Science.gov

Sample records for chromosome 1q juvenile

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

    SciTech Connect

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

    1994-01-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    SciTech Connect

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

    1995-06-01

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

  5. Exclusion of 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  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 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.

  16. Molecular characterization of a patient with an interstitial 1q deletion [del(1)(q24.1q25.3)] and distinctive skeletal abnormalities.

    PubMed

    Descartes, Maria; Hain, Julie Zenger; Conklin, Michael; Franklin, Judy; Mikhail, Fady M; Lachman, Ralph S; Nolet, Serge; Messiaen, Ludwine M

    2008-11-15

    Here we report on a patient with an interstitial deletion on the long(q) arm of chromosome 1 who presents with a unique constellation of anomalies including brachydactyly type E, Müllerian agenesis, growth hormone deficiency, as well as other abnormalities. We present the clinical details of this patient's presentation, the skeletal findings, and provide characterization of the deletion at the molecular level. We postulate that these skeletal anomalies are distinctive to 1q deletions involving the 1q24q25 region.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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 ...

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    PubMed

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

    2013-02-01

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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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 ...

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Genetics Home Reference: 1q21.1 microdeletion

    MedlinePlus

    ... symptoms. Researchers sometimes refer to 1q21.1 microdeletion as the recurrent distal 1.35-Mb deletion to distinguish it from the genetic change that causes thrombocytopenia-absent radius syndrome (TAR syndrome). TAR syndrome results from the ...

  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. 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.

  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. 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

  13. 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.

  14. 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.

  15. Assignment of 115 genes from HSA9 and HSA14 to SSC1q by RH mapping to generate a dense human-pig comparative map.

    PubMed

    Yasue, H; Kitajima, M; Tamada, Y; Rezaeian, A H; Hiraiwa, H; Hayashi, T; Shimogiri, T

    2008-06-01

    A large number of significant QTL for economically important traits including average daily gain have been located on SSC1q, which, as shown by chromosome painting, corresponds to four human chromosomes (HSA9, 14, 15 and 18). To provide a comprehensive comparative map for efficient selection of candidate genes, 81 and 34 genes localized on HSA9 and HSA14 respectively were mapped to SSC1q using a porcine 7000-rad radiation hybrid panel (IMpRH). This study, together with the cytogenetic map (http://www2.toulouse.inra.fr/lgc/pig/cyto/genmar/htm/1GM.HTM), demonstrates that SSC1q2.1-q2.13 corresponds to the region ranging from 44.6 to 63.2 Mb on HSA14q21.1-q23.1, the region from 86.5 to 86.8 Mb on HSA15q24-q25, the region from 0.9 to 27.2 Mb on HSA9p24.3-p21, the region from 35.1 to 38.0 Mb on HSA9p13, the region from 70.3 to 79.3 Mb on HSA9q13-q21 and the region from 96.4 to 140.0 Mb on HSA9q22.3-q34. The conserved synteny between HSA9 and SSC1q is interrupted by at least six sites, and the synteny between HSA14 and SSC1q is interrupted by at least one site.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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)

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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 ...

  3. [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.

  4. 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

  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. 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.

  7. De novo duplication 1q32-q42: variability of phenotypic features in partial lq trisomics.

    PubMed Central

    Lungarotti, M S; Falorni, A; Calabro, A; Passalacqua, F; Dallapiccola, B

    1980-01-01

    A de novo tandem duplication 1q32--q42 was observed in a 7-month-old mentally retarded and malformed male infant. Karyotype-phenotype correlation in other similar unbalanced trisomies has shown psychomotor retardation, micro- or retrognathia or both, and low set or malpositioned ears to be the most common features associated with this newly recognised syndrome. However, after reviewing patients with duplication of regions 1q2, 3, and 4 and 1q2 and 3, it was concluded that similar non-specific clinical features are also present in these 1q imbalances. On the whole, a rather wide range in phenotypical expression has been observed in different cases. Thus it is concluded that, at present, it is impossible to delineate the profile of the syndromes resulting from partial 1q trisomies. Images PMID:7218281

  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. 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 ...

  11. 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

  12. 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.

  13. 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…

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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…

  19. 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 ...

  20. 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 ...

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. 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.

  10. 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.

  11. 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

  12. 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

  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. 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.

  15. 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.

  16. 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…

  17. 31 CFR 30.1 - Q-1: What definitions apply in this part?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.1 Q-1: What definitions apply in this part... upon voluntary termination for good reason, involuntary termination, or termination under a window... cause, but not restrictions relating to whether the departure was a voluntary departure for good...

  18. 31 CFR 30.1 - Q-1: What definitions apply in this part?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.1 Q-1: What definitions apply in this part... upon voluntary termination for good reason, involuntary termination, or termination under a window... cause, but not restrictions relating to whether the departure was a voluntary departure for good...

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  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. 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…

  9. 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…

  10. 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.

  11. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Puzzanchera, Charles

    2009-01-01

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

  12. Juvenile Arrests, 2000. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

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

  13. Juvenile Arrests, 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…

  14. 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…

  15. 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…

  16. 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.

  17. 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…

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Synthetic chromosomes.

    PubMed

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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…

  13. 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.…

  14. 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…

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 ( ...

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  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. 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.

  11. 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.

  12. 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.

  13. 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…

  14. 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 ...

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

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

    ClinicalTrials.gov

    2017-02-07

    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

  5. 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

  6. Supernumerary small ring chromosome.

    PubMed Central

    Kaffe, S; Kim, H J; Hsu, L Y; Brill, C B; Hirschhorn, K

    1977-01-01

    A supernumerary small ring chromosome was found in 30% of cultured peripheral leucocytes and 50% of skin fibroblasts in a 6-year-old boy with mild mental retardation and midline cleft palate. The extra chromosome appeared to carry a densely staining region on Giemsa banding. The banding patterns of the remaining 46 chromosomes were normal. C banding indicated that the ring chromosome contained mainly centromeric constitutive heterochromatin. Chromosome analysis of both parents showed normal karyotypes by both conventional and banding techniques; thus the origin of the ring chromosome could not be determined. Images PMID:604496

  7. [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.

  8. 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.

  9. 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

  10. 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).

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Ring chromosome 4.

    PubMed Central

    McDermott, A; Voyce, M A; Romain, D

    1977-01-01

    A mentally and physically retarded boy with a 46,XY,ring (4) (p16q35) chromosome complement is described. Chromosome banding showed that the amount of chromosome material deleted from the ring chromosome 4 was minimal, apparently no more than the telomeres. Chromosomal aberrations appear to be restricted to the production of double-sized dicentric rings, and aneuploidy. The mosiacism resulting from the behavioural peculiarities of ring chromosomes is described as dynamic mosaicism. It is suggested that the clinical features associated with this ring chromosome are more likely to be the result of the effects of a diploid/monosomy 4/polysomy 4 mosaicism than to the deficiency of the telomeric regions of the chromosome. Images PMID:881718

  18. Chromosome Disorder Outreach

    MedlinePlus

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  19. 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.

  20. 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.

  1. 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

  2. Identification of chromosome abnormalities in screening of a family with manic depression and psoriasis: predisposition to aneuploidy.

    PubMed

    Demirhan, Osman; Demirbek, Bülent; Tunç, Erdal; Uslu, Inayet Nur; Çetiner, Salih; Serin, Ayşe

    2012-06-01

    Cytogenetic analysis is an important stage in understanding the genetic background of manic depression (MD), and may provide a valuable clue to the identification of target loci and successful search for major genes. In order to identify chromosomal regions we aimed to detect the relationships between chromosomal aberrations (CAs) and immunological markers in a family with MD and psoriasis. We used the cell cultivation and conventional G-banding. We found predominantly numerical aberrations. The most common aneuploidy was chromosome 8, followed by chromosome 22, 21, 15, X and Y. However, structural aberrations consisted of duplications, deletions, translocations and breaks, with a focus on: loci on del(1)(q12-q23), del(1)(q21.1-q24), del(1)(q21.1-q23), del(10)(p11.2-pter), der(2)t(2;4)(p25;p12), t(2;22)(p14;p13), t(19;Y)? and dup(10)(q26). The susceptibility genes of MD or psoriasis may be located on these loci. Numerical sex CAs included 4(5.8%) with 45,X, 3(4.3%) with 47,XXY, and 4(5.8%) with structural chromosome X; del(X)(q13); del(X)(p11-pter) del(X)(q21.3) and inv(Y)(q11.2). We also conducted an immunological study. According results of this study, the percentage of CD2+, CD4+ and CD8+ lymphocytes of the father were significantly higher, whereas CD4+ lymphocytes were decreased in the mother, when compared the healthy persons. The percentage of CD4 level of the son was decreased, whereas CD8+ lymphocytes were higher. The CD4/CD8 ratio of the father and the son was found to be significantly high. These results may suggest that MD and psoriasis have a significant impact on both genetic and immunological parameters.

  3. 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 ...

  4. 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.

  5. 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)

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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. The proposed simplicity of the classical model has been challenged by recent molecular analysis of the Y chromosome. Using cloned probes, several groups have shown that a major part of the Y chromosome short arm is unlikely to be homologous to the X chromosome short arm. A substantial block of sequences of the short arm are homologous to sequences of the X chromosome long arm but well outside the pairing region. In addition, the short arm contains sequences shared with the Y chromosome

  11. Proximal interstitial 1p36 deletion syndrome: the most proximal 3.5-Mb microdeletion identified on a dysmorphic and mentally retarded patient with inv(3)(p14.1q26.2).

    PubMed

    Shimojima, Keiko; Páez, Marco T; Kurosawa, Kenji; Yamamoto, Toshiyuki

    2009-09-01

    From the investigation by microarray-based comparative genomic hybridization (aCGH), a new syndrome with "atypical" proximal interstitial deletion of 1p36.23-36.11 has been suggested. Here, we report on an 8.5-year-old girl with psychomotor developmental delay and a dysmorphic appearance. Although her G-banded chromosomal analysis showed inv(3)(p14.1q26.2), detailed FISH analyses denied pathogenic deletions around the breakpoints of chromosome 3. Accordingly, aCGH analysis was performed to identify a genomic aberration related to her phenotype, and a 3.5-Mb interstitial deletion of 1p36.13-36.12 was revealed. This deletion was the most proximal interstitial deletion of 1p36. Compared to the previously reported patients, abnormally shaped teeth, delayed tooth eruption, and leg malformation are unique phenotypes only to this patient, which might be due to the centromeric unique deletion region with 0.8-Mb.

  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. 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…

  14. Chromosome instability syndromes

    SciTech Connect

    1993-12-31

    Chapter 11, discusses chromosome instability syndromes. The focus is on the most extensively studied genotypic chromosomal aberrations which include Bloom syndrome, Fanconi anemia, ataxia telangiectasia, and xeroderma pigmentosum. The great interest in these syndromes is out of proportion to their rare occurrence; however, studies of genotypic chromosome breakage have been inspired by the hope of throwing light on chromosome structure and behavior. A table is given which relates chromosomal aberrations in Bloom syndrome which may cause or promote cancer. 34 refs., 3 figs., 1 tab.

  15. [Familial juvenile hyperuricemic nephropathy].

    PubMed

    Hummel, Aurélie

    2012-04-01

    Familial juvenile hyperuricemic nephropathy is a rare autosomal dominant disease. It is characterized by abnormal handling of urate responsible for hyperuricaemia often complicated of gouty arthritis. Renal failure is due to tubulointerstitial nephritis. Ultrasonography sometimes finds renal cysts of variable size and number. Renal histology, although not specific, shows interstitial fibrosis, atrophic tubules, sometimes enlarged and with irregular membrane thickening. Renal failure progresses to end stage between 30 and 60 years of age. Allopurinol treatment is recommended at the early stages of the disease, its efficacy on slowing down the progression of the disease is however not proven. There is genetic heterogeneity in familial juvenile hyperuricemic nephropathy. Uromodulin encoding Tamm-Horsfall protein is the only gene to date identified, responsible in less than half of the families. The described mutations most often concern a cystein and are clustering in exon 4. These mutations result in abnormal retention of the protein in endoplasmic reticulum of Henle loop cells and in reduction of its urinary excretion. The pathophysiology of the disease is however still dubious. Indeed, Tamm-Horsfall protein functions are not well known (anti-infectious role, cristallisation inhibition, immunomodulating role). Knock-out mice do not develop renal phenotype but are more prone to E. coli urinary infections. Uromodulin gene mutations have also been described in medullary cystic kidney disease, an autosomal dominant tubulointerstitial nephropathy, considered at first as a distinct disorder. Genetic progress allowed us to consider familial juvenile hyperuricemic nephropathy and medullary cystic kidney disease as the two facets of a same disease, we should call uromodulin associated kidney diseases. At least two other genes have been implicated in similar clinical presentation: TCF2 and the gene encoding renin.

  16. Juvenile Justice in Rural America.

    ERIC Educational Resources Information Center

    Jankovic, Joanne, Ed.; And Others

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

  17. Iatrogenic Effect of Juvenile Justice

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  18. Juvenile Crime. Opposing Viewpoints Series.

    ERIC Educational Resources Information Center

    Sadler, A. E., Ed.

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

  19. Juvenile Courts- Terms To Know.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Offers a crossword puzzle that focuses on terms learned in this edition of "Update on Law-Related Education." Explains that the letters in the boxes spell the answer to this question: what do juvenile courts try to offer juveniles? Provides the clues and answers to the puzzle. (CMK)

  20. The exosporium of B. cereus contains a binding site for gC1qR/p33: implication in spore attachment and/or entry.

    PubMed

    Ghebrehiwet, Berhane; Tantral, Lee; Titmus, Mathew A; Panessa-Warren, Barbara J; Tortora, George T; Wong, Stanislaus S; Warren, John B

    2007-01-01

    B. cereus, is a member of a genus of aerobic, gram-positive, spore-forming rod-like bacilli, which includes the deadly, B. anthracis. Preliminary experiments have shown that gC1qR binds to B. cereus spores that have been attached to microtiter plates. The present studies were therefore undertaken, to examine if cell surface gC1qR plays a role in B. cereus spore attachment and/or entry. Monolayers of human colon carcinoma (Caco-2) and lung cells were grown to confluency on 6 mm coverslips in shell vials with gentle swirling in a shaker incubator. Then, 2 microl of a suspension of strain SB460 B. cereus spores (3x10(8)/ml, in sterile water), were added and incubated (1-4 h; 36 degrees C) in the presence or absence of anti-gC1qR mAb-carbon nanoloops. Examination of these cells by EM revealed that: (1) When B. cereus endospores contacted the apical Caco-2 cell surface, or lung cells, gC1qR was simultaneously detectable, indicating upregulation of the molecule. (2) In areas showing spore contact with the cell surface, gC1qR expression was often adjacent to the spores in association with microvilli (Caco-2 cells) or cytoskeletal projections (lung cells). (3) Furthermore, the exosporia of the activated and germinating spores were often decorated with mAb-nanoloops. These observations were further corroborated by experiments in which B.cereus spores were readily taken up by monocytes and neutrophils, and this uptake was partially inhibited by mAb 60.11, which recognizes the C1q binding site on gC1qR. Taken together, the data suggest a role, for gC1qR at least in the initial stages of spore attachment and/or entry.

