cis-regulatory effects. We performed AEI screening to detect cis-regulators for genes expressed in transformed lymphocytes of 190 Caucasian (CA) and African American (AA) subjects to identify functional variants for T2D susceptibility in the chromosome 1q21–24 region of linkage. Among transcribed SNPs studied in 115 genes, significant AEI (P < 0.001) occurred in 28 and 30 genes in CA and AA subjects, respectively. Analysis of the effect of selected AEI-SNPs (≥10% mean AEI) on total gene expression further established the cis-eQTLs in thioesterase superfamily member-4 (THEM4) (rs13320, P = 0.027), and IGSF8 (rs1131891, P = 0.02). Examination of published genome-wide association data identified significant associations (P < 0.01) of three AEI-SNPs with T2D in the DIAGRAM-v3 dataset. Six AEI single nucleotide polymorphisms, including rs13320 (P = 1.35E-04) in THEM4, were associated with glucose homeostasis traits in the MAGIC dataset. Evaluation of AEI-SNPs for association with glucose homeostasis traits in 611 nondiabetic subjects showed lower AIRG (P = 0.005) in those with TT/TC genotype for rs13320. THEM4 expression in adipose was higher (P = 0.005) in subjects carrying the T allele; in vitro analysis with luciferase construct confirmed the higher expression of the T allele. Resequencing of THEM4 exons in 192 CA subjects revealed four coding nonsynonymous variants, but did not explain transmission of T2D in 718 subjects from 67 Caucasian pedigrees. Our study indicates the role of a cis-regulatory SNP in THEM4 that may influence T2D predisposition by modulating glucose homeostasis. PMID:23673729

  11. Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: Rationale for a new nomenclature of the S100 calcium-binding protein family

    SciTech Connect

    Schaefer, B.W.; Wicki, R.; Engelkamp, D.

    1995-02-10

    S100 proteins are low-molecular-weight calcium-binding proteins of the EF- hand superfamily and appear to be involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. More than 10 members of the S100 protein family have been described from human sources so far. We have now isolated a YAC clone from human chromosome 1q21, on which 9 different genes coding for S100 calcium-binding proteins could be localized. Moreover, we have mapped the gene coding for S100P to human chromosome 4p16 and thereby completed the chromosomal assignments of all known human S100 genes. The clustered organization of S100 genes in the 1q21 region allows us to introduce a new logical nomenclature for these genes, which is based on the physical arrangement on the chromosomes. The new nomenclature should facilitate the further the understanding of this protein family and be easily expandable to other species. 31 refs., 4 figs., 1 tab.

  12. Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature.

    PubMed

    Niida, Yo; Sato, Hitoshi; Ozaki, Mamoru; Itoh, Masatsune; Ikeno, Kanju; Takase, Etsuko

    2016-01-01

    Less than 1% of the cases with Angelman syndrome (AS) are caused by chromosomal rearrangements. This category of AS is not well defined and may manifest atypical phenotypes. Here, we report a girl with AS due to der(13)t(13;15)(q14.1;q12)mat. SNP array detected the precise deletion/duplication points and the parental origin of the 15q deletion. Multicolor FISH confirmed a balanced translocation t(13;15)(q14.1;q12) in her mother. Her facial appearance showed some features of dup(13)(pter→q14). Also, she lacked the most characteristic and unique behavioral symptoms of AS, i.e., frequent laughter, happy demeanor, and easy excitability. A review of the literature indicated that AS cases caused by chromosomal rearrangements can be classified into 2 major categories and 4 groups. The first category is paternal uniparental disomy 15, which is subdivided into isodisomy by de novo rob(15;15) and heterodisomy caused by paternal translocation. The second category is the deletion of the AS locus due to maternal reciprocal translocation, which is subdivided into 2 groups associated with partial monosomy by 3:1 segregation and partial trisomy by adjacent-2 segregation. Classification into these categories facilitates the understanding of the mechanisms of chromosomal rearrangements and helps in accurate diagnosis and genetic counseling of these rare forms of AS.

  13. 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

  14. 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.

  15. Human cytomegalovirus (HCMV) and hearing impairment: infection of fibroblast cells with HCMV induces chromosome breaks at 1q23.3, between loci DFNA7 and DFNA49 -- both involved in dominantly inherited, sensorineural, hearing impairment.

    PubMed

    Nystad, Mona; Fagerheim, Toril; Brox, Vigdis; Fortunato, Elizabeth A; Nilssen, Øivind

    2008-01-01

    Human cytomegalovirus (HCMV) infection is the most common congenital infection in developed countries and is responsible for a substantial fraction of sensorineural hearing impairment (SNHI) in children. The risk of hearing impairment is associated with viral load in urine and blood collected during the first postnatal month. However, although inner ear abnormalities are observed in some children with HCMV-induced SNHI, the exact mechanism whereby congenital HCMV infection causes hearing impairment is unknown. Earlier studies using standard cytogenetic mapping techniques showed that infection of S-phase human fibroblast cells with HCMV resulted in two specific, site-directed, chromosome breaks at band positions 1q21 and 1q42 which include loci involved in dominantly and recessively inherited hearing impairment, respectively. These findings suggested that cells infected with HCMV might provide a reservoir for genetic damage and, in a clinical perspective, a scenario could be envisioned whereby hearing impairment could result from early DNA damage of dividing fetal cells rather than viral replication and cell lysis. In this work we demonstrate, using fine mapping techniques, that HCMV infection in S-phase fibroblast cells induces genetic damage at 1q23.3, within a maximal region of 37 kb, containing five low copy repeat (LCR) elements. The breakpoint is situated between two hearing impairment (HI) loci, DFNA49 and DFNA7, and in close proximity to the MPZ gene previously shown to be involved in autosomal dominant Charcot-Marie-Tooth syndrome (CMT1B) with auditory neuropathy.

  16. 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.

  17. A de novo 8.8-Mb Deletion of 21q21.1-q21.3 in an Autistic Male with a Complex Rearrangement Involving Chromosomes 6, 10, and 21

    PubMed Central

    Haldeman-Englert, Chad R.; Chapman, Kimberly A.; Kruger, Hillary; Geiger, Elizabeth A.; McDonald-McGinn, Donna M.; Rappaport, Eric; Zackai, Elaine H.; Spinner, Nancy B.; Shaikh, Tamim H.

    2009-01-01

    We report here on a normal-appearing male with pervasive developmental disorder who was found to have a de novo, apparently balanced complex rearrangement involving chromosomes 6, 10, and 21: 46,XY,ins(21;10)(q11.2;p11.2p13)t(6;21)(p23;q11.2). Further analysis by high-density oligonucleotide microarray was performed, showing an 8.8-Mb heterozygous deletion at 21q21.1-q21.3. Interestingly, the deletion is distal to the translocation breakpoint on chromosome 21. The deletion involves 19 genes, including NCAM2 and GRIK1, both of which are associated with normal brain development and function, and have been considered as possible candidate genes in autism and other neurobehavioral disorders. This case underscores the utility of genomewide microarray analysis for the detection of copy number alterations in patients with apparently balanced complex rearrangements and abnormal phenotypes. PMID:20034085

  18. Assignment of the human gene for the [alpha][sub 1] subunit of the skeletal muscle DHP-sensitive Ca[sup 2+] channel (CACNL1A3) to chromosome 1q31-q32

    SciTech Connect

    Gregg, R.G.; Couch, F.; Hogan, K.; Powers, P.A. )

    1993-01-01

    A human clone corresponding to the gene encoding the [alpha][sub 1] subunit of the skeletal muscle dihydropyridine-sensitive calcium channel (CACNL1A3) has been isolated and partially sequenced. Oligonucleotides based on this sequence were used in a polymerase chain reaction to amplify specifically the human gene in human-rodent somatic cell hybrids, allowing the assignment of CACNL1A3 to chromosome 1. A polymorphic dinucleotide repeat also was identified in the human clone and using PCR was typed on a subset of the CEPH families. Multipoint linkage analysis places the CACNL1A3 gene between D1S52 and D1S70, on chromosome 1q31-q32. 40 refs., 3 figs., 3 tabs.

  19. Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation.

    PubMed

    Rasool, Mahmood; Nawaz, Sadia; Azhar, Aysha; Wajid, Muhammad; Westermark, Per; Baig, Shahid M; Klar, Joakim; Dahl, Niklas

    2010-01-01

    Hair-nail ectodermal dysplasia (HNED; OMIM 602032) constitutes a rare subgroup of ectodermal dysplasias characterised by onychodystrophy, hypotrichosis and brittle hair. We identified a large consanguineous Pakistani family with four siblings affected by a congenital autosomal recessive form of the disease. Based on previous genetic findings in HNED we performed linkage analysis in the family using chromosome 12 markers. A genetic linkage analysis revealed a lod score of 2.92 ( = 0.0) at locus D12S368, indicating the disease gene to be located on chromosome 12. Candidate genes on chromosome 12, including the KRTHB5 gene and four additional keratin II genes, were sequenced in affected family members. Sequence analysis of the coding regions of keratin KRTHB5 gene, previously associated with a distinct clinical form of hair-nail dysplasia, revealed normal coding regions. Our study confirms linkage of a variant clinical form of hair-nail ectodermal dysplasia to chromosome 12 without any mutation in the coding sequences of the KRTHB5 gene. The results suggest this family to have either a non-coding mutation in the KRTHB5 gene, or a mutation in a yet unknown gene within the linked region on chromosome 12.

  20. Cytogenetic evaluation of a patient referred for deafness and mental retardation revealed a deletion of chromosome 7 with del(7)(q22.1q22.3)

    SciTech Connect

    Riske, C.; Stegeman, D.; Stephenson, C.F.

    1994-09-01

    A 27-year-old female was evaluated clinically for deafness and mild mental retardation. The evaluation included cytogenetic analysis which revealed a small deletion of chromosome 7, band regions q21.1 to q22.3. This is an interesting finding because of the association with deafness. Furthermore, it was easier to detect the deletion in lower resolution chromosomes because of the region in which the deletion is found. This case, with its findings and its implications, will be discussed in detail in the poster.

  1. 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

  2. Confirmation of the genetic association between the U2AF homology motif (UHM) kinase 1 (UHMK1) gene and schizophrenia on chromosome 1q23.3.

    PubMed

    Puri, Vinay; McQuillin, Andrew; Datta, Susmita; Choudhury, Khalid; Pimm, Jonathan; Thirumalai, Srinivasa; Krasucki, Robert; Lawrence, Jacob; Quested, Digby; Bass, Nicholas; Crombie, Caroline; Fraser, Gillian; Walker, Nicholas; Moorey, Helen; Ray, Manaan Kar; Sule, Akeem; Curtis, David; St Clair, David; Gurling, Hugh

    2008-10-01

    UHMK1 has previously been implicated as a susceptibility gene for schizophrenia in the 1q23.3 region by significant evidence of allelic and haplotypic association between schizophrenia and several genetic markers at UHMK1 in a London-based case-control sample. Further fine mapping of the UHMK1 gene locus in the University College London schizophrenia case-control sample was carried out with tagging SNPs. Two additional SNPs were found to be associated with schizophrenia (rs6604863 P = 0.02, rs10753578 P = 0.017). Tests of allelic and haplotypic association were then carried out in a second independent sample from Aberdeen consisting of 858 individuals with schizophrenia and 591 controls. Two of these SNPs also showed association in the Aberdeen sample (rs7513662 P = 0.0087, rs10753578 P = 0.022) and several haplotypes were associated (global permutation P = 0.0004). When the UCL and Aberdeen samples were combined three SNPs (rs7513662 P = 0.0007, rs6427680 P = 0.0252, rs6694863 P = 0.015) and several haplotypes showed association (eg HAP-A, HAP-B, HAP-C permutation P = 0.00005). The finding of allelic association with markers in the UHMK1 gene might help explain why it has not been possible, despite great effort, to satisfactorily confirm previously reported associations between schizophrenia and the genes RGS4 and NOS1AP/CAPON. These genes flank UHMK1 and all three loci are within a 700 kb region showing linkage to schizophrenia. The confirmation of association between UHMK1 and schizophrenia, rather than RGS4 and NOS1AP in the London sample, points to the possibility that previous efforts to accurately fine map a gene in the 1q23.3 region have lacked accuracy or may have suffered from methodological flaws.

  3. 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.

  4. 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

  5. The Gene for Juvenile Hyaline Fibromatosis Maps to Chromosome 4q21

    PubMed Central

    Rahman, Nazneen; Dunstan, Melanie; Teare, M. Dawn; Hanks, Sandra; Edkins, Sarah J.; Hughes, Jaime; Bignell, Graham R.; Mancini, Grazia; Kleijer, Wim; Campbell, Mary; Keser, Gokhan; Black, Carol; Williams, Nigel; Arbour, Laura; Warman, Matthew; Superti-Furga, Andrea; Futreal, P. Andrew; Pope, F. Michael

    2002-01-01

    Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition characterized by multiple subcutaneous nodular tumors, gingival fibromatosis, flexion contractures of the joints, and an accumulation of hyaline in the dermis. We performed a genomewide linkage search in two families with JHF from the same region of the Indian state of Gujarat and identified a region of homozygosity on chromosome 4q21. Dense microsatellite analyses within this interval in five families with JHF who were from diverse origins demonstrate that all are compatible with linkage to chromosome 4q21 (multipoint LOD score 5.5). Meiotic recombinants place the gene for JHF within a 7-cM interval bounded by D4S2393 and D4S395. PMID:12214284

  6. 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.

  7. Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon.

    PubMed

    Zani, V J; Asou, N; Jadayel, D; Heward, J M; Shipley, J; Nacheva, E; Takasuki, K; Catovsky, D; Dyer, M J

    1996-04-15

    Chromosome 12q24.1 is a recurrent breakpoint in high-grade B-cell non-Hodgkin lymphoma (B-NHL). To identify the genes involved at 12q24.1, molecular cloning of a three-way translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line (Wien 133) was performed; all four translocation breakpoints were cloned and sequenced. Analysis of clones encompassing the der(12)(12;14)(q24.1;q32.3) breakpoint showed a CpG island from chromosome 12q24.1 juxtaposed in a tail-to-tail configuration with a productively rearranged Ig VH4-DH-JH5 gene. A total of 4.5 kb of genomic DNA including the CpG island was sequenced and analyzed using gene-identification programs; all three programs identified a potential 92-bp exon within the centromeric boundary of the CpG island. Using this as a probe, an RNA transcript of 3.8 kb, expressed at low levels in a wide variety of normal tissues, was detected. Overlapping cDNA clones were isolated and sequenced. The longest open-reading frame predicted a serine-rich protein of 231 amino acids. This protein, termed BCL7A, exhibited no recognizable protein motifs but showed homology with the actin-binding protein, caldesmon. In Wien 133, the BCL7A breakpoint occurred within the first intron and resulted in a MYC-BCL7A fusion transcript, with exon I of BCL7A being replaced by MYC exon I. The normal, untranslocated allele of BCL7A was also expressed without mutation. One of the 11 other B-NHL cell lines examined with 12q24.1 cytogenetic abnormalities, a mediastinal B-NHL cell line (Karpas 1106), showed biallelic rearrangement within the first intron of BCL7A, which was adjacent to the breakpoint observed in Wien 133. Disruption of the amino-terminus of BCL7A defines a new mechanism in the pathogenesis of a subset of high-grade B-NHL.

  8. Sex differences in juvenile mouse social behavior are influenced by sex chromosomes and social context

    PubMed Central

    Cox, Kimberly H.; Rissman, Emilie F.

    2011-01-01

    Play behavior in juvenile primates, rats, and other species is sexually dimorphic, with males demonstrating more play than females. In mice, sex differences in juvenile play have only been examined in out-bred CD-1 mice. In this strain, contrary to other animals, male mice display less play soliciting than females. Using an established same-sex dyadic interaction test, we examined play in inbred C57BL/6J (B6) 21 day-old mice. When paired with non-siblings, males tended to be more social than females, spending more time exploring the test cage. Females displayed significantly more anogenital sniffing and solicited play more frequently than did males. To determine if the origin of the sex difference was sex chromosome genes or gonadal sex, next we used the four core genotype (FCG) mouse. We found significant interactions between gonadal sex and genotype for several behaviors. Finally, we asked if sibling pairs (as compared to non-siblings) would display qualitative or quantitatively different behavior. In fact, XX females paired with a sibling were more social and less exploratory or investigative, while XY males exhibited less investigative and play soliciting behaviors in tests with siblings. Many neurobehavioral disorders, like autism spectrum disorder (ASD), are sexually dimorphic in incidence and patients interact less than normal with other children. Our results suggest that sex chromosome genes interact with gonadal hormones to shape the development of juvenile social behavior, and that social context can drastically alter sex differences. These data may have relevance for understanding the etiology of sexually dimorphic disorders such as ASD. PMID:21414140

  9. Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked to chromosome 1q21--q23 and is associated with a common polymorphism in LMNA in Pima Indians.

    PubMed

    Weyer, C; Wolford, J K; Hanson, R L; Foley, J E; Tataranni, P A; Bogardus, C; Pratley, R E

    2001-03-01

    Large subcutaneous abdominal adipocyte size (s.c. abd. AS) is associated with insulin resistance and predicts type 2 diabetes in Pima Indians. Because type 2 diabetes is familial, we aimed to determine whether mean s.c. abd. AS is also familial and if so, to identify chromosomal regions linked to this measure. Body composition (hydrodensitometry) and mean s.c. abd. AS (fat biopsy) were measured in 295 Pima Indians (179 with normal, 80 with impaired, and 36 with diabetic glucose tolerance) representing 164 nuclear families. Mean s.c. abd. AS, adjusted for age, sex, and percentage body fat was a familial trait (heritability h(2) = 0.48, P < 0.0001). A genome-wide autosomal scan revealed suggestive evidence for linkage (LOD 1.73) of adjusted mean s.c. abd. AS to chromosome 1q21--q23, a region containing LMNA, the gene encoding for the nuclear envelope proteins lamin A/C. Rare mutations in LMNA were recently shown to underlie familial partial lipodystrophy (FPLD), a syndrome characterized by regional loss of adipose tissue, insulin resistance, and glucose intolerance. A common (allelic frequency 0.43) single nucleotide polymorphism (silent 1908C --> T substitution) in exon 10 of LMNA (GenBank X03444) was associated with reduced age-, sex- and percentage body fat-adjusted mean s.c. abd. AS [0.80 +/- 0.17 (CC), 0.76 +/- 0.15 (CT), 0.73 +/- 0.16 (TT) microg lipid/cell, P < 0.05 for CC vs TT]. These findings indicate that approximately half of the variance in mean s.c. abd. AS can be attributed to familial factors and that genetic variation in LMNA might not only underlie rare cases of FPLD, but may also contribute to variation in adipocyte size in the general population. Copyright 2001 Academic Press.

  10. 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.

  11. Exclusion of linkage to chromosomes 14q, 2q37 and 8p21.1-q11.23 in a Serbian family with idiopathic basal ganglia calcification.

    PubMed

    Kostić, Vladimir S; Lukić-Ječmenica, Milica; Novaković, Ivana; Dobričić, Valerija; Brajković, Lela; Krajinović, Maja; Klein, Christine; Pavlović, Aleksandra

    2011-09-01

    In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation.

  12. Autosomal dominant cortical myoclonus and epilepsy (ADCME) with complex partial and generalized seizures: A newly recognized epilepsy syndrome with linkage to chromosome 2p11.1-q12.2.

    PubMed

    Guerrini, R; Bonanni, P; Patrignani, A; Brown, P; Parmeggiani, L; Grosse, P; Brovedani, P; Moro, F; Aridon, P; Carrozzo, R; Casari, G

    2001-12-01

    critical region spanning 12.4 cM between markers D2S2161 and D2S1897 in 2p11.1-q12.2, with a maximum two-point LOD score of 3.46 at Theta 0.0 for marker D2S2175. Multipoint LOD score values, reaching 3.74 around D2S2175, localize the ADCME gene to the centromeric region of chromosome 2. The exclusion of the locus for familial adult myoclonic epilepsy on chromosome 8q23.3-q24 from linkage to our family and the new localization of the responsible gene to chromosome 2cen, together with the different phenotype, define a new epilepsy syndrome. We hypothesize that the responsible gene causes cortical hyperexcitability that is widespread but particularly involves the frontotemporal circuits.

  13. 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.

  14. 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.

  15. Juvenile myoclonic epilepsy: linkage to chromosome 6p12 in Mexico families.

    PubMed

    Bai, Dongsheng; Alonso, Maria E; Medina, Marco T; Bailey, Julia N; Morita, Ryoji; Cordova, Sergio; Rasmussen, Astrid; Ramos-Peek, Jaime; Ochoa, Adriana; Jara, Aurelio; Donnadieu, Francisco R; Cadena, Gilbert; Yamakawa, Kazuhiro; Delgado-Escueta, Antonio V

    2002-12-01

    Juvenile myoclonic epilepsy is a common subtype of idiopathic epilepsy accounting for 4-11% of all epilepsies. We reported previously significant evidence of linkage between chromosome 6p12-11 microsatellites and the clinical epilepsy and EEG traits of JME families from Belize and Los Angeles. To narrow the JME region, we ascertained and genotyped 31 new JME families from Mexico using a later generation of Généthon microsatellites. Two point linkage analyses obtained significant Z(max) values of 3.70 for D6S1573 and 2.65 for D6S1714 at theta(m = f) = 0.10, and 3.49 for D6S465, 2.11 for D6S1960 at theta(m = f) = 0.05 assuming autosomal dominant inheritance with 70% age-dependent penetrance. Multipoint LOD score curve peaked at 4.21 for D6S1573. Haplotype and recombination analysis reduced the JME region to 3.5 cM flanked by D6S272 and D6S1573. These results provide confirmatory evidence that a major susceptibility gene for JME exists in chromosome 6p12 in Spanish-Amerinds of Mexico.

  16. 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.

  17. De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature.

    PubMed

    Becker, Kerstin; Di Donato, Nataliya; Holder-Espinasse, Muriel; Andrieux, Joris; Cuisset, Jean-Marie; Vallée, Louis; Plessis, Ghislaine; Jean, Nolwenn; Delobel, Bruno; Thuresson, Ann-Charlotte; Annerén, Göran; Ravn, Kirstine; Tümer, Zeynep; Tinschert, Sigrid; Schrock, Evelin; Jønch, Aia Elise; Hackmann, Karl

    2012-01-01

    Interstitial 6q deletions can cause a variable phenotype depending on the size and location of the deletion. 6q14 deletions have been associated with intellectual disability and a distinct pattern of minor anomalies, including upslanted palpebral fissures with epicanthal folds, a short nose with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14 for intellectual disability might be FILIP1, MYO6, HTR1B, and SNX14. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  18. Duplication of C7orf58, WNT16 and FAM3C in an Obese Female with a t(7;22)(q32.1;q11.2) Chromosomal Translocation and Clinical Features Resembling Coffin-Siris Syndrome

    PubMed Central

    Zhu, Jun; Qiu, Jun; Magrane, Gregg; Abedalthagafi, Malak; Zanko, Andrea; Golabi, Mahin; Chehab, Farid F.

    2012-01-01

    We characterized the t(7;22)(q32;q11.2) chromosomal translocation in an obese female with coarse features, short stature, developmental delay and a hypoplastic fifth digit. While these clinical features suggest Coffin-Siris Syndrome (CSS), we excluded a CSS diagnosis by exome sequencing based on the absence of deleterious mutations in six chromatin-remodeling genes recently shown to cause CSS. Thus, molecular characterization of her translocation could delineate genes that underlie other syndromes resembling CSS. Comparative genomic hybridization microarrays revealed on chromosome 7 the duplication of a 434,682 bp region that included the tail end of an uncharacterized gene termed C7orf58 (also called CPED1) and spanned the entire WNT16 and FAM3C genes. Because the translocation breakpoint on chromosome 22 did not disrupt any apparent gene, her disorder was deemed to result from the rearrangement on chromosome 7. Mapping of yeast and bacterial artificial chromosome clones by fluorescent in situ hybridization on chromosome spreads from this patient showed that the duplicated region and all three genes within it were located on both derivative chromosomes 7 and 22. Furthermore, DNA sequencing of exons and splice junctional regions from C7orf58, WNT16 and FAM3C revealed the presence of potential splice site and promoter mutations, thereby augmenting the detrimental effect of the duplicated genes. Hence, dysregulation and/or disruptions of C7orf58, WNT16 and FAM3C underlie the phenotype of this patient, serve as candidate genes for other individuals with similar clinical features and could provide insights into the physiological role of the novel gene C7orf58. PMID:23300646

  19. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.

    PubMed

    Xu, S Y; Rosenberg, T; Gal, A

    1998-04-01

    Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been assigned to the chromosomal interval defined here.

  20. 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 Central

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

    2014-01-01

    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 4 after presenting with hematochezia due to multiple colonic juvenile polyps. He then represented 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

  1. 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. © 2015 Wiley Periodicals, Inc.

  2. 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.

  3. Molecular cloning, mapping to human chromosome 1 q21-q23, and cell binding characteristics of Spalpha, a new member of the scavenger receptor cysteine-rich (SRCR) family of proteins.

    PubMed

    Gebe, J A; Kiener, P A; Ring, H Z; Li, X; Francke, U; Aruffo, A

    1997-03-07

    CD5 and CD6, two type I cell surface antigens predominantly expressed by T cells and a subset of B cells, have been shown to function as accessory molecules capable of modulating T cell activation. Here we report the cloning of a cDNA encoding Spalpha, a secreted protein that is highly homologous to CD5 and CD6. Spalpha has the same domain organization as the extracellular region of CD5 and CD6 and is composed of three SRCR (scavenger receptor cysteine rich) domains. Chromosomal mapping by fluorescence in situ hybridization and radiation hybrid panel analysis indicated that the gene encoding Spalpha is located on the long arm of human chromosome 1 at q21-q23 within contig WC1.17. RNA transcripts encoding Spalpha were found in human bone marrow, spleen, lymph node, thymus, and fetal liver but not in non-lymphoid tissues. Cell binding studies with an Spalpha immunoglobulin (Spalpha-mIg) fusion protein indicated that Spalpha is capable of binding to peripheral monocytes but not to T or B cells. Spalpha-mIg was also found to bind to the monocyte precursor cell lines K-562 and weakly to THP-1 but not to U937. Spalpha-mIg also bound to the B cell line Raji and weakly to the T cell line HUT-78. These findings indicate that Spalpha, a novel secreted protein produced in lymphoid tissues, may regulate monocyte activation, function, and/or survival.

  4. Trisomy 1q in a patient with severe aplastic anemia.

    PubMed

    Angelidis, Prodromos; Kojouri, Kiarash; Lee, Jiyun; Kern, William; Mulvihill, John J; Li, Shibo

    2006-08-01

    Aplastic anemia is a rare, serious disease characterized by hypocellular bone marrow and pancytopenia in the peripheral blood. Most cases are acquired, idiopathic, and without gross cytogenetic abnormalities. A few chromosome abnormalities have recurred among a small subset of patients, most commonly trisomy 8 and monosomy 7. Some of these chromosome abnormalities have prognostic and therapeutic significance, although for most the clinical relevance is not known. We present the case of a 40-year-old man with idiopathic severe aplastic anemia in bone marrow cells with trisomy of the whole long arm of chromosome 1 due to an unbalanced translocation between chromosomes 1 and 15 at breakpoints of q10 and 15q10. This clonal abnormality (which, to our knowledge, has not been previously reported in a patient with aplastic anemia) suggests that genes on 1q may be involved in marrow aplasia.

  5. Developmental delay and facial dysmorphism in a child with an 8.9 Mb de novo interstitial deletion of 3q25.1-q25.32: Genotype-phenotype correlations of chromosome 3q25 deletion syndrome.

    PubMed

    Moortgat, Stephanie; Verellen-Dumoulin, Christine; Maystadt, Isabelle; Parmentier, Benoit; Grisart, Bernard; Hennecker, Jean-Luc; Destree, Anne

    2011-01-01

    Interstitial deletions of the long arm of chromosome 3 are rare and detailed genotype-phenotype correlations are not well established. We report on the clinical, cytogenetic and molecular findings of a 5-year-old patient with a de novo interstitial deletion from 3q25.1 to 3q25.32. Clinical features include relative microcephaly, developmental delay and facial dysmorphism with a coarse face, ptosis, synophrys, epicanthic folds, broad nasal bridge, long philtrum, large mouth with full lips, dysplastic and low-set ears. Revealed by conventional banding techniques, the deleted region of 8.9 Mb was confirmed by fluorescent in situ hybridization (FISH) analyses and array comparative genomic hybridization (array-CGH). To our knowledge, this is the smallest interstitial deletion reported in the 3q25 region. The phenotype of our patient is compared with the 10 previously reported cases implicating the 3q25 region.

  6. Chromosome

    MedlinePlus

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  7. 1q21.1 Microduplication expression in adults

    PubMed Central

    Dolcetti, Alessia; Silversides, Candice K.; Marshall, Christian R.; Lionel, Anath C.; Stavropoulos, Dimitri J.; Scherer, Stephen W.; Bassett, Anne S.

    2013-01-01

    Purpose Rare, recurrent chromosome 1q21.1 duplications have been associated with developmental delay, congenital anomalies, and macrocephaly in children. Data on adult clinical expression would help to inform genetic counseling. Methods A systematic review of 22 studies reporting 107 individuals (59 children and 48 adults) with 1q21.1 duplications was conducted. We compiled the available phenotypic data to attempt to identify the most highly associated clinical features and to determine expression in adults. We also report on seven adult cases newly identified in the studies of schizophrenia and tetralogy of Fallot at our center. Results Five cases were ascertained as controls, 32 as relatives of probands, and 70 as having clinical features: autism spectrum disorder (n = 15), congenital heart disease (n = 12), schizophrenia (n = 10), or other, mostly developmental, features (n = 33). The 1q21.1 duplication was significantly enriched in the cohorts with schizophrenia (P = 0.0155) and tetralogy of Fallot (P = 0.0040) at our center as compared with controls. There was a paucity of clinical data for adults; the most common features, other than those used for ascertainment, included macrocephaly and abnormalities of possible connective tissue origin (e.g., carpal tunnel syndrome). Conclusion Further data are needed to characterize lifetime expression of 1q21.1 duplications. These initial results, however, suggest that anticipatory care should include attention to later-onset conditions such as schizophrenia. PMID:23018752

  8. 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.

  9. 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.

  10. Pattern of trisomy 1q in hematological malignancies: a single institution experience.

    PubMed

    Djordjević, Vesna; Dencić-Fekete, Marija; Jovanović, Jelica; Drakulić, Danijela; Stevanović, Milena; Janković, Gradimir; Gotić, Mirjana

    2008-10-01

    An extra copy of 1q usually originates from the translocated unbalanced derivative chromosome, isochromosome, or "jumping translocation." We report a pattern of partial trisomies and unbalanced whole-arm translocations of 1q in 10 patients: 5 with myelodysplastic syndrome, 3 with acute myeloid leukemia, and a single patient with acute lymphoblastic leukemia and myeloproliferative syndrome. The trisomy of 1q was registered as the sole karyotype aberration in one patient, while it was accompanied by a limited number of additional chromosomal changes in nine patients. These patients are a subset of a larger group of 92 adults carrying a wide variety of chromosome 1 anomalies within a complex cytogenetic context observed over a period between 1994 and 2006 in a panel of 3,786 hematologic patients at the Institute of Hematology in Belgrade. Conventional cytogenetics was supplemented by fluorescence in situ hybridization with a probe specific for the paracentric region of 1q. Whole-arm 1q translocations involved chromosomes Y, 7, 14, 15, 16, and 19. This study suggests that gain of 1q as the sole cytogenetic abnormality may be sufficiently mutagenic to favor leukemogenesis and hematopoietic tissue degeneration (trilineage myelodysplasia).

  11. 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.

  12. 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.

  13. SLE and C1q: A quantitative ELISA for determining C1q levels in serum

    PubMed Central

    Dillon, Skyler P.; D’Souza, Anil; Kurien, Biji T.; Scofield, R. Hal

    2010-01-01

    C1q is of interest in SLE research due to deficiencies in its activity being associated with the disease. Current published protocols for measuring C1q vary greatly in their results and ease of reproducibility. Due to this, average C1q concentrations have been reported between 56 and 276 µg/ml in non-SLE serum. We present an improved method for quantifying C1q concentrations that employs a sandwich ELISA. This method has improved precision, cost efficiency, up-scaling, reproducibility, and uses significantly lesser volumes of serum sample when compared to RID and other methods for quantifying C1q. We report an average concentration of 113±40 µg/ml for C1q in non-SLE serum. The assay designed here will be useful in the high-throughput measurement of serum C1q in SLE cases. PMID:19370710

  14. 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.

  15. 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.

  16. Detection of a de novo duplication of 1q32-qter by fluorescence in situ hybridisation in a boy with multiple malformations: further delineation of the trisomy 1q syndrome.

    PubMed Central

    Duba, H C; Erdel, M; Löffler, J; Bereuther, L; Fischer, H; Utermann, B; Utermann, G

    1997-01-01

    We report a dysmorphic boy with a de novo partial trisomy 1q. The boy has microcephaly, bilateral cleft lip and palate, low set and dysmorphic ears, brain anomalies, pulmonary stenosis, duodenal obstruction, dysplastic kidneys, and bifid thumbs. The trisomic segment 1q32-qter is duplicated with an inverted insertion at 1p36.3. The aberration was initially detected at amniocentesis and confirmed and defined by GTG banding, chromosome microdissection, and FISH on postnatal blood samples. The parents had normal karyotypes. De novo partial duplications of chromosome 1q have rarely been reported. Comparison of our patient with other published pure trisomy 1q cases showed similarities which allowed the further delineation of the trisomy 1q syndrome. Images PMID:9138155

  17. Congenital intra-abdominal bilateral juvenile granulosa cell tumors of the testis associated with constitutional loss of material from chromosome 4.

    PubMed

    Yu, David C; Pathak, Bhavana; Vargas, Sara O; Javid, Patrick J; Hisama, Fuki M; Wilson, Jay M; Linden, Bradley C

    2011-01-01

    Juvenile granulosa cell tumor (JGCT) is an uncommon gonadal stromal tumor that occurs rarely in the testis. We report a newborn boy with bilateral intra-abdominal JGCT presenting with abdominal distention and respiratory distress at birth. He was taken to the operating room emergently, and 2 large masses connected by gubernacula to the inguinal canals were resected. Associated abnormalities included a constitutional chromosome 4 abnormality, polymicrogyria, and renal cysts. This report describes a rare presentation of JGCT with abdominal compression and expands the literature to include bilateral testicular involvement. Additionally, it is the 1st report of JGCT associated with a chromosome 4 abnormality, highlighting a genetic region that may be important in JGCT development.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Hereditary C1q deficiency: a new family with C1qA deficiency.