  1. Mental Illness and Juvenile Offenders

    PubMed Central

    Underwood, Lee A.; Washington, Aryssa

    2016-01-01

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

  2. Mental Illness and Juvenile Offenders.

    PubMed

    Underwood, Lee A; Washington, Aryssa

    2016-02-18

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

  3. 1q25.2-q31.3 Deletion in a female with mental retardation, clinodactyly, minor facial anomalies but no growth retardation

    PubMed Central

    2013-01-01

    The reports of 1q25-32 deletion cases are rare. We reported here an 11-year-old Chinese Han female with an interstitial 1q25 deletion displaying mental retardation, clinodactyly of the 5th finger and minor facial anomalies. Notably, the patient did not present growth retardation which is quite common in patients with 1q25-32 deletion encompassing LHX4. The heterozygous deletion in this patient was characterized as 46,XX,del(1)(q25.2-q31.3) with a length of 20.5 Mb according to SNP-array test results. STRP (Short Tandem Repeat Polymorphism) analysis of the family trio indicated the genomic abnormality was de novo with paternal origin. After a genotype-phenotype analysis, we proposed here the loss of a 3.1 Mb critical region including 24 genes within 1q25.2 (chr1:174.5-177.6 Mb, build 36) may account for the mental retardation in patients with 1q25-32 deletion. PMID:23915434

  4. Juvenile 'Perinasal' Angiofibroma.

    PubMed

    Mishra, Anupam; Verma, Veerendra; Mishra, Subhash Chandra

    2017-03-01

    The extranasopharyngeal angiofibroma is a separate clinical entity but those involving infratemporal fossa and cheek resemble juvenile nasopharyngeal angiofibroma (JNA) and hence have been labelled as juvenile perinasal angiofibroma (JPA) in this paper. This paper presents a 7th case of JPA and attempts to review the world literature on JPA, along with a proposal of staging the disease. A 16 year male presented with a painless compressible facial swelling since 7 months without any epistaxis or nasal obstruction. Initially a vascular lesion was suspected but JNA without nasal extension was strongly suspected on imaging. A deep trucut biopsy confirmed the histopathology. The vascular enhancement was significant and the tumour was excised through open approach (Weber Fergusson). JPA that can be regarded as a variant of JNA that fails to extend medially. Imaging demonstrates classical JNA findings with a clear nose/nasopharynx. A deep trucut biopsy under control in inpatient settings may sometimes help. JPA presents most commonly in Stage II where an open facial approach preferably following selective preoperative embolization is indicated. Hence with painless compressible (or non-compressible) cheek swelling suspected to be of a vascular etiology, a high degree of clinical suspicion for JPA needs to maintained in order to prevent a misdiagnosis.

  5. A rare mosaic interstitial deletion of 7q, 46,XX/46,XX,del(7)(q22.1q31.33), results in a mild clinical phenotype

    SciTech Connect

    Shapira, S.K.; Kochanek, S.; Shaffer, L.G.

    1994-09-01

    Constitutional mosaic structural rearrangements, including deletions, are extremely rare in the population. We present a case of mosaicism for a deletion of chromosome 7q. The patient`s phenotype is much milder than that of non-mosaic patients with a similar deletion of 7q. A 6 and 9/12-year-old Caucasian girl was evaluated because of attention deficit disorder and speech delay. She was born at 38 weeks gestation to her 37 year old G2P2 mother. Her birth weight was 2.2 kg (3rd centile), length was 47 cm (10th-25th centile), and OFC was 30.5 cm (<10th centile). Her motor development was normal. Her speech development was profoundly delayed with her first words spoken at 3 years, and 2-3 word sentences spoken at 5-6 years. At 6 and 9/12 years, she manifested mild mental retardation and profound speech delay, but only mildly dysmorphic features (protuberant ears with under-developed antihelices, flattened forehead, moderate micro-retrognathia). Height, weight, and OFC were at the 10th centile. Chromosomal analysis showed the presence of two cell lines, with 66% of the lymphocytes having a 46,XX pattern and 33% having a 46,XX,del(7)(q22.1q31.33) karyotype. Less than 20 cases of interstitial 7q deletions extending from bands 7q21 or 7q22 to 7q31 or 7q32 have been reported. Our patient represents the first documented case with a mosaic interstitial deletion of chromosome 7q. Furthermore, the deletion resulted in a relatively mild phenotype when compared to reported non-mosaic interstitial 7q deletions, and thus expands the range of clinical heterogeneity that can be anticipated in interstitial deletion patients.

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

    SciTech Connect

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

    1993-09-01

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

  7. Uncoupling complement C1s activation from C1q binding in apoptotic cell phagocytosis and immunosuppressive capacity.

    PubMed

    Colonna, Lucrezia; Parry, Graham C; Panicker, Sandip; Elkon, Keith B

    2016-02-01

    Complement activation contributes to inflammation in many diseases, yet it also supports physiologic apoptotic cells (AC) clearance and its downstream immunosuppressive effects. The roles of individual complement components in AC phagocytosis have been difficult to dissect with artificially depleted sera. Using human in vitro systems and the novel antibody complement C1s inhibitor TNT003, we uncoupled the role of the enzymatic activation of the classical pathway from the opsonizing role of C1q in mediating a) the phagocytosis of early and late AC, and b) the immunosuppressive capacity of early AC. We found that C1s inhibition had a small impact on the physiologic clearance of early AC, leaving their immunosuppressive properties entirely unaffected, while mainly inhibiting the phagocytosis of late apoptotic/secondary necrotic cells. Our data suggest that C1s inhibition may represent a valuable therapeutic strategy to control classical pathway activation without causing significant AC accumulation in diseases without defects in AC phagocytosis.

  8. Apparent transmission distortion of a pericentric chromosome one inversion in a large multi-generation pedigree.

    PubMed

    Honeywell, Christina; Argiropoulos, Bob; Douglas, Stuart; Blumenthal, Andrea L; Allanson, Judith; McGowan-Jordan, Jean; McCready, M Elizabeth

    2012-06-01

    Pericentric chromosome inversions are often associated with infertility, recurrent pregnancy loss, and an increased risk for offspring with congenital anomalies. We report on a chromosome 1 inversion between 1p36.21 and 1q42.13, one of the largest described familial pericentric inversions of chromosome 1. The inversion was ascertained following the birth of a female with multiple congenital anomalies due to a recombinant chromosome 1. The inversion was subsequently detected or inferred in 16 healthy individuals over five generations. Interestingly, with a ratio of 16 carriers to 6 noncarriers, there appears to be transmission distortion of the inverted chromosome 1 within the family. Although there is no reported difficulty conceiving in the family, the risk of miscarriage is higher than predicted at 34% (13/38). The recurrence risk of a recombinant chromosome also appears to be lower than expected based on the mode of ascertainment. This case contributes to the spectrum of clinical features of chromosome 1 recombinants and raises the question of whether or not there is a selective advantage of the inverted chromosome at meiosis, conception, or post-zygotically that has contributed to transmission distortion of the inverted chromosome.

  9. Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade

    PubMed Central

    Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

    2014-01-01

    In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it’s plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it’s current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation aggregation. We discuss our findings in the context of tick feeding physiology. PMID:25454607

  10. Juvenile justice mental health services.

    PubMed

    Thomas, Christopher R; Penn, Joseph V

    2002-10-01

    As the second century of partnership begins, child psychiatry and juvenile justice face continuing challenges in meeting the mental health needs of delinquents. The modern juvenile justice system is marked by a significantly higher volume of cases, with increasingly complicated multiproblem youths and families with comorbid medical, psychiatric, substance abuse disorders, multiple family and psychosocial adversities, and shrinking community resources and alternatives to confinement. The family court is faced with shrinking financial resources to support court-ordered placement and treatment programs in efforts to treat and rehabilitate youths. The recognition of high rates of mental disorders for incarcerated youth has prompted several recommendations for improvement and calls for reform [56,57]. In their 2000 annual report, the Coalition for Juvenile Justice advocated increased access to mental health services that provide a continuum of care tailored to the specific problems of incarcerated youth [58]. The specific recommendations of the report for mental health providers include the need for wraparound services, improved planning and coordination between agencies, and further research. The Department of Justice, Office of Juvenile Justice and Delinquency Prevention has set three priorities in dealing with the mental health needs of delinquents: further research on the prevalence of mental illness among juvenile offenders, development of mental health screening assessment protocols, and improved mental health services [59]. Other programs have called for earlier detection and diversion of troubled youth from juvenile justice to mental health systems [31,56]. Most recently, many juvenile and family courts have developed innovative programs to address specific problems such as truancy or substance use and diversionary or alternative sentencing programs to deal with first-time or nonviolent delinquents. All youths who come in contact with the juvenile justice system

  11. Polysomy of chromosomes 1 and 19: an underestimated prognostic factor in oligodendroglial tumors.

    PubMed

    Jiang, Haihui; Ren, Xiaohui; Zhang, Zhe; Zeng, Wei; Wang, Junmei; Lin, Song

    2014-10-01

    The clinical significance of chromosomes 1 and 19 deletion was well established in oligodendroglial tumors (ODGs). This study was designed to evaluate the prognostic implication of chromosomes 1 and 19 polysomy in gliomas. 584 patients with histological diagnosis of primary gliomas enrolled in the study. Chromosomes 1 and 19 status was detected with fluorescence in situ hybridization (FISH). Of the 584 cases, the frequency of 1q and 19p polysomy in mixed gliomas was significantly higher than ODGs or astrocytic tumors (1q P = 0.032 and P = 0.044; 19p P = 0.024 and P = 0.027); the frequency of 1q and 19p polysomy in low-grade gliomas (WHO II) was relatively lower compared with WHO III or WHO IV (1q P = 0.097 and P = 0.026; 19p P = 0.04 and P = 0.002). 1q, 19p and co-polysomy were confirmed as risk factors conveyed unfavorable outcomes, which has been further validated in both anaplastic oligodendroglial tumors (AOGs) (P = 0.07, P = 0.028 and P = 0.054 for PFS; P = 0.007, P = 0.001 and P = 0.002 for OS, respectively) and glioblastomas with oligodendroglioma component (GBMOs) (P = 0.005, P < 0.001 and P < 0.001 for PFS; P = 0.136, P = 0.006 and P = 0.051 for OS, respectively). Based on chromosomes 1/19 co-deletion and co-polysomy, AOGs and GBMOs could be divided into three subgroups which harbored distinct prognosis (AOGs P < 0.001 for PFS and P < 0.001 for OS; GBMOs P < 0.001 for PFS and P = 0.012 for OS). Chromosomes 1/19 polysomy are potential prognostic factors which confer unfavorable outcomes. The molecular prognostic grouping model based on chromosomes 1/19 co-polysomy and co-deletion better predicts prognosis and provides a more reliable information for treatment decision-making.

  12. Analysis of plant meiotic chromosomes by chromosome painting.

    PubMed

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  13. Paralogous sm22alpha (Tagln) genes map to mouse chromosomes 1 and 9: further evidence for a paralogous relationship.

    PubMed

    Stanier, P; Abu-Hayyeh, S; Murdoch, J N; Eddleston, J; Copp, A J

    1998-07-01

    SM22alpha (TAGLN) is one of the earliest markers of differentiated smooth muscle, being expressed exclusively in the smooth muscle cells of adult tissues and transiently in embryonic skeletal and cardiac tissues. We have identified and mapped the mouse Tagln gene and a closely related gene, Sm22alpha homolog (Tagln2). The chromosomal localization for Tagln was identified by linkage analysis to distal mouse chromosome 9 between D9Mit154 and D9Mit330, closely linked to the anchor locus D9Nds10. The localization of Tagln2 was also determined and was found to map between Fcgr2 and D1Mit149 on distal mouse chromosome 1. This localization is homologous to a region of human 1q21-q25 to which an EST representing human TAGLN2 was previously mapped. The two regions, distal mouse chromosome 1 and proximal mouse chromosome 9, and the human regions with conserved synteny (1q21-q25 and 11q22-qter) are believed to be paralogous, reflecting either conserved remnants of duplicated chromosomes or segments of chromosomes during vertebrate evolution.

  14. Miranda Rights: Implications for Juveniles with Disabilities

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  15. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    PubMed

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  16. Juvenile nasopharyngeal angiofibroma

    PubMed Central

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

    2016-01-01

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

  17. Juvenile chronic arthritis.

    PubMed

    Southwood, T R; Woo, P

    1995-05-01

    The nomenclature and classification criteria for arthritis in children should be dealt with initially as separate issues, although they are undoubtedly intertwined. The classification criteria should aim to delineate homogeneous patient populations, yet should be flexible enough to incorporate advances in disease knowledge. It should be recognized that arriving at an international consensus for classification criteria will merely provide a set of operational definitions to facilitate research, and not a set of diagnostic criteria. Indeed the only point to obtaining consensus is to begin a process of systematic ongoing review of the criteria. The labels attached to any of these diseases should facilitate accurate communication. In view of the heterogeneous nature of childhood arthritis, consideration should be given to using a broad umbrella term such as juvenile or childhood arthritis only for communicating with the lay public. Medical nomenclature should be formulated to reflect accurately homogeneous subgroups of arthritis, and should not artificially proscribe a relationship between paediatric and adult disease.