    PubMed

    Sun-Tan, Cağman; Ozgür, Tuba Turul; Kilinç, Gamze; Topaloğlu, Rezan; Gököz, Ozay; Ersoy-Evans, Sibel; Sanal, Ozden

    2010-01-01

    Hereditary deficiency of complement component C1q is a rare genetic disorder with susceptibility to recurrent infections with polysaccharide-containing encapsulated microorganisms and a high prevalence of autoimmune diseases, most often systemic lupus erythematosus (SLE). Here, we report a 29-month-old boy who presented with facial rash and history of early death of a sibling with infections, who was found to have a selective deficiency of C1q. The facial rash was composed of patchy erythematous plaques and centrally hypopigmented macules and desquamation. Two siblings had died of severe bacterial infections and his uncle had died of meningitis. Molecular study disclosed a homozygous point mutation in the C1qA chain gene. Five members of the family, including the parents and three healthy siblings, were heterozygous for this mutation.

  3. 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.

  4. Classical complement pathway component C1q: purification of human C1q, isolation of C1q collagen-like and globular head fragments and production of recombinant C1q-derivatives. Functional characterization.

    PubMed

    Kojouharova, Mihaela

    2014-01-01

    The classical complement pathway (CCP) activation is a multimolecular complex, composed of three subcomponents namely C1q, C1r, and C1s. C1q is the recognition subunit of this complex and its binding to the specific targets leads to the formation of active C1, which in turn activates the CCP in an immunoglobulin-dependent or -independent manner. C1q is a hexameric glycoprotein composed of 18 polypeptide chains of three different types (A, B, and C), organized in two fragments-collagen-like (CLR) and globular head (gC1q) possessing different functional activity. The contemporary knowledge of the C1q structure allows the isolation and purification of a C1q molecule from serum by combination of different chromatography procedures including ion-exchange, size-exclusion, and affinity chromatography, as well as the isolation of CLR and gC1q by limited enzymatic hydrolysis of the native C1q molecule. In this chapter, we described methods for purification of human C1q and its CLR and gC1q fragments, as well as methods for their biochemical and functional characterization. The production and purification of recombinant C1q derivatives ghA, ghB, and ghC (globular fragments of the individual C1q chains) are also presented.

  5. Deletion 1q43 encompassing only CHRM3 in a patient with autistic disorder.

    PubMed

    Petersen, Andrea Klunder; Ahmad, Ausaf; Shafiq, Mustafa; Brown-Kipphut, Brigette; Fong, Chin-To; Anwar Iqbal, M

    2013-02-01

    Deletions on the distal portion of the long arm of chromosome 1 result in complex and highly variable clinical phenotypes which include intellectual disability, autism, seizures, microcephaly/craniofacial dysmorphology, corpus callosal agenesis/hypogenesis, cardiac and genital anomalies, hand and foot abnormalities and short stature. Genotype-phenotype correlation reported a minimum region of 2 Mb at 1q43-q44. We report on a 3 ½ year old male patient diagnosed with autistic disorder who has social withdrawal, eating problems, repetitive stereotypic behaviors including self-injurious head banging and hair pulling, and no seizures, anxiety, or mood swings. Array comparative genomic hybridization (aCGH) showed an interstitial deletion of 473 kb at 1q43 region (239,412,391-239,885,394; NCBI build37/hg19) harboring only CHRM3 (Acetylcholine Receptor, Muscarinic, 3; OMIM: 118494). Recently, another case with a de novo interstitial deletion of 911 kb at 1q43 encompassing three genes including CHRM3 was reported. The M3 muscarinic receptor influences a multitude of central and peripheral nervous system processes via its interaction with acetylcholine and may be an important modulator of behavior, learning and memory. We propose CHRM3 as a candidate gene responsible for our patient's specific phenotype as well as the overlapping phenotypic features of other patients with 1q43 or 1q43-q44 deletions. Copyright © 2013. Published by Elsevier Masson SAS.

  6. 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.

  7. C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus.

    PubMed

    van Schaarenburg, Rosanne A; Magro-Checa, César; Bakker, Jaap A; Teng, Y K Onno; Bajema, Ingeborg M; Huizinga, Tom W; Steup-Beekman, Gerda M; Trouw, Leendert A

    2016-01-01

    C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE.

  8. C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus

    PubMed Central

    van Schaarenburg, Rosanne A.; Magro-Checa, César; Bakker, Jaap A.; Teng, Y. K. Onno; Bajema, Ingeborg M.; Huizinga, Tom W.; Steup-Beekman, Gerda M.; Trouw, Leendert A.

    2016-01-01

    C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE. PMID:28082982

  9. Role of C1q and C1q receptors in the pathogenesis of systemic lupus erythematosus.

    PubMed

    Ghebrehiwet, Berhane; Peerschke, Ellinor I

    2004-01-01

    The association between C1q and autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE) is well established. Deficiency in C1q is considered to be a strong susceptibility factor and is corroborated by the fact that > or = 92% of the known cases of hereditary deficiency in C1q develop rheumatic disease. Furthermore, the observation of the presence of high-affinity autoantibodies against C1q antibodies in patients with SLE provides a strong correlation between these antibodies and the inflammatory processes that occur in this disease. Recent evidence using C1q-deficient mice has shown the presence of glomerulonephritis with immune deposits and a large number of apoptotic bodies in the diseased glomeruli suggesting a defect in the clearance of apoptotic cell by macrophages and dendritic cells (DCs). Although these data are consistent with the hypothesis that C1q deficiency may induce a generalized failure to clear immune complexes and apoptotic cells, this concept alone cannot wholly explain why individuals with C1q deficiency are prone to develop SLE. Therefore, C1q alone or in conjunction with other surface molecules must play a much more fundamental role in immunoregulation, especially those processes that regulate T cell function and tolerance. In support of this hypothesis is the finding that C1q causes inhibition of mitrogen-induced T cell-proliferative response by interaction with C1q receptors. Furthermore, macrophages and possibly DCs not only synthesize but also display C1q as a type II cell surface molecule, especially at sites of inflammation. Although it is not yet known what role the surface-expressed C1q plays, it is tempting to assume that it plays a role in the priming of naïve T cells by DCs. This work will review the current concepts of the role of C1q and C1q receptors in autoimmunity.

  10. Burkitt-Type Acute Lymphoblastic Leukemia With Precursor B-Cell Immunophenotype and Partial Tetrasomy of 1q

    PubMed Central

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

    2016-01-01

    Abstract 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

  11. Association of a novel constitutional translocation t(1q;3q) with familial renal cell carcinoma

    PubMed Central

    Kanayama, H.; Lui, W.; Takahashi, M.; Naroda, T.; Kedra, D.; Wong, F. K.; Kuroki, Y.; Nakahori, Y.; Larsson, C.; Kagawa, S.; Teh, B. T.

    2001-01-01

    Four cases of late onset clear cell renal cell carcinoma (RCC), a case of gastric cancer, and a case of exocrine pancreatic cancer were identified in a Japanese family. In order to elucidate the underlying mechanism for tumorigenesis in this family, extensive genetic studies were performed including routine and spectral karyotyping (SKY), fluorescence in situ hybridisation (FISH), comparative genomic hybridisation (CGH), loss of heterozygosity studies (LOH), and VHL mutation analysis. A germline translocation t(1;3)(q32-q41;q13-q21) was identified by karyotyping in five members of the family including all three RCC cases tested. The translocation was refined to t(1;3)(q32;q13.3) by FISH analysis using locus specific genomic clones, and the two breakpoints were mapped to a 5 cM region in 3q13.3 and a 3.6 cM region in 1q32. Both CGH and allelotyping using microsatellite markers showed loss of the derivative chromosome 3 carrying a 1q segment in the three familial RCCs analysed. Additional chromosomal imbalances were identified by CGH, including amplifications of chromosomes 5 and 7 and loss of 8p and 9. No germline VHL mutation was found but two different somatic mutations, a splice (IVS1-2A>C) and a frameshift (726delG), were identified in two RCCs from the same patient confirming their distinct origin.Taken together, these results firmly support a three step model for tumorigenesis in this family. A constitutional translocation t(1q;3q) increased the susceptibility to loss of the derivative chromosome 3 which is then followed by somatic mutations of the RCC related tumour suppressor gene VHL located in the remaining copy of chromosome 3.


Keywords: familial renal cell carcinoma; translocation; von Hippel-Lindau disease; loss of heterozygosity PMID:11238683

  12. A tandem triplication, trp(1)(q21q32), in a patient with follicular lymphoma: a case study and review of the literature.

    PubMed

    Park, Tae Sung; Lee, Seung Tae; Song, Jaewoo; Lee, Kyung-A; Kim, Juwon; Kim, Sue Jung; Lee, Jung-Hoon; Song, Sungwook; Choi, Jong Rak

    2009-03-01

    A 1q triplication is a rare karyotypic event in hematologic malignancies, with 26 cases of 1q triplication reported in the literature. Although 1q duplication or triplication is present with a high incidence in Burkitt lymphoma and Fanconi anemia, there have been no detailed reports of an association between non-Burkitt type lymphomas and 1q triplication. Presented here is the case of a 69-year-old man with follicular lymphoma (FL) and 1q triplication, with a review of the pertinent literature. The patient was diagnosed with FL with bone marrow involvement; his bone marrow chromosome study revealed 50,XY,trp(1)(q21q32),+3,+add(3)(q21),+7,+9,add(13)(p11.2)[11]/51 approximately 52,idem,+19,+22[8]/46,XY[3]. Review of the Mitelman Database of Chromosome Aberrations in Cancer revealed 7 previous cases of non-Burkitt type lymphoma (including FL) with 1q triplication. On the basis of these eight cases, we conclude that 1q triplication represents a rare secondary genetic event with prognostic significance in patients with FL or other non-Burkitt types of lymphoma. Further studies are needed to investigate these rare 1q triplication in hematologic malignancies.

  13. 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.

  14. Juvenile angiofibroma

    MedlinePlus

    Nasal tumor; Angiofibroma - juvenile; Benign nasal tumor; Juvenile nasal angiofibroma; JNA ... Juvenile angiofibroma is not very common. It is most often found in adolescent boys. The tumor contains ...

  15. Richter's syndrome with identification of marker chromosomes.

    PubMed

    Fitzgerald, P H; McEwan, C M; Hamer, J W; Beard, M E

    1980-07-01

    A case is presented of a man with Richter's syndrome with diffuse histiocytic lymphoma following a ten-year history of untreated chronic lymphatic leukemia. He did not respond to therapy. The lymphoma cells had 61 chromosomes with aneuploidy of 13 chromosomes and 11 structurally altered chromosomes. Only chromosomes 8, 9, 12, 14, and 18 were diploid and without abnormality. Significantly, part of chromsome 1q was duplicated as in the partial trisomy of 1q reported to characterize a number of hematologic neoplasms. A large marker chromosome with subterminal centromere was a tandem duplication of chromosome 4q.

  16. Patients carrying 9q31.1-q32 deletion share common features with Cornelia de Lange Syndrome.

    PubMed

    Cao, Ruixue; Pu, Tian; Fang, Shaohai; Long, Fei; Xie, Jing; Xu, Yuejuan; Chen, Sun; Sun, Kun; Xu, Rang

    2015-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare but severe clinically heterogeneous developmental disorder characterized by facial dysmorphia, growth and cognitive retardation, and abnormalities of limb development. To determine the pathogenesis of a patient with CdLS. We studied a patient with CdLS by whole exome sequencing, karyotyping and Agilent CGH Array. The results were confirmed by quantitative real-time PCR analysis of the patient and her parents. Further comparison of our patient and cases with partially overlapping deletions retrieved from the literature and databases was undertaken. Whole exome sequencing had excluded the mutation of cohesion genes such as NIPBL,SMC1A and SMC3. The result of karyotyping showed a deletion of chromosome 9q31.1-q32 and the result of Agilent CGH Array further displayed a 12.01-Mb region of deletion at chromosome bands 9q31.1-q32. Reported cases with the deletion of 9q31.1-q32 share similar features with our CdLS patient. One of the genes in the deleted region, SMC2, belongs to the Structural Maintenance of Chromosomes (SMC) family and regulates gene expression and DNA repair. Patients carrying the deletion of 9q31.1-q32 showed similar phenotypes with CdLS. © 2015 S. Karger AG, Basel.

  17. 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.

  18. Cbln and C1q family proteins: new transneuronal cytokines.

    PubMed

    Yuzaki, M

    2008-06-01

    The C1q family is characterized by a C-terminal conserved global C1q domain, which is structurally very similar to the tumor necrosis factor homology domain. Although some C1q family members are expressed in the central nervous system, their functions have not been well characterized. Cbln1, a member of the Cbln subfamily of the C1q family, is predominantly expressed in cerebellar granule cells. Interestingly, Cbln1 was recently shown to play two unique roles at excitatory synapses formed between cerebellar granule cells and Purkinje cells: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytosis pathway. Since other Cbln subfamily members, Cbln2-Cbln4, are expressed in various regions of developing and mature brains, Cbln subfamily proteins may generally serve as a new class of transneuronal regulators of synapse development and synaptic plasticity in various brain regions.

  19. Anti-C1q antibodies in systemic lupus erythematosus.

    PubMed

    Orbai, A-M; Truedsson, L; Sturfelt, G; Nived, O; Fang, H; Alarcón, G S; Gordon, C; Merrill, Jt; Fortin, P R; Bruce, I N; Isenberg, D A; Wallace, D J; Ramsey-Goldman, R; Bae, S-C; Hanly, J G; Sanchez-Guerrero, J; Clarke, A E; Aranow, C B; Manzi, S; Urowitz, M B; Gladman, D D; Kalunian, K C; Costner, M I; Werth, V P; Zoma, A; Bernatsky, S; Ruiz-Irastorza, G; Khamashta, M A; Jacobsen, S; Buyon, J P; Maddison, P; Dooley, M A; Van Vollenhoven, R F; Ginzler, E; Stoll, T; Peschken, C; Jorizzo, J L; Callen, J P; Lim, S S; Fessler, B J; Inanc, M; Kamen, D L; Rahman, A; Steinsson, K; Franks, A G; Sigler, L; Hameed, S; Pham, N; Brey, R; Weisman, M H; McGwin, G; Magder, L S; Petri, M

    2015-01-01

    Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. Anti-C1q Antibodies in Systemic Lupus Erythematosus

    PubMed Central

    ORBAI, ANA-MARIA; TRUEDSSON, LENNART; STURFELT, GUNNAR; NIVED, OLA; FANG, HONG; ALARCÓN, GRACIELA S.; GORDON, CAROLINE; MERRILL, JOAN T.; FORTIN, PAUL R.; BRUCE, IAN N.; ISENBERG, DAVID A.; WALLACE, DANIEL J.; RAMSEY-GOLDMAN, ROSALIND; BAE, SANG-CHEOL; HANLY, JOHN G.; SANCHEZ-GUERRERO, JORGE; CLARKE, ANN E.; ARANOW, CYNTHIA B.; MANZI, SUSAN; UROWITZ, MURRAY B.; GLADMAN, DAFNA D.; KALUNIAN, KENNETH C.; COSTNER, MELISSA I.; WERTH, VICTORIA P.; ZOMA, ASAD; BERNATSKY, SASHA; RUIZ-IRASTORZA, GUILLERMO; KHAMASHTA, MUNTHER A.; JACOBSEN, SOREN; BUYON, JILL P.; MADDISON, PETER; DOOLEY, MARY ANNE; VAN VOLLENHOVEN, RONALD F.; GINZLER, ELLEN; STOLL, THOMAS; PESCHKEN, CHRISTINE; JORIZZO, JOSEPH L.; CALLEN, JEFFREY P.; LIM, S. SAM; FESSLER, BARRI J.; INANC, MURAT; KAMEN, DIANE L.; RAHMAN, ANISUR; STEINSSON, KRISTJAN; FRANKS, ANDREW G.; SIGLER, LISA; HAMEED, SUHAIL; PHAM, NEENA; BREY, ROBIN; WEISMAN, MICHAEL H.; MCGWIN, GERALD; MAGDER, LAURENCE S.; PETRI, MICHELLE

    2014-01-01

    Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs. rheumatic disease controls) and the association with SLE manifestations in an international multi-center study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE (n=308) and other rheumatologic diseases (n=389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR=2.7, 95% CI: 1.8-4, p<0.001). Anti-C1q was associated with proteinuria (OR=3.0, 95% CI: 1.7-5.1, p<0.001), red cell casts (OR=2.6, 95% CI: 1.2-5.4, p=0.015), anti-dsDNA (OR=3.4, 95% CI: 1.9-6.1, p<0.001) and anti-Smith (OR=2.8, 95% CI: 1.5-5.0, p=0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR=2.3, 95% CI: 1.3-4.2, p<0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR=14.9, 95% CI: 5.8-38.4, p<0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis. PMID:25124676

  1. Hagfish C1q: its unique binding property.

    PubMed

    Yamaguchi, Tomokazu; Takamune, Kazufumi; Kondo, Masakazu; Takahashi, Yukinori; Kato-Unoki, Yoko; Nakao, Miki; Sano, Naomi; Fujii, Tamotsu

    2014-03-01

    Hagfish C1q (HaC1q) was identified and characterized as a pattern-recognition molecule (PRM) in the hagfish complement system. The serum from hagfish, Eptatretus burgeri, was applied to a GlcNAc-agarose column and eluted sequentially with GlcNAc and EDTA. Four (31, 27, 26, and 19 kDa) and one (26 kDa) proteins were detected as bound molecules in the GlcNAc- and the EDTA-eluates, respectively. Among these, the 26 kDa protein from the EDTA eluate was found to be a homologue of mammalian C1q through cDNA analysis. HaC1q had an ability to bind to various microbes in a Ca(2+)-dependent manner and its target ligands on the microbes were lipopolysaccharide, lipoteichoic acid, and peptidoglycan. The binding of HaC1q to GlcNAc-agarose was not inhibited by an excess amount of monosaccharide such as GlcNAc. While HaC1q bound to Sepharose 6B with a matrix of GlcNAc-agarose (polymer of agarobiose), it did not bind to Sepharose 4B that contained lower concentration of agarobiose than Sepharose 6B. Therefore, the target of HaC1q on GlcNAc-agarose was concluded to be agarobiose and high density of the target moiety seemed to be required for the stable binding. This finding was in accordance with the known behavior of other lectins involved in the complement system. We have concluded that HaC1q recognizes agarobiose-like structures present on the surface of microbes and acts as a pattern-recognition molecule in the process for elimination of invading microbes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Facial Nerve Recovery in KbDb and C1q Knockout Mice: A Role for Histocompatibility Complex 1

    PubMed Central

    Akdagli, Seden; Williams, Ryan A.; Kim, Hyun J.; Yan, Yuling; Mustapha, Mirna

    2016-01-01

    Background: Understanding the mechanisms in nerve damage can lead to better outcomes for neuronal rehabilitation. The purpose of our study was to assess the effect of major histocompatibility complex I deficiency and inhibition of the classical complement pathway (C1q) on functional recovery and cell survival in the facial motor nucleus (FMN) after crush injury in adult and juvenile mice. Methods: A prospective blinded analysis of functional recovery and cell survival in the FMN after a unilateral facial nerve crush injury in juvenile and adult mice was undertaken between wild-type, C1q knockout (C1q−/−), and KbDb knockout (KbDb−/−) groups. Whisker function was quantified to assess functional recovery. Neuron counts were performed to determine neuron survival in the FMN after recovery. Results: After facial nerve injury, all adult wild-type mice fully recovered. Juvenile mice recovered incompletely corresponding to a greater neuron loss in the FMN of juveniles compared with adults. The C1q−/− juvenile and adult groups did not differ from wild type. The KbDb−/− adults demonstrated 50% recovery of whisker movement and decreased cell survival in FMN. The KbDb−/− juvenile group did not demonstrate any difference from control group. Conclusion: Histocompatibility complex I plays a role for neuroprotection and enhanced facial nerve recovery in adult mice. Inhibition of the classical complement pathway alone does not affect functional recovery or neuronal survival. The alternative and mannose binding pathways pose alternative means for activating the final components of the pathway that may lead to acute nerve damage. PMID:28293529

  3. Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease

    PubMed Central

    Tian, Erming; Heuck, Christoph J.; Epstein, Joshua; Johann, Donald J.; Swanson, Charles M.; Lukacs, Janet L.; Johnson, Marian; Binz, Regina; Boast, Angela; Sammartino, Gael; Usmani, Saad; Zangari, Maurizio; Waheed, Sarah; van Rhee, Frits; Barlogie, Bart

    2014-01-01

    Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease. PMID:24497533

  4. Juvenile Arthritis

    MedlinePlus

    ... A Patient / Caregiver Diseases & Conditions Juvenile Arthritis Juvenile Arthritis Fast Facts Arthritis in children is treatable. It ... as fevers or rash. What is juvenile idiopathic arthritis? Several types of arthritis, all involving chronic (long- ...

  5. Genetics Home Reference: 1q21.1 microdeletion

    MedlinePlus

    ... occurs on the long (q) arm of the chromosome in a region designated q21.1. This chromosomal change increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems. However, some people ...

  6. Preliminary Planet Population Statistics With Kepler Q1-Q16

    NASA Astrophysics Data System (ADS)

    Burke, Christopher J.; Mullally, Fergal; Christiansen, Jessie; Huber, Daniel; Coughlin, Jeffrey; Thompson, Susan E.; Jenkins, Jon Michael; Batalha, Natalie M.

    2014-06-01

    We present preliminary extrasolar planet population statistics from analysis of the Kepler Q1-Q16 planet candidate sample. The analysis takes advantage of the recent work on the Q1-Q16 Kepler planet candidate sample, extensive Monte-Carlo transit signal injection and recovery tests of the Kepler Pipeline, and updates to the stellar parameters provided by the Kepler Stellar Working Group. We also explore the sensitivity of the results to alternative inputs by considering a machine learning generated planet sample, systematics in the stellar sample properties, orbital eccentricity, and false positive rates.

  7. De novo interstitial direct duplication of Xq21.1q25 associated with skewed X-inactivation pattern.

    PubMed

    Tachdjian, G; Aboura, A; Benkhalifa, M; Creveaux, I; Foix-Hélias, L; Gadisseux, J F; Boespflug-Tanguy, O; Mohammed, M; Labrune, P

    2004-12-15

    Genotype-phenotype correlation in women with an abnormal phenotype associated with a duplication of the long arm of the X chromosome remains unclear. We report on prenatal diagnosis and follow-up of a girl with an Xq duplication and dysmorphic features. The abnormal phenotype included growth retardation, hypotonia, and nystagmus. In order to improve the resolution of the cytogenetic analysis, we used both conventional and array-based comparative genomic hybridization to perform a global molecular cytogenetic analysis of the genome. These molecular cytogenetic analyses showed a direct duplication Xq21.1 --> q25 without other chromosomal abnormalities. This duplication was originating from the paternal X chromosome. Moreover, a skewed X-inactivation pattern was observed leading to a partial functional disomy of the chromosomal region Xq21.1q25. This report and review of the literature suggest that functional disomy for chromosome X could explain the abnormal phenotype. In prenatal diagnosis, this can have implication for patient management and genetic counseling.

  8. Analysis of the Interaction between Globular Head Modules of Human C1q and Its Candidate Receptor gC1qR.

    PubMed

    Pednekar, Lina; Pathan, Ansar A; Paudyal, Basudev; Tsolaki, Anthony G; Kaur, Anuvinder; Abozaid, Suhair M; Kouser, Lubna; Khan, Haseeb A; Peerschke, Ellinor I; Shamji, Mohamed H; Stenbeck, Gudrun; Ghebrehiwet, Berhane; Kishore, Uday

    2016-01-01

    The heterotrimeric globular head (gC1q) domain of human C1q is made up of the C-terminal ends of the three individual chains, ghA, ghB, and ghC. A candidate receptor for the gC1q domain is a multi-functional pattern recognition protein, gC1qR. Since understanding of gC1qR and gC1q interaction could provide an insight into the pleiotropic functions of gC1qR, this study was undertaken to identify the gC1qR-binding site on the gC1q domain, using the recombinant ghA, ghB, and ghC modules and their substitution mutants. Our results show that ghA, ghB, and ghC modules can interact with gC1qR independently, thus reinforcing the notion of modularity within the gC1q domain of human C1q. Mutational analysis revealed that while Arg162 in the ghA module is central to interaction between gC1qR and C1q, a single amino acid substitution (arginine to glutamate) in residue 114 of the ghB module resulted in enhanced binding. Expression of gC1qR and C1q in adherent monocytes with or without pro-inflammatory stimuli was also analyzed by qPCR; it showed an autocrine/paracrine basis of C1q and gC1qR interaction. Microscopic studies revealed that C1q and gC1qR are colocalized on PBMCs. Cell proliferation assays indicated that ghA, ghB, and ghC modules were able to attenuate phytohemagglutinin-stimulated proliferation of PBMCs. Addition of gC1qR had an additive effect on the anti-proliferative effect of globular head modules. In summary, our results identify residues involved in C1q-gC1qR interaction and explain, to a certain level, their involvement on the immune cell surface, which is relevant for C1q-induced functions including inflammation, infection, and immunity.

  9. Analysis of the Interaction between Globular Head Modules of Human C1q and Its Candidate Receptor gC1qR

    PubMed Central

    Pednekar, Lina; Pathan, Ansar A.; Paudyal, Basudev; Tsolaki, Anthony G.; Kaur, Anuvinder; Abozaid, Suhair M.; Kouser, Lubna; Khan, Haseeb A.; Peerschke, Ellinor I.; Shamji, Mohamed H.; Stenbeck, Gudrun; Ghebrehiwet, Berhane; Kishore, Uday

    2016-01-01

    The heterotrimeric globular head (gC1q) domain of human C1q is made up of the C-terminal ends of the three individual chains, ghA, ghB, and ghC. A candidate receptor for the gC1q domain is a multi-functional pattern recognition protein, gC1qR. Since understanding of gC1qR and gC1q interaction could provide an insight into the pleiotropic functions of gC1qR, this study was undertaken to identify the gC1qR-binding site on the gC1q domain, using the recombinant ghA, ghB, and ghC modules and their substitution mutants. Our results show that ghA, ghB, and ghC modules can interact with gC1qR independently, thus reinforcing the notion of modularity within the gC1q domain of human C1q. Mutational analysis revealed that while Arg162 in the ghA module is central to interaction between gC1qR and C1q, a single amino acid substitution (arginine to glutamate) in residue 114 of the ghB module resulted in enhanced binding. Expression of gC1qR and C1q in adherent monocytes with or without pro-inflammatory stimuli was also analyzed by qPCR; it showed an autocrine/paracrine basis of C1q and gC1qR interaction. Microscopic studies revealed that C1q and gC1qR are colocalized on PBMCs. Cell proliferation assays indicated that ghA, ghB, and ghC modules were able to attenuate phytohemagglutinin-stimulated proliferation of PBMCs. Addition of gC1qR had an additive effect on the anti-proliferative effect of globular head modules. In summary, our results identify residues involved in C1q-gC1qR interaction and explain, to a certain level, their involvement on the immune cell surface, which is relevant for C1q-induced functions including inflammation, infection, and immunity. PMID:28018340

  10. A novel deletion in 2q24.1q24.2 in a girl with mental retardation and generalized hypotonia: a case report.

    PubMed

    Palumbo, Orazio; Palumbo, Pietro; Palladino, Teresa; Stallone, Raffaella; Zelante, Leopoldo; Carella, Massimo

    2012-01-03

    Chromosomal imbalances, recognized as the major cause of mental retardation, are often due to submicroscopic deletions or duplications not evidenced by conventional cytogenetic methods. To date, interstitial deletion of long arm of chromosome 2 have been reported for more than 100 cases, although studies reporting small interstitial deletions involving the 2q24.1q24.2 region are rare. With the widespread clinical use of comparative genomic hybridization chromosomal microarray technology, several cryptic chromosome imbalances have outlined new genotype-phenotype correlations and isolated a number of distinctive clinical conditions. here we report on a girl with mental retardation and generalized hypotonia. A genome-wide screen for copy number variations (CNVs) using single nucleotide polymorphisms (SNPs) array revealed a 7.5 Mb interstitial deletion of chromosome region 2q24.1q24.2 encompassing 59 genes, which was absent in parents. The gene content analysis of the deleted region and review of the literature revealed the presence of some genes that may be indicated as good candidate in generating the main clinical features of the patient. the present case represents a further patient described in the literature with an interstitial deletion of chromosome 2q24.1q24.2. Our patient shares some clinical features with the previously reported patients carriers of overlapping 2q24 deletion. Although more cases are needed to delineate the full-blown phenotype of 2q24.1q24.2 deletion syndrome, published data and present observation suggest that hemizygosity of this region results in a clinically recognizable phenotype. Considering these clinical and cytogenetic similarities, we suggest the existence of an emerging syndrome associated to 2q24.1q24.2 region.

  11. 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

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

    PubMed

    Tahtouh, Muriel; Garçon-Bocquet, Annelise; Croq, Françoise; Vizioli, Jacopo; Sautière, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Nagnan-le Meillour, Patricia; Pestel, Joël; Lefebvre, Christophe

    2012-02-22

    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. 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. 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. 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.

  13. Genomic profiling of atypical meningiomas associates gain of 1q with poor clinical outcome

    PubMed Central

    Gabeau-Lacet, Darlene; Engler, David; Gupta, Sumeet; Scangas, George A.; Betensky, Rebecca A.; Barker, Fred G.; Loeffler, Jay S.; Louis, David N.; Mohapatra, Gayatry

    2010-01-01

    Atypical meningiomas exhibit heterogeneous clinical outcomes. It is unclear which atypical meningiomas require aggressive multimodality treatment with surgery and radiation therapy versus surgery alone to prevent recurrence. Detailed molecular-genetic characterization of these neoplasms is necessary to better understand their pathogenesis and to identify genetic markers. Oligonucleotide array comparative genomic hybridization was used to identify frequent genetic alterations in 47 primary atypical meningiomas resected at Massachusetts General Hospital between August 1987 and September 2006. Eighty five percent of samples exhibited loss of 22q, including the NF2 gene. The second most frequent regions of loss were confined to the short arm of chromosome 1, particularly 1p33-p36.2 (70%) and 1p13.2 (64%). Other frequent regions of loss, detected in more than 50% of samples, included 14q, 10q, 8q, 7p, 21q, 19, 9q34, and 4p16. Frequent regions of gain were detected along 1q (59%), 17q (44%), 9q34 (30%) and 7q36 (26%). Univariate marker-by-marker analysis of all frequently identified copy number alterations showed potential correlation between gain of 1q and shorter progression free survival. Given the heterogeneous treatment outcomes of atypical meningioma, investigation of large-scale and focal genomic alterations in multi-institutional efforts may help clarify molecular-genetic signatures of clinical utility. PMID:19918127

  14. Primary Autosomal Recessive Microcephaly: MCPH5 Maps to 1q25-q32

    PubMed Central

    Jamieson, C. Ruth; Fryns, Jean-Pierre; Jacobs, Jos; Matthijs, Gert; Abramowicz, Marc J.

    2000-01-01

    Primary microcephaly is thought to result from genetic defects of the developmental program that generates large brain hemispheres in humans. Autosomal recessive inheritance is likely in most familial cases, and four loci were recently mapped by homozygosity. We report homozygosity mapping of a new locus, MCPH5, with a maximum multipoint LOD score of 3.51 at marker D1S1723, in a family of Turkish origin. The minimal critical region spans 11.4 cM between markers D1S384 and D1S2655, at 1q25-q32, and encompasses the cytogenetic breakpoints of chromosomal aberrations previously reported in unrelated patients with microcephaly. PMID:11067780

  15. C1q nephropathy: a variant of focal segmental glomerulosclerosis.

    PubMed

    Markowitz, Glen S; Schwimmer, Joshua A; Stokes, M Barry; Nasr, Samih; Seigle, Robert L; Valeri, Anthony M; D'Agati, Vivette D

    2003-10-01

    C1q nephropathy is a poorly understood and controversial entity with distinctive immunopathologic features. In order to better define the clinical-pathologic spectrum, we report the largest single-center series. Nineteen biopsies with C1q nephropathy were identified from among 8909 native kidney biopsies received from 1994 to 2002 (0.21%). Defining criteria included (1). dominant or co-dominant immunofluorescence staining for C1q, (2). mesangial electron dense deposits, and (3). no clinical or serologic evidence of systemic lupus erythematosus (SLE). The 19 patients were predominantly African American (73.7%), female (73.7%), young adults and children (range, 3 to 42 years; mean, 24.2 years). Presentation included nephrotic range proteinuria (78.9%), nephrotic syndrome (50%), renal insufficiency (27.8%), and hematuria (22.2%). No patient had hypocomplementemia or evidence of underlying autoimmune or infectious disease. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 17 (including six collapsing and two cellular) and minimal-change disease (MCD) in two. All biopsies displayed co-deposits of immunoglobulin G (IgG), with more variable IgM (84.2%), IgA (31.6%), and C3 (52.6%). Foot process effacement varied from 20% to 100% (mean, 51%). Twelve of 16 patients with available follow-up received immunosuppressive therapy. One patient had complete remission of proteinuria and six had partial remission. Four patients with FSGS pattern had progressive renal insufficiency, including two who reached end-stage renal disease (ESRD). Median time from biopsy to ESRD was 81 months. On multivariate analysis, the best correlate of renal insufficiency at biopsy and at follow-up was the degree of tubular atrophy and interstitial fibrosis (P = 0.0495 and 0.0341, respectively). C1q nephropathy falls within the clinical-pathologic spectrum of MCD/FSGS. Although further studies are needed to determine the pathomechanism of C1q deposition, we hypothesize that it may be a

  16. 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.

  17. 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.

  18. Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability.

    PubMed

    Gamba, Bruno F; Zechi-Ceide, Roseli M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C V; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

    2016-11-01

    We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

  19. Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes

    PubMed Central

    Trouw, Leendert A.; Groeneveld, Tom W.L.; Seelen, Marc A.; Duijs, Jacques M.G.J.; Bajema, Ingeborg M.; Prins, Frans A.; Kishore, Uday; Salant, David J.; Verbeek, J. Sjef; Kooten, Cees van; Daha, Mohamed R.

    2004-01-01

    Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, in SLE the presence of anti-C1q is associated with the occurrence of nephritis. We have generated mouse anti–mouse C1q mAb’s and used murine models to investigate whether anti-C1q autoantibodies actually contribute to renal pathology in glomerular immune complex disease. Administration of anti-C1q mAb JL-1, which recognizes the collagen-like region of C1q, resulted in glomerular deposition of C1q and anti-C1q autoantibodies and mild granulocyte influx, but no overt renal damage. However, combination of JL-1 with a subnephritogenic dose of C1q-fixing anti–glomerular basement membrane (anti-GBM) antibodies enhanced renal damage characterized by persistently increased levels of infiltrating granulocytes, major histological changes, and increased albuminuria. This was not observed when a non–C1q-fixing anti-GBM preparation was used. Experiments with different knockout mice showed that renal damage was dependent not only on glomerular C1q and complement activation but also on Fcγ receptors. In conclusion, anti-C1q autoantibodies deposit in glomeruli together with C1q but induce overt renal disease only in the context of glomerular immune complex disease. This provides an explanation why anti-C1q antibodies are especially pathogenic in patients with SLE. PMID:15343386

  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. 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.

  2. Identification of a de novo microdeletion 1q44 in a patient with hypogenesis of the corpus callosum, seizures and microcephaly - A case report.

    PubMed

    Westphal, Dominik S; Andres, Stephanie; Beitzel, Kirsten I; Makowski, Christine; Meitinger, Thomas; Hoefele, Julia

    2017-03-21

    Microdeletion 1q44 on the long arm of chromosome 1 leads to a phenotype that includes microcephaly, seizure, agenesis or hypogenesis of the corpus callosum, polydactyly, congenital heart defects and severe developmental delay along with characteristic facial dysmorphic signs. Until today, the distinct genetic causes for the different symptoms remain unclear. We here report a 1.2Mb de novo microdeletion 1q44 identified by performing a SNP array analysis. The female patient presented with microcephaly, seizure, hypogenesis of corpus callosum, postaxial hexadactyly, an atrial septal defect, a ventricular septal defect, hypertelorism, a long and smooth philtrum, thin vermilion borders, and micrognathia, all common features of microdeletion 1q44. An additionally performed chromosome analysis excluded any chromosomal rearrangements. The deleted region included the genes ZBTB18 as well as HNRNPU amongst others. Both are possibly candidate genes for the dysgenesis of the corpus callosum. AKT3, another candidate gene, was not affected by the deletion in this patient. Thus, the genetic findings in this case report spotlight ZBTB18 and HNRNPU in the genesis of the typical microdeletion 1q44 symptoms, especially concerning the dysgenesis of the corpus callosum, and therefore could help to unveil more of the genetic background of this syndrome.

  3. Phenotype and micro-array characterization of duplication 11q22.1-q25 and review of the literature.

    PubMed

    Ben-Abdallah-Bouhjar, Inesse; Mougou-Zerelli, Soumya; Hannachi, Hanene; Ben-Khelifa, Hela; Soyah, Najla; Labalme, Audrey; Sanlaville, Damien; Elghezal, Hatem; Saad, Ali

    2013-04-25

    Partial duplication of 11q is related to several malformations like growth retardation, intellectual disability, hypoplasia of corpus callosum, short nose, palate defects, cardiac, urinary tract abnormalities and neural tube defects. We have studied the clinical and molecular characteristics of a patient with severe intellectual disabilities, dysmorphic features, congenital inguinal hernia and congenital cerebral malformation which is referred to as cytogenetic exploration. We have used FISH and array CGH analysis for a better understanding of the double chromosomic aberration involving a 7p microdeletion along with a partial duplication of 11q due to adjacent segregation of a paternal reciprocal translocation t(7;11)(p22;q21) revealed after banding analysis. The patient's karyotype formula was: 46,XY,der(7)t(7;11)(p22;q21)pat. FISH study confirmed these rearrangement and array CGH technique showed precisely the loss of at least 140 Kb on chromosome7p22.3pter and 33.4Mb on chromosome11q22.1q25. Dysmorphic features, severe intellectual disability and brain malformations could result from the 11q22.1q25 trisomy. Our study provides an additional case for better understanding and delineating the partial duplication 11q.

  4. Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q.

    PubMed

    McGreal, Eamon P; Ikewaki, Nobunao; Akatsu, Hiroyasu; Morgan, B Paul; Gasque, Philippe

    2002-05-15

    It has been suggested that the human C1qRp is a receptor for the complement component C1q; however, there is no direct evidence for an interaction between C1q and C1qRp. In this study, we demonstrate that C1q does not show enhanced binding to C1qRp-transfected cells compared with control cells. Furthermore, a soluble recombinant C1qRp-Fc chimera failed to interact with immobilized C1q. The proposed role of C1qRp in the phagocytic response in vivo is also unsupported in that we demonstrate that this molecule is not expressed by macrophages in a variety of human tissues and the predominant site of expression is on endothelial cells. Studies on the rodent homolog of C1qRp, known as AA4, have suggested that this molecule may function as an intercellular adhesion molecule. Here we show that C1qRp is the Ag recognized by several previously described mAbs, mNI-11 and two anti-CD93 Abs (clones X2 and VIMD2b). Interestingly, mNI-11 (Fab') has been shown to promote monocyte-monocyte and monocyte-endothelial cell adhesive interactions. We produced a recombinant C1qRp-Fc chimera containing the C-type lectin-like domain of C1qRp and found specific binding to vascular endothelial cells in sections of inflamed human tonsil, indicating the presence of a C1qRp ligand at this site. This interaction was Ca(2+) independent and was not blocked by our anti-C1qRp mAb BIIG-4, but was blocked by the proadhesive mAb mNI-11. Collectively, these data indicate that C1qRp is not a receptor for C1q, and they support the emerging role of C1qRp (here renamed CD93) in functions relevant to intercellular adhesion.

  5. PE-1, a novel ETS oncogene family member, localizes to chromosome 1q21-q23

    SciTech Connect

    Klemsz, M.; Hromas, R.; Bruno, E.; Hoffman, R. ); Raskind, W. )

    1994-03-15

    The v-ets oncogene family shares a conserved peptide motif called the ETS domain that mediates sequence-specific DNA binding. This motif is unique among transcription factor families. Using partially degenerate oligonucleotides from conserved regions of the ETS domain and the polymerase chain reaction, the authors isolated a new member of v-ets family designated PE-1 from HL60 cells. PE-1 was expressed as an approximately 7.5-kb transcript in most cell lines tested. In the hairy cell leukemia line Eskol, there was an additional 1.8-kb transcript observed. PE-1 was the most common ETS domain gene found in CD34[sup +]HLA-DR[sup [minus

  6. Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone

    PubMed Central

    Han, Mei; Zhang, Ji-chun; Hashimoto, Kenji

    2017-01-01

    Objective Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. Results Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. Conclusion Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA. PMID:28138113

  7. Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency.

    PubMed

    Namjou, B; Keddache, M; Fletcher, D; Dillon, S; Kottyan, L; Wiley, G; Gaffney, P M; Wakeland, B E; Liang, C; Wakeland, E K; Scofield, R H; Kaufman, K; Harley, J B

    2012-09-01

    Homozygous C1q deficiency is an extremely rare condition and strongly associated with systemic lupus erythematosus. To assess and characterize C1q deficiency in an African-American lupus pedigree, C1q genomic region was evaluated in the lupus cases and family members. Genomic DNA from patient was obtained and C1q A, B and C gene cluster was sequenced using next generation sequencing method. The identified mutation was further confirmed by direct Sanger sequencing method in the patient and all blood relatives. C1q levels in serum were measured using sandwich ELISA method. In an African-American patient with lupus and C1q deficiency, we identified and confirmed a novel homozygote start codon mutation in C1qA gene that changes amino acid methionine to arginine at position 1. The Met1Arg mutation prevents protein translation (Met1Arg). Mutation analyses of the patient's family members also revealed the Met1Arg homozygote mutation in her deceased brother who also had lupus with absence of total complement activity consistent with a recessive pattern of inheritance. The identification of new mutation in C1qA gene that disrupts the start codon (ATG to AGG (Met1Arg)) has not been reported previously and it expands the knowledge and importance of the C1q gene in the pathogenesis of lupus especially in the high-risk African-American population.

  8. Crystal structure of zebrafish complement 1qA globular domain.

    PubMed

    Yuan, Hongyu; Chen, Rong; Tariq, Mansoor; Liu, Yanjie; Sun, Yaping; Xia, Chun

    2016-10-01

    C1q contains three globular domains (C1qgD) that are the key functional component of the classical complement system. C1qgD can interact with important immune molecules, including IgG and C-reactive protein (CRP) to form defense systems to protect animals. Here, the first non-mammalian structure, zebrafish C1qA globular domain (Dare-C1qAgD) was solved. Although the overall architecture of Dare-C1qAgD is similar to human C1qA, residues involved in C1qBgD, C1qCgD, and CRP binding are somewhat different while residues involved in IgG binding are not present in zebrafish. The structure gives insight into how human and fish C1qA evolved from an ancestral protein.

  9. 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

  10. Crystallization and preliminary crystallographic studies of the complement 1qA globular domain from zebrafish, Dare-C1qAgD.

    PubMed

    Yuan, Hongyu; Chen, Rong; Liu, Yanjie; Tariq, Mansoor; Sun, Yaping; Xia, Chun

    2014-07-01

    Complement 1q (C1q) is the first component of the complement system which can initiate the classical complement pathway. In human, C1q is composed of 18 polypeptide chains: six C1qA chains, six C1qB chains and six C1qC chains. Each chain has a signal peptide and is comprised of a collagen-like region and a C-terminal C1q globular domain (C1qgD), which is organized as a heterotrimer. C1qgD can recognize antigen-antibody complexes containing IgG and IgM or can bind directly to the C-reactive protein. Although the classical complement pathway is found from fish to mammals, only the human C1qgD structure has been determined. Compared with that of mammals, fish C1q exhibits similar immune functions and genome arrangement. In order to illustrate the structure of C1qgD in fish, zebrafish (Danio rerio) C1qA globular domain (Dare-C1qAgD) was expressed, purified and crystallized. X-ray diffraction data were collected from a crystal to a resolution of 2.05 Å; the crystal belonged to the orthorhombic space group P2₁2₁2₁, with unit-cell parameters a=50.347, b=85.059, c=95.560 Å. It contained three molecules in the asymmetric unit. The Matthews coefficient value VM was 2.31 Å3 Da(-1), with a calculated solvent content of 46.7%. The data will help to give insight into the structural basis of C1qA in fish species.

  11. Identification and function of a novel C1q domain-containing (C1qDC) protein in triangle-shell pearl mussel (Hyriopsis cumingii).

    PubMed

    Huang, Ying; Wang, Wen; Ren, Qian

    2016-11-01

    C1q is the target recognition sequence of the classical complement pathway and a major link that connects innate and acquired immunity. In this study, a C1qDC homolog, HcC1qDC5, from the triangle-shell pearl mussel (Hyriopsis cumingii) was identified. The complete nucleotide sequence of HcC1qDC5 cDNA consists of a 5'-untranslated terminal region (UTR) of 123 bp, a 3'-UTR of 105 bp with a poly(A) tail, and an open reading frame (ORF) of 1344 bp, which encodes a polypeptide of 447 amino acids. HcC1qDC5 contains a signal peptide and three typical C1q domains. The HcC1qDC5 gene was expressed in all tested tissues, with the highest expression in the mantle. Staphylococcus aureus or Vibrio parahaemolyticus infection increased the mRNA transcript levels of HcC1qDC5 in the hepatopancreas and mantle. The recombinant HcC1qDC5 protein could bind to Gram-negative and Gram-positive bacteria as well as to different PAMPs (LPS and PGN). RNAi results showed that HcC1qDC5 was involved in V. parahaemolyticus-induced HcTNF and HcWAP expression. The combined results demonstrated that HcC1qDC5 participates in the innate immunity of H. cumingii. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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.

  13. The production and secretion of complement component C1q by human mast cells.

    PubMed

    van Schaarenburg, Rosanne A; Suurmond, Jolien; Habets, Kim L L; Brouwer, Mieke C; Wouters, Diana; Kurreeman, Fina A S; Huizinga, Tom W J; Toes, René E M; Trouw, Leendert A

    2016-10-01

    C1q is the initiation molecule of the classical pathway of the complement system and is produced by macrophages and immature dendritic cells. As mast cells share the same myeloid progenitor cells, we have studied whether also mast cells can produce and secrete C1q. Mast cells were generated in vitro from CD34+ progenitor cells from buffy coats or cord blood. Fully differentiated mast cells were shown by both RNA sequencing and qPCR to express C1QA, C1QB and C1QC. C1q produced by mast cells has a similar molecular make-up as serum C1q. Reconstituting C1q depleted serum with mast cell supernatant in haemolytic assays, indicated that C1q secreted by mast cells is functionally active. The level of C1q in supernatants produced under basal conditions was considerably enhanced upon stimulation with LPS, dexamethasone in combination with IFN- γ or via FcεRI triggering. Mast cells in human tissues stained positive for C1q in both healthy and in inflamed tissue. Moreover, mast cells in healthy and diseased skin appear to be the predominant C1q positive cells. Together, our data reveal that mast cells are able to produce and secrete functional active C1q and indicate mast cells as a local source of C1q in human tissue.

  14. 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 ...

  15. The soluble recombinant form of a binding protein/receptor for the globular domain of C1q (gC1qR) enhances blood coagulation.

    PubMed

    Peerschke, E I; Jesty, J; Reid, K B; Ghebrehiwet, B

    1998-01-01

    The gC1qR is a ubiquitously expressed, 33 kDa cellular protein which recognizes the globular domains of C1q. Recent evidence suggests that the gC1qR also serves as the Zn(++)-dependent endothelial cell binding site for factor XII and high-molecular-weight kininogen, and activates intrinsic coagulation and kinin pathways in purified systems. In addition, activated lymphocytes have been reported to release soluble gC1qR. Thus, the present study investigated the procoagulant potential of soluble gC1qR in human plasma using the recombinant protein (rgC1qR). rgC1qR supported a dose-dependent shortening of extrinsic coagulation using the prothrombin time in the presence of diluted (1/50-1/500) thromboplastin. Maximum enhancement of the prothrombin time resulted in shortening of the clotting time from 78.8 +/- 0.4 s to 68.5 +/- 0.6 s (mean +/- SD, n = 8) in the presence of 50 micrograms/ml (1.5 mumol/l) rgC1qR. rgC1qR also enhanced the intrinsic pathway of coagulation evaluated in the absence of activators of the contact system, as demonstrated by a shortening of the plasma recalcification time from 348 +/- 66 s to 140 +/- 23 s (n = 4). rgC1qR, however, had no effect on intrinsic coagulation in the presence of undiluted kaolin or ellagic acid, and under these conditions failed to shorten the activated partial thromboplastin time of factor VIII or factor-IX-deficient plasma. rgC1qR further failed to affect thrombin and factor Xa generation assayed using chromogenic substrates, and did not enhance thrombin-induced conversion of fibrinogen to fibrin. Interestingly, the procoagulant activity of the rgC1qR was measurable in either factor-XII- or factor-XI-deficient plasma, suggesting that it was not exclusively focused on the contact system of coagulation. Although the mechanism of action of gC1qR on blood coagulation remains obscure, the data suggest a potential role for this protein in hemostatic and thrombotic events.

  16. 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.

  17. Biosynthesis of normal and low-molecular-mass complement component C1q by cultured human monocytes and macrophages.

    PubMed Central

    Hoekzema, R; Brouwer, M C; de Graeff-Meeder, E R; van Helden, H P; Hack, C E

    1989-01-01

    High levels of low-molecular-mass complement component C1q (LMM-C1q), a haemolytically inactive form of C1q, are found in serum of individuals with inherited complete (functional) C1q deficiency and in serum of patients with systemic lupus erythematosus, whereas lower levels are present in normal serum [Hoekzema, Hannema, Swaak, Paardekooper & Hack (1985) J. Immunol. 135, 265-271]. To investigate whether LMM-C1q is a (by-)product of C1q synthesis or the result of degradation of C1q, cultures of blood monocytes and of alveolar macrophages, which secrete functional C1q, were studied. A considerable portion of C1q-like protein secreted by these cells was found to be LMM-C1q. In contrast with the C1q fragments that resulted from degradation of normal C1q during phagocytosis, culture-derived LMM-C1q appeared to be identical with LMM-C1q found in serum, as judged by sedimentation behaviour, subunit structure and recognition by poly- and mono-clonal antibodies raised against C1q. The presence of LMM-C1q in cytoplasmic organelles compatible with the Golgi apparatus and the inability to generate LMM-C1q by impeding hydroxylation and triple-helix formation of C1q further argues against degradation as its source. Monocyte cultures of homozygous probands from two families with complete functional C1q deficiency reflected the abnormalities in serum, i.e. absence of functional C1q, but increased levels of LMM-C1q. By contrast, secretion of C1q and LMM-C1q by cells from healthy individuals was clearly co-ordinate, indicating that LMM-C1q in serum may provide a unique marker of C1q synthesis in vivo. Images Fig. 1. Fig. 3. Fig. 4. Fig. 6. PMID:2649076

  18. Serum C1q as a novel biomarker of sarcopenia in older adults.

    PubMed

    Watanabe, Shinya; Sato, Koji; Hasegawa, Natsuki; Kurihara, Toshiyuki; Matsutani, Kenji; Sanada, Kiyoshi; Hamaoka, Takafumi; Fujita, Satoshi; Iemitsu, Motoyuki

    2015-03-01

    Aging-induced elevation in C1q secretion activates the Wnt signaling pathway in muscles, leading to the development of muscle fibrosis. However, the association between serum C1q level and muscle mass and strength remains unclear in humans. The aim of the study was to elucidate whether serum C1q level is associated with aging- and resistance training-induced changes in muscle mass and strength. First, in a cross-sectional study, we investigated the association between serum C1q level and muscle mass and strength in 131 healthy subjects, aged 20-81 yr. Second, in an intervention study, we examined the association between the effects of serum C1q level and muscle mass and strength on 12 wk resistance training in 11 healthy older adults (60-81 yr). In the cross-sectional study, serum C1q level increased with aging and was negatively correlated with muscle mass and strength. Furthermore, 12 wk resistance training in older adults reduced the age-associated elevation in serum C1q levels. The training effect of serum C1q level significantly correlated with the change in the cross-sectional area of the thigh (r = -0.703; P < 0.01). Serum C1q level may reflect loss of muscle mass; therefore, C1q may be a novel biomarker of sarcopenia. © FASEB.

  19. 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.

  20. Breast Tumors with Elevated Expression of 1q Candidate Genes Confer Poor Clinical Outcome and Sensitivity to Ras/PI3K Inhibition

    PubMed Central

    Viveka Thangaraj, Soundara; Periasamy, Jayaprakash; Bhaskar Rao, Divya; Barnabas, Georgina D.; Raghavan, Swetha; Ganesan, Kumaresan

    2013-01-01

    Genomic aberrations are common in cancers and the long arm of chromosome 1 is known for its frequent amplifications in breast cancer. However, the key candidate genes of 1q, and their contribution in breast cancer pathogenesis remain unexplored. We have analyzed the gene expression profiles of 1635 breast tumor samples using meta-analysis based approach and identified clinically significant candidates from chromosome 1q. Seven candidate genes including exonuclease 1 (EXO1) are consistently over expressed in breast tumors, specifically in high grade and aggressive breast tumors with poor clinical outcome. We derived a EXO1 co-expression module from the mRNA profiles of breast tumors which comprises 1q candidate genes and their co-expressed genes. By integrative functional genomics investigation, we identified the involvement of EGFR, RAS, PI3K / AKT, MYC, E2F signaling in the regulation of these selected 1q genes in breast tumors and breast cancer cell lines. Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA–drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors. Thus, we identified seven 1q candidate genes strongly associated with the poor survival of breast cancer patients and identified the possibility of targeting them with EGFR/RAS/PI3K inhibitors. PMID:24147022

  1. Dermatomyositis (Juvenile)

    MedlinePlus

    ... of children with JDM may have a more chronic course that is less responsive to therapy. Juvenile ... disease and arthritis. Since the myopathies can be chronic diseases, it is important for patients to have ...

  2. 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)

  3. Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13.

    PubMed

    Karakoula, Katherine; Suarez-Merino, Blanca; Ward, Samantha; Phipps, Kim P; Harkness, William; Hayward, Richard; Thompson, Dominic; Jacques, Thomas S; Harding, Brian; Beck, John; Thomas, David G T; Warr, Tracy J

    2008-11-01

    Loss of chromosome 22 and gain of 1q are the most frequent genomic aberrations in ependymomas, indicating that genes mapping to these regions are critical in their pathogenesis. Using real-time quantitative PCR, we measured relative copy numbers of 10 genes mapping to 22q12.3-q13.33 and 10 genes at 1q21-32 in a series of 47 pediatric intracranial ependymomas. Loss of one or more of the genes on 22 was detected in 81% of cases, with RAC2 and C22ORF2 at 22q12-q13.1 being deleted most frequently in 38% and 32% of ependymoma samples, respectively. Combined analysis of quantitative-PCR with methylation-specific PCR and bisulphite sequencing revealed a high rate (>60% ependymoma) of transcriptional inactivation of C22ORF2, indicating its potential importance in the development of pediatric ependymomas. Increase of relative copy numbers of at least one gene on 1q were detected in 61% of cases, with TPR at 1q25 displaying relative copy number gains in 38% of cases. Patient age was identified as a significant adverse prognostic factor, as a significantly shorter overall survival time (P = 0.0056) was observed in patients <2 years of age compared with patients who were >2 years of age. Loss of RAC2 at 22q13 or amplification of TPR at 1q25 was significantly associated with shorter overall survival in these younger patients (P = 0.0492 and P = < 0.0001, respectively). This study identifies candidate target genes within 1q and 22q that are potentially important in the pathogenesis of intracranial pediatric ependymomas.

  4. Anti-C1q Autoantibodies, Novel Tests, and Clinical Consequences

    PubMed Central

    Mahler, Michael; van Schaarenburg, Rosanne A.; Trouw, Leendert A.

    2013-01-01

    Although anti-C1q autoantibodies have been described more than four decades ago a constant stream of papers describing clinical associations or functional consequences highlights that anti-C1q antibodies are still hot and happening. By far the largest set of studies focus on anti-C1q antibodies is systemic lupus erythematosus (SLE). In SLE anti-C1q antibodies associate with involvement of lupus nephritis in such a way that in the absence of anti-C1q antibodies it is unlikely that a flare in nephritis will occur. Anti-C1q antibodies occur in several autoimmune conditions but also in healthy individuals. Although considerable progress has been made in the understanding of how anti-C1q antibodies may contribute to tissue injury there is still a lot to learn about the processes involved in the breaking of tolerance to this protein. There has been considerable improvement in the assays employed to test for the presence of anti-C1q antibodies. Hopefully with these new and standardized assays at hand larger clinical association studies will be conducted with independent replication. Such large-scale studies will reveal the true value of clinical testing for anti-C1q autoantibodies in several clinical conditions. PMID:23717311

  5. Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q.

    PubMed

    Rehmus, E H; Greene, B M; Everson, B A; Ratnoff, O D

    1987-08-01

    Hageman factor (HF, Factor XII) is activated by glass, collagen, and ellagic acid, and initiates blood coagulation via the intrinsic pathway. C1q inhibits collagen-induced platelet aggregation and adherence of platelets to glass, effects attributable to the collagen-like region of C1q. We examined the actions of C1q on HF activation. Incubation of C1q with HF before addition of HF-deficient plasma extended the activated partial thromboplastin time. Similarly, when glass tubes were coated with C1q before testing, the partial thromboplastin time of normal plasma was increased. C1q reduced the activation of HF by ellagic acid, as measured by the release of p-nitroaniline from the synthetic substrate H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride, an effect inhibited by monoclonal anti-human C1q murine IgG and by digestion of C1q by collagenase. Thus, C1q inhibits activation of HF in vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation.

  6. Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q.

    PubMed Central

    Rehmus, E H; Greene, B M; Everson, B A; Ratnoff, O D

    1987-01-01

    Hageman factor (HF, Factor XII) is activated by glass, collagen, and ellagic acid, and initiates blood coagulation via the intrinsic pathway. C1q inhibits collagen-induced platelet aggregation and adherence of platelets to glass, effects attributable to the collagen-like region of C1q. We examined the actions of C1q on HF activation. Incubation of C1q with HF before addition of HF-deficient plasma extended the activated partial thromboplastin time. Similarly, when glass tubes were coated with C1q before testing, the partial thromboplastin time of normal plasma was increased. C1q reduced the activation of HF by ellagic acid, as measured by the release of p-nitroaniline from the synthetic substrate H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride, an effect inhibited by monoclonal anti-human C1q murine IgG and by digestion of C1q by collagenase. Thus, C1q inhibits activation of HF in vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation. PMID:3038961

  7. 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

  8. 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.

  9. Reciprocal translocation between Y chromosome long arm euchromatin and the short arm of chromosome 1.

    PubMed

    Pabst, Brigitte; Glaubitz, Ralf; Schalk, Thomas; Schneider, Ulrich; Schulze, Wolfgang; Miller, Konstantin

    2002-01-01

    A case with an apparently balanced reciprocal translocation between the long arm of the Y chromosome and the short arm of chromosome 1 t(Y;1)(q11.2;p34.3) is described. The translocation was found in a phenotypically normal male ascertained by infertility and presenting for intra-cytoplasmatic sperm injection treatment. Histological examination of testicular biopsies revealed spermatogenic failure. Chromosome painting with probes for chromosome 1 and for the euchromatic part of the Y chromsome confirmed the translocation of euchromatic Y chromosomal material onto the short arm of chromosome 1 and of a substantial part of the short arm of chromosome 1 onto the Y chromosome. Among the Y/autosome translocations, the rearrangements involving long arm euchromatin of the Y chromosome are relatively rare and mostly associated with infertility. Microdeletion screening at the azoospermia locus revealed no deletions, suggesting another mechanism causing infertility in this translocation carrier.

  10. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Comparative study of three C1q domain containing proteins from pacific oyster Crassostrea gigas.

    PubMed

    Lv, Zhao; Qiu, Limei; Wang, Mengqiang; Jia, Zhihao; Wang, Weilin; Xin, Lusheng; Liu, Zhaoqun; Wang, Lingling; Song, Linsheng

    2017-09-18

    C1q domain containing proteins (C1qDCs) are a family of proteins containing a globular head C1q domain (ghC1q) in C-terminus, which serve as pattern recognition receptors (PRRs) and mediate a series of immune responses. In the present study, three C1qDC proteins from pacific oyster Crassostrea gigas (CgC1qDC-2, CgC1qDC-3, CgC1qDC-4) were characterized and comparatively investigated to understand their roles in the immune response. All the three recombinant CgC1qDC proteins (rCgC1qDCs) could bind lipopolysaccharide (LPS) significantly but they could not bind lipoteichoic acid (LTA), β-1,3-glucan (GLU), mannan (MAN), and polyinosinic-polycytidylic acid (Poly I:C). Correspondingly, they all exhibited higher binding activities towards Gram-negative bacteria Vibrio anguillarum and V. splendidus. Moreover, they could enhance the phagocytosis of oyster hemocytes, and the enhancements towards Gram-negative bacteria were significantly higher than that towards Gram-positive bacteria (p < 0.01). The LPS binding affinity of rCgC1qDC-3 (KD = 8.74 × 10(-7) M) was higher than that of rCgC1qDC-2 (KD = 7.76 × 10(-5) M) and rCgC1qDC-4 (KD = 1.09 × 10(-5) M). Meanwhile, rCgC1qDC-3 exhibited significantly higher enhancement on phagocytosis of oyster hemocytes towards Gram-negative bacteria than that of rCgC1qDC-2 and rCgC1qDC-4 (p < 0.05). After the secondary challenge with V. splendidus, the up-regulations of CgC1qDC-2 and CgC1qDC-4 mRNA in hemocytes occurred at 6 h, while that of CgC1qDC-3 was observed at 3 h and lasted for 24 h. And CgC1qDC-3 responded with high mRNA level for tested 24 h upon the secondary challenge with V. anguillarum as well. These results collectively suggested that three CgC1qDCs could serve as PRRs to specifically recognize certain Gram-negative bacteria and opsonins to enhance phagocytosis. CgC1qDC-3, with higher binding affinity to LPS, stronger opsonization and more rapid and persistent mRNA expression response upon the secondary

  12. Genetic associations of the interleukin locus at 1q32.1 with clinical outcomes of cutaneous melanoma

    PubMed Central

    Rendleman, Justin; Vogelsang, Matjaz; Bapodra, Anuj; Adaniel, Christina; Silva, Ines; Moogk, Duane; Martinez, Carlos N; Fleming, Nathaniel; Shields, Jerry; Shapiro, Richard; Berman, Russell; Pavlick, Anna; Polsky, David; Shao, Yongzhao; Osman, Iman; Krogsgaard, Michelle; Kirchhoff, Tomas

    2016-01-01

    Background Due to high melanoma immunogenicity, germline genetic variants in immune pathways have been studied for association with melanoma prognosis. However, limited candidate selection, inadequate power, or lack of independent validation have hampered the reproducibility of these prior findings, preventing personalised clinical applicability in melanoma prognostication. Our objective was to assess the prognostic utility of genetic variants in immunomodulatory pathways for prediction of melanoma clinical outcomes. Methods We genotyped 72 tag single nucleotide polymorphisms (SNPs) in 44 immunomodulatory genes in a population sample of 1022 melanoma patients and performed Cox regression analysis to test the association between SNPs and melanoma recurrence-free (RFS) and overall survival (OS). We have further investigated the most significant associations using a fine mapping strategy and followed with functional analyses in CD4+ T cells in a subset of 75 melanoma patients. Results The most significant associations were found with melanoma OS for rs3024493 in IL10 at chromosome 1q32.1 (heterozygous HR 0.58, 95% CI 0.39 to 0.86; p = 0.0006), a variant previously shown to be linked with autoimmune conditions. Multiple additional SNPs at 1q32.1 were also nominally associated with OS confirming at least two independent association signals in this locus. In addition, we found rs3024493 associated with the downregulation of interleukin 10 (IL10) secretion in CD4+ T cells. Conclusions We discovered novel associations of IL10 with melanoma survival at 1q32.1, suggesting this locus should be considered as a novel melanoma prognostic biomarker with potential for aiding melanoma patient management. Our findings also provide further support for an alternative role of IL10 in stimulation of anti-tumour immune response. PMID:25604082

  13. eQTL analysis links inflammatory bowel disease associated 1q21 locus to ECM1 gene.

    PubMed

    Repnik, Katja; Potočnik, Uroš

    2016-08-01

    Genome-wide association studies (GWAS) have been highly successful in inflammatory bowel disease (IBD) with 163 confirmed associations so far. We used expression quantitative trait loci (eQTL) mapping to analyze IBD associated regions for which causative gene from the region is still unknown. First, we performed an extensive literature search and in silico analysis of published GWAS in IBD and eQTL studies and extracted 402 IBD associated SNPs assigned to 208 candidate loci, and 9562 eQTL correlations. When crossing GWA and eQTL data we found that for 50 % of loci there is no eQTL gene, while for 31.2 % we can determine one gene, for 11.1 % two genes and for the remaining 7.7 % three or more genes. Based on that we selected loci with one, two, and three or more eQTL genes and analyzed them in peripheral blood lymphocytes and intestine tissue samples of 606 Slovene patients with IBD and in 449 controls. Association analysis of selected SNPs showed statistical significance for three (rs2631372 and rs1050152 on 5q locus and rs13294 on 1q locus) out of six selected SNPs with at least one phenotype. Furthermore, with eQTL analysis of selected chromosomal regions, we confirmed a link between SNP and gene for four (SLC22A5 on 5q, ECM1 on 1q, ORMDL3 on 17q, and PUS10 on 2p locus) out of five selected regions. For 1q21 loci, we confirmed gene ECM1 as the most plausible gene from this region to be involved in pathogenesis of IBD and thereby contributed new eQTL correlation from this genomic region.

  14. 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 ...

  15. [Structure, distribution, classification, and function of C1q protein family: a review].

    PubMed

    Liu, Ge; Pang, Yue; Liu, Xin; Li, Qing-Wei

    2013-09-01

    The C1q protein family consists of many proteins containing a Clq domain, which exists widely within organisms from bacteria to mammals. The domain organization of these proteins mainly includes a leading signal peptide, a collagen-like region, and a globular Clq domain. According to their structural characteristics, the C1q protein family can be divided into three subgroups: C1q, C1q-like and ghC1q. C1q, as the first subcomponent of classical pathway in the complement system, has the ability to bind immune complexes and triggers activation of the classical complement pathway. In addition, it can be a pattern recognition receptor with the unique ability to sense an amazing variety of ligands. C1q-like protein contains a collagen-like region and a globular Clq domain which is similar to Clq molecule. It involves in leech central nervous system repair. However, in vertebrates, its function converts from a lectin to an immunoglobulin binding molecule and it involves in the activation of complement system. The structure of ghC1q protein is composed of a globular Clq domain and a short N-terminal sequence. This protein contains secreted globular head C1q proteins and cellular globular head C1q proteins. The sghClq protein plays an important role in the innate immune system of invertebrates. The sghC1q proteins that belong to vertebrates may serve as a new class of transneuronal regulators of synapse development and synaptic plasticity in various brain regions. The earliest cghC1q gene can be traced back to bacteria of the genus Bacillus. Its stereotypical gC1q jelly roll topology substantiates that the gC1q domain has an ancient evolutionary history and a highly conserved structure. This review focuses on the structure, distribution, classification, and function of C1q family proteins, providing valuable clues for the future research in this field.

  16. 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. © 2014 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

  17. 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.

  18. 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.

  19. Interstitial Deletions at 6q14.1q15 Associated with Developmental Delay and a Marfanoid Phenotype

    PubMed Central

    Lowry, R.B.; Chernos, J.E.; Connelly, M.S.; Wyse, J.P.H.

    2013-01-01

    There are a number of reports of interstitial deletions of the long arm of chromosome 6 that have developmental delay and obesity suggesting that this is a distinct phenotype almost like Prader-Willi syndrome. Here we report a patient with a similar deletion but a strikingly different phenotype, one more in keeping with Marfan syndrome, although he does not fulfil the criteria for that syndrome. Array comparative genomic hybridization was performed to investigate a patient with a striking phenotype. This revealed an interstitial deletion of 6q14.1q15. Parental FISH studies were normal, indicating that this is a de novo deletion. Our patient has a completely different phenotype compared to other patients reported to have similar deletions. The common feature is developmental delay, but the body features are quite different in that our patient is tall, strikingly thin with pectus excavatum, scoliosis, skin striae, arachnodactyly, pes planus, cataracts, and a high-arched palate. This contrasts with other patients who have a similar deletion but have short stature and obesity. 6q14.1q15 interstitial deletions can have a very variable phenotype and do not necessarily conform to a clinical recognizable microdeletion syndrome caused by haploinsufficiency of dosage-sensitive genes in that region as proposed by others. PMID:24167463

  20. Phenotypic Variability Associated with a Large Recurrent 1q21.1 Microduplication in a Three-Generation Family

    PubMed Central

    Verhagen, Judith M.A.; de Leeuw, Nicole; Papatsonis, Dimitri N.M.; Grijseels, Els W.M.; de Krijger, Ronald R.; Wessels, Marja W.

    2015-01-01

    Recurrent copy number variants of the q21.1 region of chromosome 1 have been associated with variable clinical features, including developmental delay, mild to moderate intellectual disability, psychiatric and behavioral problems, congenital heart malformations, and craniofacial abnormalities. A subset of individuals is clinically unaffected. We describe a unique 3-generation family with a large recurrent 1q21.1 microduplication (BP2-BP4). Our observations underline the incomplete penetrance and phenotypic variability of this rearrangement. We also confirm the association with congenital heart malformations, chronic depression, and anxiety. Furthermore, we report a broader range of dysmorphic features. The extreme phenotypic heterogeneity observed in this family suggests that additional factors modify the clinical phenotype. PMID:26279651

  1. [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.

  2. 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

  3. The presence of two rare genomic syndromes, 1q21 deletion and Xq28 duplication, segregating independently in a family with intellectual disability.