  18. Recidivism of juvenile homicide offenders.

    PubMed

    Vries, Anne M; Liem, Marieke

    2011-01-01

    Serious offenses against persons perpetrated by juveniles raise fundamental questions about the background, causes, and prevention of future crime. The current study addresses the potential of future crime of all juvenile homicide offenders (JHOs) in the Netherlands in the period 1992-2007. In contrast to former research on recidivism of JHOs, which has been merely descriptive, the present study integrates theoretical perspectives as to why some of these juveniles turn back to crime, while others do not. To this end, relationships are investigated between recidivism behavior and risk factors. Results indicate that male JHOs, and JHOs who maintain relationships with delinquents, run a greater risk of reoffending.

  19. Structural Chromosome Abnormalities Associated with Obesity: Report of Four New subjects and Review of Literature

    PubMed Central

    Dasouki, Majed J; Youngs, Erin L; Hovanes, Karine

    2011-01-01

    Obesity in humans is a complex polygenic trait with high inter-individual heritability estimated at 40–70%. Candidate gene, DNA linkage and genome-wide association studies (GWAS) have allowed for the identification of a large set of genes and genomic regions associated with obesity. Structural chromosome abnormalities usually result in congenital anomalies, growth retardation and developmental delay. Occasionally, they are associated with hyperphagia and obesity rather than growth delay. We report four new individuals with structural chromosome abnormalities involving 10q22.3-23.2, 16p11.2 and Xq27.1-q28 chromosomal regions with early childhood obesity and developmental delay. We also searched and summarized the literature for structural chromosome abnormalities reported in association with childhood obesity. PMID:22043167

  20. Juvenile homosexual homicide.

    PubMed

    Myers, Wade C; Chan, Heng Choon Oliver

    2012-01-01

    Limited information exists on juvenile homosexual homicide (JHH), that is, youths who perpetrate sexual homicides against same-sex victims. Only a handful of cases from the United States and internationally have been described in the literature. This study, the first of its kind, examines the epidemiology, victimology, victim-offender relationship, and weapon-use patterns in JHH offenders using a large U.S. database on homicide spanning three decades. The data for this study were derived from the Federal Bureau of Investigation's Supplementary Homicide Reports (SHRs) for the years 1976 through 2005. A total of 93 cases of JHH were identified. On average, three of these crimes occurred annually in the U.S., and there was a marked decline in its incidence over the study period. Ninety-five percent were male offender-male victim cases and 5% were female offender-female victim cases. JHH offenders were over-represented amongst all juvenile sexual murderers, similar to their adult counterparts. The majority of these boys were aged 16 or 17 and killed adult victims. They were significantly more likely to kill adult victims than other age groups, to be friends or acquaintances of the victims, and to use contact/edged weapons or firearms. Most offenders killed same-race victims, although Black offenders were significantly more likely than White offenders to kill interracially. A case report is provided to illustrate JHH. Further research is needed to promote our understanding of the pathogenesis, etiology, and associated risk factors for this aberrant form of murder by children.

  1. [A case of juvenile Huntington's disease presenting dystonia and confirmed by DNA analysis].

    PubMed

    Ozawa, H; Takeda, M; Sasaki, M; Sugai, K; Hashimoto, T; Honma, T

    1997-07-01

    We reported a 13-year-old boy with juvenile Huntington disease diagnosed by DNA analysis. Symptoms started with dysarthria at 6 years of age, which was followed by progressive dysgraphia and gait disturbance due to dystonia from 7 years, and by epileptic seizures from 12 years. Magnetic resonance imaging revealed atrophy of the bilateral caudate nuclei and T2- and proton-weighted high intensity area in both putamina. The CAG (cytosine-adenine-guanine) trinucleotide repeat on chromosome 4 p16 was markedly expanded to 81. For a child with dystonia with mental deterioration, juvenile Huntington disease should be considered in the differential diagnosis.

  2. Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q

    PubMed Central

    1994-01-01

    This work describes the functional characterization, cDNA cloning, and expression of a novel cell surface protein. This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular "heads" of C1q molecules, at physiological ionic strength, and also to inhibit complement-mediated lysis of sheep erythrocytes by human serum. The NH2-terminal amino acid sequence of the first 24 residues of the C1q-binding protein was determined and this information allowed the synthesis of two degenerate polymerase chain reaction primers for use in the preparation of a probe in the screening of a B cell cDNA library. The cDNA isolated, using this probe, was found to encode a pre-pro protein of 282 residues. The NH2 terminus of the protein isolated from Raji cells started at residue 74 of the predicted pre-pro sequence. The cDNA sequence shows that the purified protein has three potential N-glycosylation residues and is a highly charged, acidic molecule. Hence, its binding to C1q may be primarily but not exclusively due to ionic interactions. The "mature" protein, corresponding to amino acid residues 74-282 of the predicted pre-pro sequence, was overexpressed in Escherichia coli and was purified to homogeneity. This recombinant protein was also able to inhibit the complement-mediated lysis of sheep erythrocytes by human serum and was shown to be a tetramer by gel filtration in nondissociating conditions. Northern blot and RT-PCR studies showed that the C1q-binding protein is expressed at high levels in Raji and Daudi cell lines, at moderate levels in U937, Molt-4, and HepG2 cell lines, and at a very low level in the HL60 cell line. However, it is not expressed in the K562 cell line. Comparison of gC1q-R NH2-terminal sequence with that of the receptor for the collagen-like domain of C1q (cC1q-R) showed no similarity. Furthermore, antibodies to gC1q-R or an 18-amino acid residue-long NH2-terminal synthetic gC1q-R peptide did not cross-react with

  3. Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites

    PubMed Central

    Bally, Isabelle; Ancelet, Sarah; Moriscot, Christine; Gonnet, Florence; Mantovani, Alberto; Daniel, Régis; Schoehn, Guy; Arlaud, Gérard J.; Thielens, Nicole M.

    2013-01-01

    Complement C1q is a hexameric molecule assembled from 18 polypeptide chains of three different types encoded by three genes. This versatile recognition protein senses a wide variety of immune and nonimmune ligands, including pathogens and altered self components, and triggers the classical complement pathway through activation of its associated proteases C1r and C1s. We report a method for expression of recombinant full-length human C1q involving stable transfection of HEK 293-F mammalian cells and fusion of an affinity tag to the C-terminal end of the C chain. The resulting recombinant (r) C1q molecule is similar to serum C1q as judged from biochemical and structural analyses and exhibits the characteristic shape of a bunch of flowers. Analysis of its interaction properties by surface plasmon resonance shows that rC1q retains the ability of serum C1q to associate with the C1s-C1r-C1r-C1s tetramer, to recognize physiological C1q ligands such as IgG and pentraxin 3, and to trigger C1r and C1s activation. Functional analysis of rC1q variants carrying mutations of LysA59, LysB61, and/or LysC58, in the collagen-like stems, demonstrates that LysB61 and LysC58 each play a key role in the interaction with C1s-C1r-C1r-C1s, with LysA59 being involved to a lesser degree. We propose that LysB61 and LysC58 both form salt bridges with outer acidic Ca2+ ligands of the C1r and C1s CUB (complement C1r/C1s, Uegf, bone morphogenetic protein) domains. The expression method reported here opens the way for deciphering the molecular basis of the unusual binding versatility of C1q by mapping the residues involved in the sensing of its targets and the binding of its receptors. PMID:23650384

  4. Comparison of the role of tyrosine residues in human IgG and rabbit IgG in binding of complement subcomponent C1q.

    PubMed Central

    McCall, M N; Easterbrook-Smith, S B

    1989-01-01

    Treatment of covalently cross-linked or heat-aggregated oligomers of human IgG with 4 mM-tetranitromethane abrogated their C1q-binding activity. In contrast, tetranitromethane modification of rabbit IgG oligomers, under identical conditions, had no effect upon their C1q-binding activity. The tetranitromethane treatment led to nitration of about ten tyrosine residues per IgG molecule in both species, and the modification was specific for tyrosine residues. Reduction of the nitrated protein with Na2S2O4 did not lead to recovery of C1q-binding activity in human IgG oligomers or to loss of activity in rabbit IgG oligomers. Tryptic peptides from the nitrated proteins were isolated and a peptide containing nitrotyrosine-319 was recovered from human IgG, as well as peptides from both species corresponding to the region around nitrotyrosine-278. These data are consistent with the inactivation of C1q-binding activity in human IgG being the result of nitration of tyrosine-319; the rabbit IgG is unaffected by nitration because position 319 is phenylalanine. The evidence supports the C1q-receptor site proposed by Burton, Boyd, Brampton, Easterbrook-Smith, Emanuel, Novotny, Rademacher, van Schravendijk, Sternberg & Dwek [(1980) Nature (London) 288, 338-344]: residues 316-338. PMID:2784672

  5. Inferring Planet Occurrence Rates With a Q1-Q17 Kepler Planet Candidate Catalog Produced by a Machine Learning Classifier

    NASA Astrophysics Data System (ADS)

    Catanzarite, Joseph; Jenkins, Jon Michael; McCauliff, Sean D.; Burke, Christopher; Bryson, Steve; Batalha, Natalie; Coughlin, Jeffrey; Rowe, Jason; mullally, fergal; thompson, susan; Seader, Shawn; Twicken, Joseph; Li, Jie; morris, robert; smith, jeffrey; haas, michael; christiansen, jessie; Clarke, Bruce

    2015-08-01

    NASA’s Kepler Space Telescope monitored the photometric variations of over 170,000 stars, at half-hour cadence, over its four-year prime mission. The Kepler pipeline calibrates the pixels of the target apertures for each star, produces light curves with simple aperture photometry, corrects for systematic error, and detects threshold-crossing events (TCEs) that may be due to transiting planets. The pipeline estimates planet parameters for all TCEs and computes diagnostics used by the Threshold Crossing Event Review Team (TCERT) to produce a catalog of objects that are deemed either likely transiting planet candidates or false positives.We created a training set from the Q1-Q12 and Q1-Q16 TCERT catalogs and an ensemble of synthetic transiting planets that were injected at the pixel level into all 17 quarters of data, and used it to train a random forest classifier. The classifier uniformly and consistently applies diagnostics developed by the Transiting Planet Search and Data Validation pipeline components and by TCERT to produce a robust catalog of planet candidates.The characteristics of the planet candidates detected by Kepler (planet radius and period) do not reflect the intrinsic planet population. Detection efficiency is a function of SNR, so the set of detected planet candidates is incomplete. Transit detection preferentially finds close-in planets with nearly edge-on orbits and misses planets whose orbital geometry precludes transits. Reliability of the planet candidates must also be considered, as they may be false positives. Errors in detected planet radius and in assumed star properties can also bias inference of intrinsic planet population characteristics.In this work we infer the intrinsic planet population, starting with the catalog of detected planet candidates produced by our random forest classifier, and accounting for detection biases and reliabilities as well as for radius errors in the detected population.Kepler was selected as the 10th mission

  6. Chromosomal differentiation of cells

    SciTech Connect

    1993-12-31

    Chapter 16, discusses the chromosomal differentiation of cells. The chromosomes of differentiated cells have been much less studies than those of meristematic or germline cells, probably because such cells do not usually divide spontaneously. However, in many cases they can be induced to undergo mitosis. 26 refs., 2 figs.

  7. Diversity of breakpoints of variant Philadelphia chromosomes in chronic myeloid leukemia in Brazilian patients

    PubMed Central

    Chauffaille, Maria de Lourdes Lopes Ferrari; Bandeira, Ana Carolina de Almeida; da Silva, Aline Schiavoni Guarnieri

    2014-01-01

    Background Chronic myeloid leukemia is a myeloproliferative disorder characterized by the Philadelphia chromosome or t(9;22)(q34.1;q11.2), resulting in the break-point cluster region-Abelson tyrosine kinase fusion gene, which encodes a constitutively active tyrosine kinase protein. The Philadelphia chromosome is detected by karyotyping in around 90% of chronic myeloid leukemia patients, but 5–10% may have variant types. Variant Philadelphia chromosomes are characterized by the involvement of another chromosome in addition to chromosome 9 or 22. It can be a simple type of variant when one other chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. Few studies have reported the incidence of variant Philadelphia chromosomes or the breakpoints involved among Brazilian chronic myeloid leukemia patients. Objective The aim of this report is to describe the diversity of the variant Philadelphia chromosomes found and highlight some interesting breakpoint candidates for further studies. Methods the Cytogenetics Section Database was searched for all cases with diagnoses of chronic myeloid leukemia during a 12-year period and all the variant Philadelphia chromosomes were listed. Results Fifty (5.17%) cases out of 1071 Philadelphia-positive chronic myeloid leukemia were variants. The most frequently involved chromosome was 17, followed by chromosomes: 1, 20, 6, 11, 2, 10, 12 and 15. Conclusion Among all the breakpoints seen in this survey, six had previously been described: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 and 17q21. The fact that some regions get more frequently involved in such rare rearrangements calls attention to possible predisposition that should be further studied. Nevertheless, the pathological implication of these variants remains unclear. PMID:25638762

  8. Juvenile onset spondyloarthropathies: therapeutic aspects

    PubMed Central

    Burgos-Vargas, R

    2002-01-01

    Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFα) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFα antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFα therapy may confer similar benefits in patients with juvenile onset SpA. PMID:12381509

  9. XYY chromosome anomaly and schizophrenia.

    PubMed

    Rajagopalan, M; MacBeth, R; Varma, S L

    1998-02-07

    Sex chromosome anomalies have been associated with psychoses, and most of the evidence is linked to the presence of an additional X chromosome. We report a patient with XYY chromosome anomaly who developed schizophrenia.

  10. Sexually antagonistic chromosomal cuckoos

    PubMed Central

    Rice, William R.; Gavrilets, Sergey; Friberg, Urban

    2009-01-01

    The two kinds of sex chromosomes in the heterogametic parent are transmitted to offspring with different sexes, causing opposite-sex siblings to be completely unrelated for genes located on these chromosomes. Just as the nest-parasitic cuckoo chick is selected to harm its unrelated nest-mates in order to garner more shared resources, sibling competition causes the sex chromosomes to be selected to harm siblings that do not carry them. Here we quantify and contrast this selection on the X and Y, or Z and W, sex chromosomes. We also develop a hypothesis for how this selection can contribute to the decay of the non-recombining sex chromosome. PMID:19364719

  11. Capturing Chromosome Conformation

    NASA Astrophysics Data System (ADS)

    Dekker, Job; Rippe, Karsten; Dekker, Martijn; Kleckner, Nancy

    2002-02-01

    We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.