    PubMed

    Ha, Kyungsoo; Shen, Yiping; Graves, Tyler; Kim, Cheol-Hee; Kim, Hyung-Goo

    2016-01-01

    1q21 microdeletion syndrome is a rare contiguous gene deletion disorder with de novo or autosomal dominant inheritance patterns and its phenotypic features include intellectual disability, distinctive facial dysmorphism, microcephaly, cardiac abnormalities, and cataracts. MECP2 duplication syndrome is an X-linked recessive neurodevelopmental disorder characterized by intellectual disability, global developmental delay, and other neurological complications including late-onset seizures. Previously, these two different genetic syndromes have not been reported segregating independently in a same family. Here we describe two siblings carrying either a chromosome 1q21 microdeletion or a chromosome Xq28 duplication. Using a comparative genomic hybridization (CGH) array, we identified a 1.24 Mb heterozygous deletion at 1q21 resulting in the loss of 9 genes in a girl with learning disability, hypothyroidism, short stature, sensory integration disorder, and soft dysmorphic features including cupped ears and a unilateral ear pit. We also characterized a 508 kb Xq28 duplication encompassing MECP2 in her younger brother with hypotonia, poor speech, cognitive and motor impairment. The parental CGH and quantitative PCR (qPCR) analyses revealed that the 1q21 deletion in the elder sister is de novo, but the Xq28 duplication in the younger brother was originally inherited from the maternal grandmother through the mother, both of whom are asymptomatic carriers. RT-qPCR assays revealed that the affected brother has almost double the amount of MECP2 mRNA expression compared to other family members of both genders including maternal grandmother and mother who have the same Xq28 duplication with no phenotype. This suggests the X chromosome with an Xq28 duplication in the carrier females is preferentially silenced. From our understanding, this would be the first report showing the independent segregation of two genetically unrelated syndromes, 1q21 microdeletion and Xq28 duplication

  4. Relevance of anti-C1q autoantibodies to lupus nephritis.

    PubMed

    Tsirogianni, Alexandra; Pipi, Elena; Soufleros, Kostantinos

    2009-09-01

    The first component of the classical pathway of the complement system (C1q) is considered to have a crucial role in the clearance of immune complexes (ICs) as well as in the removal of waste material originating from apoptotic cells. A prolonged exposure of C1q epitopes to the immune system could eventually lead to an autoimmune response against itself. Although autoantibodies against C1q are found in several diseases, their clinical interest originates from their strong association to active lupus nephritis (LN). Several studies indicate that anti-C1q autoantibodies could serve as a reliable serologic marker in the assessment of LN activity compared to other immunological tests. Additionally, it was suggested that anti-C1q autoantibodies could play a role in LN pathogenesis. Their potential pathogenic actions likely depend on genetic background, titers, Ig classes and subclasses, and specific epitopes of anti-C1q autoantibodies as well as C1q availability and allocation. It is still unclear which different types of anti-C1q autoantibodies dominate in each case and if their upregulation is pathogenic, an epiphenomenon of aberrant tissue damage, or compensatory to an uncontrolled immune response.

  5. Enhanced synaptic connectivity and epilepsy in C1q knockout mice.

    PubMed

    Chu, Yunxiang; Jin, Xiaoming; Parada, Isabel; Pesic, Alexei; Stevens, Beth; Barres, Ben; Prince, David A

    2010-04-27

    Excessive CNS synapses are eliminated during development to establish mature patterns of neuronal connectivity. A complement cascade protein, C1q, is involved in this process. Mice deficient in C1q fail to refine retinogeniculate connections resulting in excessive retinal innervation of lateral geniculate neurons. We hypothesized that C1q knockout (KO) mice would exhibit defects in neocortical synapse elimination resulting in enhanced excitatory synaptic connectivity and epileptiform activity. We recorded spontaneous and evoked field potential activity in neocortical slices and obtained video-EEG recordings from implanted C1q KO and wild-type (WT) mice. We also used laser scanning photostimulation of caged glutamate and whole cell recordings to map excitatory and inhibitory synaptic connectivity. Spontaneous and evoked epileptiform field potentials occurred at multiple sites in neocortical slices from C1q KO, but not WT mice. Laser mapping experiments in C1q KO slices showed that the proportion of glutamate uncaging sites from which excitatory postsynaptic currents (EPSCs) could be evoked ("hotspot ratio") increased significantly in layer IV and layer V, although EPSC amplitudes were unaltered. Density of axonal boutons was significantly increased in layer V pyramidal neurons of C1q KO mice. Implanted KO mice had frequent behavioral seizures consisting of behavioral arrest associated with bihemispheric spikes and slow wave activity lasting from 5 to 30 s. Results indicate that epileptogenesis in C1q KO mice is related to a genetically determined failure to prune excessive excitatory synapses during development.

  6. Anti-C1q autoantibodies in patients with neuromyelitis optica spectrum disorders.

    PubMed

    Yoshikura, Nobuaki; Kimura, Akio; Hayashi, Yuichi; Inuzuka, Takashi

    2017-09-15

    We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 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

  8. Phenotypic and genetic characterization of a patient with a de novo interstitial 14q24.1q24.3 deletion

    PubMed Central

    2014-01-01

    Background Interstitial deletions of chromosome bands 14q24.1q24.3 are very rare with only three reported cases. Results We describe a 7-year-old boy with a 5.345 Mb de novo interstitial deletion at 14q24.1q24.3 band detected by array-CGH who had a complex phenotype characterized by seizures, congenital heart defects, dysmorphisms, psychomotor delay, and bronchopulmonary, skeletal, and brain anomalies. Conclusion The deleted region contains numerous genes, but we focused our attention on three of them (C14orf169, NUMB, and PSEN1), which could account, at least partially, for the phenotype of the boy. We therefore discuss the involvement of these genes and the observed phenotype compared to that of previously described patients. PMID:25076984

  9. Delineation of the phenotype associated with 7q36.1q36.2 deletion: long QT syndrome, renal hypoplasia and mental retardation.

    PubMed

    Caselli, Rossella; Mencarelli, Maria Antonietta; Papa, Filomena Tiziana; Ariani, Francesca; Longo, Ilaria; Meloni, Ilaria; Vonella, Giuseppina; Acampa, Maurizio; Auteri, Alberto; Vicari, Stefano; Orsi, Alessandra; Hayek, Giuseppe; Renieri, Alessandra; Mari, Francesca

    2008-05-01

    Terminal deletions of the long arm of chromosome 7 are well known and are frequently associated with hypotelorism or holoprosencephaly due to the involvement of the SHH gene located in 7q36.3. These deletions are easily detectable with routine subtelomeric MLPA analysis. Deletions affecting a more proximal part of 7q36, namely bands 7q36.1q36.2 are less common, and may be missed by subtelomeric MLPA analysis. We report a 9-year-old girl with a 5.27 Mb deletion in 7q36.1q36.2, and compare her to literature patients proposing a phenotype characterized by mental retardation, unusual facial features, renal hypoplasia and long QT syndrome due to loss of the KCNH2 gene. These characteristics are sufficiently distinct that the syndrome may be diagnosed on clinical grounds.

  10. 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

  11. C1q as a unique player in angiogenesis with therapeutic implication in wound healing.

    PubMed

    Bossi, Fleur; Tripodo, Claudio; Rizzi, Lucia; Bulla, Roberta; Agostinis, Chiara; Guarnotta, Carla; Munaut, Carine; Baldassarre, Gustavo; Papa, Giovanni; Zorzet, Sonia; Ghebrehiwet, Berhane; Ling, Guang Sheng; Botto, Marina; Tedesco, Francesco

    2014-03-18

    We have previously shown that C1q is expressed on endothelial cells (ECs) of newly formed decidual tissue. Here we demonstrate that C1q is deposited in wound-healing skin in the absence of C4 and C3 and that C1q mRNA is locally expressed as revealed by real-time PCR and in situ hybridization. C1q was found to induce permeability of the EC monolayer, to stimulate EC proliferation and migration, and to promote tube formation and sprouting of new vessels in a rat aortic ring assay. Using a murine model of wound healing we observed that vessel formation was defective in C1qa(-/-) mice and was restored to normal after local application of C1q. The mean vessel density of wound-healing tissue and the healed wound area were significantly increased in C1q-treated rats. On the basis of these results we suggest that C1q may represent a valuable therapeutic agent that can be used to treat chronic ulcers or other pathological conditions in which angiogenesis is impaired, such as myocardial ischemia.

  12. 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 ...

  13. 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

  14. Ultraviolet-radiation-induced keratinocyte apoptosis in C1q-deficient mice.

    PubMed

    Pickering, M C; Fischer, S; Lewis, M R; Walport, M J; Botto, M; Cook, H T

    2001-07-01

    Exposure to ultraviolet B radiation is an important trigger of both systemic and cutaneous disease flares in individuals with systemic lupus erythematosus. More than 90% of individuals with homozygous C1q deficiency develop a systemic-lupus-erythematosus-like illness, which is typically associated with a severe photosensitive rash. Apoptotic, human keratinocytes have been shown in vitro to bind C1q, in the absence of antibody. These observations, together with the hypothesis that a major source of the autoantigens driving the immune response in systemic lupus erythematosus comes from apoptotic cells, led us to investigate the effects of murine C1q deficiency on ultraviolet-radiation-induced keratinocyte apoptosis in vivo. In this work, we demonstrated C1q binding to apoptotic murine keratinocytes in vitro and showed for the first time that C1q is also present on sunburn cells in vivo. In addition to C1q, we detected C3 deposition on sunburn cells in both wild-type and C1q-deficient mice, suggesting activation of the alternative pathway. Following acute ultraviolet exposure in vivo, no difference in the rate of clearance of sunburn cells was found in C1q-deficient mice from three different genetic backgrounds, compared with strain-matched wild-type controls. Furthermore, chronic ultraviolet exposure did not result in the production of autoantibodies or the development of glomerulonephritis. Our findings suggest that C1q does not play a critical role in the physiologic clearance of apoptotic murine keratinocytes in vivo.

  15. [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.

  16. Prenatal Diagnosis of a 2.5 Mb De Novo 17q24.1q24.2 Deletion Encompassing KPNA2 and PSMD12 Genes in a Fetus with Craniofacial Dysmorphism, Equinovarus Feet, and Syndactyly

    PubMed Central

    Naud, Marie-Emmanuelle; Martinovic, Jelena; Saada, Julien; Métay, Corinne; Drévillon, Loïc; Benoit, Virginie; Brisset, Sophie; Tachdjian, Gérard

    2017-01-01

    Interstitial 17q24.1 or 17q24.2 deletions were reported after conventional cytogenetic analysis or chromosomal microarray analysis in patients presenting intellectual disability, facial dysmorphism, and/or malformations. We report on a fetus with craniofacial dysmorphism, talipes equinovarus, and syndactyly associated with a de novo 2.5 Mb 17q24.1q24.2 deletion. Among the deleted genes, KPNA2 and PSMD12 are discussed for the correlation with the fetal phenotype. This is the first case of prenatal diagnosis of 17q24.1q24.2 deletion. PMID:28465847

  17. Prenatal Diagnosis of a 2.5 Mb De Novo 17q24.1q24.2 Deletion Encompassing KPNA2 and PSMD12 Genes in a Fetus with Craniofacial Dysmorphism, Equinovarus Feet, and Syndactyly.

    PubMed

    Naud, Marie-Emmanuelle; Tosca, Lucie; Martinovic, Jelena; Saada, Julien; Métay, Corinne; Drévillon, Loïc; Benoit, Virginie; Brisset, Sophie; Tachdjian, Gérard

    2017-01-01

    Interstitial 17q24.1 or 17q24.2 deletions were reported after conventional cytogenetic analysis or chromosomal microarray analysis in patients presenting intellectual disability, facial dysmorphism, and/or malformations. We report on a fetus with craniofacial dysmorphism, talipes equinovarus, and syndactyly associated with a de novo 2.5 Mb 17q24.1q24.2 deletion. Among the deleted genes, KPNA2 and PSMD12 are discussed for the correlation with the fetal phenotype. This is the first case of prenatal diagnosis of 17q24.1q24.2 deletion.

  18. Juvenile Justice in Milwaukee

    ERIC Educational Resources Information Center

    Williams, Gary L.; Greer, Lanetta

    2010-01-01

    Historically, there have been several attempts made to address issues surrounding juvenile delinquency. The Wisconsin Legislature outlines the objectives of the juvenile justice system in the Juvenile Justice Code in s. 939.01, ?to promote a juvenile justice system capable of dealing with the problem of juvenile delinquency, a system which will…

  19. 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.

  20. Role of complement component C1q in the onset of preeclampsia in mice.

    PubMed

    Singh, Jameel; Ahmed, Abdulwahab; Girardi, Guillermina

    2011-10-01

    Preeclampsia (PE) is a life-threatening, pregnancy-induced disease and a leading cause of maternal and fetal morbidity and mortality. Despite considerable research, the causes of PE remain unclear, and there is no effective treatment. Studies in animal models that resemble this complex pregnancy-related disorder may help to identify possible therapies for PE. Complement component C1q has an important role in trophoblast migration, spiral arteries remodeling, and normal placentation. Here we show that pregnant C1q-deficient (C1q(-/-)) mice recapitulate the key features of human PE: hypertension, albuminuria, endotheliosis, decreased placental vascular endothelial growth factor (VEGF) and elevated levels of soluble VEGF receptor 1 (sFlt-1) that correlate with increased fetal death. In addition, decreased blood flow and increased oxidative stress are observed in placentas from C1q(-/-) mice. Treatment of C1q(-/-) mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of PE. Serum-soluble receptors for VEGF-1 levels were reduced and placental VEGF levels were significantly increased in C1q(-/-) mice treated with pravastatin compared with untreated C1q(-/-) mice (VEGF: 1067±171 versus 419±194 pg/mL; P<0.01). Pravastatin treatment reduced hypertension (change in mean arterial pressure: 1±1 versus 18±3 mm Hg in C1q(-/-) untreated mice), and albuminuria (of creatinine) was reduced from 820±175 to 117±45 μg/mg (both P<0.01). Renal damage and endothelial dysfunction were significantly attenuated with pravastatin. This model that highlights the causative role of impaired trophoblast invasion in the pathogenesis of PE allowed us to identify pravastatin as a good therapeutic option to prevent PE.

  1. Juvenile xanthogranuloma.

    PubMed

    Singh, R; Ghazali, W

    1992-05-01

    Juvenile xanthogranuloma is a benign cutaneous growth presenting as papules or nodules. It is characterized by an intradermal collection of lipid-laden macrophages and varying degrees of fibroblastic proliferation. We have recently observed two patients with xanthogranulomas: one was found to have a papular type and the second patient had multiple nodular growths. We present these cases, which should be considered in the differential diagnosis of skin nodules.

  2. A dramatic increase of C1q protein in the CNS during normal aging.

    PubMed

    Stephan, Alexander H; 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

    2013-08-14

    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.

  3. Atomic resolution model of the antibody Fc interaction with the complement C1q component.

    PubMed

    Schneider, Sebastian; Zacharias, Martin

    2012-05-01

    The globular C1q heterotrimer is a subunit of the C1 complement factor. Binding of the C1q subunit to the constant (Fc) part of antibody molecules is a first step and key event of complement activation. Although three-dimensional structures of C1q and antibody Fc subunits have been determined experimentally no atomic resolution structure of the C1q-Fc complex is known so far. Based on systematic protein-protein docking searches and Molecular Dynamics simulations a structural model of the C1q-IgG1-Fc-binding geometry has been obtained. The structural model is compatible with available experimental data on the interaction between the two partner proteins. It predicts a binding geometry that involves mainly the B-subunit of the C1q-trimer and both subunits of the IgG1-Fc-dimer with small conformational adjustments with respect to the unbound partners to achieve high surface complementarity. In addition to several charge-charge and polar contacts in the rim region of the interface it also involves nonpolar contacts between the two proteins and is compatible with the carbohydrate moiety of the Fc subunit. The model for the complex structure provides a working model for rationalizing available biochemical data on this important interaction and can form the basis for the design of Fc variants with a greater capacity to activate the complement system for example on binding to cancer cells or other target structures.

  4. Complement Protein C1q Forms a Complex with Cytotoxic Prion Protein Oligomers

    PubMed Central

    Erlich, Paul; Dumestre-Pérard, Chantal; Ling, Wai Li; Lemaire-Vieille, Catherine; Schoehn, Guy; Arlaud, Gérard J.; Thielens, Nicole M.; Gagnon, Jean; Cesbron, Jean-Yves

    2010-01-01

    A growing number of studies have investigated the interaction between C1q and PrP, but the oligomeric form of PrP involved in this interaction remains to be determined. Aggregation of recombinant full-length murine PrP in the presence of 100 mm NaCl allowed us to isolate three different types of oligomers by size-exclusion chromatography. In contrast to PrP monomers and fibrils, these oligomers activate the classical complement pathway, the smallest species containing 8–15 PrP protomers being the most efficient. We used Thioflavine T fluorescence to monitor PrP aggregation and showed that, when added to the reaction, C1q has a cooperative effect on PrP aggregation and leads to the formation of C1q-PrP complexes. In these complexes, C1q interacts through its globular domains preferentially with the smallest oligomers, as shown by electron microscopy, and retains the ability to activate the classical complement pathway. Using two cell lines, we also provide evidence that C1q inhibits the cytotoxicity induced by the smallest PrP oligomers. The cooperative interaction between C1q and PrP could represent an early step in the disease, where it prevents elimination of the prion seed, leading to further aggregation. PMID:20410306

  5. Complement component C1q as potential diagnostic but not predictive marker of preeclampsia.

    PubMed

    Agostinis, Chiara; Stampalija, Tamara; Tannetta, Dionne; Loganes, Claudia; Vecchi Brumatti, Liza; De Seta, Francesco; Celeghini, Claudio; Radillo, Oriano; Sargent, Ian; Tedesco, Francesco; Bulla, Roberta

    2016-12-01

    We have previously found that C1q is constitutively expressed by invading trophoblast and endothelial cells of decidua and contributes to vascular and tissue remodeling. Based on these findings, we sought to determine whether there were changes in the circulating level of C1q that may be used as a diagnostic and predictive marker of preeclampsia. We measured the levels of C1q, C4, and complement activation products in serum or plasma of normal pregnant women and preeclamptic patients from different cohorts. We observed a marked decrease in the concentration of C1q associated with a reduced level of C4 in preeclamptic patients as compared to matched healthy pregnant woman but no significant difference in the circulating level of the activating products C5a and the soluble terminal complement complex sC5b-9. Analysis of serum samples collected at early phase of pregnancy from women who later developed preeclampsia failed to show a decrease in C1q level. The results of the present investigation demonstrate that low levels of C1q and C4 are associated with preeclampsia but cannot be used as predictive markers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Alternative functions of the complement protein C1q at embryo implantation site.

    PubMed

    Agostinis, Chiara; Tedesco, Francesco; Bulla, Roberta

    2017-02-01

    Complement component C1q is one of the recognition molecules of the complement system which can serve several functions unrelated to complement activation. This molecule is produced at foeto-maternal interface by macrophages as wells as by decidual endothelial cells and invading trophoblast. Foetal trophoblast cells migrating through the decidua in the early stages of pregnancy synthesize and express C1q on their surface, which is actively involved in promoting trophoblast endovascular and interstitial invasion of the decidua. These functions are mediated by two cell surface receptors, gC1qR and α4β1 integrin, which promote trophoblast adhesion and migration through the activation of ERK1/2 MAPKs. C1q(-/-) mice manifest increased frequency of foetal resorption, reduced foetal weight, and smaller litter size when compared to their wild-type counterparts, suggesting that defective local production of C1q may be involved in pregnancy disorders, such as pre-eclampsia. C1q acts also as a strong angiogenic factor and promotes neovascularization. These studies suggest novel and unexpected roles of this complement component in physiological and pathological pregnancies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Post-transplant development of C1q-positive HLA antibodies and kidney graft survival.

    PubMed

    Piazza, Antonina; Poggi, Elvira; Ozzella, Giuseppina; Adorno, Domenico

    2013-01-01

    The development of de novo human leukocyte antigen (HLA) donor specific antibodies (DSA), detected by both cytotoxic or solid phase assays, was considered the major risk factor for allograft failure in kidney transplantation. However, it was shown that not all patients with persistent production of DSA suffered loss of their grafts. Modified Luminex-Single Antigen assays, able to identify C1q-fixing antibodies, represent a new strategy in assessing the clinical relevance of detected DSA. This study demonstrated that C1q-fixing capability of de novo DSA is a clinically relevant marker of worse outcome and inferior graft survival in kidney transplantation. In fact, our findings evidenced a very low graft survival only in the patients who developed DSA able to fix C1q during post-transplant course, while patients producing C1q-negative DSA had good graft survival, which was comparable to that found in our previous study for DSA-negative patients. Moreover, anti-HLA class II antibodies had a higher incidence than anti-HLA class I, and the ability to fix C1q was significantly more frequent among anti-DQ DSA than anti-DR DSA. Monitoring of de novo C1q-DSA production represents a useful, non-invasive tool for risk stratification and prediction of graft outcome in kidney transplantation.

  8. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... for You Healthy School Lunch Planner Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic Arthritis (JIA) ... people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people as much ...

  9. 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 ...

  10. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic ... can affect people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people ...

  11. Marker chromosomes.

    PubMed

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  12. 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

  13. 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…

  14. DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells

    PubMed Central

    Hosszu, Kinga K.; Valentino, Alisa; Vinayagasundaram, Uma; Vinayagasundaram, Rama; Joyce, M. Gordon; Ji, Yan; Peerschke, Ellinor I. B.

    2012-01-01

    C1q modulates the differentiation and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because the 2 C1q receptors found on the DC surface—gC1qR and cC1qR—lack a direct conduit into intracellular elements, we postulated that the receptors must form complexes with transmembrane partners. In the present study, we show that DC-SIGN, a C-type lectin expressed on DCs, binds directly to C1q, as assessed by ELISA, flow cytometry, and immunoprecipitation experiments. Surface plasmon resonance analysis revealed that the interaction was specific, and both intact C1q and the globular portion of C1q bound to DC-SIGN. Whereas IgG reduced this binding significantly, the Arg residues (162-163) of the C1q-A chain, which are thought to contribute to the C1q-IgG interaction, were not required for C1q binding to DC-SIGN. Binding was reduced significantly in the absence of Ca2+ and by preincubation of DC-SIGN with mannan, suggesting that C1q binds to DC-SIGN at its principal Ca2+-binding pocket, which has increased affinity for mannose residues. Antigen-capture ELISA and immunofluorescence microscopy revealed that C1q and gC1qR associate with DC-SIGN on blood DC precursors and immature DCs. The results of the present study suggest that C1q/gC1qR may regulate DC differentiation and function through the DC-SIGN–mediated induction of cell-signaling pathways. PMID:22700724

  15. Complement component c1q mediates mitochondria-driven oxidative stress in neonatal hypoxic-ischemic brain injury.

    PubMed

    Ten, Vadim S; Yao, Jun; Ratner, Veniamin; Sosunov, Sergey; Fraser, Deborah A; Botto, Marina; Sivasankar, Baalasubramanian; Morgan, B Paul; Silverstein, Samuel; Stark, Raymond; Polin, Richard; Vannucci, Susan J; Pinsky, David; Starkov, Anatoly A

    2010-02-10

    Hypoxic-ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report a novel pathway mediating oxidative brain injury after hypoxia-ischemia in which C1q plays a central role. Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia-ischemia. Only C1q(-/-) mice exhibited neuroprotection coupled with attenuated oxidative brain injury. This was associated with reduced production of reactive oxygen species (ROS) in C1q(-/-) brain mitochondria and preserved activity of the respiratory chain. Compared with C1q(+/+) neurons, cortical C1q(-/-) neurons exhibited resistance to oxygen-glucose deprivation. However, postischemic exposure to exogenous C1q increased both mitochondrial ROS production and mortality of C1q(-/-) neurons. This C1q toxicity was abolished by coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thus, the C1q component of complement, accelerating mitochondrial ROS emission, exacerbates oxidative injury in the developing HI brain. The terminal complement complex is activated in the HI neonatal brain but appeared to be nonpathogenic. These findings have important implications for design of the proper therapeutic interventions against HI neonatal brain injury by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative stress over the C1q deposition-triggered terminal complement activation.

  16. 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.

  17. C1q complement component and -antibodies reflect SLE activity and kidney involvement.

    PubMed

    Horák, P; Hermanová, Z; Zadrazil, J; Ciferská, H; Ordeltová, M; Kusá, L; Zurek, M; Tichý, T

    2006-07-01

    The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM1q antibodies were measured by the Enzyme-Linked Immunosorbent Assay (ELISA) test, while radial immunodiffusion according to Mancini was used to measure the C1q complement component. The mean serum levels were 90.89+/-13 IU/ml for anti-C1q antibodies and 145+/-52 mg/l for C1q. The significant difference in C1q antibodies levels was found between individuals with and without lupus nephritis (117.5+/-52 IU/ml vs. 28.2+/-12.2 IU/ml, p=0.0001) and between those with active and nonactive SLE (154.6+/-115 IU/ml vs. 50.6+/-73, p=0.001). C1q complement component was statistically lower in patients with lupus nephritis (144+/-30 mg/l vs. 175+/-50 mg/ml, p=0.002) and in active patients (138+/-40 mg/l vs. 202+/-20 mg/l, p=0.001). If the two parameters are measured together, they seem to have a mirror-like pattern of serum concentration, and they are potential markers of SLE activity and of the presence of lupus nephritis.

  18. 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

  19. 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.

  20. A single-center study of C1q nephropathy in children.

    PubMed

    Roberti, Isabel; Baqi, Noosha; Vyas, Shefali; Kim, Dae Un

    2009-01-01

    C1q nephropathy (C1qN) is a rare idiopathic glomerulopathy typically seen in adolescents and young adults. All kidney biopsies done from 2002 to 2007 were analyzed (264). Thirteen cases of C1qN from 212 (6.6%) native biopsies and one case out of 52 (1.9%) transplant biopsies were reviewed regarding demographic features, clinical presentation, histopathology, treatment, and outcome. Age varied from 1 to 18 years; half were boys. Ten children (71.4%) presented with nephrotic syndrome (NS). The most common histopathology found was diffuse mesangial proliferative glomerulonephritis (DMP) by light microscopy (LM), with diffuse granular staining for C1q predominantly in the mesangium. Children with either NS or persistent gross hematuria received prednisone and angiotensin-converting enzyme inhibitors (ACEi) (11). Median follow-up was 36 months. Steroid response was complete in 6 patients (54.5%). Those with steroid resistance (5) or steroid dependence (2) received further immunosuppression with mycophenolate mofetil (MMF) or tacrolimus (Tac). Three children achieved complete remission and four partial remission. Frequent relapses were seen in 4/14 patients. Renal survival was 100%. Our report reveals a high incidence of C1qN in pediatric patients, with variable clinical presentation. Despite a high incidence of steroid resistance among those with NS, an excellent response was observed with the addition of further immunosuppression.

  1. 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. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. C1q deficiency: identification of a novel missense mutation and treatment with fresh frozen plasma.

    PubMed

    Topaloglu, Rezan; Taskiran, Ekim Z; Tan, Cagman; Erman, Baran; Ozaltin, Fatih; Sanal, Ozden

    2012-07-01

    A Turkish patient with C1q deficiency presented with a lupus-like disease, and a new missense mutation at A chain is presented. To characterize the genetic defect, all exons of the genes for the A, B, and C chains of C1q were sequenced in the patient. This revealed a missense mutation in the collagen-like domain of the A chain, p.Gly31 Arg. No other sequence variants, including the common silent mutations, were found in the three chains. Exon 1 of the C1q A chain was sequenced in 105 samples from healthy controls for this particular mutation. None of these carried the mutation. The C1q-deficient patient was treated with fresh frozen plasma infusions. Our findings showed that Turkish patients may have different mutations than the previously described common mutation, and once again, not only nonsense mutations but also missense mutations cause hereditary C1q deficiency. Regular fresh frozen plasma infusions to the patient have been clinically and therapeutically successful.

  3. 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…

  4. 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. © 2013 Wiley Periodicals, Inc.

  5. A mild phenotype associated with a de novo microdeletion 10q23.1-q23.2: a new patient with a novel feature.

    PubMed

    Pavone, Piero; Praticò, Andrea D; Campisi, Corrado; Falsaperla, Raffaele

    2016-04-18

    Chromosome 10q23 contains several genes, includingPTENandBMPR1A, the mutations or microdeletion of which are associated with aggressive polyposis and malignancies in children. Deletions in this chromosomal region have also been associated with heart anomalies, developmental delay and macrocephaly. Most of the cases reported involve thePTENandBMPR1Agenes, usually associated with complex and severe anomalies. We report a case of a boy with a de novo interstitial microdeletion in 10q23.1-q23.2 spanning 6.7 Mb with boundaries from 82 087 077 to 88 847 906, not includingPTENandBMPR1A Clinical features consisted of mildly dysmorphic facies, frontal telangiectasias, poor scholastic performance and hyperactivity. Furthermore, the boy presented toe anomalies, which appeared to be novel features associated with 10q23 deletion. Further observations of 10q23.1-q23.2 deletions are necessary to confirm the clinical features observed in the proband, and to show that deletion or mutations not involvingPTENandBMPR1Amay not be associated with severe neurological impairment and malformation anomalies. 2016 BMJ Publishing Group Ltd.

  6. Hemiconvulsion-hemiplegia-epilepsy syndrome with 1q44 microdeletion: causal or chance association.

    PubMed

    Gupta, Rekha; Agarwal, Meenal; Boqqula, Vijay R; Phadke, Rajendra V; Phadke, Shubha R

    2014-01-01

    Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare syndrome characterized by childhood onset partial motor convulsions, hemiplegia, and epilepsy in sequence. Exact pathogenesis is not clear. Here we are describing a 3-year-old girl with HHE syndrome with cytogenetic microarray (CMA) showing deletion of 1.8 Mb in 1q44 region. Along with HHE syndrome, the patient also had global developmental delay, subtle facial dysmorphism, and preaxial polydactyly. Clinical phenotype of 1q44 microdeletion syndrome is quite variable. Main clinical features are microcephaly, seizures, and abnormality of corpus callosum. We compared the patient's phenotype with other patients in 10 previously published papers of 1q44 microdeletion syndrome. HNRNPU and FAM36A are two important genes in the deleted region. HNRNPU gene mediate long range control of SHH gene which is likely explanation of preaxial polydactyly in the present patient. HHE may be a chance co-occurrence. © 2013 Wiley Periodicals, Inc.

  7. Complement protein C1q promotes macrophage anti-inflammatory M2-like polarization during the clearance of atherogenic lipoproteins

    PubMed Central

    Spivia, Weston; Magno, Patrick S.; Le, Patrick; Fraser, Deborah A.

    2016-01-01

    Objective Innate immune protein C1q plays a dual role in the chronic inflammatory disease of atherosclerosis. Complement activation via C1q exacerbates pathology in the atherosclerotic lesion in later stages of the disease. However, in early stages of disease C1q is protective. We hypothesize that complement-independent activities of C1q are involved in reprogramming macrophage inflammatory polarization. Methods The influence of C1q on macrophage inflammatory responses during clearance of oxLDL was examined. Changes in cytokines at the gene and protein level were measured by quantitative PCR and ELISA assay. Results C1q modulated cytokine expression in Raw264.7 macrophages during ingestion of oxLDL. Levels of proinflammatory cytokines IL-1β and IL-6 were downregulated by C1q, whereas levels of the anti-inflammatory cytokine IL-10 were increased. In addition, data from an NFκB-luciferase gene reporter assay suggest that C1q suppresses activation of NFκB during lipoprotein clearance in macrophages, providing one mechanism by which C1q downregulates pro-inflammatory cytokine production. Conclusions C1q-polarization of macrophages toward an anti-inflammatory (M2-like) phenotype may be important in dampening inflammation in the early atherosclerotic lesion. Further investigation of molecular pathways targeted by C1q may provide novel therapeutic targets for this disease. PMID:25091012

  8. Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss.

    PubMed

    Sutherland, Scott M; Chen, Ge; Sequeira, Flavia A; Lou, Calvin D; Alexander, Steven R; Tyan, Dolly B

    2012-02-01

    Long-term outcomes following renal transplantation remain disappointing. Recently, interest has focused on the antibody-mediated component of allograft injury and the deleterious effects of DSA. We applied a novel C1q solid-phase assay in parallel with the standard IgG SAB assay to identify DSA with the potential to activate complement by binding C1q. Among 193 consecutive renal transplants at our center, 19.2% developed de novo DSA following transplantation. Of the patients with DSA, 43% had antibodies that bound C1q in vitro [C1q+ DSA]. Patients with C1q+ DSA were more likely to develop allograft loss than patients with DSA that did not bind C1q (46.7% vs. 15%; p = 0.04); patients with C1q+ DSA were nearly six times more likely to lose their transplant than those with C1q- DSA. Additionally, patients with C1q+ DSA who underwent allograft biopsy were more likely to demonstrate C4d deposition (50% vs. 8%; p = 0.03) and meet criteria for acute rejection (60% vs. 17%; p = 0.02) when compared with patients with DSA that did not bind C1q. These data suggest that DSA with the ability to activate complement, as determined by this novel C1q assay, are associated with greater risk of acute rejection and allograft loss.

  9. Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury

    PubMed Central

    Galvan, Manuel D.; Luchetti, Sabina; Burgos, Adrian M.; Nguyen, Hal X.; Hooshmand, Mitra J.; Anderson, Aileen J.; Hamers, Frank P.T.

    2009-01-01

    Although studies have suggested a role for the complement system in the pathophysiology of spinal cord injury (SCI), that role remains poorly defined. Additionally, the relative contribution of individual complement pathways in SCI is unknown. Our initial studies revealed that systemic complement activation was strongly influenced by genetic background and gender. Thus, to investigate the role of the classical complement pathway in contusion-induced SCI, male C1q knockout (KO) and wildtype (WT) mice on a complement sufficient background (BUB) received a mild-moderate T9 contusion injury with the Infinite Horizon (IH) impactor. BUB C1q KO mice exhibited greater locomotor recovery in comparison to BUB WT mice (p < 0.05). Improved recovery observed in BUB C1q KO mice was also associated with decreased threshold for withdrawal from a mild stimulus using von Frey filament testing. Surprisingly, quantification of microglia/macrophages (F4/80) by FACS analysis showed that BUB C1q KO mice exhibited a significantly greater percentage of macrophages in the spinal cord compared to BUB WT mice 3 days post injury (p < 0.05). However, this increased macrophage response appeared to be transient as stereological assessment of spinal cord tissue obtained 28 days post injury revealed no difference in F4/80 positive cells between groups. Stereological assessment of spinal cord tissue showed that BUB C1q KO mice had reduced lesion volume and an increase in tissue sparing in comparison to BUB WT mice (p < 0.05). Taken together, these data suggest that initiation of the classical complement pathway via C1q is detrimental to recovery after SCI. PMID:19091977

  10. 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…

  11. 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…

  12. Treating Juvenile Crime.

    ERIC Educational Resources Information Center

    Gelber, Seymour

    1983-01-01

    Although juvenile crime rates have not changed significantly in the last five years, the juvenile courts' ability to handle crime has deteriorated. To treat the problem of juvenile crime effectively requires intervention at the earliest sign of delinquency and an assessment of the juvenile courts and school system. (AM)

  13. Results of Hg speciation testing on tank 39 and 1Q16 tank 50 samples

    SciTech Connect

    Bannochie, C. J.

    2016-03-07

    The Savannah River National Laboratory (SRNL) was tasked with preparing and shipping samples for Hg speciation by Eurofins Frontier Global Sciences, Inc. in Seattle, WA on behalf of the Savannah River Remediation (SRR) Mercury Task Team.i,ii The seventeenth shipment of samples was designated to include two Tank 39 samples and the 1Q16 Tank 50 Quarterly WAC sample. The surface Tank 39 sample was pulled at 262.1” from the tank bottom, and the depth Tank 39 sample was pulled at 95” from the tank bottom. The 1Q16 Tank 50 WAC sample was drawn from the 1-L variable depth sample received by SRNL.

  14. Complement C1q Activates Tumor Suppressor WWOX to Induce Apoptosis in Prostate Cancer Cells

    PubMed Central

    Hong, Qunying; Sze, Chun-I; Lin, Sing-Ru; Lee, Ming-Hui; He, Ruei-Yu; Schultz, Lori; Chang, Jean-Yun; Chen, Shean-Jen; Boackle, Robert J.; Hsu, Li-Jin; Chang, Nan-Shan

    2009-01-01

    Background Tissue exudates contain low levels of serum complement proteins, and their regulatory effects on prostate cancer progression are largely unknown. We examined specific serum complement components in coordinating the activation of tumor suppressors p53 and WWOX (also named FOR or WOX1) and kinases ERK, JNK1 and STAT3 in human prostate DU145 cells. Methodology/Principal Findings DU145 cells were cultured overnight in 1% normal human serum, or in human serum depleted of an indicated complement protein. Under complement C1q- or C6-free conditions, WOX1 and ERK were mainly present in the cytoplasm without phosphorylation, whereas phosphorylated JNK1 was greatly accumulated in the nuclei. Exogenous C1q rapidly restored the WOX1 activation (with Tyr33 phosphorylation) in less than 2 hr. Without serum complement C9, p53 became activated, and hyaluronan (HA) reversed the effect. Under C6-free conditions, HA induced activation of STAT3, an enhancer of metastasis. Notably, exogenous C1q significantly induced apoptosis of WOX1-overexpressing DU145 cells, but not vehicle-expressing cells. A dominant negative and Y33R mutant of WOX1 blocked the apoptotic effect. C1q did not enhance p53-mediated apoptosis. By total internal reflection fluorescence (TIRF) microscopy, it was determined that C1q destabilized adherence of WOX1-expressing DU145 cells by partial detaching and inducing formation of clustered microvilli for focal adhesion particularly in between cells. These cells then underwent shrinkage, membrane blebbing and death. Remarkably, as determined by immunostaining, benign prostatic hyperplasia and prostate cancer were shown to have a significantly reduced expression of tissue C1q, compared to age-matched normal prostate tissues. Conclusions/Significance We conclude that complement C1q may induce apoptosis of prostate cancer cells by activating WOX1 and destabilizing cell adhesion. Downregulation of C1q enhances prostate hyperplasia and cancerous formation due to

  15. Planet Population Statistics With Kepler Q1-Q16: Stellar Effective Temperature Dependence

    NASA Astrophysics Data System (ADS)

    Burke, Christopher J.; Mullally, Fergal; Christiansen, Jessie; Huber, Daniel; Seader, Shawn; Catanzarite, Joseph; Bryson, Steve; Coughlin, Jeffrey; Rowe, Jason; Thompson, Susan E.; Clarke, Bruce; Tenenbaum, Peter; Batalha, Natalie M.; Haas, Michael R.; Jenkins, Jon Michael; Kepler Project

    2015-01-01

    We explore extrasolar planet population statistics and the dependence of planet occurrence rates on stellar effective temperature from analysis of the Kepler Q1-Q16 planet candidate sample. The analysis takes advantage of the recent work on the Q1-Q16 Kepler planet candidate sample, extensive Monte-Carlo transit signal injection and recovery tests of the Kepler Pipeline, and updates to the stellar parameters provided by the Kepler Stellar Working Group. Results focus of intermediate orbital periods, 50< Porb<300 day, where astrophysical and instrumental contamination of the planet sample is low.

  16. C1q binding to Dengue Virus inhibits infection of THP-1 and cellular inflammatory responses

    PubMed Central

    Douradinha, Bruno; McBurney, Sean P.; de Melo, Klecia M. Soares; Smith, Amanda P.; Krishna, Neel K.; Barratt-Boyes, Simon M.; Evans, Jared D.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A

    2014-01-01

    Summary Dengue virus infection elicits a spectrum of clinical presentations ranging from asymptomatic to severe disease. The mechanisms leading to severe dengue are not known, however it has been reported that the complement system is hyper-activated in severe dengue. Screening of complement proteins demonstrated that C1q, a pattern recognition molecule, can bind directly to Dengue Virus Envelope protein and to whole Dengue Virus serotype 2. Incubation of Dengue Virus serotype 2 with C1q prior to infection of THP-1 cells led to decreased virus infectivity and modulation of mRNA expression of immunoregulatory molecules suggesting reduced inflammatory responses. PMID:24246304

  17. del(X)(p22.1)/r(X)(p22.1q28) Dynamic mosaicism in a Turner syndrome patient.

    PubMed

    Gutiérrez-Angulo, Melva; Lazalde, Brissia; Vasquez, Ana I; Leal, Caridad; Corral, Elisa; Rivera, Horacio

    2002-01-01

    We report on a 16-year-old patient with Turner syndrome who presented a mos 46,X,del(X)(p22.1)[35]/45,X [19]/46,X,r(X)(p22.1q28)[6]GTG-band karyotype. The R-banding showed that the abnormal X-chromosome was inactive in all 61 cells analyzed. Fluorescence in situ hybridization with a Xp/Yp subtelomeric probe revealed that both abnormal chromosomes lacked the complementary sequences, a fact consistent with a terminal deletion. Besides, the molecular analysis of the human androgen receptor gene showed that the rearranged chromosome was paternal in origin. Since the deleted and the ring chromosomes had the same size and banding pattern, and because the former was the predominant cell line, it was inferred that the Xp- formed a ring in some cells apparently without further loss of genetic material. However, the reverse sequence and even a simultaneous origin due to a complex intrachromosomal exchange are also conceivable. The mild Turner syndrome phenotype is explained by the mosaicism and by the size of the deleted segment.

  18. Constitutional t(5;7)(q11;p15) rearranged to acquire monosomy 7q and trisomy 1q in a patient with myelodysplastic syndrome transforming to acute myelocytic leukemia.

    PubMed

    Ganly, Peter; McDonald, Margaret; Spearing, Ruth; Morris, Christine M

    2004-03-01

    We report the case of a 61-year-old woman who presented with a myelodysplastic syndrome (MDS) and a t(5;7)(q11.2;p15) in her bone marrow cells. Subsequent analysis of phytohemagglutinin-stimulated peripheral blood lymphocytes and cultured skin fibroblasts showed that the translocation was constitutional. Disruption of chromosome bands 5q11.2 and 7p15 has been described recurrently in MDS and acute myelocytic leukemia (AML) and, although the age of onset was not earlier than usual, it is nonetheless possible that genes interrupted by this translocation may been a predisposing factor for her condition. With progression to AML, a further rearrangement of the constitutional der(7)t(5;7) occurred, involving chromosome arm 1q. Fluorescence in situ hybridization (FISH) with whole-chromosome paints showed that the result of the second rearrangement, a t(1;7)(q32.1;q32), was observed, leading to trisomy of the segment 1q32.1 approximately qter and monosomy of the segment 7q32.1 approximately qter. The acquired imbalances, particularly loss of 7q, are commonly associated with MDS/AML and a poor prognosis; however, this patient remained in remission after treatment for more than two years before AML relapse, perhaps because the affected regions fall outside of the critical regions of imbalance.

  19. Role of collectins and complement protein C1q in pregnancy and parturition.

    PubMed

    Madhukaran, Shanmuga Priyaa; Alhamlan, Fatimah S; Kale, Kavita; Vatish, Manu; Madan, Taruna; Kishore, Uday

    2016-11-01

    Collectins such as surfactant proteins SP-A, SP-D, and mannan-binding lectin (MBL), as well as complement protein C1q are evolutionarily conserved innate immune molecules. They are known to opsonize a range of microbial pathogens (bacteria, fungi, virus, and parasites) and trigger effector clearance mechanisms involving phagocytosis and/or complement activation. Collectins and C1q have also attracted attention in studies involving pregnancy as they are expressed in the female reproductive tissues during pregnancy; a unique state of immune suppression with increased susceptibility to infectious diseases. Recent studies are beginning to unravel their functional significance in implantation, placentation, pregnancy maintenance and parturition in normal and adverse pregnancies. Collectins and C1q, expressed in gestational tissues during pregnancy, might alter the status of mother's immune response to the allogenic fetus and the microenvironment, thereby serving as important regulators of fetus-mother interaction. Here, we discuss the functional roles that have been assigned to SP-A, SP-D, MBL and C1q in pregnancy and parturition. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

    PubMed

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

    2014-04-19

    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). 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. 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. 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.

  1. Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from chromosome 18 and associated with a reciprocal translocation involving chromosomes 17 and 18.

    PubMed

    Chen, Chih-Ping; Lin, Chyi-Chyang; Su, Yi-Ning; Tsai, Fuu-Jen; Chen, Ju-Ting; Chern, Schu-Rern; Lee, Chen-Chi; Town, Dai-Dyi; Chen, Li-Feng; Wu, Pei-Chen; Wang, Wayseen

    2010-06-01

    Prenatal diagnosis of small supernumerary marker chromosomes (sSMC) gives rise to difficulties in genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping, fluorescence in situ hybridization, multicolor-fluorescence in situ hybridization, or array-comparative genomic hybridization to identify the nature of the aberrant chromosome. We report such a case associated with a reciprocal translocation. A 36-year-old woman, gravida 7, para 1, abortus 5, was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a reciprocal translocation between chromosomes 17q and 18q and an sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2), +mar. Chromosome preparations from blood lymphocytes revealed that she had the same reciprocal translocation and sSMC. Spectral karyotyping showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18. The derivative chromosome 17 had positive 17p terminal (17pTEL) and chromosome 17 centromeric (cep17) signals but did not have a positive chromosome 18 centromeric signal (cep18). The derivative chromosome 18 had positive 18p terminal (18pTEL), chromosome 18 centromeric (cep18) and cep17 signals. The sSMC had only a positive cep18 signal. These findings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromosome 18. The karyotype of the fetus was thus 47,XY,t(17;18)(q11.1;q11.2), +mar.ish der(17)t(17;18)(q11.1;q11.2)(17pTEL+,D17Z1+),der(18)t(17;18)(q11.1;q11.2)(18pTEL+,D18Z1+,D17Z1+), + der(18)(D18Z1+). Oligonucleotide-based array comparative genomic hybridization demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18. Our case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 without phenotypic consequences. Copyright 2010 Taiwan Association

  2. Variation in complement protein C1q is not a major contributor to cognitive impairment in Parkinson’s disease

    PubMed Central

    Carbutt, Sophia; Duff, Jennifer; Yarnall, Alison; Burn, David J.; Hudson, Gavin

    2015-01-01

    Traditional dogma regarding the brain as an immune exempt organ has changed in recent years. New research has highlighted the role of the classical complement cascade in both synaptic elimination and function, driven largely by the role of the pathway initiating protein C1q. Given the links between C1q and cognitive function we assessed the genetic variability of the C1q encoding genes: C1QA, C1QB and C1QC between PD patients and matched controls. Despite a strong link between C1Q/cognitive decline and PD/cognitive decline we were unable to find a link between common C1Q variation and PD. We conclude that common C1Q-A/B/C genetic variation is unlikely to contribute to cognitive decline or the missing heritability in PD. PMID:25817358

  3. Human C1q Induces Apoptosis in an Ovarian Cancer Cell Line via Tumor Necrosis Factor Pathway

    PubMed Central

    Kaur, Anuvinder; Sultan, Sami H. A.; Murugaiah, Valarmathy; Pathan, Ansar A.; Alhamlan, Fatimah S.; Karteris, Emmanouil; Kishore, Uday

    2016-01-01

    Complement protein C1q is the first recognition subcomponent of the complement classical pathway that plays a vital role in the clearance of immune complexes, pathogens, and apoptotic cells. C1q also has a homeostatic role involving immune and non-immune cells; these functions not necessarily involve complement activation. Recently, C1q has been shown to be expressed locally in the microenvironment of a range of human malignant tumors, where it can promote cancer cell adhesion, migration, and proliferation, without involving complement activation. C1q has been shown to be present in the ascitic fluid formed during ovarian cancers. In this study, we have examined the effects of human C1q and its globular domain on an ovarian cancer cell line, SKOV3. We show that C1q and the recombinant globular head modules induce apoptosis in SKOV3 cells in a time-dependent manner. C1q expression was not detectable in the SKOV3 cells. Exogenous treatment with C1q and globular head modules at the concentration of 10 µg/ml induced apoptosis in approximately 55% cells, as revealed by immunofluorescence microscopy and FACS. The qPCR and caspase analysis suggested that C1q and globular head modules activated tumor necrosis factor (TNF)-α and upregulated Fas. The genes of mammalian target of rapamycin (mTOR), RICTOR, and RAPTOR survival pathways, which are often overexpressed in majority of the cancers, were significantly downregulated within few hours of the treatment of SKOV3 cells with C1q and globular head modules. In conclusion, C1q, via its globular domain, induced apoptosis in an ovarian cancer cell line SKOV3 via TNF-α induced apoptosis pathway involving upregulation of Bax and Fas. This study highlights a potentially protective role of C1q in certain cancers. PMID:28066412

  4. Identification of a C1q family member associated with cortical granules and follicular cell apoptosis in Carassius auratus gibelio.

    PubMed

    Mei, Jie; Chen, Bo; Yue, Huamei; Gui, Jian-Fang

    2008-07-16

    C1q family proteins with C1q domain have been reported in vertebrates, but their biological roles are currently unknown. In this study, a C1q-like factor, designated Carassius auratus gibelio ovary-specific C1q-like factor (CagOC1q-like), was identified as a cortical granules component. Immunofluorescence localization revealed that the C1q family member was specifically expressed in follicular epithelial cells, and associated with cortical granules in fully grown oocytes. Moreover, it was discharged to the perivitelline space and egg envelope upon fertilization. As it is the first identified C1q family member that is expressed in follicular cells that surround oocyte, CagOC1q-like was applied to detection of follicular cell apoptosis and deletion. The entire cytological process of follicular cell apoptosis and deletion was clearly seen from double visualizations of follicular cells with CagOC1q-like immunofluorescence and apoptotic follicular cells labeled by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) during oocyte maturation and ovulation.

  5. Clinical relevance of pretransplant anti-HLA donor-specific antibodies: does C1q-fixation matter?

    PubMed

    Crespo, Marta; Torio, Alberto; Mas, Virginia; Redondo, Dolores; Pérez-Sáez, Maria J; Mir, Marisa; Faura, Anna; Guerra, Rita; Montes-Ares, Olga; Checa, Maria D; Pascual, Julio

    2013-12-01

    Anti-HLA donor-specific antibodies (DSA) identified by single antigen bead array (SAB) are questioned for their excess in sensitivity and lack of event prediction after transplantation. We retrospectively evaluated specific types of preformed DSA (class I, class II or C1q-fixing) and their impact on graft survival. Kidney transplantations performed across negative CDC-crossmatch were included (n=355). Anti-HLA antibodies were tested using SAB to identify DSA and their capacity to fix C1q. Twenty-eight patients with pretransplant DSA(+) with MFI>2000 were selected to assess C1q fixation. DSA were C1q+ in 15 patients and C1q- in 13, without significant differences in demographics, acute rejection, graft loss or renal function. The maximum MFI of DSA in patients with C1q-fixing DSA was significantly higher (p=0.008). Patients with DSA class-I suffered more antibody-mediated rejection (AMR) and had worse graft survival than class-II. The capacity of DSA I to fix C1q did not correlate with rejection, graft function or graft loss. C1q testing in pretransplant sera with DSA was unable to predict acute antibody-mediated rejection or early graft loss, but the presence of DSA class I compared to DSA only class II did. Despite non-fixing complement in vitro, pretransplant C1q-negative DSA I can mediate rejection and graft loss. © 2013.

  6. 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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. 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.)

  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. Non-nephronal hematuria misdiagnosed as C1q nephropathy: Look before you leap.

    PubMed

    Mandal, S N; Jha, R; Fatima, R; Swarnalata, G

    2012-05-01

    A 19-year-old male presented with persistent macroscopic hematuria for last 3 months. On initial evaluation, he was found to have minimal proteinuria, normal renal function, and normal complement with negative lupus serology. Light microscopy, immunofluorescence and electron microscopy of renal tissue confirmed the presence of C1q nephropathy. Because of poor response to immunosuppressive agent (prednisolone and mycophenolate mofetil), passage of urinary clot once and vexing persistent macroscopic hematuria, alternative diagnosis was considered. Cystourethroscopy showed urethritis of prostatic urethra. Immunosuppressives were stopped and doxycycline started to which hematuria responded dramatically. This case report illustrates that hematuria in this patient was because of undiagnosed urethritis rather than incidental C1q nephropathy.

  10. Presence of C1q-reactive immune complexes in patients with leprosy

    PubMed Central

    Rojas-Espinosa, O.; Mendez-Navarrete, I.; Estrada-Parra, S.

    1972-01-01

    Presence of soluble immune complexes was investigated in sera from persons with a well documented clinical diagnosis of leprosy. The complexes were detected by their reactivity with the C1q component of complement. More than 70% of the studied patients with lepromatous-leprosy had immune complexes demonstrable by this method (39/51), while only a small proportion of the healthy control group (1/35 or about 3%) had precipitable complexes. Two out of nine sera from patients with tuberculoid leprosy reacted when tested with C1q component. The presence of free-antibody to mycobacterial antigens was determined as well. The possible relationship between the presence of such immune complexes and the pathology of some reactional states of the disease is discussed. ImagesFig. 1 PMID:4630778

  11. The C1q complement family of synaptic organizers: not just complementary.

    PubMed

    Yuzaki, Michisuke

    2017-02-17

    Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions.

  12. Hemifacial microsomia in cat-eye syndrome: 22q11.1-q11.21 as candidate loci for facial symmetry.

    PubMed

    Quintero-Rivera, Fabiola; Martinez-Agosto, Julian A

    2013-08-01

    Cat-Eye syndrome (CES), (OMIM 115470) also known as chromosome 22 partial tetrasomy or inverted duplicated 22q11, was first reported by Haab [1879] based on the primary features of eye coloboma and anal atresia. However, >60% of the patients lack these primary features. Here, we present a 9-month-old female who at birth was noted to have multiple defects, including facial asymmetry with asymmetric retrognathia, bilateral mandibular hypoplasia, branchial cleft sinus, right-sided muscular torticollis, esotropia, and an atretic right ear canal with low-to-moderate sensorineural hearing loss, bilateral preauricular ear tag/pits, and two skin tags on her left cheek. There were no signs of any colobomas or anal atresia. Hemifacial microsomia (HFM) was suspected clinically. Chromosome studies and FISH identified an extra marker originated from 22q11 consistent with CES, and this was confirmed by aCGH. This report expands the phenotypic variability of CES and includes partial tetrasomy of 22q11.1-q11.21 in the differential diagnosis of HFM. In addition, our case as well as the previous association of 22q11.2 deletions and duplications with facial asymmetry and features of HFM, supports the hypothesis that this chromosome region harbors genes important in the regulation of body plan symmetry, and in particular facial harmony.

  13. 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.

  14. Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.

    PubMed

    Tahtouh, Muriel; Croq, Françoise; Vizioli, Jacopo; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Daha, Mohamed R; Pestel, Joël; Lefebvre, Christophe

    2009-02-01

    In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.

  15. Evaluation of C1q genomic region in minority racial groups of lupus

    PubMed Central

    Namjou, Bahram; Gray-McGuire, Courtney; Sestak, Andrea L.; Gilkeson, Gary S.; Jacob, Chaim O.; Merrill, Joan T; James, Judith A; Wakeland, Edward K.; Li, Quan-Zhen; Langefeld, Carl D.; Divers, Jasmin; Ziegler, Julie; Moser, Kathy L.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Harley, John B.

    2009-01-01

    Complement cascade plasma proteins have a complex role in the etiopathogenesis of SLE. Hereditary C1q deficiency has been strongly related to SLE; however, there are very few published SLE studies that evaluate the polymorphisms of the genes encoding for C1q (A, B, and C). In this study, we evaluated 17 single nucleotide polymorphisms (SNPs) across 37 kb of C1QA, B and C in a lupus cohort of peoples of African-American and Hispanic origin. In a case only analysis, significant association at multiple SNPs in the C1QA gene was detected in African-Americans with kidney nephritis (best p=4.91 × 10−6). In addition, C1QA was associated with SLE in African-Americans with a lack of nephritis and accompanying photosensitivity when compared to normal controls (p=6.80 × 10−6). A similar trend was observed in the Hispanic subjects (p=0.003). Quantitative analysis demonstrates that some SNPs in the C1q genes might be correlated with C3 complement levels in an additive model among African-Americans (best p=0.0001). The CIQA gene is associated with subphenotypes of lupus in African-American and Hispanic subjects. Further studies with higher SNP densities in this region and other complement components are necessary to elucidate the complex genetics and phenotypic interactions between complement components and SLE. PMID:19440201

  16. Roles of Complement C1q in Pneumococcus-Host Interactions.

    PubMed

    Agarwal, Vaibhav; Blom, Anna M

    2015-01-01

    The fight between a human host and a bacterial pathogen is highly complicated; each party tries to outshine the other in the race for survival. In humans, the innate immune system--in particular the complement system--functions as the first line of defence against invading pathogens. During the course of evolution, however, pathogens, in order to survive and perpetuate within a host, developed multiple strategies to counteract the host complement system and to colonize. One such pathogen is Streptococcus pneumoniae (pneumococcus), a gram-positive bacterial pathogen often commensal in the human respiratory tract. Depending on the host's susceptibility, pneumococci can transform into an infectious agent, disseminating within the human host and causing mild to life-threatening diseases. This transition from commensal to infectious agent is a highly complex process, and understanding of this mechanism is essential in controlling the pathogenicity of pneumococci. Using its intricate arsenal of weapons, such as surface-presenting adhesins as well as recruitment of host factor, pneumococci successfully colonize the host, a prerequisite for establishing infection. This review describes C1q, the first subunit of the classical complement pathway, and its role in pneumococcus-host interactions, whereby pneumococci exploit C1q as a molecular bridge facilitating host cellular adherence and invasion, a function not akin to the role of C1q in the defence mechanism.

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. Modeling Chromosomes

    ERIC Educational Resources Information Center

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  5. Modeling Chromosomes

    ERIC Educational Resources Information Center

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  6. Juvenile Justice Glossary.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Provides a list of terms pertaining to the juvenile justice system, such as appeal and due process, that are used throughout this edition of "Update on Law-Related Education," in particular, with the teaching strategies "The Case of Gerry Gault" (SO 532 196) "Today's Juvenile Court" (SO 532 197), and "Using the Juvenile Justice Poster" (SO 532…

  7. 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.

  8. Juvenile systemic lupus erythematosus and dermatomyositis associated with urticarial vasculitis syndrome: a unique presentation.

    PubMed

    Macêdo, Patrícia A; Garcia, Carolina B; Schmitz, Monique K; Jales, Levi H; Pereira, Rosa M R; Carvalho, Jozélio F

    2012-11-01

    To report a case of triple association of juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis and urticarial vasculitis as well as a review of the relevant literature. A 12-year-old male patient diagnosed with overlap syndrome between SLE and juvenile dermatomyositis since 2004 evolved with erythematous plaques, which were compatible with an urticarial rash. Clinical, laboratory and histopathological findings indicated a diagnosis of urticarial vasculitis. The patient previously had a C1q deficiency. Using the established treatment with methylprednisolone (1 g/day for 3 days), increasing doses of deflazacort and introduction of a dapsone, as well as mycophenolate mofetil regimen, with the suspension of azathioprine resulted in complete resolution of skin lesions. Urticarial vasculitis can present in various diseases. In SLE, presentation of urticarial vasculitis in children is rarely found. The triple association of juvenile-onset SLE, juvenile dermatomyositis and urticarial vasculitis is unusual, and this is the first case described in literature.

  9. Popliteal pterygium syndrome in a Swedish family--clinical findings and genetic analysis with the van der Woude syndrome locus at 1q32-q41.

    PubMed

    Wong, F K; Gustafsson, B

    2000-04-01

    The present study describes a Swedish family in which the mother and her son were affected with signs of popliteal pterygium syndrome (PPS, OMIM 119500). Both individuals had bilateral complete cleft lip and palate, oral synechiae, paramedian pits on the lower lip, toe syndactyly and a piece of triangular skin overgrowth on the great toes. The son also presented with soft tissue syndactyly of the 2nd and 3rd fingers. Although popliteal pterygium was not found, the above clinical features were diagnostic for PPS. Chromosomal abnormalities were not revealed in either case by cytogenetic analyses. A test for microdeletion in the VWS region at 1q32-q41 was performed in the family using 5 polymorphic microsatellite markers from the region. The affected son was found to be heterozygous for all 5 markers, suggesting that microdeletion at the VWS region was unlikely. The VWS locus, however, was not excluded by haplotype analysis of the family.

  10. Translocation t(12;17)(q24.1;q21) as the sole anomaly in a nasal chondromesenchymal hamartoma arising in a patient with pleuropulmonary blastoma.

    PubMed

    Behery, Radwa El; Bedrnicek, Jiri; Lazenby, Audrey; Nelson, Marilu; Grove, Jennifer; Huang, Dali; Smith, Russell; Bridge, Julia A

    2012-01-01

    The identification of recurrent chromosomal abnormalities in benign and malignant mesenchymal neoplasms has provided important pathogenetic insight as well as powerful diagnostic adjuncts. Nasal chondromesenchymal hamartoma (NCMH), an extremely rare benign tumor arising in the sinonasal tract of infants and children, has not been previously subjected to cytogenetic analysis. Histopathologically composed of mixed mesenchymal elements, NCMH exhibits a relatively wide differential diagnosis to include chondromyxoid fibroma, chondroblastoma, aneurysmal bone cyst, fibrous dysplasia, and osteochondromyxoma. An interesting association with pleuropulmonary blastoma has been reported in a small subset of NCMH patients. In the current study, cytogenetic analysis of a NCMH arising in an 11-year-old boy with a past medical history of pleuropulmonary blastoma revealed a novel 12;17 translocation, t(12;17)(q24.1;q21), as the sole anomaly.

  11. Complement Component C1q Mediates Mitochondria-Driven Oxidative Stress in Neonatal Hypoxic–Ischemic Brain Injury

    PubMed Central

    Ten, Vadim S.; Yao, Jun; Ratner, Veniamin; Sosunov, Sergey; Fraser, Deborah A.; Botto, Marina; Baalasubramanian, Sivasankar; Morgan, B. Paul; Silverstein, Samuel; Stark, Raymond; Polin, Richard; Vannucci, Susan J.; Pinsky, David; Starkov, Anatoly A.

    2010-01-01

    Hypoxic–ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report a novel pathway mediating oxidative brain injury after hypoxia–ischemia in which C1q plays a central role. Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia–ischemia. Only C1q−/− mice exhibited neuroprotection coupled with attenuated oxidative brain injury. This was associated with reduced production of reactive oxygen species (ROS) in C1q−/− brain mitochondria and preserved activity of the respiratory chain. Compared with C1q+/+ neurons, cortical C1q−/− neurons exhibited resistance to oxygen– glucose deprivation. However, postischemic exposure to exogenous C1q increased both mitochondrial ROS production and mortality of C1q−/− neurons. This C1q toxicity was abolished by coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thus, the C1q component of complement, accelerating mitochondrial ROS emission, exacerbates oxidative injury in the developing HI brain. The terminal complement complex is activated in the HI neonatal brain but appeared to be nonpathogenic. These findings have important implications for design of the proper therapeutic interventions against HI neonatal brain injury by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative stress over the C1q deposition-triggered terminal complement activation. PMID:20147536

  12. Neonatal pancytopenia associated with de novo 1q43-44 deletion and 10p15 duplication.

    PubMed

    Treskov, Inna; Al-Hosni, Mohamad; Havranek, Thomas; Batanian, Jacqueline

    2013-04-01

    Deletion of 1q43-44 has been reported in >50 cases. Phenotype-genotype correlation of this deletion has recently been described based on 20 pure cases. This led to the definition of critical regions and candidate genes for microcephaly, corpus callosum abnormalities, and seizure disorders. Variable penetrance and expressivity are associated with 1q43-44 microdeletion syndrome, explaining the lack of correlation in rare cases. Despite variation in size of the deletion, most cases are characterized by typical dysmorphic features, but none have demonstrated neonatal pancytopenia. We report on a newborn with partial monosomy 1q43-44 and partial trisomy 10p15.1→10pter born with dysmorphic features and neonatal pancytopenia. Array-CGH analysis characterizes the deletion and the duplication as terminal with estimated sizes of 8 to 9 and 5 to 6 Mb, respectively. Conventional cytogenetic analysis showed the 10p duplication as unbalanced and translocated onto 1q. The deletion in the 1q43-44 region is the largest among the 20 cases reported most recently. The 10p partnership with the derivative 1q43-44 region is unique. We discuss the association of neonatal pancytopenia with 1q deletion and 10p duplication, in light of a recent published case of acute lymphoblastic leukemia in a constitutional case of 1q deletion and 1p duplication.

  13. Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia.

    PubMed

    Goodbourn, P T; Bosten, J M; Bargary, G; Hogg, R E; Lawrance-Owen, A J; Mollon, J D

    2014-02-01

    Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so-called frequency-doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome-wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency-doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642 758 single nucleotide polymorphism (SNP) markers. A significant association (P = 7.9 × 10(-9) ) was found with the SNP marker rs1797052, situated in the 5'-untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α = 0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N-methyl-d-aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements.

  14. 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

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

    PubMed

    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.

  16. 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

  17. Juvenile polyposis syndrome.

    PubMed

    Brosens, Lodewijk Aa; Langeveld, Danielle; van Hattem, W Arnout; Giardiello, Francis M; Offerhaus, G Johan A

    2011-11-28

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.

  18. Juvenile polyposis syndrome

    PubMed Central

    Brosens, Lodewijk AA; Langeveld, Danielle; van Hattem, W Arnout; Giardiello, Francis M; Offerhaus, G Johan A

    2011-01-01

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called “landscaper mechanism” where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome. PMID:22171123

  19. Chromosome Abnormalities

    MedlinePlus

    ... division. There are two kinds of cell division, mitosis and meiosis. Mitosis results in two cells that are duplicates of ... 23 paired sets of chromosomes in nonreproductive cells. Mitosis: Cell division resulting in cells that have paired ...

  20. New heritable fragile site with spontaneous expression at 1q41

    SciTech Connect

    Dar, H.; Bar-El, H.; Ziv, M.

    1995-01-16

    The report presents a family ascertained through recurrent spontaneous abortions in which a new heritable fragile site located at 1q41 is segregating. The fragile site is present in the mother and her son. It is expressed spontaneously in 100% of the metaphases from lymphocyte culture using standard conditions. The use of folate deficient medium and the addition of FUdR to the medium did not affect the appearance nor the level of expression of the fragile site. 9 refs., 1 fig., 1 tab.

  1. 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.

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

    PubMed

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

    2016-02-01

    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.

  3. Anti-C1q in chronic hepatitis C virus genotype IV infection: association with autoimmune rheumatologic manifestations.

    PubMed

    Fadda, Samia H; Bassyouni, Iman H; Hamdy, Ahmed; Foad, Nermeen A; Wali, Iman E

    2015-01-01

    A growing body of evidence suggests that anti-complement-1q (anti-C1q) antibodies are elevated in a variety of autoimmune disease. Therefore, we investigated their prevalence and clinical significance in plasma of patients with hepatitis C virus (HCV) genotype IV in the presence and absence of autoimmune extra hepatic manifestations in comparison to normal healthy individuals. Plasma Anti-C1q Abs levels were assessed by an Enzyme Linked Immunosorbant Assay in 91 chronic HCV-infected patients (51 with and 40 without autoimmune rheumatic manifestations) and 40 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. Positive Anti-C1q antibodies were more frequent among HCV patients with extra-hepatic autoimmune involvement, than those without and healthy control subjects. No significant correlations were found between Anti-C1q levels with either the liver activity or the fibrosis scores. In HCV-patients with autoimmune involvements, plasma Anti-C1q levels were significantly higher in patients with positive cryoglobulin, and in those with lymphoma than in those without. These results were confirmed by multivariate analysis. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies among HCV infected patients with positive cryoglobulinaemia and lymphoma.

  4. 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.

  5. Planetary Candidates Observed by Kepler IV: Planet Sample from Q1-Q8 (22 Months)

    NASA Astrophysics Data System (ADS)

    Burke, Christopher J.; Bryson, Stephen T.; Mullally, F.; Rowe, Jason F.; Christiansen, Jessie L.; Thompson, Susan E.; Coughlin, Jeffrey L.; Haas, Michael R.; Batalha, Natalie M.; Caldwell, Douglas A.; Jenkins, Jon M.; Still, Martin; Barclay, Thomas; Borucki, William J.; Chaplin, William J.; Ciardi, David R.; Clarke, Bruce D.; Cochran, William D.; Demory, Brice-Olivier; Esquerdo, Gilbert A.; Gautier, Thomas N., III; Gilliland, Ronald L.; Girouard, Forrest R.; Havel, Mathieu; Henze, Christopher E.; Howell, Steve B.; Huber, Daniel; Latham, David W.; Li, Jie; Morehead, Robert C.; Morton, Timothy D.; Pepper, Joshua; Quintana, Elisa; Ragozzine, Darin; Seader, Shawn E.; Shah, Yash; Shporer, Avi; Tenenbaum, Peter; Twicken, Joseph D.; Wolfgang, Angie

    2014-02-01

    We provide updates to the Kepler planet candidate sample based upon nearly two years of high-precision photometry (i.e., Q1-Q8). From an initial list of nearly 13,400 threshold crossing events, 480 new host stars are identified from their flux time series as consistent with hosting transiting planets. Potential transit signals are subjected to further analysis using the pixel-level data, which allows background eclipsing binaries to be identified through small image position shifts during transit. We also re-evaluate Kepler Objects of Interest (KOIs) 1-1609, which were identified early in the mission, using substantially more data to test for background false positives and to find additional multiple systems. Combining the new and previous KOI samples, we provide updated parameters for 2738 Kepler planet candidates distributed across 2017 host stars. From the combined Kepler planet candidates, 472 are new from the Q1-Q8 data examined in this study. The new Kepler planet candidates represent ~40% of the sample with R P ~ 1 R ⊕ and represent ~40% of the low equilibrium temperature (T eq < 300 K) sample. We review the known biases in the current sample of Kepler planet candidates relevant to evaluating planet population statistics with the current Kepler planet candidate sample.