  12. Negative anti-C1q antibody titers may influence therapeutic decisions and reduce the number of renal biopsies in systemic lupus erythematosus.

    PubMed

    Moura, Carlos Geraldo Guerreiro de; Mangueira, Cristóvão Luis Pitangueira; Cruz, Luzia Arlinda Sampaio; Cruz, Constança Margarida Sampaio

    2011-01-01

    In a cross-sectional study involving 62 patients with systemic lupus erythematosus (SLE), we found that patients with biopsy-proven lupus nephritis (LN) had higher titers of anti-C1q antibodies than active SLE without nephritis patients. Anti-C1q was associated with a negative predictive value of 94.59%, a positive predictive value of 52%, a sensitivity of 86.66% and a specificity of 74.47% for the diagnosis of LN. We conclude that high titers of anti-C1q antibodies are strongly associated with the presence of active LN, and the negative predictive value of this test for diagnosing LN is very high; therefore, it can influence therapeutic decisions and reduce the number of renal biopsies in patients with SLE.

  13. Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants.

    PubMed

    Martínez-Quintana, Efrén; Medina-Gil, José M; Rodríguez-González, Fayna; Garay-Sánchez, Paloma; Limiñana, José M; Saavedra, Pedro; Tugores, Antonio

    2014-08-01

    There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant.

  14. VizieR Online Data Catalog: Transit metric for Q1-Q17 Kepler candidates (Thompson+, 2015)

    NASA Astrophysics Data System (ADS)

    Thompson, S. E.; Mullally, F.; Coughlin, J.; Christiansen, J. L.; Henze, C. E.; Haas, M. R.; Burke, C. J.

    2016-02-01

    We describe a new metric that uses machine learning to determine if a periodic signal found in a photometric time series appears to be shaped like the signature of a transiting exoplanet. This metric uses dimensionality reduction and k-nearest neighbors to determine whether a given signal is sufficiently similar to known transits in the same data set. This metric is being used by the Kepler Robovetter to determine which signals should be part of the Q1-Q17 DR24 catalog of planetary candidates. The Kepler Mission reports roughly 20000 potential transiting signals with each run of its pipeline, yet only a few thousand appear to be sufficiently transit shaped to be part of the catalog. The other signals tend to be variable stars and instrumental noise. With this metric, we are able to remove more than 90% of the non-transiting signals while retaining more than 99% of the known planet candidates. When tested with injected transits, less than 1% are lost. This metric will enable the Kepler mission and future missions looking for transiting planets to rapidly and consistently find the best planetary candidates for follow-up and cataloging. (1 data file).

  15. Aptamer–biotin–streptavidin–C1q complexes can trigger the classical complement pathway to kill cancer cells.

    PubMed

    Bruno, John Gordon

    2010-02-01

    Nucleic acid aptamers are regarded as rivals for antibodies and as such are being investigated for their therapeutic potential. In the present work, it is shown that two different high-affinity DNA aptamers developed previously by Ferreira et al. against MUC1 antigen (designated MUC1-5TR-1 and MUC1-S1.3/S2.2) on MCF7 breast cancer cells can be linked to the first component of complement (C1q) via a biotin–streptavidin system and induce significant killing of MCF7 cells in vitro. Cell viability was assessed by Trypan blue uptake and absorbance at 590 nm of stained cells following buffer washes and lysis in 1% SDS. While the killing effect is demonstrable versus various controls, dependent on aptamer dose, and reproducible, it appears to kill maximally about half of treated MCF7 cells. Possible reasons for the marginal killing effect include antigenic shedding in vitro and membrane-bound complement regulatory proteins (mCRPs) on the cell surface such as CD46, CD55, and CD59 which act to inhibit complement-mediated lysis of cells. Future in vitro research could benefit from application of mCRP-specific aptamers in combination with anti-MUC1 aptamers to overcome surface protective mechanisms while attacking the plasma membrane of MCF7 cells or other MUC1-expressing cancer cells. However, in vivo such a combination could have deleterious effects on normal MUC1-expressing cells as well.

  16. HYDRAULIC CONDUCTIVITY OF SALTSTONE FORMULATED USING 1Q11, 2Q11 AND 3Q11 TANK 50 SLURRY SAMPLES

    SciTech Connect

    Reigel, M.; Nichols, R.

    2012-06-27

    As part of the Saltstone formulation work requested by Waste Solidification Engineering (WSE), Savannah River National Laboratory (SRNL) was tasked with preparing Saltstone samples for fresh property analysis and hydraulic conductivity measurements using actual Tank 50 salt solution rather than simulated salt solution. Samples of low level waste salt solution collected from Tank 50H during the first, second, and third quarters of 2011 were used to formulate the Saltstone samples. The salt solution was mixed with premix (45 wt % slag, 45 wt % fly ash, and 10 wt % cement), in a ratio consistent with facility operating conditions during the quarter of interest. The fresh properties (gel, set, bleed) of each mix were evaluated and compared to the recommended acceptance criteria for the Saltstone Production Facility. ASTM D5084-03, Method C was used to measure the hydraulic conductivity of the Saltstone samples. The hydraulic conductivity of Saltstone samples prepared from 1Q11 and 2Q11 samples of Tank 50H is 4.2E-9 cm/sec and 2.6E-9 cm/sec, respectively. Two additional 2Q11 and one 3Q11 sample were not successfully tested due to the inability to achieve stable readings during saturation and testing. The hydraulic conductivity of the samples made from Tank 50H salt solution compare well to samples prepared with simulated salt solution and cured under similar conditions (1.4E-9 - 4.9E-8 cm/sec).

  17. Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

    PubMed

    Juhl, David; Marget, Matthias; Hallensleben, Michael; Görg, Siegfried; Ziemann, Malte

    2017-01-12

    Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation.

  18. The Exosporium of B.cereus Contains a Binding Site for gC1qR/p33: Implication in Spore Attachment and/or Entry.

    SciTech Connect

    GHEBREHIWET,B.; TANTRAL, L.; TITMUS, M.A.; PANESSA-WARREN, B.J.; TORTORA, G.T.; WONG, S.S.; WARREN, J.B.

    2008-01-01

    B. cereus, is a member of a genus of aerobic, gram-positive, spore-forming rod-like bacilli, which includes the deadly, B. anthracis. Preliminary experiments have shown that gC1qR binds to B.cereus spores that have been attached to microtiter plates. The present studies were therefore undertaken, to examine if cell surface gC1qR plays a role in B.cereus spore attachment and/or entry. Monolayers of human colon carcinoma (Caco-2) and lung cells were grown to confluency on 6 mm coverslips in shell vials with gentle swirling in a shaker incubator. Then, 2 {micro}l of a suspension of strain SB460 B.cereus spores (3x10{sup 8}/ml, in sterile water), were added and incubated (1-4 h; 36{sup 0} C) in the presence or absence of anti-gC1qR mAb-carbon nanoloops. Examination of these cells by EM revealed that: (1) When B. cereus endospores contacted the apical Caco-2 cell surface, or lung cells, gClqR was simultaneously detectable, indicating upregulation of the molecule. (2) In areas showing spore contact with the cell surface, gClqR expression was often adjacent to the spores in association with microvilli (Caco-2 cells) or cytoskeletal projections (lung cells). (3) Furthermore, the exosporia of the activated and germinating spores were often decorated with mAb-nanoloops. These observations were further corroborated by experiments in which B.cereus spores were readily taken up by monocytes and neutrophils, and this uptake was partially inhibited by mAb 60.11, which recognizes the C1q binding site on gC1qR. Taken together, the data suggest a role, for gC1qR at least in the initial stages of spore attachment and/or entry.

  19. Protruding disordered loop of gC1qR is specifically exposed and related to antiapoptotic property in germ cell lineage.

    PubMed

    Kitazawa, Sohei; Takenaka, Atsushi; Kondo, Takeshi; Mizoguchi, Akira; Kitazawa, Riko

    2006-12-01

    We established a monoclonal antibody (MAb), 5G9, with the use of a fixed seminoma tissue from an archival paraffin-embedded specimen, as an immunogen. Without antigen retrieval, positive 5G9-immunohistochemical staining was confined mostly to primordial germ cells, spermatogonia and various germ cell tumors. 5G9 recognized a mitochondrial 32-kD protein with an isoelectric point of pH 4.2, identified as a multifunctional ubiquitous protein, receptor for globular head of C1q (gC1qR), whose epitope was mapped in a disordered loop connecting the beta3 and the beta4 strands. Reflecting the ubiquitous distribution of gC1qR, with antigen retrieval, 5G9 was found reactive to a wide range of normal and tumor tissues. Since several co-precipitated and phosphorylated bands were observed in various human cell lines but not in germ cell tumor cell lines by in vitro phosphorylation assay, we speculate that the epitope of gC1qR is specifically unmasked in the germ cell lineage. By reducing gC1qR by siRNA, a significant increase was observed in the number of apoptotic cells in ITO-II and TCam-2 cell lines, but to a lesser extent in the Colo201 colon cancer cell line, showing an antiapoptotic property of gC1qR in the germ cells. Since protein-protein interaction is partially preserved by fixation, archival paraffin-embedded specimens can be a valuable source of immunogens for generating monoclonal antibodies (MAbs) that recognize tissue-specific protein conformation.

  20. Managing juvenile Huntington's disease.

    PubMed

    Quarrell, Oliver W J; Nance, Martha A; Nopoulos, Peggy; Paulsen, Jane S; Smith, Jonathan A; Squitieri, Ferdinando

    2013-06-01

    Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience.

  1. Sequential cloning of chromosomes

    DOEpatents

    Lacks, Sanford A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  2. Sequential cloning of chromosomes

    DOEpatents

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  3. Human chromosome 22.

    PubMed Central

    Kaplan, J C; Aurias, A; Julier, C; Prieur, M; Szajnert, M F

    1987-01-01

    The acrocentric chromosome 22, one of the shortest human chromosomes, carries about 52 000 kb of DNA. The short arm is made up essentially of heterochromatin and, as in other acrocentric chromosomes, it contains ribosomal RNA genes. Ten identified genes have been assigned to the long arm, of which four have already been cloned and documented (the cluster of lambda immunoglobulin genes, myoglobin, the proto-oncogene c-sis, bcr). In addition, about 10 anonymous DNA segments have been cloned from chromosome 22 specific DNA libraries. About a dozen diseases, including at least four different malignancies, are related to an inherited or acquired pathology of chromosome 22. They have been characterised at the phenotypic or chromosome level or both. In chronic myelogenous leukaemia, with the Ph1 chromosome, and Burkitt's lymphoma, with the t(8;22) variant translocation, the molecular pathology is being studied at the DNA level, bridging for the first time the gap between cytogenetics and molecular genetics. PMID:3550088

  4. Sequential cloning of chromosomes

    SciTech Connect

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  5. Rehabilitation Treatment of a Child Diagnosed With Duplication of 1q42-q44: A Case Report

    PubMed Central

    2016-01-01

    Trisomy 1 is a rare chromosomal anomaly and has never been reported in Korea. Clinical features of trisomy 1 include macrocephaly, prominent forehead, flat nasal bridge, low set ears, and micrognathia, all of which result in a very distinguishable facial structure. A child with trisomy 1 also suffers from mental retardation and/or developmental delays. In this case report, the child was diagnosed with de novo trisomy 1 without receiving any treatment until visiting our hospital. The child suffered from foot and ankle deformities, leading her unable to stand independently. Here we report the surgical treatment and rehabilitation treatment that enabled the child to walk independently. PMID:27847725

  6. THE HUMAN CHROMOSOME

    PubMed Central

    Abuelo, J. G.; Moore, Dorothy E.

    1969-01-01

    Human lymphocytes were grown in short-term tissue culture and were arrested in metaphase with Colcemid. Their chromosomes were prepared by the Langmuir trough-critical point drying technique and were examined under the electron microscope. In addition, some chromosomes were digested with trypsin, Pronase, or DNase. The chromosomes consist entirely of tightly packed, 240 ± 50-A chromatin fibers. Trypsin and Pronase treatments induce relaxation of fiber packing and reveal certain underlying fiber arrangements. Furthermore, trypsin treatment demonstrates that the chromatin fiber has a 25–50 A trypsin-resistant core surrounded by a trypsin-sensitive sheath. DNase digestion suggests that this core contains DNA. PMID:5775795

  7. Chromosome Segregation Mechanisms

    PubMed Central

    Nicklas, R. Bruce

    1974-01-01

    Most aspects of chromosome distribution to the daughter cells in meiosis and mitosis are now understood, at the cellular level. The most striking evidence that the proposed explanation is valid is that it correctly predicts the outcome of experiments on living cells in which the experimenter (1) can determine the distribution of any chosen chromosome to a chosen daughter cell, (2) can induce a mal-orientation, and (3) can stabilize a mal-orientation, causing non-disjunction of a chosen bivalent. Recent reviews of chromosome distribution mechanisms are also considered, in an attempt to clarify the remaining unsolved problems. PMID:4442702

  8. Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval.

    PubMed

    Allamand, V; Broux, O; Richard, I; Fougerousse, F; Chiannilkulchai, N; Bourg, N; Brenguier, L; Devaud, C; Pasturaud, P; Pereira de Souza, A

    1995-06-01

    A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to approximately 3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Réunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Réunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population.

  9. Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval

    SciTech Connect

    Allamand, V.; Broux, O.; Richard, I.

    1995-06-01

    A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to {approximately}3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Reunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Reunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population. 40 refs., 4 figs., 4 tabs.

  10. Juveniles tried as adults: the age of the juvenile matters.

    PubMed

    Semple, Jaclyn K; Woody, William Douglas

    2011-08-01

    Serious juvenile crimes require evaluation of a child as a criminal defendant in adult court. In such cases, it is crucial to understand jurors' attitudes, biases, and ability to follow legal instructions and maintain fairness. 308 undergraduate psychology students served as mock jurors, were randomly separated into four groups, and each group read the same realistic summary of a trial with the defendant's age presented as 13, 15, 17, or 21 years. Participants were asked to render guilty or not guilty verdicts and, if guilty, to suggest sentences. Chi-squared analysis indicated 13- and 15-year-old defendants were convicted less often than 17- and 21-year-old defendants, showing that jurors distinguished between juvenile defendants of different ages, but not minors and adults as defined by law. Additional analysis showed that age did not affect sentencing recommendations. Decision processes jurors use for juveniles tried as adults are discussed.