  6. Fenamiphos is recalcitrant to the hydrolysis by alloforms PON1 Q192R of human serum.

    PubMed

    Damianys, Almenares-López; Fernanda, Martínez-Salazar María; Laura, Ortiz-Hernández María; Rafael, Vazquez-Duhalt; Antonio, Monroy-Noyola

    2013-03-01

    Fenamiphos (ethyl 4-methylthio-m-tolyl isopropylphosphoramidate) is a racemic organophosphorus nematicide widely used in agriculture around the world. The paraoxonase 1 from human serum (PON1) is a phosphotriesterase (PTE) that hydrolyses several xenobiotics including drugs and organophosphorus compounds (OPs). In this work, the separation of the enantiomers of fenamiphos by HPLC using the column CHIRALCEL OJ and a mobile phase of hexane/ethanol (99/1) is presented. A liquid-liquid extraction method was implemented for the characterization of commercial nematicide hydrolysis by PON1 Q192R alloforms of human serum from children and adults. The results show a recovery of 94% for each isomer from the biological matrix. The method resulted linear response in a range concentration between 50 and 800μM with a detection and quantification limit between 0.6 and 2μM for the (+)-fenamiphos, and between 0.7 and 2.3μM for the (-)-fenamiphos. The levels of the Ca(2+)-dependent hydrolysis (residual concentration [μM]) quantified during 30min of reaction were only just 4-14% for both fenamiphos enantiomers with the three alloforms of PON1 Q192R of the two groups of serum studied. These results demonstrate that human serum PON1 is could be involved in the detoxification of a limited number of organophosphorus insecticides. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Kepler Stellar Properties Catalog Update for Q1-Q17 DR25 Transit Search

    NASA Technical Reports Server (NTRS)

    Mathur, Savita; Huber, Daniel

    2016-01-01

    Huber et al. (2014) presented revised stellar properties for 196,468 Kepler targets, which were used for the Q1-Q16 TPSDV planet search (Tenenbaum et al. 2014). The catalog was based on atmospheric properties (i.e., temperature (Teff), surface gravity (log(g)), and metallicity ([FeH])) published in the literature using a variety of methods (e.g., asteroseismology, spectroscopy, exoplanet transits, photometry), which were then homogeneously fitted to a grid of Dartmouth (DSEP) isochrones (Dotter et al. 2008). The catalog was updated in early 2015 for the Q1-Q17 Data Release (DR) 24 transit search (Seader et al. 2015) based on the latest classifications of Kepler targets in the literature at that time. The methodology followed Huber et al. (2014). Here we provide updated stellar properties of 197,096 Kepler targets. Like the previous catalog, this update is based on atmospheric properties that were either published in the literature or provided by the Kepler community follow-up program (CFOP). The input values again come from different methods: asteroseismology, spectroscopy, flicker, and photometry. This catalog update was developed to support the SOC 9.3 TPSDV planet search (Twicken et al. 2016), which is expected to be the final search and data release by the Kepler project.In this document, we describe the method and the inputs that were used to build the catalog. The methodology follows Huber et al. (2014) with a few improvements as described in Section 2.

  8. 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

  9. 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. © 2013 Wiley Periodicals, Inc.

  10. CHROMOSOME MICROMANIPULATION

    PubMed Central

    Nicklas, R. Bruce; Koch, Carol A.

    1969-01-01

    Kinetochore reorientation is the critical process ensuring normal chromosome distribution. Reorientation has been studied in living grasshopper spermatocytes, in which bivalents with both chromosomes oriented to the same pole (unipolar orientation) occur but are unstable: sooner or later one chromosome reorients, the stable, bipolar orientation results, and normal anaphase segregation to opposite poles follows. One possible source of stability in bipolar orientations is the normal spindle forces toward opposite poles, which slightly stretch the bivalent. This tension is lacking in unipolar orientations because all the chromosomal spindle fibers and spindle forces are directed toward one pole. The possible role of tension has been tested directly by micromanipulation of bivalents in unipolar orientation to artificially create the missing tension. Without exception, such bivalents never reorient before the tension is released; a total time "under tension" of over 5 hr has been accumulated in experiments on eight bivalents in eight cells. In control experiments these same bivalents reoriented from a unipolar orientation within 16 min, on the average, in the absence of tension. Controlled reorientation and chromosome segregation can be explained from the results of these and related experiments. PMID:5824068

  11. Juvenile myoclonic epilepsy.

    PubMed

    Buchanan, N

    1995-08-01

    Juvenile myoclonic epilepsy is a relatively common, though under diagnosed, form of epilepsy that commences in adolescence. The distinguishing symptoms, diagnosis and medical management are discussed.

  12. 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

  13. 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.

  14. Chromosome imbalance, normal phenotype, and imprinting.

    PubMed Central

    Bortotto, L; Piovan, E; Furlan, R; Rivera, H; Zuffardi, O

    1990-01-01

    A duplication of the sub-bands 1q42.11 and 1q42.12 was found in a boy and his mother. The proband has short stature (around the 10th centile) but a normal phenotype and psychomotor development. His mother is also asymptomatic. We found 30 published cases of normal subjects with an imbalance of autosomal euchromatic material. In these cases the imbalance involved either only one G positive band or a G positive and a G negative band. Thus the absence of a phenotypic effect cannot always be ascribed to the deficiency in the G positive bands of coding DNA. Moreover, in some cases, the method of transmission of the chromosome abnormality was such that an imprinting effect could be postulated. Images PMID:2231652

  15. Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria

    PubMed Central

    Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau; Lavstsen, Thomas; Aide, Pedro; Jiménez, Alfons; Turner, Louise; Gupta, Himanshu; De Las Salas, Briegel; Mandomando, Inacio; Wang, Christian W.; Petersen, Jens E. V.; Muñoz, Jose; Gascón, Joaquim; Macete, Eusebio; Alonso, Pedro L.; Chitnis, Chetan E.

    2016-01-01

    Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLβ12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLβ12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction. PMID:27835682

  16. Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria.

    PubMed

    Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau; Lavstsen, Thomas; Aide, Pedro; Rubio, Mercedes; Jiménez, Alfons; Turner, Louise; Valmaseda, Aida; Gupta, Himanshu; De Las Salas, Briegel; Mandomando, Inacio; Wang, Christian W; Petersen, Jens E V; Muñoz, Jose; Gascón, Joaquim; Macete, Eusebio; Alonso, Pedro L; Chitnis, Chetan E; Bassat, Quique; Mayor, Alfredo

    2016-11-01

    Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLβ12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLβ12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction.

  17. Nucleosomes and C1q bound to glomerular endothelial cells serve as targets for autoantibodies and determine complement activation.

    PubMed

    O'Flynn, Joseph; Flierman, Roelof; van der Pol, Pieter; Rops, Angelique; Satchell, Simon C; Mathieson, Peter W; van Kooten, Cees; van der Vlag, Johan; Berden, Jo H; Daha, Mohamed R

    2011-10-01

    Various studies indicate a role for both anti-nucleosome and anti-C1q autoantibodies in glomerulonephritis in patients with systemic lupus erythematosus. However, a causal relationship between these autoantibodies and the development of lupus nephritis has not been fully established. Since injury of the endothelium is a major target in lupus nephritis we assessed the interaction of C1q and nucleosomes with glomerular endothelial cells in vitro in the presence or absence of autoantibodies against these antigens. We demonstrate a direct and dose-dependent binding of both nucleosomes and C1q to immortalized human glomerular endothelial cells (GEnC) in vitro, which in part is mediated by cell surface heparan sulfate. We demonstrate that nucleosomes and C1q serve as targets for monoclonal and polyclonal antibodies as well as for anti-nuclear autoantibodies from patients with systemic lupus erythematosus. An additive effect of anti-C1q autoantibodies on anti-nucleosome mediated complement activation was observed. Furthermore, we showed that the activation of complement on glomerular endothelial cells is mediated by the classical pathway since the deposition of C3 on GEnC is abrogated by MgEGTA and does not occur in C1q-depleted serum. Taken together, our studies demonstrate a direct binding of both nucleosomes and C1q to glomerular endothelial cells in vitro. The subsequent binding of autoantibodies against nucleosomes in patients with systemic lupus erythematosus is potentially pathogenic and autoantibodies against C1q seem to have an additional effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Fibronectin mediates cell attachment to C1q: a mechanism for the localization of fibrosis in inflammatory disease.

    PubMed Central

    Rennard, S I; Chen, Y F; Robbins, R A; Gadek, J E; Crystal, R G

    1983-01-01

    Chronic inflammatory processes frequently lead to the abnormal replacement of normal tissue elements by increased numbers of fibroblasts and fibrous connective tissue, i.e., fibrosis. Since the growth of fibroblasts requires that these cells be attached to an extracellular support, the current study was designed to determine if the interaction between the fibroblast attachment factor fibronectin and the C1q component of complement could support fibroblast attachment and growth and thus could form a basis for the attachment of fibroblasts in abnormal tissue locations in those inflammatory states where C1q is bound. Fibronectin purified from human plasma supported attachment of both Chinese hamster ovary cells and of normal fetal lung fibroblasts (HFL-1) to C1q coated substrates. The attachment activity was approximately twice that of attachment to collagen, and was specific, as no attachment occurred to albumin coated substrates. Cells attached to C1q substrates demonstrated characteristic 'spreading' similar to those on collagen. Moreover, the C1q substrate resembled collagen in its ability to support fibroblast growth. Further, the ability of the interaction between C1q and fibronectin to mediate attachment of fibroblasts to immune complexes was demonstrated by the formation of fibroblast-red blood cell-immune complex rosettes, a process that was dependent on both fibronectin and C1q. Thus, the interaction between fibronectin and C1q could serve as the basis for fibroblast attachment and growth in abnormal tissue sites where immune complexes are formed and could be a contributing factor to the development of fibrosis. Images Fig. 1 Fig. 3 Fig. 5 PMID:6604609

  19. The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis.

    PubMed

    Bandini, Silvio; Macagno, Marco; Hysi, Albana; Lanzardo, Stefania; Conti, Laura; Bello, Amanda; Riccardo, Federica; Ruiu, Roberto; Merighi, Irene Fiore; Forni, Guido; Iezzi, Manuela; Quaglino, Elena; Cavallo, Federica

    2016-01-01

    There is an ever increasing amount of evidence to support the hypothesis that complement C1q, the first component of the classical complement pathway, is involved in the regulation of cancer growth, in addition to its role in fighting infections. It has been demonstrated that C1q is expressed in the microenvironment of various types of human tumors, including breast adenocarcinomas. This study compares carcinogenesis progression in C1q deficient (neuT-C1KO) and C1q competent neuT mice in order to investigate the role of C1q in mammary carcinogenesis. Significantly accelerated autochthonous neu(+) carcinoma progression was paralleled by accelerated spontaneous lung metastases occurrence in C1q deficient mice. Surprisingly, this effect was not caused by differences in the tumor-infiltrating cells or in the activation of the complement classical pathway, since neuT-C1KO mice did not display a reduction in C3 fragment deposition at the tumor site. By contrast, a significant higher number of intratumor blood vessels and a decrease in the activation of the tumor suppressor WW domain containing oxidoreductase (WWOX) were observed in tumors from neuT-C1KO as compare with neuT mice. In parallel, an increase in Her2/neu expression was observed on the membrane of tumor cells. Taken together, our findings suggest that C1q plays a direct role both on halting tumor angiogenesis and on inducing apoptosis in mammary cancer cells by coordinating the signal transduction pathways linked to WWOX and, furthermore, highlight the role of C1q in mammary tumor immune surveillance regardless of complement system activation.

  20. Chromosome Territories

    PubMed Central

    Cremer, Thomas; Cremer, Marion

    2010-01-01

    Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenomics is considered, followed by a historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT architecture, and of structural interactions with other CTs is provided as well as the dynamics of CT arrangements during cell cycle and postmitotic terminal differentiation. The article concludes with a discussion of open questions and new experimental strategies to answer them. PMID:20300217

  1. [Investigation of 1q21 amplification in patients with multiple myeloma using I-FISH and cIg-FISH].

    PubMed

    Yang, Rui-fang; Li, Chun-ming; Qiu, Hai-rong; Lu, Hua; Wu, Han-xin; Xu, Jia-ren; Zhang, Peng; Li, Jian-yong; Chen, Li-juan

    2011-12-01

    To investigate the prevlance of 1q21 amplification in patients with multiple myeloma (MM) and its correlation with the progression and prognosis of the disease. 1q21 amplification was detected in 48 patients with MM using cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization analysis (cIg-FISH) and interphase fluorescence in situ hybridization (I-FISH) analysis combined with CD138 immunomagnetic cell sorting (MACS). 1q21 amplification (≥ 3 red signals) was detected in 26/48(54.2%) cases by cIg-FISH and 31/48 (64.6%) cases by I-FISH combined with CD138 MACS. There was a good consistency between the two methods (P>0.05). The mortality of patients with 1q21 amplification was significantly higher than those without (P< 0.05). No significant difference was detected in terms of sex, age, Durie-Salmon stage, subgroup and international staging system (ISS) stage between patients with 1q21 amplification and those without (P>0.05). The frequency of 1q21 amplification in MM is high. There was also an association between the amplification and poor prognosis. cIg-FISH is consistent with CD138 MACS combined with I-FISH.

  2. A unique patient with an Ullrich-Turner syndrome variant and mosaicism for a tiny r(X) and a partial proximal duplication 1q.

    PubMed

    Dawson, A J; Wickstrom, D E; Riordan, D; Cardwell, S; Casey, R; Baldry, S; Brown, C

    2004-01-30

    A 7-year old female with global cognitive impairment, short attention span, hyperactivity, impulsivity, and many compulsive behaviors was referred to the Genetics Clinic. Height was below the 5th centile and weight was at the 5th centile while head circumference was at the 50th centile. Minor anomalies included bluish sclera, low set and slightly posteriorly rotated auricles and a narrow palate with marked overbite. There was no significant family history. Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient, suggesting the presence of an inactive X chromosome. Inactivation was confirmed by detection of a methylated allele of androgen receptor. This methylated allele was under-represented in undigested DNA, consistent with it arising from the r(X) which was present in only a minority of the patient's cells. The clinical phenotype of the tiny r(X) syndrome in our patient is obviously further influenced by mosaicism for the dup(1). Few cases of duplication of the proximal portion of chromosome 1 have been reported. Of these, the duplication either was present in all cells or involved different band regions so that a direct comparison would be difficult. However, the lower percentage of mosaicism for the dup(1) in our patient would suggest a milder influence on the clinical phenotype. Copyright 2003 Wiley-Liss, Inc.

  3. Absolute sputtering yields from solid Ne by low energy He+ and Arq+ (1 >= q >= 6) impact

    NASA Astrophysics Data System (ADS)

    Fujita, Shinya; Tachibana, Takayuki; Koizumi, Tetsuo; Hirayama, Takato

    2009-04-01

    Absolute sputtering yields from the surface of solid Ne by low energy He+ and Arq+ (1 >= q >= 6) impact are measured. Very large sputtering yields (300 atoms/ion for 1 keV He+ impact, and 3000 atoms/ion for 1keV Ar+ impact) have been observed. A significant dependence of the sputtering yields on the chage state, i.e. the potential energy, of the incident ion for Arq+ has not been observed because it is estimated to be much smaller than that of the kinetic sputtering, which suggests that the mechanism of potential sputtering is similar to those known for the electron- and photon-stimulated desorption processes.

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

    PubMed

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

    2014-06-27

    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.

  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. 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…

  7. Juvenile Delinquency Intervention.

    ERIC Educational Resources Information Center

    Lipsey, Mark W.

    1988-01-01

    Three meta-analyses by C. J. Garrett (1984, 1985), P. Kaufman (1985), and W. S. Davidson and others (1984) of juvenile delinquency interventions are summarized. This systematic literature review indicates that interventions to reduce juvenile delinquency may have small, but meaningful, impacts. Promising avenues for future research are suggested.…

  8. Juvenile generalized pustular psoriasis.

    PubMed

    Xiao, Ting; Li, Bo; He, Chun-Di; Chen, Hong-Duo

    2007-08-01

    Generalized pustular psoriasis (GPP) is an erythrodermic, generalized form of pustular psoriasis. GPP is rare in children. The present study describes a case of juvenile GPP and reviews 12 juvenile GPP inpatients treated at our hospital in the period 1978-2005.

  9. Juvenile Rights. Second Edition.

    ERIC Educational Resources Information Center

    Eaneman, Paulette S.; And Others

    These classroom materials are part of the Project Benchmark series designed to teach secondary students about our legal concepts and systems. This unit focuses on juvenile rights and responsibilities under the law. The materials outline juvenile rights and responsibilities in the areas of parental control, education, free expression, search and…

  10. Distinguishing juvenile homicide from violent juvenile offending.

    PubMed

    DiCataldo, Frank; Everett, Meghan

    2008-04-01

    Juvenile homicide is a social problem that has remained a central focus within juvenile justice research in recent years. The term juvenile murderer describes a legal category, but it is purported to have significant scientific meaning. Research has attempted to conceptualize adolescent murderers as a clinical category that can be reliably distinguished from their nonhomicidal counterparts. This study examined 33 adolescents adjudicated delinquent or awaiting trial for murder and 38 adolescents who committed violent, nonhomicidal offenses to determine whether the two groups differed significantly on family history, early development, delinquency history, mental health, and weapon possession variables. The nonhomicide group proved more problematic on many of these measures. Two key factors did distinguish the homicide group: These adolescents endorsed the greater availability of guns and substance abuse at the time of their commitment offenses. The significance of this finding is discussed, and the implications for risk management and policy are reviewed.

  11. Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities

    PubMed Central

    Ballif, Blake C.; Theisen, Aaron; Rosenfeld, Jill A.; Traylor, Ryan N.; Gastier-Foster, Julie; Thrush, Devon Lamb; Astbury, Caroline; Bartholomew, Dennis; McBride, Kim L.; Pyatt, Robert E.; Shane, Kate; Smith, Wendy E.; Banks, Valerie; Gallentine, William B.; Brock, Pamela; Rudd, M. Katharine; Adam, Margaret P.; Keene, Julia A.; Phillips, John A.; Pfotenhauer, Jean P.; Gowans, Gordon C.; Stankiewicz, Pawel; Bejjani, Bassem A.; Shaffer, Lisa G.

    2010-01-01

    Segmental duplications, which comprise ∼5%–10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are ∼2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is ∼2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome. PMID:20206336

  12. Identification of a recurrent microdeletion at 17q23.1q23.2 flanked by segmental duplications associated with heart defects and limb abnormalities.

    PubMed

    Ballif, Blake C; Theisen, Aaron; Rosenfeld, Jill A; Traylor, Ryan N; Gastier-Foster, Julie; Thrush, Devon Lamb; Astbury, Caroline; Bartholomew, Dennis; McBride, Kim L; Pyatt, Robert E; Shane, Kate; Smith, Wendy E; Banks, Valerie; Gallentine, William B; Brock, Pamela; Rudd, M Katharine; Adam, Margaret P; Keene, Julia A; Phillips, John A; Pfotenhauer, Jean P; Gowans, Gordon C; Stankiewicz, Pawel; Bejjani, Bassem A; Shaffer, Lisa G

    2010-03-12

    Segmental duplications, which comprise approximately 5%-10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are approximately 2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is approximately 2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome. Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. Juvenile Huntington's disease: report of one case.

    PubMed

    Sue, W C; Hwu, W L; Chen, C Y

    1998-01-01

    Huntington's disease (HD) is caused by mutation of the IT 15gene (chromosome 4p16.3), with elongation of (CAG) n repeats. Most juvenile Huntington disease patients acquire the genetic defect through paternal transmission due to amplification of the repeat number during spermatogenesis, and thus causing early age of disease onset and increased disease severity. We here report one case that instead of choreoathetosis presents symptoms of developmental regression, such as seizure and rigid/bradykinesia. EEG showed occipital dominant 4-5 Hz high-amplitude spike-wave activities. MRI showed advanced atrophy and abnormal increase in signal intensity on T2-weighted and proton-density-weighted images of the caudate nuclei and putamina early in the course. The clinical diagnosis is confirmed by PCR study of HD (CAG) n repeats. This is the first case of juvenile Hunington's disease reported in Taiwan.

  14. Chromosomal Imbalances in Primary Lymphomas of the Central Nervous System

    PubMed Central

    Rickert, Christian H.; Dockhorn-Dworniczak, Barbara; Simon, Ronald; Paulus, Werner

    1999-01-01

    Twenty-two primary central nervous system lymphomas of immunocompetent adults were studied by comparative genomic hybridization. All were high-grade diffuse large B cell lymphomas. Comparative genomic hybridization revealed an average of 5.5 chromosomal changes per tumor, with gains being more common than losses (3.5 vs. 2.0). The most frequent DNA copy number changes were gains on chromosomes 1, 12, 18 (41% each), 7 (23%), and 11 (18%) and losses involving chromosomes 6 (59%), 18, and 20 (18% each). Commonly involved regions were +12q (41%), +18q (36%), +1q (32%), and +7q (23%), as well as −6q (50%), −6p (18%), −17p, and −18p (14% each). High-level gains were found on 7 chromosomes, mainly involving chromosomes 18q (23%), 12q (18%), and 1q (14%). Minimal common regions of over- and underrepresentation were found on +1q25–31, −6q16–21, +7q11.2, +12p11.2–13, +12q12–14, +12q22–24.1, and +18q12.2–21.3. A significant correlation between loss of DNA copy numbers on chromosome 6q and shorter survival could be established (10.2 vs. 22.3 months; P < 0.05). Our findings suggest that chromosomal imbalances of primary central nervous system lymphomas are similar to those of diffuse large B cell lymphomas at other locations and are probably not related to cerebral presentation; however, they may be prognostically relevant. PMID:10550299

  15. 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…

  16. 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.

  17. 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.

  18. C1q ablation exacerbates amyloid deposition: A study in a transgenic mouse model of ATTRV30M amyloid neuropathy.

    PubMed

    Panayiotou, Elena; Fella, Eleni; Papacharalambous, Revekka; Malas, Stavros; Saraiva, Maria Joao; Kyriakides, Theodoros

    2017-01-01

    ATTRV30M amyloid neuropathy is a lethal autosomal dominant sensorimotor and autonomic neuropathy, caused by deposition of amyloid fibrils composed of aberrant transthyretin (TTR). Ages of onset and penetrance exhibit great variability and genetic factors have been implicated. Complement activation co-localizes with amyloid deposits in amyloidotic neuropathy and is possibly involved in the kinetics of amyloidogenesis. A candidate gene approach has recently identified C1q polymorphisms to correlate with disease onset in a Cypriot cohort of patients with ATTRV30M amyloid neuropathy. In the current study we use a double transgenic mouse model of ATTRV30M amyloid neuropathy in which C1q is ablated to elucidate further a possible modifier role for C1q. Amyloid deposition is found to be increased by 60% in the absence of C1q. Significant up regulation is also recorded in apoptotic and cellular stress markers reflecting extracellular toxicity of pre-fibrillar and fibrillar TTR. Our data further indicate that in the absence of C1q there is marked reduction of macrophages in association with amyloid deposits and thus less effective phagocytosis of TTR.

  19. Activation of the Complement Classical Pathway (C1q Binding) by Mesophilic Aeromonas hydrophila Outer Membrane Protein

    PubMed Central

    Merino, Susana; Nogueras, Maria Mercedes; Aguilar, Alicia; Rubires, Xavier; Albertí, Sebastian; Benedí, Vicente Javier; Tomás, Juan M.

    1998-01-01

    The mechanism of killing of Aeromonas hydrophila serum-sensitive strains in nonimmune serum by the complement classical pathway has been studied. The bacterial cell surface component that binds C1q more efficiently was identified as a major outer membrane protein of 39 kDa, presumably the porin II described by D. Jeanteur, N. Gletsu, F. Pattus, and J. T. Buckley (Mol. Microbiol. 6:3355–3363, 1992), of these microorganisms. We have demonstrated that the purified form of porin II binds C1q and activates 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 of factor D). Binding of C1q to other components of the bacterial outer membrane, in particular to rough lipopolysaccharide, could not be demonstrated. Activation of the classical pathway by this lipopolysaccharide was also much less efficient than activation by the outer membrane protein. The strains possessing O-antigen lipopolysaccharide bind less C1q than the serum-sensitive strains, because the outer membrane protein is less accessible, and are resistant to complement-mediated killing. Finally, a similar or identical outer membrane protein (presumably porin II) that binds C1q was shown to be present in strains from the most common mesophilic Aeromonas O serogroups. PMID:9673268

  20. Entamoeba histolytica Cell Surface Calreticulin Binds Human C1q and Functions in Amebic Phagocytosis of Host Cells

    PubMed Central

    Vaithilingam, Archana; Teixeira, Jose E.; Miller, Peter J.; Heron, Bradley T.

    2012-01-01

    Phagocytosis of host cells is characteristic of tissue invasion by the intestinal ameba Entamoeba histolytica, which causes amebic dysentery and liver abscesses. Entamoeba histolytica induces host cell apoptosis and uses ligands, including C1q, on apoptotic cells to engulf them. Two mass spectrometry analyses identified calreticulin in amebic phagosome preparations, and, in addition to its function as an endoplasmic reticulum chaperone, calreticulin is believed to be the macrophage receptor for C1q. The purpose of this study was to determine if calreticulin functions as an E. histolytica C1q receptor during phagocytosis of host cells. Calreticulin was localized to the surface of E. histolytica during interaction with both Jurkat lymphocytes and erythrocytes and was present in over 75% of phagocytic cups during amebic erythrophagocytosis. Presence of calreticulin on the cell surface was further demonstrated using a method that selectively biotinylated cell surface proteins and by flow cytometry using trophozoites overexpressing epitope-tagged calreticulin. Regulated overexpression of calreticulin increased E. histolytica's ability to phagocytose apoptotic lymphocytes and calcium ionophore-treated erythrocytes but had no effect on amebic adherence to or destruction of cell monolayers or surface expression of the GalNAc lectin and serine-rich E. histolytica protein (SREHP) receptors. Finally, E. histolytica calreticulin bound specifically to apoptotic lymphocytes and to human C1q. Collectively, these data implicate cell surface calreticulin as a receptor for C1q during E. histolytica phagocytosis of host cells. PMID:22473608

  1. 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

  2. Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome, but not overweight or obesity.

    PubMed

    Bortolasci, Chiara Cristina; Vargas, Heber Odebrecht; Souza-Nogueira, André; Gastaldello Moreira, Estefania; Vargas Nunes, Sandra Odebrecht; Berk, Michael; Dodd, Seetal; Barbosa, Décio Sabbatini; Maes, Michael

    2014-11-01

    Background The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence. Aims and methods This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale. Results PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder. Discussion PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.

  3. Juvenile ankylosing spondylitis in Turner syndrome.

    PubMed

    Sandhya, P; Danda, Debashish; Danda, Sumita; Srivastava, Vivi M

    2013-01-01

    Juvenile ankylosing spondylitis (JAS) is a chronic autoimmune disorder which causes considerable morbidity when left untreated; it occurs predominantly in men. We describe an Asian Indian woman who had JAS with phenotypic features of Turner syndrome (TS) and was found to be a mosaic for 45, X/46, X, psu idic (X) (p11) by karyotyping and fluorescence in situ hybridization (FISH) studies of peripheral blood. The absence of Y chromosome material was confirmed by FISH. Haplo-insufficiency of the X chromosome can predispose to autoimmunity. To the best of our knowledge, this is the first report of JAS in association with mosaic Turner syndrome. This case highlights the possible effects of gene dosage in development of an autoimmune disease.

  4. Language Impairment Resulting from a de novo Deletion of 7q32.1q33.

    PubMed

    Jiménez-Romero, María S; Barcos-Martínez, Montserrat; Espejo-Portero, Isabel; Benítez-Burraco, Antonio

    2016-10-01

    We report on a girl who presents with hearing loss, behavioral disturbances (according to the Inventory for Client and Agency Planning) as well as motor and cognitive delay (according to Battelle Developmental Inventories) which have a significant impact on her speech and language abilities [according to the Peabody Picture Vocabulary Test (ed 3), and the Prueba de Lenguaje Oral de Navarra-Revisada (Navarra Oral Language Test, Revised)]. Five copy number variations (CNVs) were identified in the child: arr[hg18] 7q32.1q33(127109685-132492196)×1, 8p23.1(7156900-7359099) ×1, 15q13.1(26215673-26884937)×1, Xp22.33(17245- 102434)×3, and Xp22.33(964441-965024)×3. The pathogenicity of similar CNVs is mostly reported as unknown. The largest deletion is found in a hot spot for cognitive disease and language impairment and contains several genes involved in brain development and function, many of which have been related to developmental disorders encompassing language deficits (dyslexia, speech-sound disorder, and autism). Some of these genes interact with FOXP2. The proband's phenotype may result from a reduced expression of some of these genes.

  5. Language Impairment Resulting from a de novo Deletion of 7q32.1q33

    PubMed Central

    Jiménez-Romero, María S.; Barcos-Martínez, Montserrat; Espejo-Portero, Isabel; Benítez-Burraco, Antonio

    2016-01-01

    We report on a girl who presents with hearing loss, behavioral disturbances (according to the Inventory for Client and Agency Planning) as well as motor and cognitive delay (according to Battelle Developmental Inventories) which have a significant impact on her speech and language abilities [according to the Peabody Picture Vocabulary Test (ed 3), and the Prueba de Lenguaje Oral de Navarra-Revisada (Navarra Oral Language Test, Revised)]. Five copy number variations (CNVs) were identified in the child: arr[hg18] 7q32.1q33(127109685-132492196)×1, 8p23.1(7156900-7359099) ×1, 15q13.1(26215673-26884937)×1, Xp22.33(17245- 102434)×3, and Xp22.33(964441-965024)×3. The pathogenicity of similar CNVs is mostly reported as unknown. The largest deletion is found in a hot spot for cognitive disease and language impairment and contains several genes involved in brain development and function, many of which have been related to developmental disorders encompassing language deficits (dyslexia, speech-sound disorder, and autism). Some of these genes interact with FOXP2. The proband's phenotype may result from a reduced expression of some of these genes. PMID:27867345

  6. ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma.

    PubMed

    Marchesini, Matteo; Ogoti, Yamini; Fiorini, Elena; Aktas Samur, Anil; Nezi, Luigi; D'Anca, Marianna; Storti, Paola; Samur, Mehmet Kemal; Ganan-Gomez, Irene; Fulciniti, Maria Teresa; Mistry, Nipun; Jiang, Shan; Bao, Naran; Marchica, Valentina; Neri, Antonino; Bueso-Ramos, Carlos; Wu, Chang-Jiun; Zhang, Li; Liang, Han; Peng, Xinxin; Giuliani, Nicola; Draetta, Giulio; Clise-Dwyer, Karen; Kantarjian, Hagop; Munshi, Nikhil; Orlowski, Robert; Garcia-Manero, Guillermo; DePinho, Ronald A; Colla, Simona

    2017-07-10

    Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage. The intimate link between 1q21-amplified ILF2 and the regulation of RNA splicing of DNA repair genes may be exploited to optimize the use of DNA-damaging agents in patients with high-risk MM. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Resolution of C1q deposition but not of the clinical nephrotic syndrome after immunomodulating therapy in focal sclerosis

    PubMed Central

    Tibor Fülöp, Tibor; Csongrádi, Éva; Lerant, Anna A.; Lewin, Matthew; Lewin, Jack R.

    2015-01-01

    Background: The natural evolution of C1q nephropathy (C1qNP) during immunosuppressive treatment is relatively little studied or understood. Case Presentation: A 30 year-old Caucasian female was referred to us for further management of biopsy-proven C1qNP and severe nephrotic syndrome. Serologic work-up remained negative, including complement C3 and C4 levels and repeated testing for antinuclear antibodies. A renal biopsy revealed minimal change nephropathy vs. focal sclerosis on light microscopy and C1qNP on immunopathology. She has failed trials of high-dose oral prednisone, mycophenolate mofetil 1,500 mg twice a day and a subsequent regimen of monthly IV cyclophosphamide 750 mg × 9 cycles. She also received the maximum tolerated angiotensin-converting enzyme inhibitor and spironolactone therapy. Random urine protein-to-creatinine (UPC) ratio predicted proteinuria in the range between 5-35 gm/day, while serum creatinine rose progressively from 1.0 mg/dL to 1.4 mg/dL (to convert to μmol/L, multiply by 88.4). A decision was made to repeat renal biopsy to reassess the underlying histology. The biopsy revealed focal sclerosis but no C1q deposition. Conclusions: Our case illustrates at least two points: first, an established pathologic diagnosis does not obviate the need for repeated renal biopsy later on, should diagnostic uncertainty persist. Second, histological diagnoses may evolve over time, especially in a patient receiving active and powerful immune-modulating treatment. In our case, the clinical nephrosis did not change with immunosuppressive therapy while C1q deposition ceased, making this latter entity likely the immunologically mediated process. PMID:25964890

  8. Synapse organization and modulation via C1q family proteins and their receptors in the central nervous system.

    PubMed

    Matsuda, Keiko

    2016-11-12

    Several C1q family members, related to the C1q complement component are extensively expressed in the central nervous system. Cbln1, which belongs to the Cbln subfamily of C1q proteins and released from cerebellar granule cells, plays an indispensable role in the synapse formation and function at parallel fiber-Purkinje cell synapses. This is achieved by formation of a trans-synaptic tripartite complex which is composed of one unit of the Cbln1 hexamer, monomeric neurexin (NRX) containing a splice site 4 insertion at presynaptic terminals and the postsynaptic GluD2 dimers. Recently an increasing number of soluble or transmembrane proteins have been identified to bind directly to the amino-terminal domains of iGluR and regulate the recruitment and function of iGluRs at synapses. Especially at mossy fiber (MF)-CA3 synapses in the hippocampus, postsynaptic kainate-type glutamate receptors (KARs) are involved in synaptic network activity through their characteristic channel kinetics. C1ql2 and C1ql3, which belong to the C1q-like subfamily of C1q proteins, are produced by MFs and serve as extracellular organizers to recruit functional postsynaptic KAR complexes at MF-CA3 synapses via binding to the amino-terminal domains of GluK2 and GluK4 KAR subunits. In addition, C1ql2 and C1ql3 directly bind to NRX3 containing sequences encoded by exon 25b insertion at splice site 5. In the present review, we highlighted the generality of the strategy by tripartite complex formation of the specific type of NRX and iGluR via C1q family members.

  9. The role of complement-fixing donor specific antibodies identified by a C1q assay after heart transplantation.

    PubMed

    Farrero Torres, M; Pando, M J; Luo, C; Luikart, H; Valantine, H; Khush, K

    2017-09-22

    The development of donor-specific antibodies (DSA) to human leukocyte antigens (HLA) has been associated with acute rejection and allograft failure after heart transplantation. Not all DSA, however, can fix complement. To determine the association between complement-fixing DSA and heart transplant outcomes, we retrospectively analyzed results obtained using the C1q solid-phase assay that specifically detects complement-fixing DSA in parallel with the standard IgG assay in 121 adult heart transplant recipients. The 52 recipients who developed post-transplant DSA had a higher incidence of acute cellular rejection (58% vs. 19%, p<0.001) and antibody-mediated rejection (29% vs. 7%, p<0.001) than the 69 recipients without DSA. The 24 recipients with C1q+ DSA had more antibody mediated rejection than the 28 recipients with C1q- DSA (46% vs. 14%, p=0.012), but there was no difference in the incidence of acute cellular rejection between these two groups. Patients with post-transplant DSA had higher mortality than patients with no DSA (29% vs. 13%, p=0.031), mainly due to increased incidence of acute rejection. No differences in survival were found between recipients with C1q+ DSA and C1q- DSA. Routine monitoring of DSA post-transplant, and their characterization using the C1q assay, may provide prognostic information for acute rejection after heart transplantation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Evaluation of C1q Status and Titer of De Novo Donor-Specific Antibodies as Predictors of Allograft Survival.

    PubMed

    Wiebe, C; Gareau, A J; Pochinco, D; Gibson, I W; Ho, J; Birk, P E; Blydt-Hansen, T; Karpinski, M; Goldberg, A; Storsley, L; Rush, D N; Nickerson, P W

    2017-03-01

    De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post-dnDSA graft loss was observed more frequently in recipients with C1q-positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.

  11. C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

    2015-12-04

    The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium.

  12. Clonal chromosome abnormalities in 54 cases of ovarian carcinoma.

    PubMed

    Thompson, F H; Emerson, J; Alberts, D; Liu, Y; Guan, X Y; Burgess, A; Fox, S; Taetle, R; Weinstein, R; Makar, R

    1994-03-01

    As a prelude to assessing the relationship of chromosome alterations to clinical outcome in ovarian carcinoma, we report on the cytogenetic analysis on short-term cultures from 54 patients. All patients had histopathologically confirmed malignancy, with the majority of cases demonstrating serous ovarian adenocarcinomas. Structural alterations were evident in 52 cases, whereas numeric changes were identified in 13 cases. The most notable numeric abnormalities were loss of the X-chromosome (9/13 total cases) and +7 (3/9 diploid cases). Structural alterations most frequently involved chromosomes 1, 3, 6, 7, 11, and 12. Chromosomal breakpoints were shown to cluster in several chromosomal banding regions, including 1p36, 1p11-q21, 3p23-p10, 7p (especially 7p22), 11p, 11q, 12p13-q12, and 12q24. The frequency of structural alterations involving the following chromosome arms was found to be significantly increased: 1p (p < 0.01), 7p (p < 0.01), 11p (p < 0.01), 11q (p < 0.05), and 12p (p < 0.05). An analysis of the net gain or loss of chromosome segments was also performed, with the most consistent tendency observed being over-representation of 1q and chromosome 7, deletion of 1p, and loss of the X chromosome.

  13. 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.

  14. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... rule out other conditions or infections, such as Lyme disease , that may cause similar symptoms or occur along ... ESR) Bones, Muscles, and Joints Evaluate Your Child's Lyme Disease Risk Word! Arthritis Arthritis Lupus Juvenile Idiopathic Arthritis ( ...

  15. C1q nephropathy in an old woman with acute renal failure: a case report and literature review.

    PubMed

    Zhao, Yu; Fan, Heng; Bao, Bei-yan; Liu, Ting; You, Xiao-Qing; Li, Guo-fu

    2014-08-01

    Reports on the clinical entity of C1q nephropathy have focused on older children and young adult, data on old people are rare. In this report, we would introduce a 77-year-old woman who was diagnosed as C1q nephropathy by means of electron microscopic and immunofluorescence examination. Facial and lower extremity edema was the main reason for her to go for medical treatment, and she developed into acute renal failure within 5 d. Complete remission was observed after hemodialysis and steroid drugs treatments.

  16. PON1 Q192R genotype influences clopidogrel responsiveness by relative platelet inhibition instead of on-treatment platelet reactivity.

    PubMed

    Li, Xiaoqi; Zhang, Lanning; Chen, Xi; Qu, Fei; Li, Jiayue; Ma, Cong; Yang, Jie; Xu, Bin; Wang, Hongjuan; Xu, Qiang; Zhang, Yuxiao; Li, Yang; Lu, Caiyi; Yin, Tong

    2013-10-01

    paraoxonase-1 (PON1) was recently identified as the crucial enzyme for clopidogrel bioactivation, with PON1 Q192R (rs662) polymorphism determining the clopidogel antiplatelet efficacy. However, subsequent studies showed controversies over the findings. This study aimed to evaluate the impact of PON1 Q192R in parallel to that of CYP2C19*2 (rs4244285) on clopidogrel responsiveness in a cohort of Chinese patients with unstable angina pectoris. One hundred and eighty Chinese-Han patients diagnosed with unstable angina pectoris and treated with clopidogrel were consecutively recruited. Clopidogrel responsiveness, measured by relative platelet inhibition {RI=[(pretreatment aggregation-posttreatment aggregation at 5days)/(pretreatment aggregation)] x100%}, was assessed in relation to PON1 Q192R and CYP2C19*2 genotypes. RI values were stratified into four quartiles, with patients in quartile 1 defined as individuals of clopidogrel non-responsiveness. The contributions of PON1 Q192R and CYP2C19*2 to on-treatment platelet reactivity (OTPR) at 5days maintenance dose of clopidogrel were also evaluated. For PON1 Q192R genotypes, RI values were significantly lower in patients with QR and RR alleles than in patients with QQ alleles (p=0.01). OTPR values at 5days maintenance dose of clopidogrel were similar across all the PON1 Q192R genotypes (p=0.41). PON1 192 QR and RR conferred increased risks for clopidogrel non-responsiveness [OR 3.64; 95% CI (1.21-10.92), p=0.02]. For CYP2C19*2 genotypes, compared to CYP2C19*1/*1 wild type carriers, CYP2C19*2 carriers showed a significantly higher OTPR (p=0.009), and a trend for lower RI values (p=0.06). An increased risk for clopidogrel non-responsiveness was found in patients with CYP2C19*2 genotype [OR 2.02; 95% CI (1.03-3.96), p=0.04]. Both PON1 Q192R and CYP2C19*2 genotypes influence clopidogrel responsiveness, with the impact of PON1 Q192R mainly on relative platelet inhibition instead of OTPR of clopidogrel. © 2013.

  17. Role of C1q complement fixing antibody assay in therapeutic plasma exchange management of pediatric cardiac antibody mediated rejection.

    PubMed

    Onwuemene, Oluwatoyosi A; Heath, Deneen M; Hartman, Carol; Wong, Edward C C

    2017-08-01

    Pediatric cardiac transplant patients with antibody-mediated rejection (AMR) often undergo therapeutic plasma exchange (TPE) to remove pathologic donor specific antibodies (DSA). In cases where DSA persist, it is unclear how long TPE should be continued. We report a case of a 17-year-old cardiac transplant patient with AMR where use of a C1q complement fixing antibody assay helped guide TPE cessation. This report adds to the existing literature that highlights the potential clinical significance of C1q antibodies in AMR management. © 2016 Wiley Periodicals, Inc.

  18. Molecular cytogenetic characterization of a 2q35-q37 duplication and a 4q35.1-q35.2 deletion in two cousins: a genotype-phenotype analysis.

    PubMed

    Ronzoni, Luisa; Peron, Angela; Bianchi, Vera; Baccarin, Marco; Guerneri, Silvana; Silipigni, Rosamaria; Lalatta, Faustina; Bedeschi, Maria Francesca

    2015-07-01

    The 2q3 duplication and 4q3 deletion are two distinct conditions with variable phenotypes including developmental delay, intellectual disability, Pierre Robin sequence (PRS), and cardiovascular, craniofacial, digital and skeletal anomalies. We describe two cousins, a 37-year-old man (Patient 1) and a 17-year-old girl (Patient 2), with a derivative chromosome leading to a 4q35 deletion-2q35q37 duplication. Conventional karyotype showed in both patients the same rearrangement derived from unbalanced segregation of a parental reciprocal translocation involving the long arms of chromosome 2 and 4. Patient 1's father and Patient 2's mother were identified as the carriers of a balanced translocation t(2;4)(q35;q35). Array-CGH analysis, performed to characterize the rearrangement, documented in both patients the presence of a 26 Mb duplication of the 2q35-q37.3 region of chromosome 2 and a 6.3 Mb deletion of the 4q35.1-q35.2 region of chromosome 4. Both patients showed intellectual disability, minor facial, and digital anomalies, hearing, ocular, and genitourinary abnormalities. The comparison of their features with those of published cases of 2q3 duplication and 4q3 deletion allowed us to further delineate the genotype-phenotype correlation as well as the combined effect of partial 2q duplication and 4q deletion syndromes in adulthood.

  19. Complement component 1, q subcomponent binding protein is a marker for proliferation in breast cancer.

    PubMed

    Scully, Olivia Jane; Yu, Yingnan; Salim, Agus; Thike, Aye Aye; Yip, George Wai-Cheong; Baeg, Gyeong Hun; Tan, Puay-Hoon; Matsumoto, Ken; Bay, Boon Huat

    2015-07-01

    Complement component 1, q subcomponent binding protein (C1QBP), is a multi-compartmental protein with higher mRNA expression reported in breast cancer tissues. This study evaluated the association between immunohistochemical expression of the C1QBP protein in breast cancer tissue microarrays (TMAs) and clinicopathological parameters, in particular tumor size. In addition, an in vitro study was conducted to substantiate the breast cancer TMA findings. Breast cancer TMAs were constructed from pathological specimens of patients diagnosed with invasive ductal carcinoma. C1QBP protein and proliferating cell nuclear antigen (PCNA) immunohistochemical analyses were subsequently performed in the TMAs. C1QBP immunostaining was detected in 131 out of 132 samples examined. The C1QBP protein was predominantly localized in the cytoplasm of the breast cancer cells. Univariate analysis revealed that a higher C1QBP protein expression was significantly associated with older patients (P = 0.001) and increased tumor size (P = 0.002). Multivariate analysis showed that C1QBP is an independent predictor of tumor size in progesterone-positive tumors. Furthermore, C1QBP was also significantly correlated with expression of PCNA, a known marker of proliferation. Inhibition of C1QBP expression was performed by transfecting C1QBP siRNA into T47D breast cancer cells, a progesterone receptor-positive breast cancer cell line. C1QBP gene expression was analyzed by real-time RT-PCR, and protein expression by Western blot. Cell proliferation assays were also performed by commercially available assays. Down-regulation of C1QBP expression significantly decreased cell proliferation and growth in T47D cells. Taken together, our findings suggest that the C1QBP protein could be a potential proliferative marker in breast cancer.

  20. Chromosome 1 loci in Finnish schizophrenia families.

    PubMed

    Ekelund, J; Hovatta, I; Parker, A; Paunio, T; Varilo, T; Martin, R; Suhonen, J; Ellonen, P; Chan, G; Sinsheimer, J S; Sobel, E; Juvonen, H; Arajärvi, R; Partonen, T; Suvisaari, J; Lönnqvist, J; Meyer, J; Peltonen, L

    2001-07-15

    We have earlier reported evidence for linkage to two regions on chromosome 1q32--q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.

  1. Chromosome structure and function

    SciTech Connect

    Risley, M.S.

    1986-01-01

    This book presents topics in chromosome structure and function. Topics covered include: the structure of interphase chromatin; chromatin structure, gene expression and differentiation; organization of mitotic chromosomes; organization of meiotic chromosomes and synaptonimal complexes; the lampbrush chromsome of animal oocytes; dosage compensation in mammals: x chromosome inactivation; and polytene chromosomes.

  2. Case Report of S1Q3T3 Electrocardiographic Abnormality in a Pregnant Asthmatic Patient During Acute Bronchospasm

    PubMed Central

    Arshad, Hafiza; Khan, Rana Rahel; Khaja, Misbahuddin

    2017-01-01

    Patient: Female, 33 Final Diagnosis: S1Q3T3 electrocardiographic abnormality in a pregnant asthmatic during acute bronchospasm Symptoms: Cough • shortness of breath Medication: — Clinical Procedure: EKG Specialty: Pulmonology Objective: Rare co-existance of disease or pathology Background: Asthma is the most common chronic pulmonary disease during pregnancy. Several previous reports have documented reversible electrocardiographic changes during severe acute asthma attacks, including tachycardia, P pulmonale, right bundle branch block, right axis deviation, and ST segment and T wave abnormalities. Case Report: We present the case of a pregnant patient with asthma exacerbation in which acute bronchospasm caused S1Q3T3 abnormality on an electrocardiogram (ECG). The complete workup of ECG findings of S1Q3T3 was negative and correlated with bronchospasm. The S1Q3T3 electrocardiographic abnormality can be seen in acute bronchospasm in pregnant women. The other causes like pulmonary embolism, pneumothorax, acute lung disease, cor pulmonale, and left posterior fascicular block were excluded. Conclusions: Asthma exacerbations are of considerable concern during pregnancy due to their adverse effect on the fetus, and optimization of asthma treatment during pregnancy is vital for achieving good outcomes. Prompt recognition of electrocardiographic abnormality and early treatment can prevent adverse perinatal outcomes. PMID:28144025

  3. C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases.

    PubMed

    Gupta, Ruchika; Sharma, Alok; Agarwal, Sanjay K; Dinda, Amit K

    2015-11-01

    C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN) has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH). Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman's capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

  4. Vocational Teachers' Role in Serving Juvenile Offenders.

    ERIC Educational Resources Information Center

    Meers, Gary D.

    1983-01-01

    Educators need to understand the juvenile justice system to understand what juvenile offenders go through while completing their sentences. This article reviews cases and juvenile charge classifications, and presents a model for alternative sentencing options for juveniles. (JOW)

  5. [Investigation of chromosome 1 aberrations in patients with multiple myeloma using cIg-FISH method and its significance].

    PubMed

    Yang, Rui-Fang; Li, Chun-Ming; Qiu, Hai-Rong; Lu, Hua; Wu, Han-Xin; Xu, Jia-Ren; Li, Jian-Yong; Chen, Li-Juan

    2010-12-01

    To investigate the incidence of 1q21 amplification and 1p12 deletion, and analyze the correlation between these aberrations with disease progression, prognosis and outcome in patients with multiple myeloma (MM). Cytoplasm light chain immunofluorescence with simultaneous interphase fluorescence in situ hybridization (cIg-FISH) was used to detecte the 1q21 amplification and 1p12 deletion in 48 patients with MM. 1q21 amplification (≥ 3 red signals) was determined in 26 of 48(54.2%) cases. The mortality of patients with 1q21 amplification was significantly higher than that of those lacking 1q21 amplification (P < 0.05). The sex, age, D-S stage, subgroup and ISS stage between patients with and without 1q21 amplification had no significant difference (P > 0.05). There was a significant difference in D-S stage and mortality between patients with 3 and with 4 copies of 1q21 (P < 0.05). No significant difference in sex, age, subgroup, ISS stage, and isotype was found between them (P > 0.05). 1p12 deletion (< 2 green signals) was found in 14 of 48 (29.2%) cases. There was no significant difference in sex, age, D-S stage, ISS stage, isotype, subgroup, and mortality between patients with and without 1p12 deletion. The frequency of chromosome 1 aberrations in multiple myeloma is high and 1q21 amplification is a poor prognosis factor.

  6. Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

    PubMed

    Olsson, Richard F; Hagelberg, Stefan; Schiller, Bodil; Ringdén, Olle; Truedsson, Lennart; Åhlin, Anders

    2016-06-01

    Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.

  7. Spectral karyotyping and chromosome banding studies of primary breast carcinomas and their lymph node metastases.

    PubMed

    Adeyinka, A; Kytola, S; Mertens, F; Pandis, N; Larsson, C

    2000-03-01

    Three primary breast tumors and their lymph node metastases were characterized by G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH). In each case, the karyotypic abnormalities detected were similar in the primary tumor and its matched metastasis. Two of the pairs had near-diploid karyotypes with three to four chromosomal aberrations, whereas the third pair had a near-pentaploid chromosome content and many marker chromosomes in the primary tumor and a near-tetraploid chromosome number with almost the same marker chromosomes in the metastasis. SKY and FISH confirmed the karyotypic similarities between the primary tumors and their metastases and, in addition, improved the identification and characterization of marker chromosomes. One of the tumor pairs with near-diploid karyotypes had gain of 8q, 16q, and 17q, whereas the other had gain of 1q and chromosome 8 material in the form of ring chromosomes. The third pair had more complex chromosomal translocations and numerical changes resulting in net gain of material from chromosomes X, 1, 2, 6, 7, 14, 16, 19, and 20, and chromosome arms 8q and 11q, as well as net loss of material from chromosomes 3, 13, 18, 21, and 22. The present study underscores the need to combine conventional chromosome banding and molecular cytogenetic techniques in the cytogenetic analysis of solid tumors.

  8. Juvenile xanthogranuloma with clonal proliferation in the bone marrow.

    PubMed

    Mały, Ewa; Przyborska, Marta; Rybczyńska, Aleksandra; Konatkowska, Benigna; Nowak, Jerzy; Januszkiewicz, Danuta

    2012-04-01

    The triple association between juvenile xanthogranuloma (JXG), juvenile myelomonocytic leukemia and neurofibromatosis was described in literature in about 20 cases. In this paper, the case of an 11-month-old infant boy with a disseminated JXG with unusual cytogenetic representation in the bone marrow was reported. Neurofibromatosis and juvenile myelomonocytic leukemia were excluded, just the same as other leukemias. Bone marrow and peripheral blood cytogenetic analysis revealed a karyotype with many rearrangements 46,XY,-6,der(12)t(6;12)(p21;p13),del(7)(p13p22),+9 once described in the literature as a B-acute lymphoblastic leukemia case. On the contrary, in our patient immunologic testing demonstrated a high activity of T lymphocytes, however, inflammation was excluded. To the best of our knowledge this is the first described case of systemic JXG with determined karyotype representing unusual chromosomal aberrations.

  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.

  10. Extending juvenility in grasses

    DOEpatents

    Kaeppler, Shawn; de Leon Gatti, Natalia; Foerster, Jillian

    2017-04-11

    The present invention relates to compositions and methods for modulating the juvenile to adult developmental growth transition in plants, such as grasses (e.g. maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G362718, GRMZM2G096016, or homologs thereof. Modulation of expression of one or more additional genes which affect juvenile to adult developmental growth transition such as Glossy15 or Cg1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G362718 and/or GRMZM2G096016 are also contemplated, as are transgenic plants and products produced there from, that demonstrate altered, such as extended juvenile growth, and display associated phenotypes such as enhanced yield, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

  11. The prevalence and clinical significance of C1q-binding donor-specific anti-HLA antibodies early and late after kidney transplantation.

    PubMed

    Calp-Inal, Sumeyye; Ajaimy, Maria; Melamed, Michal L; Savchik, Christina; Masiakos, Peter; Colovai, Adriana; Akalin, Enver

    2016-01-01

    We aimed to determine the prevalence and clinical significance of complement-binding donor-specific antibodies (DSA) detected up to 30 years after kidney transplantation. Group 1 patients included 284 consecutive DSA negative patients who underwent kidney transplantation after 1 May 2009. Group 2 included 405 patients transplanted before this date and followed at our center with functioning allografts. DSA were tested using Luminex Single Antigen and the C1q assay. In Group 1 patients, who were monitored prospectively, 31 (11%) developed de novo DSA during a median follow-up of 2.5 (1.9, 3.6) years. Of these, 11 (4%) had C1q+ and 20 (7%) had C1q negative DSA. In Group 2 patients, 77 (19%) displayed DSA. Among these, 33 (8%) had C1q+ and 44 (11%) had C1q negative DSA. The incidence of acute antibody-mediated rejection (AMR) was significantly higher in C1q+DSA patients in both Group 1 (45%) and Group 2 (15%) compared with C1q negative DSA (5% and 2%) and DSA negative patients (1% and 3%; P < 0.001 and P = 0.001). The incidence of chronic AMR was 36% (Group 1) and 51% (Group 2) in patients with C1q+DSA. In contrast, chronic AMR occurred in 5% and 25% of C1q negative DSA, and 2% and 6% of DSA negative Group 1 and 2 patients, respectively (P < 0.001). Although the graft survival was lower in Group 1 C1q+DSA patients (73%) compared with C1q negative DSA (95%) and DSA negative (94%) patients, the difference was not statistically significant by Kaplan-Meier survival analysis (P = 0.21). Our results indicated that the presence of C1q+ DSA was associated with acute and chronic AMR. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody-mediated rejection episode: a retrospective cohort study.

    PubMed

    Moktefi, Anissa; Parisot, Juliette; Desvaux, Dominique; Canoui-Poitrine, Florence; Brocheriou, Isabelle; Peltier, Julie; Audard, Vincent; Kofman, Tomek; Suberbielle, Caroline; Lang, Philippe; Rondeau, Eric; Grimbert, Philippe; Matignon, Marie

    2017-03-01

    After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q-binding impact on allograft survival. We compared clinical, histological and serological features of C4d- and C4d+ AMR, C1q+ and C1q- DSA AMR and analysed C4d and C1q-binding impact on allograft survival. Among 500 for-cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11-6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q- AMR.

  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 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The genome of the Pacific oyster Crassostrea gigas brings new insights on the massive expansion of the C1q gene family in Bivalvia.

    PubMed

    Gerdol, Marco; Venier, Paola; Pallavicini, Alberto

    2015-03-01

    C1q domain-containing (C1qDC) proteins are regarded as important players in the innate immunity of bivalve mollusks and other invertebrates and their highly adaptive binding properties indicate them as efficient pathogen recognition molecules. Although experimental studies support this view, the molecular data available at the present time are not sufficient to fully explain the great molecular diversification of this family, present in bivalves with hundreds of C1q coding genes. Taking advantage of the fully sequenced genome of the Pacific oyster Crassostrea gigas and more than 100 transcriptomic datasets, we: (i) re-annotated the oyster C1qDC loci, thus identifying the correct genomic organization of 337 C1qDC genes, (ii) explored the expression pattern of oyster C1qDC genes in diverse developmental stages and adult tissues of unchallenged and experimentally treated animals; (iii) investigated the expansion of the C1qDC gene family in all major bivalve subclasses. Overall, we provide a broad description of the functionally relevant features of oyster C1qDC genes, their comparative expression levels and new evidence confirming that a gene family expansion event has occurred during the course of Bivalve evolution, leading to the diversification of hundreds of different C1qDC genes in both the Pteriomorphia and Heterodonta subclasses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Opposite chromosome constitutions due to a familial translocation t(1;21)(q43;q22) in 2 cousins with development delay and congenital anomalies: A case report.

    PubMed

    Aleksiūnienė, Beata; Matulevičiūtė, Rugilė; Matulevičienė, Aušra; Burnytė, Birutė; Krasovskaja, Natalija; Ambrozaitytė, Laima; Mikštienė, Violeta; Dirsė, Vaidas; Utkus, Algirdas; Kučinskas, Vaidutis

    2017-04-01

    Chromosomal rearrangements are the major cause of multiple congenital abnormalities and intellectual disability. We report 2 first cousins with unbalanced chromosomal aberrations of chromosomes 1 and 21, resulting from balanced familial translocation. Chromosome microarray analysis revealed 8.5 Mb1q43q44 duplication/21q22.2q22.3 deletion and 6.8 Mb 1q43q44 deletion/21q22.2q22.3 duplication. Among other features, cognitive and motor development delay and craniofacial anomalies are present in both patients, whereas congenital heart defect and hearing impairment is only present in patient carrying 1q43q44 duplication/21q22.2q22.3 deletion. In this report, we provide detailed analysis of the phenotypic features of both patients as well as compare our data with previously published reports of similar aberrations and discuss possible functional effects of AKT3, CEP170, ZBTB18, DSCAM, and TMPRSS3 genes included in the deleted and/or duplicated regions. Partial trisomy 1q/monosomy 21q has only been reported once before, and this is the first report of partial monosomy 1q/trisomy 21q. The expressed phenotype of mirroring chromosomal aberrations in our patients supports the previous suggestion that the dosage effect of some of the genes included in deleted/duplicated regions may result in opposite phenotypes of the patients.

  17. 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.

  18. Phenotypic variability of a deletion and duplication 6q16.1 → q21 due to a paternal balanced ins(7;6)(p15;q16.1q21).

    PubMed

    Spreiz, Ana; Müller, Doris; Zotter, Sibylle; Albrecht, Ursula; Baumann, Matthias; Fauth, Christine; Erdel, Martin; Zschocke, Johannes; Utermann, Gerd; Kotzot, Dieter

    2010-11-01

    Constitutional insertional translocations are rare findings in clinical cytogenetics. Here, we report on the unbalanced segregation of a balanced paternal insertional translocation ins(7;6)(p15;q16.1q21) to three children. Investigations by conventional karyotyping, FISH with locus-specific probes, microsatellite marker analysis, and SNP-array based copy number analysis revealed a direct orientation of the inserted segment, a size of 11.3 Mb, and breakpoints between rs4370337 and rs12660854 and rs12110990 and rs4946730 on 6q16.1 and 6q21, respectively, as well as within BAC clone RP11-182J2 on 7p15. A 17-year-old daughter inherited the der(6) chromosome and was affected by severe mental retardation, obesity, and minor anomalies. Two further children inherited the der(7) chromosome. A daughter shows an almost unremarkable phenotype and only minor features in neuropsychological testing at 19 years of age. Her 14-year-old half-brother demonstrates a mild delay in cognitive development most likely jointly caused by the chromosomal rearrangement and asphyxia during delivery. The patient with the deletion confirms the previously reported phenotype of severe mental retardation and obesity in patients with del(6)(q16.2), while both patients with partial trisomy for the same segment of chromosome 6 are further examples for a generally less severe phenotype associated with duplications than with deletions, and even for the recent insight that chromosomal aneusomies of several megabases may go without major clinical consequences.

  19. Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients.

    PubMed

    Schmid, T E; Brinkworth, M H; Hill, F; Sloter, E; Kamischke, A; Marchetti, F; Nieschlag, E; Wyrobek, A J

    2004-06-01

    Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of ICSI, which can enable men with severely impaired sperm production to father children. Several papers have been published reporting aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolour ACM fluorescence in situ hybridization (FISH) assay that utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome 1 disomy, or in diploidy. Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.

  20. 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

  1. 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…

  2. What Is Juvenile Arthritis?

    MedlinePlus

    ... the possible causes of juvenile arthritis. They are studying genetic and environmental factors that they think are involved. They are also trying to improve current treatments and find new medicines that will work better with fewer side effects. Research supported by ...

  3. Juvenile Victimization and Delinquency.

    ERIC Educational Resources Information Center

    Esbensen, Finn-Aage; Huizinga, David

    1991-01-01

    Demographic characteristics of juvenile victims of crime and a potential relationship between victimization and self-reported delinquency are examined for 877 adolescents from a large midwestern city. Lifetime victimization rates (LVRs) are higher for those involved in delinquency, and LVRs rise with age and higher levels of delinquent behavior.…

  4. 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…

  5. 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.…

  6. Refined genetic mapping of a gene for familial juvenile nephronophthisis (NPH1) and physical mapping of linked markers

    SciTech Connect

    Hildebrandt, F.; Singh-Sawhney, I.; Schnieders, B.

    1995-01-20

    We have recently assigned a gene for familial juvenile nephronophthisis (NPH1) to chromosome 2q between microsatellite markers at loci D2S135 and D2S110. Here we have extended and refined our previous linkage analysis by studying five additional NPH families and by testing five additional markers. By haplotype analysis in a large family yielding proof of linkage, D2S135 and D2S283 were defined with certainty as flanking the NPH1 critical region within a 14-cM interval. These data now allow cytogenetic assignment of the NPH1 critical region to 2q11.1-q21.1. Furthermore, haplotype analysis in 12 small families helped to define as flanking markers D2S293 and D2S363, which span an 8-cM interval. Multipoint linkage analysis by the location score method resulted in a maximum multipoint lod score of 10.30. The {sub max}-1 support interval spans 6.9 cM and is flanked by marker loci D2S293 and D2S363. Since IL1A maps to this region and has been cytogenetically mapped to 2q13 in the literature, NPH1 can be assigned more closely to 2q13 or adjacent bands. Contigs of CEPH mega-YAC clones in the region were established by screening the clones with microsatellite markers, adding marker IL1A to the physical map as a novel assignment. We conclude that the NPH1 gene most probably localizes to an interval of 6.9 cM between marker loci D2S293 and D2S363 in the vicinity of 2q13. This contig mapping provides the basis for cloning of this interval and for isolation of the NPH1 gene. 18 refs., 3 figs., 1 tab.

  7. A C1q Domain Containing Protein from Scallop Chlamys farreri Serving as Pattern Recognition Receptor with Heat-Aggregated IgG Binding Activity

    PubMed Central

    Wang, Leilei; Wang, Lingling; Zhang, Huan; Zhou, Zhi; Siva, Vinu S.; Song, Linsheng

    2012-01-01

    Background The C1q domain containing (C1qDC) proteins refer to a family of all proteins that contain the globular C1q (gC1q) domain, and participate in a series of immune responses depending on their gC1q domains to bind a variety of self and non-self binding ligands. Methodology In the present study, the mRNA expression patterns, localization, and activities of a C1qDC protein from scallop Chlamys farreri (CfC1qDC) were investigated to understand its possible functions in innate immunity. The relative expression levels of CfC1qDC mRNA in hemocytes were all significantly up-regulated after four typical PAMPs (LPS, PGN, β-glucan and polyI:C) stimulation. During the embryonic development of scallop, the mRNA transcripts of CfC1qDC were detected in all the stages, and the expression level was up-regulated from D-hinged larva and reached the highest at eye-spot larva. The endogenous CfC1qDC was dominantly located in the hepatopancreas, gill, kidney and gonad of adult scallop through immunofluorescence. The recombinant protein of CfC1qDC (rCfC1qDC) could not only bind various PAMPs, such as LPS, PGN, β-glucan as well as polyI:C, but also enhance the phagocytic activity of scallop hemocytes towards Escherichia coli. Meanwhile, rCfC1qDC could interact with human heat-aggregated IgG, and this interaction could be inhibited by LPS. Conclusions All these results indicated that CfC1qDC in C. farreri not only served as a PRR involved in the PAMPs recognition, but also an opsonin participating in the clearance of invaders in innate immunity. Moreover, the ability of CfC1qDC to interact with immunoglobulins provided a clue to understand the evolution of classical pathway in complement system. PMID:22905248

  8. Determining donor-specific antibody C1q-binding ability improves the prediction of antibody-mediated rejection in human leucocyte antigen-incompatible kidney transplantation.

    PubMed

    Malheiro, Jorge; Tafulo, Sandra; Dias, Leonídio; Martins, La Salete; Fonseca, Isabel; Beirão, Idalina; Castro-Henriques, António; Cabrita, António

    2017-04-01

    Detrimental impact of preformed donor-specific antibodies (DSAs) against human leucocyte antigens on outcomes after kidney transplantation are well documented, however, the value of their capacity to bind complement for predicting antibody-mediated rejection (AMR) and graft survival still needs to be confirmed. We aimed to study DSA characteristics (strength and C1q binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen bead (SAB) assays (IgG and C1q kits), from a cohort of 517 kidney graft recipients (124 with detectable anti-HLA antibodies). Patients were divided into DSA strength (MFI < vs. ≥ 15 000) and C1q-binding ability. AMR frequency was high (30%) and it increased with DSA strength (P = 0.002) and C1q+ DSA (P < 0.001). The performance of DSA C1q-binding ability as a predictor of AMR was better than DSA strength (diagnostic odds ratio 16.3 vs. 6.4, respectively). Furthermore, a multivariable logistic regression showed that C1q+ DSA was a risk factor for AMR (OR = 16.80, P = 0.001), while high MFI DSAs were not. Graft survival was lower in high MFI C1q+ DSA in comparison with patients with C1q- high or low MFI DSA (at 6 years, 38%, 83% and 80%, respectively; P = 0.001). Both DSA strength and C1q-binding ability assessment seem valuable for improving pretransplant risk assessment. Since DSA C1q-binding ability was a better predictor of AMR and correlated with graft survival, C1q-SAB may be a particularly useful tool.

  9. Report on the radiochemical and environmental isotope character for monitoring well UE-1-q: Groundwater Characterization Program

    SciTech Connect

    Davisson, M.L.; Hudson, G.B.; Kenneally, J.; Nimz, G.J.; Rego, J.H.

    1993-06-01

    Well UE-1-q is located in the northeastern portion of area 1 of the Nevada Test Site in southwestern Nevada, 1244.1 meters above sea level. The well was originally an exploratory hole drilled to a depth of 743 meters below the surface (mbs) by LANL in November of 1980. In May 1992, the Groundwater Characterization Program (GCP) extended the total depth to approximately 792.5 mbs. UE-1-q is cased to a total depth of 749.5 mbs, with the remaining uncased depth exposed exclusively to Paleozoicaged carbonate rock, the principle zone of groundwater sampling. Geologic logging indicates approximately 390 meters of tuffaceous and calcareous alluvium overlies 320 meters of Tertiary-aged volcanic ash-flow and bedded tuffs. Paleozoic carbonate lithology extends from 716 mbs to the total well depth and is separated from the overlying Tertiary volcanic deposits by 6 meters of paleocolluvium. This report outlines the results and interpretations of radiochemical and environmental isotopic analyses of groundwater sampled from UE-1-q on July 10, 1992 during the well pump test following well development. In addition, results of the field tritium monitoring performed during the well drilling are reported in Appendix 1. Sampling, analytical techniques, and analytical uncertainties for the groundwater analyses are presented in Appendix 2.

  10. Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

    PubMed Central

    Benavente, Francisca; Flanagan, Lisa; Uchida, Nobuko; Anderson, Aileen J.

    2017-01-01

    Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect of immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular and humoral components of innate immunity alter fate and migration of human neural stem cells (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis and promoted cell migration in vitro. PMN were shown to generate C1q and C3a; exposure of hNSC to PMN-synthesized concentrations of these complement proteins promoted astrogliogenesis and cell migration. Furthermore, in vitro, Abs directed against C1q and C3a reversed the fate and migration effects observed. In a proof-of-concept in vivo experiment, blockade of C1q and C3a transiently altered hNSC migration and reversed astroglial fate after spinal cord injury. Collectively, these data suggest that modulation of the innate/humoral inflammatory microenvironment may impact the potential of cell-based therapies for recovery and repair following CNS pathology. PMID:28687659

  11. Human chromosome 8.

    PubMed Central

    Wood, S

    1988-01-01

    The role of human chromosome 8 in genetic disease together with the current status of the genetic linkage map for this chromosome is reviewed. Both hereditary genetic disease attributed to mutant alleles at gene loci on chromosome 8 and neoplastic disease owing to somatic mutation, particularly chromosomal translocations, are discussed. PMID:3070042

  12. Mitotic chromosome structure

    SciTech Connect

    Heermann, Dieter W.

    2012-07-15

    Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

  13. 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

  14. 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.

  15. Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere.

    PubMed

    Andersen, M K; Pedersen-Bjergaard, J

    2000-01-01

    Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining. Leukemia (2000) 14, 105-111.