  11. Consistent chromosome abnormalities including double minutes (dms) in adenocarcinoma of the pancreas

    SciTech Connect

    Griffin, C.A.; Morsberger, L.; Ellingham, T.

    1994-09-01

    Little is known about the somatic genetic changes which characterize pancreatic adenocarcinoma (PA), and identification of acquired genomic alterations would further our understanding of the biology of this neoplasm. We have studied 62 primary specimens of PA using classical and FISH methods. Clonally abnormal karyotypes were observed in 44 neoplasms. Karyotypes were generally complex (greater than 3 abnormalities) including both numerical and structural chromosome changes. Many tumors contained at least one marker chromosome. The most frequent whole chromosomal gains were chromosomes 20 (7 tumors) and 7 (5 tumors). Losses were much more frequent: chromosome 18 was lost in 22 tumors, followed by chromosomes 13 (15 tumors), 12 (13 tumors), and 6 (12 tumors). Structural abnormalities were common. 200 chromosome breakpoints were identified. Excluding Robertsonian translocations, chromosomal arms most frequently involved were 6q (12 chromosomes), 1p and 3p (10 each), 11p and 17p (9 each), 1q (8), 8p and 19q (7 each). Of particular interest, we found dms in 6 cases. These represent the first PAs with cytogenetic evidence of gene amplification, and are under investigation using chromosome microdissection. To begin to define the smallest region of 6q which is deleted, 5 tumors with 6q deletions were hybridized with a biotin-labeled probe, made by microdissection of 6q24-qter. Loss of one copy of this region was verified in 4/5 tumors; additional probes are being made. Our results are similar to those of 34 other reported PAs, and the combined data suggest that gains of chromosomes 7 and 20 and deletions and rearrangements of 1p and 6q may be particularly important in the biology of adenocarcinoma of the pancreas.

  12. Forensic aspects of juvenile violence.

    PubMed

    Haller, L H

    2000-10-01

    The juvenile justice system was created because it was recognized that youthful offenders needed to be managed differently from adults. They were to receive habilitation services instead of punishment. It is now more than a century since the creation of the first juvenile court. After 67 years, the US Supreme Court, in Kent v United States stated that the model was not working because juveniles in the criminal justice system received no treatment and they had no rights. Because the issue that had been appealed was the lack of rights (not lack of treatment), the Court mandated that juveniles, like adults, be given certain rights. The following year, in In re Gault, the Court expanded these rights. Subsequent Supreme Court cases have dealt with these kinds of issues--that is, whether juvenile offenders are entitled to the same rights as adults and subject to the same penalties. The Supreme Court has never heard a "right to treatment" case, which is the other part of the juvenile court system. Cases have been brought in lower courts (e.g., Nelson v. Heyne, 1972) alleging inadequate treatment services, but no national impact has resulted. Thus, in general, children in the juvenile court system do not have an enforceable right to treatment and can obtain only what services are available in their jurisdictions. The services often are woefully inadequate. Sentencing a youth to probation, with the requirement that he or she participate in counseling or mental health treatment, is meaningless if services are not available. Community-based, model programs that provide effective treatment do exist. They are, as yet, the rare exception rather than the norm and, therefore, are not available to most youthful offenders. Incarcerated juveniles, obviously, cannot avail themselves of community programs. Litigation to give these youth the same rights as adults in penal institutions is not the answer because incarcerated adults don't have a right to treatment, only a right to be free

  13. Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression

    PubMed Central

    Yabumoto, Chizuru; Akazawa, Hiroshi; Yamamoto, Rie; Yano, Masamichi; Kudo-Sakamoto, Yoko; Sumida, Tomokazu; Kamo, Takehiro; Yagi, Hiroki; Shimizu, Yu; Saga-Kamo, Akiko; Naito, Atsuhiko T.; Oka, Toru; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Uejima, Etsuko; Komuro, Issei

    2015-01-01

    Disruption of angiotensin II type 1 (AT1) receptor prolonged life span in mice. Since aging-related decline in skeletal muscle function was retarded in Atgr1a−/− mice, we examined the role of AT1 receptor in muscle regeneration after injury. Administration of AT1 receptor blocker irbesartan increased the size of regenerating myofibers, decreased fibrosis, and enhanced functional muscle recovery after cryoinjury. We recently reported that complement C1q, secreted by macrophages, activated Wnt/β-catenin signaling and promoted aging-related decline in regenerative capacity of skeletal muscle. Notably, irbesartan induced M2 polarization of macrophages, but reduced C1q expression in cryoinjured muscles and in cultured macrophage cells. Irbesartan inhibited up-regulation of Axin2, a downstream gene of Wnt/β-catenin pathway, in cryoinjured muscles. In addition, topical administration of C1q reversed beneficial effects of irbesartan on skeletal muscle regeneration after injury. These results suggest that AT1 receptor blockade improves muscle repair and regeneration through down-regulation of the aging-promoting C1q-Wnt/β-catenin signaling pathway. PMID:26571361

  14. Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

    SciTech Connect

    Sjoewall, Christopher; Askendal, Agneta; Almroth, Gunnel

    2007-01-05

    C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fc{gamma} receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups.

  15. Pelvic inflammatory disease isolates of Neisseria gonorrhoeae are distinguished by C1q-dependent virulence for newborn rats and by the sac-4 region.

    PubMed Central

    Nowicki, S; Ram, P; Pham, T; Goluszko, P; Morse, S; Anderson, G D; Nowicki, B

    1997-01-01

    The virulence mechanism of Neisseria gonorrhoeae in pelvic inflammatory disease (PID) is not well understood, and an objective diagnostic method to identify patients with PID is lacking. We investigated the hypothesis that development of PID was associated with a C1q-dependent virulence property of gonococcal strains. Recent development of a C1q-dependent experimental model of gonococcal infection (S. Nowicki, M. Martens, and B. Nowicki, Infect. Immun. 63:4790-4794, 1995) created an opportunity to evaluate this hypothesis in vivo. Therefore, the virulence of 32 clinical isolates (18 PID isolates and 14 local infection [LI] isolates) was evaluated in experimental rat pups. A serum bactericidal assay was used to characterize a gonococcal serum-resistant (ser(r)) phenotype. PCR primers designed to amplify a suitable-size gonococcal sac-4 DNA fragment (unique for serum-resistant donor JC1) were used to evaluate the association of serum-resistant genotype sac-4 with two phenotypes: C1q-dependent virulence expressed in vivo and resistance to bactericidal activity of human serum expressed in vitro. Strains were also characterized by auxotyping and serotyping. Of 32 gonococcal strains, 15 (46.7%) caused C1q-dependent bacteremia in rat pups and were sac-4 positive and ser(r). However, of the 15 isolates, 13 (87%) represented strains associated with human PID and 2 (13%) were associated with LI. None of the strains that were completely serum-sensitive (ser(s)) and sac-4 negative produced C1q-dependent bacteremia in rat pups, suggesting that both ser(r) and sac-4 were required for infection. The serum-resistant recombinant recipient of sac-4 produced C1q-dependent bacteremia in the rat model similarly to the serum-resistant donor of sac-4; the serum-sensitive parent strain did not produce bacteremia. These data suggest that sac-4-mediated serum resistance conferred C1q-dependent virulence and is a unique characteristic associated with PID. These newly identified features may

  16. Genetics Home Reference: juvenile polyposis syndrome

    MedlinePlus

    ... and symptoms of the disorder. Juvenile polyposis of infancy is characterized by polyps that occur throughout the gastrointestinal tract during infancy. Juvenile polyposis of infancy is the most severe ...

  17. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  18. Chromosome evolution in Eulipotyphla.

    PubMed

    Biltueva, L; Vorobieva, N

    2012-01-01

    We integrated chromosome painting information on 5 core-insectivora species available in the literature with new Zoo-FISH data for Iberian shrew (Sorex granarius) and Altai mole (Talpa altaica). Our analysis of these 7 species allowed us to determine the chromosomal features of Eulipotyphla genomes and to update the previously proposed ancestral karyotype for 2 main groups of the Sorex genus. The chromosome painting evidence with human painting probes (HSA) reveals the presence of the 2 unique associations HSA4/5 and 1/10p/12/22b, which support Eulipotyphla. There are a series of synapomorphies both for Erinaceidae (HSA3/1/5, 3/17, 11/15 and 10/20) and for Soricinae (HSA5/9, 6/7/16, 8/3/21 and 11/12/22). We found associations that link Talpidae/Erinaceidae (HSA7/8, 1/5 and 1/19p), Talpidae/Soricidae (HSA1/8/4) and Erinaceidae/Soricidae (HSA4/20 and 2/13). Genome conservation in Eulipotyphla was estimated on the basis of the number of evolutionary breaks in the ancestral mammalian chromosomes. In total, 7 chromosomes of the boreo-eutherian ancestor (BEA8 or 10, 9, 17, 18, 20-22) were retained in all eulipotyphlans studied; among them moles show the highest level of chromosome conservation. The integration of sequence data into the chromosome painting information allowed us to further examine the chromosomal syntenies within a phylogenetic perspective. Based on our analysis we offer the most parsimonious reconstruction of phylogenetic relationships in Eulipotyphla. The cytogenetic reconstructions based on these data do not conflict with molecular phylogenies supporting basal position of Talpidae in the order.

  19. [Sex chromosomes and meiosis].

    PubMed

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  20. Genetic markers on chromosome 7.

    PubMed Central

    Tsui, L C

    1988-01-01

    Chromosome 7 is frequently associated with chromosome aberrations, rearrangements, and deletions. It also contains many important genes, gene families, and disease loci. This brief review attempts to summarise these and other interesting aspects of chromosome 7. With the rapid accumulation of cloned genes and polymorphic DNA fragments, this chromosome has become an excellent substrate for molecular genetic studies. PMID:3290488

  1. Skin pigmentary anomalies and mosaicism for an acentric marker chromosome originating from 3q

    PubMed Central

    Portnoi, M.; Boutchnei, S.; Bouscarat, F.; Morlier, G.; Nizard, S.; Dersarkissian, H.; Crickx, B.; Nouchy, M.; Taillemite, J.; Belaich, S.

    1999-01-01

    We report on a 22 year old man with hyperpigmentation distributed along the lines of Blaschko in whom cytogenetic analysis showed mosaicism for an unusual supernumerary marker chromosome. The patient was of normal intelligence and was not dysmorphic. The marker was present in 30% of his lymphocytes and in 6% of his skin fibroblasts from a dark area, while fibroblasts from a light area showed a normal karyotype, 46,XY.We have identified the origin of the marker using fluorescence in situ hybridisation (FISH) with whole chromosome painting probes and YAC specific clones. The marker was found to consist of duplicated chromosome material from the distal part of chromosome 3q and was interpreted as inv dup(3)(qter→q27.1::q27.1→qter). Hence, this marker did not include any known centromeric region and no alpha satellite DNA could be detected at the site of the primary constriction. The patient was therefore tetrasomic for 3q27-q29 in the cells containing the marker chromosome. We postulate that, in our case, pigmentary anomalies may result directly from the gain of specific pigmentation genes localised on chromosome 3q. 


Keywords: pigmentary anomalies; acentric marker chromosome; mosaicism; tetrasomy 3q PMID:10204855

  2. Comparative bacteriology of juvenile periodontitis.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Palcanis, K G; Ranney, R R

    1985-01-01

    Statistical comparisons of the floras associated with juvenile periodontitis, severe periodontitis, and moderate periodontitis indicated that differences in the bacterial compositions of affected sites in these populations were not statistically significant. The subgingival flora of affected juvenile periodontitis sites was statistically significantly different from the adjacent supragingival flora and from the subgingival floras of people with healthy gingiva and of children with developing (experimental) gingivitis. However, the subgingival flora of affected juvenile periodontitis sites was not significantly different from the flora of sites with gingival index scores of 1 or 2 in adults with developing (experimental) gingivitis. Of 357 bacterial taxa among over 18,000 isolates, 54 non-treponemal species, 2 treponemal species, and mycoplasma were most associated with diseased periodontal sulci. These species comprised an increasing proportion of the flora during developing gingivitis and constituted over half of the cultivable flora of diseased sites. PMID:3988344

  3. Epilepsy and chromosomal abnormalities

    PubMed Central

    2010-01-01

    Background Many chromosomal abnormalities are associated with Central Nervous System (CNS) malformations and other neurological alterations, among which seizures and epilepsy. Some of these show a peculiar epileptic and EEG pattern. We describe some epileptic syndromes frequently reported in chromosomal disorders. Methods Detailed clinical assessment, electrophysiological studies, survey of the literature. Results In some of these congenital syndromes the clinical presentation and EEG anomalies seems to be quite typical, in others the manifestations appear aspecific and no strictly linked with the chromosomal imbalance. The onset of seizures is often during the neonatal period of the infancy. Conclusions A better characterization of the electro clinical patterns associated with specific chromosomal aberrations could give us a valuable key in the identification of epilepsy susceptibility of some chromosomal loci, using the new advances in molecular cytogenetics techniques - such as fluorescent in situ hybridization (FISH), subtelomeric analysis and CGH (comparative genomic hybridization) microarray. However further studies are needed to understand the mechanism of epilepsy associated with chromosomal abnormalities. PMID:20438626

  4. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

    SciTech Connect

    Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron D.; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.; Furlong, Clement E.

    2005-08-01

    The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

  5. Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity

    PubMed Central

    Maiorani, Orlando; Pivetta, Eliana; Capuano, Alessandra; Modica, Teresa Maria Elisa; Wassermann, Bruna; Bucciotti, Francesco; Colombatti, Alfonso; Doliana, Roberto; Spessotto, Paola

    2017-01-01

    The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context. PMID:28074935

  6. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus.

    PubMed Central

    Tsao, B P; Cantor, R M; Kalunian, K C; Chen, C J; Badsha, H; Singh, R; Wallace, D J; Kitridou, R C; Chen, S L; Shen, N; Song, Y W; Isenberg, D A; Yu, C L; Hahn, B H; Rotter, J I

    1997-01-01

    Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups. PMID:9045876

  7. Type I bipolar disorder associated with a fragile site on chromosome 1

    SciTech Connect

    Turecki, G.; Mari, J.J.; M. de Smith, A.C.