  16. Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis

    PubMed Central

    Kim, Beom-Chan; Hwang, Hyun-Jung; An, Hyoung-Tae; Lee, Hyun; Park, Jun-Sub; Hong, Jin; Ko, Jesang; Kim, Chungho; Lee, Jae-Seon; Ko, Young-Gyu

    2016-01-01

    We previously demonstrated that cell-surface gC1qR is a key regulator of lamellipodia formation and cancer metastasis. Here, we screened a monoclonal mouse antibody against gC1qR to prevent cell migration by neutralizing cell-surface gC1qR. The anti-gC1qR antibody prevented growth factor-stimulated lamellipodia formation, cell migration and focal adhesion kinase activation by inactivating receptor tyrosine kinases (RTKs) in various cancer cells such as A549, MDA-MB-231, MCF7 and HeLa cells. The antibody neutralization of cell-surface gC1qR also inhibited angiogenesis because the anti-gC1qR antibody prevented growth factor-stimulated RTK activation, lamellipodia formation, cell migration and tube formation in HUVEC. In addition, we found that A549 tumorigenesis was reduced in a xenograft mouse model by following the administration of the anti-gC1qR antibody. With these data, we can conclude that the antibody neutralization of cell-surface gC1qR could be a good therapeutic strategy for cancer treatment. PMID:27363031

  17. Activation of Wnt signaling pathway by AF1q enriches stem-like population and enhance mammosphere formation of breast cells.

    PubMed

    Tse, Charlotte Olivia; Kim, Soojin; Park, Jino

    2017-03-18

    Wnt signaling pathway is believed to be responsible for control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state. Moreover, dysregulated Wnt signaling pathway is strongly associated with several diseases including cancer. Previously, we have shown that AF1q associates with a poor prognosis in leukemia, myelodysplastic syndromes, multiple myeloid, ovarian cancer, and breast cancer. Also, AF1q plays a pivotal role as an oncogene and metastasis enhancer in breast cancer via activation of Wnt signaling pathway. AF1q is highly expressed in stem cells, and this expression is diminished by differentiation. To understand the role of AF1q in stem-like population, we examined stem-like cells derived from breast cells which dysregulated Wnt signaling pathway by alteration of AF1q expression. The effect of Wnt signaling pathway by AF1q on EMT marker expression, stem cell marker expression, and sphere formation was determined. Activated Wnt signaling pathway by AF1q enriched stem-like population showed enhanced sphere formation ability. Interestingly, Wnt signaling pathway inhibitor, Quercetin, decreased the sphere formation in these cells. These results suggest that AF1q would have a role as an enhancer in generation of stem-like population through activation of Wnt signaling pathway.

  18. Chromosome Painting in Trogon s. surrucura (Aves, Trogoniformes) Reveals a Karyotype Derived by Chromosomal Fissions, Fusions, and Inversions.

    PubMed

    Degrandi, Tiago M; Del Valle Garnero, Analía; O'Brien, Patricia C M; Ferguson-Smith, Malcolm A; Kretschmer, Rafael; de Oliveira, Edivaldo H C; Gunski, Ricardo J

    2017-01-01

    Trogons are forest birds with a wide distribution, being found in Africa, Asia, and America, and are included in the order Trogoniformes, family Trogonidae. Phylogenetic studies using molecular data have not been able to determine the phylogenetic relationship among the different genera of trogons. So far, no cytogenetic data for these birds exist. Hence, the aim of this study was to characterize the karyotype of Trogon surrucura surrucura by means of classical and molecular cytogenetics. We found a diploid chromosome number of 2n = 82, similar to most birds, with several derived features compared to chicken and the putative ancestral avian karyotype. T. s. surrucura showed 3 pairs of microchromosomes bearing 18S rDNA clusters. The Z and W sex chromosomes were of similar size but could readily be identified by morphological differences. Using chromosome painting with whole chromosome probes from Gallus gallus and Leucopternis albicollis, we found that the chromosomes homologous to chicken chromosomes 2 and 5 correspond to 2 different pairs in T. s. surrucura and L. albicollis, due to the occurrence of centric fissions. Paracentric inversions were detected in the segment homologous to chicken chromosome 1q, and we confirmed the recurrence of breakpoints when our results were compared to other species of birds already analyzed by FISH or by in silico genome assembly. © 2017 S. Karger AG, Basel.

  19. 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.

  20. Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer.

    PubMed

    Silva, Grace O; He, Xiaping; Parker, Joel S; Gatza, Michael L; Carey, Lisa A; Hou, Jack P; Moulder, Stacy L; Marcom, Paul K; Ma, Jian; Rosen, Jeffrey M; Perou, Charles M

    2015-07-01

    A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent CNAs is key to advancing therapeutics because it is likely that these regions contain breast tumor 'drivers' (i.e., cancer causal genes). This study aims to characterize the genomic landscape of breast cancer CNAs and identify potential subtype-specific drivers using a large set of human breast tumors and genetically engineered mouse (GEM) mammary tumors. Using a novel method called SWITCHplus, we identified subtype-specific DNA CNAs occurring at a 15% or greater frequency, which excluded many well-known breast cancer-related drivers such as amplification of ERBB2, and deletions of TP53 and RB1. A comparison of CNAs between mouse and human breast tumors identified regions with shared subtype-specific CNAs. Additional criteria that included gene expression-to-copy number correlation, a DawnRank network analysis, and RNA interference functional studies highlighted candidate driver genes that fulfilled these multiple criteria. Numerous regions of shared CNAs were observed between human breast tumors and GEM mammary tumor models that shared similar gene expression features. Specifically, we identified chromosome 1q21-23 as a Basal-like subtype-enriched region with multiple potential driver genes including PI4KB, SHC1, and NCSTN. This step-wise computational approach based on a cross-species comparison is applicable to any tumor type for which sufficient human and model system DNA copy number data exist, and in this instance, highlights that a single region of amplification may in fact harbor multiple driver genes.

  1. Relationship among C1q-fixing de novo donor specific antibodies, C4d deposition and renal outcome in transplant glomerulopathy.

    PubMed

    Messina, Maria; Ariaudo, Claudia; Praticò Barbato, Loredana; Beltramo, Silvia; Mazzucco, Gianna; Amoroso, Antonio; Ranghino, Andrea; Cantaluppi, Vincenzo; Fop, Fabrizio; Segoloni, Giuseppe Paolo; Biancone, Luigi

    2015-09-01

    The C1q-binding properties of donor specific antibodies (DSA) may be related to antibody-mediated rejection and poor outcome. We retrospectively studied 35 kidney transplant recipients with transplant glomerulopathy (TG) and de novo DSA (dnDSA). C1q dnDSA were measured in the serum stored at renal biopsy and the association among C1q-fixing dnDSA, C4d deposition and graft loss was examined. Of the 35 patients with dnDSA and TG, 15 (42.9%) had C1q-positive dnDSA and 20 (57.1%) had C1q-negative dnDSA. Ten out of 15 patients with C1q-positive dnDSA (66.6%) and 5 with C1q-negative dnDSA (25%) had C4d positive staining renal biopsies (P=0.02), being the C1q-negative dnDSA/C4d-negative TG 42.9% of the total. The C1q-positive dnDSA group has significantly higher IgG DSA Class II MFI than the C1q-negative dnDSA group (P=0.004). Patients with C4d deposits have significantly higher IgG DSA MFI for both Class I and Class II than those without C4d deposits (P=0.02). We found a trend toward higher graft loss in the C1q-positive dnDSA group (60%) versus the C1q-negative dnDSA group (40%) without a statistical significance (P=0.31). Our study provides further characterization of TG associated with dnDSA. The major part of dnDSA-associated TG was C1q-negative and the presence of C1q-fixing dnDSA did not significantly correlate with graft outcome. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD).

    PubMed

    Kantojärvi, Katri; Kotala, Ilona; Rehnström, Karola; Ylisaukko-Oja, Tero; Vanhala, Raija; von Wendt, Taina Nieminen; von Wendt, Lennart; Järvelä, Irma

    2011-06-01

    About 80% of cases with autism express intellectual disability. Both in autism and in mental retardation without autism the majority of the cases are males, suggesting a X-chromosomal effect. In fact, some molecular evidence has been obtained for a common genetic background for autism spectrum disorders (ASD) and X-linked mental retardation (XLMR). In several genome-wide scans (GWS), evidence for linkage at X-chromosome has been reported including the GWS of Finnish ASD families with the highest multipoint lod score (MLS) of 2.75 obtained close to DXS7132 at Xq11.1. To further dissect the relationship between autism and genes implicated in XLMR, we have fine-mapped Xq11.1-q21.33 and analyzed five candidate genes in the region. We refined the region using 26 microsatellite markers and linkage analysis in 99 Finnish families with ASD. The most significant evidence for linkage was observed at DXS1225 on Xq21.1 with a nonparametric multipoint NPL(all) value of 3.43 (P = 0.0004). We sequenced the coding regions and splice sites of RPS6KA6 and ZNF711 residing at the peak region in 42 male patients from families contributing to the linkage. We also analyzed ACSL4 and DLG3, which have previously been known to cause XLMR and IL1RAPL2, a homologous gene for IL1RAPL1 that is mutated in autism and XLMR. A total of six novel and 11 known single nucleotide polymorphisms were identified. Further studies are warranted to analyze the candidate genes at Xq11.1-q21.33.

  3. Assignment of human G-protein-coupled inward rectifier K{sup +} channel homolog GIRK3 gene to chromosome 1q21-q23

    SciTech Connect

    Lesage, F.; Fink, M.; Barhanin, J.

    1995-10-10

    More than 20 genes that encode voltage-gated and Ca{sup 2+}-dependent K{sup +} channels have been identified. These channels are involved in a wide variety of biological functions such as neuronal and muscle excitability, hormone secretion, and osmotic regulation. Two voltage-gated K{sup +} channel genes, KCNA1 and HERG, have been related to neurological and cardiac inherited disorders in humans. Missense mutations in the KCNA1 gene lead to episodic ataxia/myokimia syndrome. Missense, splice donor, and deletion mutations in the HERG gene have been shown to cause long QT syndrome. These two channels belong to the superfamily of cationic channels, which share the characteristic structural features of six transmembrane domains and one segment (called 115) involved in pore formation. 17 refs., 1 fig.

  4. 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.

  5. B Chromosomes - A Matter of Chromosome Drive.

    PubMed

    Houben, Andreas

    2017-01-01

    B chromosomes are supernumerary chromosomes which are often preferentially inherited, deviating from usual Mendelian segregation. The balance between the so-called chromosome drive and the negative effects that the presence of Bs applies on the fitness of their host determines the frequency of Bs in a particular population. Drive is the key for understanding most B chromosomes. Drive occurs in many ways at pre-meiotic, meiotic or post-meiotic divisions, but the molecular mechanism remains unclear. The cellular mechanism of drive is reviewed based on the findings obtained for the B chromosomes of rye, maize and other species. How novel analytical tools will expand our ability to uncover the biology of B chromosome drive is discussed.

  6. 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

  7. 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

  8. Complement Protein C1q Interacts with DC-SIGN via Its Globular Domain and Thus May Interfere with HIV-1 Transmission.

    PubMed

    Pednekar, Lina; Pandit, Hrishikesh; Paudyal, Basudev; Kaur, Anuvinder; Al-Mozaini, Maha Ahmed; Kouser, Lubna; Ghebrehiwet, Berhane; Mitchell, Daniel A; Madan, Taruna; Kishore, Uday

    2016-01-01

    Dendritic cells (DCs) are the most potent antigen-presenting cells capable of priming naïve T-cells. Its C-type lectin receptor, DC-SIGN, regulates a wide range of immune functions. Along with its role in HIV-1 pathogenesis through complement opsonization of the virus, DC-SIGN has recently emerged as an adaptor for complement protein C1q on the surface of immature DCs via a trimeric complex involving gC1qR, a receptor for the globular domain of C1q. Here, we have examined the nature of interaction between C1q and DC-SIGN in terms of domain localization, and implications of C1q-DC-SIGN-gC1qR complex formation on HIV-1 transmission. We first expressed and purified recombinant extracellular domains of DC-SIGN and its homologue DC-SIGNR as tetramers comprising of the entire extra cellular domain including the α-helical neck region and monomers comprising of the carbohydrate recognition domain only. Direct binding studies revealed that both DC-SIGN and DC-SIGNR were able to bind independently to the recombinant globular head modules ghA, ghB, and ghC, with ghB being the preferential binder. C1q appeared to interact with DC-SIGN or DC-SIGNR in a manner similar to IgG. Mutational analysis using single amino acid substitutions within the globular head modules showed that Tyr(B175) and Lys(B136) were critical for the C1q-DC-SIGN/DC-SIGNR interaction. Competitive studies revealed that gC1qR and ghB shared overlapping binding sites on DC-SIGN, implying that HIV-1 transmission by DCs could be modulated due to the interplay of gC1qR-C1q with DC-SIGN. Since C1q, gC1qR, and DC-SIGN can individually bind HIV-1, we examined how C1q and gC1qR modulated HIV-1-DC-SIGN interaction in an infection assay. Here, we report, for the first time, that C1q suppressed DC-SIGN-mediated transfer of HIV-1 to activated pooled peripheral blood mononuclear cells, although the globular head modules did not. The protective effect of C1q was negated by the addition of gC1qR. In fact, gC1qR enhanced DC

  9. [Clinical variability of Juvenile Huntington's Disease phenotype].

    PubMed

    Błaszczyk, Magdalena; Boczarska-Jedynak, Magdalena; Rudzińska, Monika

    2015-01-01

    Huntington's disease is rare, genetically determinated, neurodegenerative disorder. It is determined by dynamic mutation of IT15 gene on short arm of 4 chromosome. Characteristic symptomatology include involuntary movements, cognitive decline and wide spectrum of mood and behaviour disorders. It typically becomes noticeable in mid-adult life, but there are reported cases of appaers of symptoms between 2 and 80 year of life. Especially interesting is juvenile Huntington's disease- the Westphal variant with the beginning in childchood (before 20 year of age) because of clinical differences causing diagnostic difficulties. It affects 5-10% of carries of the mutant gene. Symptoms became noticeable before 10 year of age only in 1% of them.

  10. Juvenile offenders assessment.

    PubMed

    Folino, Jorge O; Mayer, Elizabeth L

    2011-09-01

    Evaluation of juveniles is an integral process that includes a broad bio-psycho-social clinical perspective together with the use of auxiliary instruments. The aim of this review is to report relevant issues for this process found in recent publications. Several evidences lead to broadening the assessment process of children and youngsters to include family functioning style. Mental health services allow the evaluation of multiple factors associated with antisocial behavior that may lead to devising preventive actions. In the Juvenile Justice System a wide-ranging evaluation must include the exploration of general personality characteristics and psychopathic traits in particular; attention deficit/hyperactivity disorder; intelligence; substance abuse and conduct disorder must be considered. A number of factors that have an impact on juvenile antisocial behavior have been identified and can be assessed using the appropriate methodology. The exploration of these factors at different developmental stages and in their various manifestations provide guidelines for devising preventive and therapeutic actions as well as for supporting judicial decisions. Though enriching the present state of the art is always a challenge, it is imperative to encourage the governments to utilize this knowledge to improve the care system of children and adolescents.

  11. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-09-06

    Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  12. Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover

    PubMed Central

    Hamad, Islam; Hunter, A. Christy; Rutt, Kenneth J.; Liu, Zhuang; Dai, Hongjie; Moghimi, S. Moein

    2010-01-01

    We have investigated the interaction between long circulating poly(ethylene glycol)-stabilized single-walled carbon nanotubes (SWNTs) and the complement system. Aminopoly(ethylene glycol)5000–distearoylphosphatidylethanolamine (aminoPEG5000–DSPE) and methoxyPEG5000–DSPE coated as-grown HIPco SWNTs activated complement in undiluted normal human serum as reflected in significant rises in C4d and SC5b-9 levels, but not the alternative pathway split-product Bb, thus indicating activation exclusively through C4 cleavage. Studies in C2-depleted serum confirmed that PEGylated nanotube-mediated elevation of SC5b-9 was C4b2a convertase-dependent. With the aid of monoclonal antibodies against C1s and human serum depleted from C1q, nanotube-mediated complement activation in C1q-depleted serum was also shown to be independent of classical pathway. Nanotube-mediated C4d elevation in C1q-depleted serum, however, was inhibited by N-acetylglucosamine, Futhan (a broad-spectrum serine protease inhibitor capable of preventing complement activation through all three pathways) and anti-MASP-2 antibodies; this strongly suggests a role for activation of MASP-2 in subsequent C4 cleavage and assembly of C4b2a covertases. Intravenous injection of PEGylated nanotubes in some rats was associated with a significant rise in plasma thromboxane B2 levels, indicative of in vivo nanotube-mediated complement activation. The clinical implications of these observations are discussed. PMID:18602161

  13. Mice lacking C1q are protected from high fat diet-induced hepatic insulin resistance and impaired glucose homeostasis.

    PubMed

    Hillian, Antoinette D; McMullen, Megan R; Sebastian, Becky M; Roychowdhury, Sanjoy; Rowchowdhury, Sanjoy; Kashyap, Sangeeta R; Schauer, Philip R; Kirwan, John P; Feldstein, Ariel E; Nagy, Laura E

    2013-08-02

    Complement activation is implicated in the development of obesity and insulin resistance, and loss of signaling by the anaphylatoxin C3a prevents obesity-induced insulin resistance in mice. Here we have identified C1q in the classical pathway as required for activation of complement in response to high fat diets. After 8 weeks of high fat diet, wild-type mice became obese and developed glucose intolerance. This was associated with increased apoptotic cell death and accumulation of complement activation products (C3b/iC3b/C3c) in liver and adipose tissue. Previous studies have shown that high fat diet-induced apoptosis is dependent on Bid; here we report that Bid-mediated apoptosis was required for complement activation in adipose and liver. Although C1qa deficiency had no effect on high fat diet-induced apoptosis, accumulation of complement activation products and the metabolic complications of high fat diet-induced obesity were dependent on C1q. When wild-type mice were fed a high fat diet for only 3 days, hepatic insulin resistance was associated with the accumulation of C3b/iC3b/C3c in the liver. Mice deficient in C3a receptor were protected against this early high fat diet-induced hepatic insulin resistance, whereas mice deficient in the negative complement regulator CD55/DAF were more sensitive to the high fat diet. C1qa(-/-) mice were also protected from high fat diet-induced hepatic insulin resistance and complement activation. Evidence of complement activation was also detected in adipose tissue of obese women compared with lean women. Together, these studies reveal an important role for C1q in the classical pathway of complement activation in the development of high fat diet-induced insulin resistance.

  14. VizieR Online Data Catalog: Kepler planetary candidates. V. 3yr Q1-Q12 (Rowe+, 2015)

    NASA Astrophysics Data System (ADS)

    Rowe, J. F.; Coughlin, J. L.; Antoci, V.; Barclay, T.; Batalha, N. M.; Borucki, W. J.; Burke, C. J.; Bryson, S. T.; Caldwell, D. A.; Campbell, J. R.; Catanzarite, J. H.; Christiansen, J. L.; Cochran, W.; Gilliland, R. L.; Girouard, F. R.; Haas, M. R.; Helminiak, K. G.; Henze, C. E.; Hoffman, K. L.; Howell, S. B.; Huber, D.; Hunter, R. C.; Jang-Condell, H.; Jenkins, J. M.; Klaus, T. C.; Latham, D. W.; Li, J.; Lissauer, J. J.; McCauliff, S. D.; Morris, R. L.; Mullally, F.; Ofir, A.; Quarles, B.; Quintana, E.; Sabale, A.; Seader, S.; Shporer, A.; Smith, J. C.; Steffen, J. H.; Still, M.; Tenenbaum, P.; Thompson, S. E.; Twicken, J. D.; van Laerhoven, C.; Wolfgang, A.; Zamudio, K. A.

    2015-04-01

    We began with the transit-event candidate list from Tenenbaum et al. (2013ApJS..206....5T) based on a wavelet, adaptive matched filter to search 192313 Kepler targets for periodic drops in flux indicative of a transiting planet. Detections are known as Threshold Crossing Events (TCEs). Tenenbaum et al. utilized three years of Kepler photometric observations (Q1-Q12) -the same data span employed by this study based on SOC 8.3 as part of Data Release 21 (Thompson S. E., Christiansen J. L., Jenkins J. M. et al. Kepler (KSCI-19061-001)). (3 data files).

  15. 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

  16. C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight*

    PubMed Central

    Byerly, Mardi S.; Petersen, Pia S.; Ramamurthy, Santosh; Seldin, Marcus M.; Lei, Xia; Provost, Elayne; Wei, Zhikui; Ronnett, Gabriele V.; Wong, G. William

    2014-01-01

    CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, ∼34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance. PMID:24366864

  17. Endocrine disruptors, polychlorinated biphenyls-induced gC1qR-dependent apoptosis in human trophoblast cell line HTR-8/SVneo.

    PubMed

    Gu, Ping-Qing; Gao, Ling-Juan; Li, Li; Liu, Zhu; Luan, Fu-qi; Peng, Yu-Zhu; Guo, Xi-Rong

    2012-02-01

    Although an association exists between exposure to polychlorinated biphenyls (PCBs) and spontaneous miscarriage, the mechanisms underlying this phenomenon remain unclear. In this study, PCBs content in plasma was detected by gas chromatography-mass spectrometry (GC-MS) and decidua tissues were examined for the expression of globular heads of C1q receptor (gC1qR) using Western blot in patients who underwent induced abortion and spontaneous abortion. Results showed increased PCBs content and gC1qR expression in patients who experienced spontaneous abortion. In vitro, Western blot analysis demonstrated significantly higher caspase 3 expression and apoptotic cell counts in green fluorescent protein (GFP)-gC1qR vector group. Additionally, gC1qR and caspase 3 showed decreased expression following PCBs plus gC1qR small interfering RNA (siRNA) treatment. The percentage of apoptotic cells increased in cells treated with PCBs alone or PCB plus negative siRNA. These data suggest that maternal exposure to PCBs is associated with adverse pregnancy outcomes and that upregulation of gC1qR is important for PCBs-mediated trophoblast cell apoptosis.

  18. IgG autoantibodies to C1q do not detectably influence complement activation in vivo and in vitro in systemic lupus erythematosus.

    PubMed

    Siegert, C E; Daha, M R; Lobatto, S; van der Voort, E A; Breedveld, F C

    1992-01-01

    The influence of IgG antibodies to C1q (C1qAb) on activation of the classical pathway of the complement system was investigated in patients with systemic lupus erythematosus (SLE). In in vivo experiments, a prototype for immune complexes was administered intravenously to 14 patients and 9 healthy controls. Eight SLE patients had increased C1qAb titers. The increase of C3a levels, which was measured as a parameter of C1 activation, was significantly lower in SLE patients than in the healthy controls (p = 0.01). No correlation was found between C3a increases and C1qAb titers. In in vitro experiments the influence on C1 activation of monomeric IgG isolated from serum of 11 SLE patients, 7 of whom had increased C1qAb titers, was measured in a C4 consumption assay. The presence of C1qAb did not influence C4 consumption. The results demonstrate that C1qAb do not influence C1 activation by immune complexes in SLE patients.

  19. Telepsychiatry in juvenile justice settings.

    PubMed

    Kaliebe, Kristopher E; Heneghan, James; Kim, Thomas J

    2011-01-01

    Telepsychiatry is emerging as a valuable means of providing mental health care in juvenile justice settings. Youth in the juvenile justice system have high levels of psychiatric morbidity. State and local juvenile justice systems frequently struggle to provide specialized psychiatric care, as these systems have limited resources and often operate in remote locations. Case studies in the use of telepsychiatry to provide improved care in juvenile corrections in 4 states are described, along with a review of advantages and disadvantages of telepsychiatry in these settings.

  20. Genetics Home Reference: juvenile idiopathic arthritis

    MedlinePlus

    ... Home Health Conditions juvenile idiopathic arthritis juvenile idiopathic arthritis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Juvenile idiopathic arthritis refers to a group of conditions involving joint ...

  1. Genetics Home Reference: juvenile primary osteoporosis

    MedlinePlus

    ... Home Health Conditions juvenile primary osteoporosis juvenile primary osteoporosis Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Juvenile primary osteoporosis is a skeletal disorder characterized by thinning of ...

  2. Genetics Home Reference: juvenile myoclonic epilepsy

    MedlinePlus

    ... Home Health Conditions juvenile myoclonic epilepsy juvenile myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). ...

  3. Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation

    PubMed Central

    Kittlesen, David J.; Chianese-Bullock, Kimberly A.; Yao, Zhi Qiang; Braciale, Thomas J.; Hahn, Young S.

    2000-01-01

    Hepatitis C virus (HCV) is an important human pathogen that is remarkably efficient at establishing persistent infection. The HCV core protein is the first protein expressed during the early phase of HCV infection. Our previous work demonstrated that the HCV core protein suppresses host immune responses, including anti-viral cytotoxic T-lymphocyte responses in a murine model. To investigate the mechanism of HCV core-mediated immunosuppression, we searched for host proteins capable of associating with the core protein using a yeast two-hybrid system. Using the core protein as bait, we screened a human T cell–enriched expression library and identified a gene encoding the gC1q receptor (gC1qR). C1q is a ligand of gC1qR and is involved in the early host defense against infection. Like C1q, HCV core can inhibit T-cell proliferative responses in vitro. This core-induced anti–T-cell proliferation is reversed by addition of anti-gC1qR Ab in a T-cell proliferation assay. Furthermore, biochemical analysis of the interaction between core and gC1qR indicates that HCV core binds the region spanning amino acids 188 to 259 of gC1qR, a site distinct from the binding region of C1q. The inhibition of T-cell responsiveness by HCV core may have important implications for HCV persistence in humans. PMID:11086025

  4. 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.

  5. De novo donor-specific anti-HLA antibodies after kidney transplantation are associated with impaired graft outcome independently of their C1q-binding ability.

    PubMed

    Kauke, Teresa; Oberhauser, Cornelia; Lin, Viviane; Coenen, Michaela; Fischereder, Michael; Dick, Andrea; Schoenermarck, Ulf; Guba, Markus; Andrassy, Joachim; Werner, Jens; Meiser, Bruno; Angele, Martin; Stangl, Manfred; Habicht, Antje

    2017-04-01

    Many aspects of post-transplant monitoring of donor-specific (DSA) and non-donor-specific (nDSA) anti-HLA antibodies on renal allograft survival are still unclear. Differentiating them by their ability to bind C1q may offer a better risk assessment. We retrospectively investigated the clinical relevance of de novo C1q-binding anti-HLA antibodies on graft outcome in 611 renal transplant recipients. Acute rejection (AR), renal function, and graft survival were assessed within a mean follow-up of 6.66 years. Post-transplant 6.5% patients developed de novo DSA and 11.5% de novo nDSA. DSA (60.0%; P < 0.0001) but not nDSA (34.1%, P = 0.4788) increased rate of AR as compared with controls (27.4%). C1q-binding anti-HLA antibodies did not alter rate of AR in both groups. Renal function was only significantly diminished in patients with DSAC1q(+) . However, DSA significantly impaired 5-year graft survival (65.2%; P < 0.0001) in comparison with nDSA (86.7%; P = 0.0054) and controls (90.7%). While graft survival did not differ between DSAC1q(-) and DSAC1q(+) recipients, 5-year allograft survival was reduced in nDSAC1q(+) (80.9%) versus nDSAC1q(-) (90.7%, P = 0.0251). De novo DSA independently of their ability to bind C1q are associated with diminished graft survival. © 2016 Steunstichting ESOT.

  6. 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

  7. Chromosome Disorder Outreach

    MedlinePlus

    ... Visit our Photo Gallery Education, Advocacy, Information & Support Chromosome Disorder Outreach, Inc is a non-profit organization. ... Inc. All Rights Reserved You are donating to : Chromosome Disorder Outreach, Inc, a 501c non-profit organization. ...

  8. Human X chromosome

    SciTech Connect

    1993-12-31

    Chapter 21, describes in detail the human X chromosome. X chromatin (or Barr body) formation, inactivation and reactivation of the X chromosome, X;Y translocations, and sex reversal are discussed. 30 refs., 3 figs.

  9. Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus

    PubMed Central

    Marto, N; Bertolaccini, M; Calabuig, E; Hughes, G; Khamashta, M

    2005-01-01

    Objective: To investigate antibodies to complement 1q (anti-C1q) and investigate the correlation between anti-C1q titres and renal disease in systemic lupus erythematosus (SLE). Methods: 151 SLE patients were studied. In patients with biopsy proven lupus nephritis (n = 77), activity of renal disease was categorised according to the BILAG renal score. Sera were tested for anti-C1q by enzyme immunoassay. Serum samples were randomly selected from 83 SLE patients who had no history of renal disease, and the positive and negative predictive value of the antibodies was studied. Results: Patients with active lupus nephritis (BILAG A or B) had a higher prevalence of anti-C1q than those with no renal disease (74% v 32%; relative risk (RR) = 2.3 (95% confidence interval, 1.6 to 3.3)) (p<0.0001). There was no significant difference in anti-C1q prevalence between SLE without nephritis and SLE with non-active nephritis (BILAG C or D) (32% v 53%, p = 0.06) or between active and non-active nephritis (74% v 53%, p = 0.06). Patients with nephritis had higher anti-C1q levels than those without nephritis (36.0 U/ml (range 4.9 to 401.0) v 7.3 U/ml (4.9 to 401.0)) (p<0.001). Anti-C1q were found in 33 of 83 patients (39%) without history of renal disease. Nine of the 33 patients with anti-C1q developed lupus nephritis. The median renal disease-free interval was nine months. One patient with positive anti-C1q was diagnosed as having hypocomplementaemic urticarial vasculitis syndrome during follow up. Conclusions: Anti-C1q in SLE are associated with renal involvement. Monitoring anti-C1q and their titres in SLE patients could be important for predicting renal flares. PMID:15286009

  10. 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

  11. Improving Literacy Skills of Juvenile Detainees. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Hodges, Jane; And Others

    The Office of Juvenile and Delinquency Prevention funded a model designed to improve the literacy level of youth in juvenile detention and correctional facilities. The model specified training language arts teachers and relevant staff and volunteers in direct instruction methods for rapid improvement of students' comprehension, particularly for…

  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. Juvenile Firesetting: A Research Overview. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Putnam, Charles T.; Kirkpatrick, John T.

    2005-01-01

    In 2002, the National Association of State Fire Marshals (NASFM) began developing applied research initiatives to help professionals curtail juvenile firesetting. The project included a review of the research literature, a conference of researchers and professionals involved in preventing juvenile firesetting, and a final report, upon which this…

  14. 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.

  15. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

    PubMed

    Yuzaki, Michisuke

    2010-07-01

    Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer.

  16. Common Variation at 1q24.1 (ALDH9A1) Is a Potential Risk Factor for Renal Cancer

    PubMed Central

    Henrion, Marc Y. R.; Purdue, Mark P.; Scelo, Ghislaine; Broderick, Peter; Frampton, Matthew; Ritchie, Alastair; Meade, Angela; Li, Peng; McKay, James; Johansson, Mattias; Lathrop, Mark; Larkin, James; Rothman, Nathaniel; Wang, Zhaoming; Chow, Wong-Ho; Stevens, Victoria L.; Diver, W. Ryan; Albanes, Demetrius; Virtamo, Jarmo; Brennan, Paul; Eisen, Timothy; Chanock, Stephen; Houlston, Richard S.

    2015-01-01

    So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation. PMID:25826619

  17. Complement Protein C1q Interacts with DC-SIGN via Its Globular Domain and Thus May Interfere with HIV-1 Transmission

    PubMed Central

    Pednekar, Lina; Pandit, Hrishikesh; Paudyal, Basudev; Kaur, Anuvinder; Al-Mozaini, Maha Ahmed; Kouser, Lubna; Ghebrehiwet, Berhane; Mitchell, Daniel A.; Madan, Taruna; Kishore, Uday

    2016-01-01

    Dendritic cells (DCs) are the most potent antigen-presenting cells capable of priming naïve T-cells. Its C-type lectin receptor, DC-SIGN, regulates a wide range of immune functions. Along with its role in HIV-1 pathogenesis through complement opsonization of the virus, DC-SIGN has recently emerged as an adaptor for complement protein C1q on the surface of immature DCs via a trimeric complex involving gC1qR, a receptor for the globular domain of C1q. Here, we have examined the nature of interaction between C1q and DC-SIGN in terms of domain localization, and implications of C1q–DC-SIGN-gC1qR complex formation on HIV-1 transmission. We first expressed and purified recombinant extracellular domains of DC-SIGN and its homologue DC-SIGNR as tetramers comprising of the entire extra cellular domain including the α-helical neck region and monomers comprising of the carbohydrate recognition domain only. Direct binding studies revealed that both DC-SIGN and DC-SIGNR were able to bind independently to the recombinant globular head modules ghA, ghB, and ghC, with ghB being the preferential binder. C1q appeared to interact with DC-SIGN or DC-SIGNR in a manner similar to IgG. Mutational analysis using single amino acid substitutions within the globular head modules showed that TyrB175 and LysB136 were critical for the C1q–DC-SIGN/DC-SIGNR interaction. Competitive studies revealed that gC1qR and ghB shared overlapping binding sites on DC-SIGN, implying that HIV-1 transmission by DCs could be modulated due to the interplay of gC1qR-C1q with DC-SIGN. Since C1q, gC1qR, and DC-SIGN can individually bind HIV-1, we examined how C1q and gC1qR modulated HIV-1–DC-SIGN interaction in an infection assay. Here, we report, for the first time, that C1q suppressed DC-SIGN-mediated transfer of HIV-1 to activated pooled peripheral blood mononuclear cells, although the globular head modules did not. The protective effect of C1q was negated by the addition of gC1qR. In fact, gC1qR enhanced

  18. 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)

  19. 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)

  20. 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.

  1. 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.

  2. The human Y chromosome.

    PubMed Central

    Goodfellow, P; Darling, S; Wolfe, J

    1985-01-01

    Despite its central role in sex determination, genetic analysis of the Y chromosome has been slow. This poor progress has been due to the paucity of available genetic markers. Whereas the X chromosome is known to include at least 100 functional genetic loci, only three or four loci have been ascribed to the Y chromosome and even the existence of several of these loci is controversial. Other factors limiting genetic analysis are the small size of the Y chromosome, which makes cytogenetic definition difficult, and the absence of extensive recombination. Based on cytogenetic observation and speculation, a working model of the Y chromosome has been proposed. In this classical model the Y chromosome is defined into subregions; an X-Y homologous meiotic pairing region encompassing most of the Y chromosome short arm and, perhaps, including a pseudoautosomal region of sex chromosome exchange; a pericentric region containing the sex determining gene or genes; and a long arm heterochromatic genetically inert region. The classical model has been supported by studies on the MIC2 loci, which encode a cell surface antigen defined by the monoclonal antibody 12E7. The X linked locus MIC2X, which escapes X inactivation, maps to the tip of the X chromosome short arm and the homologous locus MIC2Y maps to the Y chromosome short arm; in both cases, these loci are within the proposed meiotic pairing region. MIC2Y is the first biochemically defined, expressed locus to be found on the human Y chromosome. T