    1995-06-19

    The objective of this paper is to study the association between chromosomal fragile sites and type I bipolar disorder. This case-control study compares bipolar patients with normal controls. Ten cases of type I bipolar disorder diagnosed according to DSM-III-R criteria and the Composite International Diagnostic Interview (CIDI) were selected from the Escola Paulista affective disorders outpatient clinic and 10 healthy controls (CIDI negative for psychiatric diagnoses) matched for sex and age were drawn from the otorhinolaryngologic outpatient clinic of the same hospital. The cytogenetic analysis was carried out with blood lymphocytes, which were cultured in a folic acid-free medium. A total of 100 mitoses per subject were blindly analyzed to the psychiatric diagnostic assignment, and fragile sites were identified according to a minimum expected frequency of events per band in conformity with a Poisson distribution. A higher frequency of chromosomal lesions for cases than controls was found for the following bands: 1q32, 5q31, and 11q23, the 1q32 being considered a fragile site. Although no evident neuropsychiatric etiological component has been mapped to the 1q32 region so far, this finding may lead to further investigation of a possible linkage between genetic markers of this region and bipolar disorder. 40 refs., 2 tabs.

  8. Micromechanics of human mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Sun, Mingxuan; Kawamura, Ryo; Marko, John F.

    2011-02-01

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed.

  9. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice.

    PubMed

    Cox, Kimberly H; Quinnies, Kayla M; Eschendroeder, Alex; Didrick, Paula M; Eugster, Erica A; Rissman, Emilie F

    2015-01-01

    Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders.

  10. Disability and Juvenile Delinquency: Issues and Trends

    ERIC Educational Resources Information Center

    Morris, Kimberly A.; Morris, Richard J.

    2006-01-01

    The US juvenile justice system has gone through many changes since its inception in the late 1890s. Even with these changes and more than 100 years of empirical research, there is a paucity of literature published on juvenile delinquents with disabilities. The present article focuses on juvenile delinquents with disabilities, addressing…

  11. Guidelines for Juvenile Information Sharing. OJJDP Report

    ERIC Educational Resources Information Center

    Mankey, Jennifer; Baca, Patricia; Rondenell, Stephanie; Webb, Marilyn; McHugh, Denise

    2006-01-01

    The juvenile information sharing (JIS) guidelines were prepared by the Center for Network Development (CND) for the Office of Juvenile Justice and Delinquency Prevention (OJJDP). The guidelines suggest a course of action for key agency and organization stakeholders involved in a state or local effort to implement and sustain juvenile information…

  12. Juvenile Myelomonocytic Leukemia (JMML) (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > For Parents > Juvenile Myelomonocytic Leukemia (JMML) ... Treatment Coping en español Leucemia mielomonocítica juvenil About Leukemia Leukemia is a type of cancer that affects ...

  13. School-Related Characteristics of Male Juveniles.

    ERIC Educational Resources Information Center

    Sapp, Gary L.; Abbott, Gypsy A.

    School-related characteristics of 256 male juveniles under the jurisdiction of a Family Court system were examined by perusing court records and conducting individual interviews with the juveniles. Results indicated that most juveniles last attended eighth grade, more than 81% had failed at least once, and more than half had fought frequently at…

  14. On the Prevention of Juvenile Crime

    ERIC Educational Resources Information Center

    Lelekov, V. A.; Kosheleva, E. V.

    2008-01-01

    Crimes committed by juveniles are among the most urgent social problems. Juvenile crime is as prevalent as crime itself is, and it has not been solved completely in any society and cannot be solved through law enforcement measures alone. In this article, the authors discuss the dynamics and structure of juvenile crime in Russia and present data…

  15. Do Juveniles Bully More than Young Offenders?

    ERIC Educational Resources Information Center

    Ireland, Jane L.

    2002-01-01

    Study compares bullying behavior among juvenile and young offenders. Ninety-five male juvenile and 196 male young offenders completed two questionnaires, measuring bullying directly and behaviors indicative of "being bullied" or of "bullying others". Juveniles perceived a higher extent of bullying and reported significantly…

  16. Intensive Reading Instruction in Juvenile Correctional Settings

    ERIC Educational Resources Information Center

    Williams, Jacob L.; Wexler, Jade; Roberts, Greg; Carpenter, Clint

    2011-01-01

    Despite 60 years of evidence linking juvenile illiteracy and delinquency, practitioners and policymakers have been painfully slow in the implementation of evidence-based reading interventions for incarcerated juveniles. We will present the Texas Juvenile Justice Tiered Instructional Model, an evidence-based reading program model created…

  17. Sex Differences in Attributions of Juvenile Delinquency.

    ERIC Educational Resources Information Center

    Sagatun, Inger J.

    This paper is an application of attribution theory to the processing of juvenile delinquents in an attempt to understand the differential treatment of female and male offenders within the juvenile justice system. The paper explores the attributions of juvenile delinquency both by male and female minors, by male and female parents, and by male and…

  18. The Juvenile Court: Changes and Challenges.

    ERIC Educational Resources Information Center

    Feld, Barry C.

    2000-01-01

    Explores the changes in the juvenile court system, in particular, the juvenile waiver and sentencing laws, as it transformed from a social welfare agency into a type of criminal court system for young offenders. Addresses whether states should create an integrated juvenile and criminal justice system. (CMK)

  19. Reforming Our Expectations about Juvenile Justice

    ERIC Educational Resources Information Center

    Rodriguez, Pamela F.; Baille, Daphne M.

    2010-01-01

    Typing the term "juvenile justice reform" into a Google[TM] search will result in 60 pages of entries. But what is meant by juvenile justice reform? What does it look like? How will one know when it is achieved? This article defines juvenile justice reform, discusses the principles of effective reform, and describes the practice of…

  20. Hyponatremia secondary to reset osmostat in a child with a central nervous system midline defect and a chromosomal abnormality.

    PubMed

    Gupta, P; Mick, G; Fong, C T; Jospe, N; McCormick, K

    2000-01-01

    A newborn with a CNS midline defect and persistent hyponatremia was diagnosed with a "reset" osmostat using a 3% hypertonic saline test. The diagnosis was established by measuring urinary arginine vasopressin (UAVP) and plasma osmolality (P(Osmoil)). In this infant a chromosome abnormality with the karyotype 46, X, -X, +der(X) t(X;13) (p22.1;q22) was associated with the midline defect and a reset osmostat.

  1. Special Education and the Juvenile Justice System. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Burrell, Sue; Warboys, Loren

    This bulletin summarizes provisions of federal law as they pertain to special education and juvenile justice. It discusses provisions of the Individuals with Disabilities Education Act 1997 including: the definition of disability; free appropriate public education; identification, referral, and evaluation; the individualized education program…

  2. Mobilizing Communities To Prevent Juvenile Crime. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Bownes, Donna; Ingersoll, Sarah

    Through Title V Incentive Grants for Local Delinquency Prevention Programs (Community Prevention Grants), the Office of Juvenile Justice and Delinquency Prevention (OJJDP) allocated $20 million in fiscal year 1997 to states to complement law enforcement and justice system efforts by helping local communities foster strong families and nurture…

  3. Prevention of Serious and Violent Juvenile Offending. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Wasserman, Gail A.; Miller, Laurie S.; Cothern, Lynn

    This bulletin explores the proximal risk factors for juvenile offending, reviews the early developmental precursors to violent offending, and summarizes approaches to prevention. It also discusses components of intervention programs, limitations of single-focus prevention, examples of multi systemic interventions, and limitations of prevention…

  4. Race as a Factor in Juvenile Arrests. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Pope, Carl E.; Snyder, Howard E.

    This bulletin examines the effect of race on police decisions to take juvenile offenders into custody. Analysis of 1997 and 1998 data on 17 states from the Federal Bureau of Investigation's National Incident-Based Reporting System indicates that there is no evidence to support the hypothesis that police are more likely to arrest nonwhite juvenile…

  5. Philadelphia chromosome duplication as a ring-shaped chromosome.

    PubMed

    Borjas-Gutierrez, Cesar; Gonzalez-Garcia, Juan Ramon

    2016-01-01

    The gain of a second copy of the Philadelphia chromosome is one of the main secondary chromosomal changes related to the clonal evolution of cells with t(9;22) in chronic myelogenous leukemia. This gain causes the acquisition of another copy of the BCR/ABL1 fusion gene. Isochromosomes of the der(22) chromosome or double minute chromosomes are well known to lead an increased copy number of BCR/ABL1 gene. There is no antecedent of Philadelphia chromosome duplication as a ring chromosome. A recent published report contains evidence that strongly suggests that the Philadelphia chromosome was duplicated as a ring chromosome, observation that was overlooked by the authors. The instability inherent to the ring chromosome increases the risk of emergence of clones containing more and more BCR/ABL1 gene copies, which would produce increased fitness for clonal selection, resulting in worsening of the patient's prognosis.

  6. Linkage mapping in Papio baboons: Conservation of a syntenic group of six markers on human chromosome 1

    SciTech Connect

    Rogers, J.; Witte, S.M.; Kammerer, C.M.; Hixson, J.E.; MacCluer, J.W.

    1995-07-20

    We have established multipoint genetic linkage among six loci in baboons (Papio hamadryas). Published PCR primers designed to amplify five human microsatellite loci were used to amplify homologous loci in 229 pedigreed baboons. Southern blotting was used to type two RFLPs in a functional gene (anti-thrombin III) in a subset of those animals. All six loci are known to map to human chromosome 1q, a region of the genome predicted by karyotype studies to be conserved in baboons. Pairwise recombination frequencies and lod scores indicate that the six loci are also linked in baboons. Recombination distances among the loci are similar to those reported for humans. Like humans, the baboons exhibit higher rates of recombination in females than in males. This study demonstrates that (1) microsatellite loci first described and characterized in the human genome can be effectively used for genetic linkage mapping in nonhuman primates, (2) a group of genetic loci known to be linked on human chromosome 1q are also linked in the baboon genome, and (3) sex differences in recombination frequencies among loci on human chromosome 1q are also observe din the genome of this Old World monkey. This constitutes the first reported multipoint linkage map in any nonhuman primate. 26 refs., 1 fig., 3 tabs.

  7. "Chromosome": a knowledge-based system for the chromosome classification.

    PubMed

    Ramstein, G; Bernadet, M

    1993-01-01

    Chromosome, a knowledge-based analysis system has been designed for the classification of human chromosomes. Its aim is to perform an optimal classification by driving a tool box containing the procedures of image processing, pattern recognition and classification. This paper presents the general architecture of Chromosome, based on a multiagent system generator. The image processing tool box is described from the met aphasic enhancement to the fine classification. Emphasis is then put on the knowledge base intended for the chromosome recognition. The global classification process is also presented, showing how Chromosome proceeds to classify a given chromosome. Finally, we discuss further extensions of the system for the karyotype building.

  8. Juvenile Justice: A Bibliographic Essay.

    ERIC Educational Resources Information Center

    Kondak, Ann

    1979-01-01

    Provides information on the background and legal framework of the juvenile justice system, the issues that confront it, and the pressures for change, as well as noting some sources of information on the system. Available from American Association of Law Libraries, 53 West Jackson Blvd., Suite 1201, Chicago, Illinois 60604; sc $4.00. (Author/IRT)

  9. Treatment of juvenile recurrent parotitis.

    PubMed

    Katz, Philippe; Hartl, Dana M; Guerre, Agnès

    2009-12-01

    Juvenile recurrent parotitis (JRP) can be a debilitating illness in children. Knowing how to recognize and diagnose it for early treatment avoids recurrences that could lead to significant destruction of the glandular parenchyma. This article discusses the various therapeutic modalities proposed in the literature (medical treatment or sialendoscopy) and describes the authors' treatment of choice of combining antibiotics and iodinated oil sialography.

  10. Juvenile Court: Today and Tomorrow.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Discusses whether juveniles who commit criminal law violations should be tried in the same courts as adults. Addresses the issue of transfers that is a legal mechanism used to move youth to criminal court. Considers alternative proposals for handling youth brought to the judicial system and the role of the federal government. (CMK)

  11. Juvenile Diabetes and Rehabilitation Counseling.

    ERIC Educational Resources Information Center

    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  12. Juvenile Justice and Substance Use

    ERIC Educational Resources Information Center

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad…

  13. Juvenile Criminals: Who Are They?

    ERIC Educational Resources Information Center

    Antonov, A. I.; Lebed, O. L.

    2005-01-01

    Many adolescents who were born in the late 1970s and 1980s in Russia became juvenile criminals due to the change in the social structure, the proclamation of the values of the comfortable way of life, the institution of property ownership and so forth. Many young people have to help relatives who are in need, and this as well often causes them to…

  14. Complex chromosomal abnormalities in a patient with HTLV-1 positive T-cell leukemia

    SciTech Connect

    Hyde, P.; Macera, M.J.; Gogineni, S.K.

    1994-09-01

    HTLV-1 positive adult T-cell leukemia (ATL) is associated with numerous chromosomal abnormalities. The chromosomal rearrangements can be extremely complex and additional material is often present, making precise identification by routine cytogenetic techniques difficult. We report a case of ATL that was established of bone marrow cells by both QFQ and GTG banding techniques revealed a highly complex 49,XX,der(2)t(2;?)(q37;?),+5,+2mar karyotype in the dividing cells. The identical cytogenetic findings were also seen in unstimulated peripheral blood collected one week later. Using the FISH-technique, we applied spectrum green-labeled No. 1- and No. 7-specific WCP, spectrum orange-labeled No. 2- and No. 5-specific WCP (GIBCO/BRL, Gaithersburg, MD) and biotin-labeled No. 18-specific WCP (Oncor, Gaithersburg, MD) to metaphase chromosomes. The large marker chromosome was identified as an extra 1q arm, the material attached to the distal 2q was additional 7q. The presence of three No. 5 chromosomes was verified and the small marker was determined to be an extra partial 5p in Robertsonian translocation with an additional partial 18q arm. The karyotype was revised to 49,XX,+1q,der(2)t(2;7)(q37;q22),+5,+t(5;18)(p14{r_arrow}p11::q11{r_arrow}q12). Identification of the numerous chromosomal anomalies associated with the disease by molecular techniques shall lead to a better understanding of this deadly cancer.

  15. Sex Chromosome Drive

    PubMed Central

    Helleu, Quentin; Gérard, Pierre R.; Montchamp-Moreau, Catherine

    2015-01-01

    Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species. PMID:25524548

  16. Meiotic sex chromosome inactivation.

    PubMed

    Turner, James M A

    2007-05-01

    X chromosome inactivation is most commonly studied in the context of female mammalian development, where it performs an essential role in dosage compensation. However, another form of X-inactivation takes place in the male, during spermatogenesis, as germ cells enter meiosis. This second form of X-inactivation, called meiotic sex chromosome inactivation (MSCI) has emerged as a novel paradigm for studying the epigenetic regulation of gene expression. New studies have revealed that MSCI is a special example of a more general mechanism called meiotic silencing of unsynapsed chromatin (MSUC), which silences chromosomes that fail to pair with their homologous partners and, in doing so, may protect against aneuploidy in subsequent generations. Furthermore, failure in MSCI is emerging as an important etiological factor in meiotic sterility.

  17. Vibrios Commonly Possess Two Chromosomes

    PubMed Central

    Okada, Kazuhisa; Iida, Tetsuya; Kita-Tsukamoto, Kumiko; Honda, Takeshi

    2005-01-01

    The prevalence of the two-chromosome configuration was investigated in 34 species of vibrios and closely related species. Pulsed-field gel electrophoresis of undigested genomic DNA suggested that vibrios commonly have two chromosomes. The size of the large chromosome is predominantly within a narrow range (3.0 to 3.3 Mb), whereas the size of the small chromosome varies considerably among the vibrios (0.8 to 2.4 Mb). This fact suggests that the structure of the small chromosome is more flexible than that of the large chromosome during the evolution of vibrios. PMID:15629946

  18. Juvenile Crime, Juvenile Justice. Panel on Juvenile Crime: Prevention, Treatment, and Control.

    ERIC Educational Resources Information Center

    McCord, Joan, Ed.; Widom, Cathy Spatz, Ed.; Crowell, Nancy A., Ed.

    This book discusses patterns and trends in crimes committed by children and adolescents, analyzing youth crime as a subset of general crime and studying the impact of race and gender. It evaluates different approaches to forecasting future crime rates. Data come from a national panel that examined what is known about juvenile crime and its…

  19. Chromosomes and clinical anatomy.

    PubMed

    Gardner, Robert James McKinlay

    2016-07-01

    Chromosome abnormalities may cast light on the nature of mechanisms whereby normal anatomy evolves, and abnormal anatomy arises. Correlating genotype to phenotype is an exercise in which the geneticist and the anatomist can collaborate. The increasing power of the new genetic methodologies is enabling an increasing precision in the delineation of chromosome imbalances, even to the nucleotide level; but the classical skills of careful observation and recording remain as crucial as they always have been. Clin. Anat. 29:540-546, 2016. © 2016 Wiley Periodicals, Inc.

  20. Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU.

    PubMed

    Depienne, Christel; Nava, Caroline; Keren, Boris; Heide, Solveig; Rastetter, Agnès; Passemard, Sandrine; Chantot-Bastaraud, Sandra; Moutard, Marie-Laure; Agrawal, Pankaj B; VanNoy, Grace; Stoler, Joan M; Amor, David J; Billette de Villemeur, Thierry; Doummar, Diane; Alby, Caroline; Cormier-Daire, Valérie; Garel, Catherine; Marzin, Pauline; Scheidecker, Sophie; de Saint-Martin, Anne; Hirsch, Edouard; Korff, Christian; Bottani, Armand; Faivre, Laurence; Verloes, Alain; Orzechowski, Christine; Burglen, Lydie; Leheup, Bruno; Roume, Joelle; Andrieux, Joris; Sheth, Frenny; Datar, Chaitanya; Parker, Michael J; Pasquier, Laurent; Odent, Sylvie; Naudion, Sophie; Delrue, Marie-Ange; Le Caignec, Cédric; Vincent, Marie; Isidor, Bertrand; Renaldo, Florence; Stewart, Fiona; Toutain, Annick; Koehler, Udo; Häckl, Birgit; von Stülpnagel, Celina; Kluger, Gerhard; Møller, Rikke S; Pal, Deb; Jonson, Tord; Soller, Maria; Verbeek, Nienke E; van Haelst, Mieke M; de Kovel, Carolien; Koeleman, Bobby; Monroe, Glen; van Haaften, Gijs; Attié-Bitach, Tania; Boutaud, Lucile; Héron, Delphine; Mignot, Cyril

    2017-04-01

    Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.

  1. Alzheimer's β-amyloid peptides can activate the early components of complement classical pathway in a C1q-independent manner

    PubMed Central

    Bergamaschini, L; Canziani, S; Bottasso, B; Cugno, M; Braidotti, P; Agostoni, A

    1999-01-01

    β-Amyloid (β-A) accumulates in the brain of patients with Alzheimer's disease (AD) and is presumably involved in the pathogenesis of this disease, on account of its neurotoxicity and complement-activating ability. Although assembly of β-A in particular aggregates seems to be crucial, soluble non-fibrillar β-A may also be involved. Non-fibrillar β-A does not bind C1q, so we investigated alternative mechanisms of β-A-dependent complement activation in vitro. On incubation with normal human plasma, non-fibrillar β-A 1-42, and truncated peptide 1–28, induced dose-dependent activation of C1s and C4, sparing C3, as assessed by densitometric analysis of immunostained membrane after SDS–PAGE and Western blotting. The mechanism of C4 activation was not dependent on C1q, because non-fibrillar β-A can still activate C1s and C4 in plasma genetically deficient in C1q (C1qd). In Factor XII-deficient plasma (F.XIId) the amount of cleaved C4 was about 5–10% less that in C1qd and in normal EDTA plasma; the reconstitution of F.XIId plasma with physiologic concentrations of F.XII resulted in an increased (8–15%) β-A-dependent cleavage of C4. Thus our results indicate that the C1q-independent activation of C1 and C4 can be partially mediated by the activation products of contact system. Since the activation of contact system and of C4 leads to generation of several humoral inflammatory peptides, non-fibrillar β-A might play a role in initiating the early inflammatory reactions leading to a multistep cascade contributing to neuronal and clinical dysfunction of AD brain. PMID:10193429

  2. Alzheimer's beta-amyloid peptides can activate the early components of complement classical pathway in a C1q-independent manner.

    PubMed

    Bergamaschini, L; Canziani, S; Bottasso, B; Cugno, M; Braidotti, P; Agostoni, A

    1999-03-01

    beta-Amyloid (beta-A) accumulates in the brain of patients with Alzheimer's disease (AD) and is presumably involved in the pathogenesis of this disease, on account of its neurotoxicity and complement-activating ability. Although assembly of beta-A in particular aggregates seems to be crucial, soluble non-fibrillar beta-A may also be involved. Non-fibrillar beta-A does not bind C1q, so we investigated alternative mechanisms of beta-A-dependent complement activation in vitro. On incubation with normal human plasma, non-fibrillar beta-A 1-42, and truncated peptide 1-28, induced dose-dependent activation of C1s and C4, sparing C3, as assessed by densitometric analysis of immunostained membrane after SDS-PAGE and Western blotting. The mechanism of C4 activation was not dependent on C1q, because non-fibrillar beta-A can still activate C1s and C4 in plasma genetically deficient in C1q (C1qd). In Factor XII-deficient plasma (F.XIId) the amount of cleaved C4 was about 5-10% less that in C1qd and in normal EDTA plasma; the reconstitution of F.XIId plasma with physiologic concentrations of F.XII resulted in an increased (8-15%) beta-A-dependent cleavage of C4. Thus our results indicate that the C1q-independent activation of C1 and C4 can be partially mediated by the activation products of contact system. Since the activation of contact system and of C4 leads to generation of several humoral inflammatory peptides, non-fibrillar beta-A might play a role in initiating the early inflammatory reactions leading to a multistep cascade contributing to neuronal and clinical dysfunction of AD brain.

  3. [Phenotypic variability of the 1q21.1 microdeletion syndrome in members of the same family: relevance of detection of neuropsychiatric disorders for diagnosis of genetic syndromes].

    PubMed

    Natera-De Benito, Daniel; Vidal-Esteban, Arantxa; Sanchez-Del Pozo, Jaime; Moreno-Garcia, Marta; Suela-Rubio, Javier; Cruz-Rojo, Jaime; Rivero-Martin, María José

    2015-12-16

    Introduccion. El sindrome de microdelecion 1q21.1 esta causado por una delecion recurrente de aproximadamente 800 kb que incluye al menos siete genes y se asocia a un fenotipo variable. Esta variacion en el numero de copias patogenica puede aparecer de novo o ser heredada de uno de los progenitores. La presencia de trastornos psiquiatricos se ha descrito en muchos de los casos publicados, pero se desconoce su prevalencia exacta. Objetivo. Exponer la variabilidad fenotipica de los individuos que presentan una microdelecion 1q21.1. Casos clinicos. Se incluyen cuatro individuos portadores de una delecion de 1,74 Mb en 1q21.1, todos miembros de la misma familia. El estudio genetico del caso indice se llevo a cabo mediante array de hibridacion genomica comparada, y el del resto de familiares mediante hibridacion in situ fluorescente, con una sonda especifica para la region delecionada. Los individuos presentan un fenotipo heterogeneo, y es comun a todos ellos la presencia de alteraciones psiquiatricas o del comportamiento, con un claro predominio de la presencia de trastornos relacionados con las dificultades para el control de impulsos en sus diferentes subtipos. Conclusiones. El sindrome de microdelecion 1q21.1 es fenotipicamente heterogeneo, incluso entre los miembros de una misma familia. Destaca la presencia de alteraciones psiquiatricas o del comportamiento como rasgo comun en todos los pacientes que presentamos. Existen formas paucisintomaticas en las que el individuo portador de la delecion presenta exclusivamente alteraciones psiquiatricas.

  4. Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: complement component C1q and Prnp polymorphisms

    USGS Publications Warehouse

    Blanchong, Julie A.; Heisey, Dennis M.; Scribner, Kim T.; Libants, Scot V.; Johnson, Chad; Aiken, Judd M.; Langenberg, Julia A.; Samuel, Michael D.

    2009-01-01

    The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p < 0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.

  5. Platelet activation by C1q results in the induction of alpha IIb/beta 3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity

    PubMed Central

    1993-01-01

    C1q receptors (C1qR) have been identified on a variety of somatic and cultured cells including peripheral blood platelets. Since platelets are likely to encounter both circulating C1q multimers and C1q associated with the extracellular matrix after complement activation by the classical pathway, the present study was designed to assess the effect of fluid phase and immobilized C1q on platelet function. Platelet adhesion to C1q-coated surfaces was accompanied by the induction of fibrinogen receptors. Scatchard analysis of fibrinogen binding to adherent platelets revealed the binding of approximately 10,000 molecules of fibrinogen per platelet with a Kd of 0.1 +/- 0.03 microM (mean +/- SD, n = 4). Furthermore, fluid phase C1q multimers were noted to aggregate platelets at doses > 5 micrograms/ml. This aggregation was preceded by a rise in inositol-1,4,5-trisphosphate (IP3) (6.9 +/- 2.4 pmoles/10(9) platelets at 15 s, n = 4), and activation of GPIIb-IIIa complexes supporting fibrinogen binding. Platelet aggregation in response to C1q multimers was accompanied by the aspirin-inhibitable release of granule contents and P-selectin (CD62) expression. Platelet aggregation was inhibited by the collagenous domain of C1q (c-Clq) and a monoclonal antibody directed against C1q receptors, suggesting the direct involvement of the 67-kD platelet C1qR. Antibodies against the very late antigen 2 or CD36 collagen receptors were without effect. Platelet exposure to C1q multimers was also accompanied by the expression of procoagulant activity, as demonstrated by the dose-dependent shortening of the kaolin recalcification time of normal plasma from 108 +/- 12 s in the presence of unstimulated platelets to 62 +/- 14 s in the presence of platelets that had been preincubated (5 min, 37 degrees C) with 100 micrograms/ml multimeric C1q (n = 3). These data suggest that platelet interactions with C1q multimers or immobilized C1q, resulting in the activation of GPIIb-IIIa fibrinogen binding

  6. C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low Sensitivity When Predicting Flow Crossmatch

    PubMed Central

    Castelán, Natalia; de Santiago, Adrián; Arvizu, Adriana; Gonzalez-Tableros, Norma; López, Mayra; Salcedo, Isaac; Vilatobá, Mario; Granados, Julio

    2016-01-01

    The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80–259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27–19.68, P = 0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06–1.49, P = 0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85–100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3–100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity. PMID:27688904

  7. A Practical Approach to Juvenile Dermatomyositis and Juvenile Scleroderma.

    PubMed

    McCann, Liza J; Pain, Clare E

    2016-02-01

    Juvenile dermatomyositis and juvenile scleroderma are rare multisystem autoimmune disorders. Although they share some pathognomonic hallmarks with adult onset myositis or scleroderma, there are significant differences in presentation, characteristics and associated features when the diseases present in childhood. In view of this, and the rarity of the conditions, it is important for care to be led by teams with expertise in pediatric rheumatology conditions. Prognosis has improved significantly in the West; likely due to early diagnosis and aggressive treatment with immunosuppressive medications. However, this trend is not replicated in the developing world. Early recognition of these diseases is crucial to achieve rapid and sustained remission and prevent disease or medication associated complications. This article aims to provide a practical overview for recognition, diagnosis and treatment of these conditions.

  8. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma.

    PubMed

    Zettl, Andreas; Ott, German; Makulik, Angela; Katzenberger, Tiemo; Starostik, Petr; Eichler, Thorsten; Puppe, Bernhard; Bentz, Martin; Müller-Hermelink, Hans Konrad; Chott, Andreas

    2002-11-01

    Genetic alterations in enteropathy-type T-cell lymphoma (ETL) are unknown so far. In this series, 38 cases of ETL were analyzed by comparative genomic hybridization (CGH). CGH revealed chromosomal imbalances in 87% of cases analyzed, with recurrent gains of genetic material involving chromosomes 9q (in 58% of cases), 7q (24%), 5q (18%), and 1q (16%). Recurrent losses of genetic material occurred on chromosomes 8p and 13q (24% each), and 9p (18%). In this first systematic genetic study on ETL, chromosomal gains on 9q (minimal overlapping region 9q33-q34) were found to be highly characteristic of ETL. Fluorescence in situ hybridization analysis on four cases of ETL, using a probe for 9q34, indicated frequent and multiple gains of chromosomal material at 9q34 (up to nine signals per case). Among 16 patients with ETL who survived initial disease presentation, patients with more than three chromosomal gains or losses (n = 11) followed a worse clinical course than those with three or less imbalances (n = 5). The observation of similar genetic alterations in ETL and in primary gastric (n = 4) and colonic (n = 1) T-cell lymphoma, not otherwise specified, is suggestive of a genetic relationship of gastrointestinal T-cell lymphomas at either localization.

  9. Deletion of chromosome 21 in a girl with congenital hypothyroidism and mild mental retardation

    SciTech Connect

    Ahlbom, B.E.; Anneren, G.; Sidenvall, R.

    1996-08-23

    We report on a girl with a large interstitial deletion of the long arm of chromosome 21 and with mild mental retardation, congenital hypothyroidism, and hyperopia. The deletion [del(21)(q11.1-q22.1)] extends molecularly from marker D21S215 to D21S213. The distal breakpoint is not clearly defined but is situated between markers D21S213 and IFNAR. This patient has the largest deletion of chromosome 21 known without having severe mental retardation or malformations. The deletion does not involve the {open_quotes}Down syndrome chromosome{close_quotes} region, the region of chromosome 21 which in trisomy causes most of the manifestations of Down syndrome. Apparently, the proximal part of the long arm of chromosome 21 does not include genes that are responsible for severe clinical effects in the event of either deletion or duplication, since several reported patients with either trisomy or deletion of this region have mild phenotypic abnormalities. Congenital hypothyroidism is much more common in Down syndrome than in the average population. Thus, the congenital hypothyroidism of the present patient might indicate that there is one or several genes on the proximal part of chromosome 21, which might be of importance for the thyroid function. 24 refs., 4 figs., 2 tabs.

  10. Characterization of chromosomal architecture in Arabidopsis by chromosome conformation capture

    PubMed Central

    2013-01-01

    Background The packaging of long chromatin fibers in the nucleus poses a major challenge, as it must fulfill both physical and functional requirements. Until recently, insights into the chromosomal architecture of plants were mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation capture technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalized description of nuclear organization. Results Employing circular chromosome conformation capture, this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organization of chromosomes is reflected in the genome-wide interactome. In addition, we study the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 maintains a pericentromere-like interaction profile and interactome despite its euchromatic surrounding. Conclusion Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: heterochromatin and euchromatin represent two distinct interactomes; interactions between chromosomes correlate with the linear position on the chromosome arm; and distal chromosome regions have a higher potential to interact with other chromosomes. PMID:24267747

  11. Chromosome Variations And Human Behavior

    ERIC Educational Resources Information Center

    Soudek, D.

    1974-01-01

    Article focused on the science of cytogenetics, which studied the transmission of the units of heredity called chromosomes, and considered the advantage of proper diagnosis of genetic diseases, treated on the chromosomal level. (Author/RK)

  12. Chromosomes, cancer and radiosensitivity

    SciTech Connect

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  13. Why Chromosome Palindromes?

    PubMed Central

    Betrán, Esther; Demuth, Jeffery P.; Williford, Anna

    2012-01-01

    We look at sex-limited chromosome (Y or W) evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the “palindromes as protectors” view: (1) genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2) under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes. PMID:22844637

  14. The Y Chromosome

    ERIC Educational Resources Information Center

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  15. Segregation analysis of juvenile myoclonic epilepsy

    SciTech Connect

    Weissbecker, K.A.; Delgado-Escueta, A.V.; Medina, M.T.

    1994-09-01

    Juvenile myoclonic epilepsy (JME) is a non-progressive epilepsy characterized by involuntary jerks and an adolescent age of onset. There conflicting reports regarding the mode of inheritance of JME - polygenic, autosomal recessive, and two-locus models have all been proposed. We performed a segregation analysis of 53 nuclear families of JME probands using the Elston and Stewart algorithm (S.A.G.E version 2.1). Relatives of the proband were classified as affected if they had a confirmed history of JME, absence or grand mal epilepsy, or if they were clinically asymptomatic but had 3.5-6 Hz multispike wave complexes on electroencephalography. Using these criteria, 40 relatives were affected in addition to the 53 probands. All Mendelian models were rejected when compared to the unrestricted model which estimated transmission probabilities. The environmental models were also rejected. Of the Mendelian modes, the most parsimonious model was the autosomal recessive model with 53% penetrance and a rate of sporadic cases of 0.0039. We conclude that although there is evidence for a genetic component contributing to the familiality of JME, this component can not be explained by a single major gene. These results, along with contradictory reports regarding the linkage of JME to the short arm of chromosome 6, suggest the presence of genetic heterogeneity and/or a more complex mode of inheritance, such as a two-locus model. Since lod score linkage analyses are dependent on the assumption of a single major gene mode, these findings emphasize the necessity of performing non-parametric linkage analyses when studying JME.

  16. [Dicentric Y chromosome].

    PubMed

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  17. 8 CFR 236.3 - Detention and release of juveniles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Detention and release of juveniles. 236.3... Aliens Prior to Order of Removal § 236.3 Detention and release of juveniles. (a) Juveniles. A juvenile is defined as an alien under the age of 18 years. (b) Release. Juveniles for whom bond has been posted,...

  18. Juvenile morphology in baleen whale phylogeny

    NASA Astrophysics Data System (ADS)

    Tsai, Cheng-Hsiu; Fordyce, R. Ewan

    2014-09-01

    Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

  19. Juvenile morphology in baleen whale phylogeny.

    PubMed

    Tsai, Cheng-Hsiu; Fordyce, R Ewan

    2014-09-01

    Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

  20. Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

    PubMed Central

    Hidalgo, Alfredo; Monroy, Alberto; Arana, Rosa Ma; Taja, Lucía; Vázquez, Guelaguetza; Salcedo, Mauricio

    2003-01-01

    Background Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation. Methods We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients. Results All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Conclusions Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma. PMID:12659655

  1. [Chromosomal organization of the genomes of small-chromosome plants].

    PubMed

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species.

  2. Complex small supernumerary marker chromosomes – an update

    PubMed Central

    2013-01-01

    Background Complex small supernumerary marker chromosomes (sSMC) constitute one of the smallest subgroups of sSMC in general. Complex sSMC consist of chromosomal material derived from more than one chromosome; the best known representative of this group is the derivative chromosome 22 {der(22)t(11;22)} or Emanuel syndrome. In 2008 we speculated that complex sSMC could be part of an underestimated entity. Results Here, the overall yet reported 412 complex sSMC are summarized. They constitute 8.4% of all yet in detail characterized sSMC cases. The majority of the complex sSMC is contributed by patients suffering from Emanuel syndrome (82%). Besides there are a der(22)t(8;22)(q24.1;q11.1) and a der(13)t(13;18)(q11;p11.21) or der(21)t(18;21)(p11.21;q11.1) = der(13 or 21)t(13 or 21;18) syndrome. The latter two represent another 2.6% and 2.2% of the complex sSMC-cases, respectively. The large majority of complex sSMC has a centric minute shape and derives from an acrocentric chromosome. Nonetheless, complex sSMC can involve material from each chromosomal origin. Most complex sSMC are inherited form a balanced translocation in one parent and are non-mosaic. Interestingly, there are hot spots for the chromosomal breakpoints involved. Conclusions Complex sSMC need to be considered in diagnostics, especially in non-mosaic, centric minute shaped sSMC. As yet three complex-sSMC-associated syndromes are identified. As recurrent breakpoints in the complex sSMC were characterized, it is to be expected that more syndromes are identified in this subgroup of sSMC. Overall, complex sSMC emphasize once more the importance of detailed cytogenetic analyses, especially in patients with idiopathic mental retardation. PMID:24171835

  3. Intrachromosomal rearrangements in two representatives of the genus Saltator (Thraupidae, Passeriformes) and the occurrence of heteromorphic Z chromosomes.

    PubMed

    dos Santos, Michelly da Silva; Kretschmer, Rafael; Silva, Fabio Augusto Oliveira; Ledesma, Mario Angel; O'Brien, Patricia C M; Ferguson-Smith, Malcolm A; Del Valle Garnero, Analía; de Oliveira, Edivaldo Herculano Corrêa; Gunski, Ricardo José

    2015-10-01

    Saltator is a genus within family Thraupidae, the second largest family of Passeriformes, with more than 370 species found exclusively in the New World. Despite this, only a few species have had their karyotypes analyzed, most of them only with conventional staining. The diploid number is close to 80, and chromosome morphology is similar to the usual avian karyotype. Recent studies using cross-species chromosome painting have shown that, although the chromosomal morphology and number are similar to many species of birds, Passeriformes exhibit a complex pattern of paracentric and pericentric inversions in the chromosome homologous to GGA1q in two different suborders, Oscines and Suboscines. Hence, considering the importance and species richness of Thraupidae, this study aims to analyze two species of genus Saltator, the golden-billed saltator (S. aurantiirostris) and the green-winged saltator (S. similis) by means of classical cytogenetics and cross-species chromosome painting using Gallus gallus and Leucopternis albicollis probes, and also 5S and 18S rDNA and telomeric sequences. The results show that the karyotypes of these species are similar to other species of Passeriformes. Interestingly, the Z chromosome appears heteromorphic in S. similis, varying in morphology from acrocentric to metacentric. 5S and 18S probes hybridize to one pair of microchromosomes each, and telomeric sequences produce signals only in the terminal regions of chromosomes. FISH results are very similar to the Passeriformes already analyzed by means of molecular cytogenetics (Turdus species and Elaenia spectabilis). However, the paracentric and pericentric inversions observed in Saltator are different from those detected in these species, an observation that helps to explain the probable sequence of rearrangements. As these rearrangements are found in both suborders of Passeriformes (Oscines and Suboscines), we propose that the fission of GGA1 and inversions in GGA1q have occurred very

  4. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

    Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

  5. Diagnosing Juvenile Recurrent Parotitis. Case Reports.

    PubMed

    Schorr, Brittany; Mandel, Louis

    2016-01-01

    Diagnosis of juvenile recurrent parotitis is based upon clinical symptomatology, because no positive serologic signs have been identified. Objective confirmation is best obtained from sialographic or ultrasound studies.

  6. Juvenile offenders: competence to stand trial.

    PubMed

    Soulier, Matthew

    2012-12-01

    This article details the legal background and assists the reader in the preparation and practical conduct of evaluations regarding juvenile adjudicative competency. The material is presented to be useful as a guide to direct questions of competency and covers aspects of evaluation that include: legal standard for competency to stand trial, developmental immaturity, current practice in juvenile competency to stand trial, forensic evaluation of juvenile competency to stand trial, organizing the evaluation, collateral sources of information, psychiatric evaluation of juvenile adjudicative competency, assessment of mental disorder and intellectual disability, assessment of developmental status, assessment of functional abilities for adjudicative competence, and reaching the forensic opinion.

  7. Juvenile Practice Is Not Child's Play: A Handbook for Attorneys Who Represent Juveniles in Texas.

    ERIC Educational Resources Information Center

    2002

    This handbook is an attempt to summarize the most important aspects of juvenile law for a new practitioner, and to offer some additional ideas and strategies to any juvenile defense attorney. The goal is to help improve representation of juveniles across the state of Texas. References to useful books, cases, and statutes are included. The handbook…

  8. Runaway Juvenile Crime? The Context of Juvenile Arrests in America. Research in Brief.

    ERIC Educational Resources Information Center

    Ziedenberg, Jason; Schiraldi, Vincent

    The Violent and Repeat Juvenile Offender Act of 1997 (S-10) was to be debated in the Senate in spring 1998. This bill would blur the distinction between juvenile and adult criminal systems, making it easier to imprison children as young as 14. Supporters of S-10 were citing statistics to indicate that juvenile crime was on the rise. In fact, the…

  9. JUVENILE DELINQUENCY AND YOUTH CRIME, TASK FORCE REPORT, REPORT ON JUVENILE JUSTICE AND CONSULTANTS PAPERS.

    ERIC Educational Resources Information Center

    President's Commission on Law Enforcement and Administration of Justice, Washington, DC.

    THIS REPORT CONSISTS OF A DETAILED DISCUSSION OF THE JUVENILE COURT SYSTEM AND THE PREVENTION OF DELINQUENCY. THE COMMISSION'S RECOMMENDATIONS ON JUVENILE DELINQUENCY INCLUDE THE AREAS OF THE JUVENILE JUSTICE SYSTEM, HOUSING AND RECREATION, FAMILIES, INVOLVING YOUTHS IN COMMUNITY LIFE, SCHOOLS, AND EMPLOYMENT. THE APPENDIXES, WHICH CONSTITUTE THE…

  10. Black Juveniles in the Juvenile Justice System: A Cause for Alarm.

    ERIC Educational Resources Information Center

    LeFlore, Larry

    This report examines the representation of black youth in the juvenile justice system, describes changes in juvenile justice philosophy, and discusses policy implications. Black youth are overrepresented at all stages of the juvenile justice system compared to white youth. Positivist theories explain this overrepresentation as the result of…

  11. A Handbook for Juveniles and Parents on Maine's Juvenile Justice System.

    ERIC Educational Resources Information Center

    Mehnert, Irene

    This guide explains Maine's juvenile justice system so that juveniles and/or their parents can know what to expect or what to do in a situation involving juveniles, public officials and the law. Although it is geographically specific, it could serve as a model to other states. The booklet can serve as a checklist to make sure law enforcement…

  12. Planning for Juvenile Detention Reforms: A Structured Approach. Pathways to Juvenile Detention Reform 1.

    ERIC Educational Resources Information Center

    Steinhart, David

    This report is a guide to juvenile detention planning, based largely on the experiences of Juvenile Detention Alternatives Initiative (JDAI) sites. Its eight chapters include: (1) "Why Is Comprehensive Juvenile Detention Planning Needed?"; (2) "Guiding Principles" (e.g., detention planning must be based on adequate data, must…

  13. National Implications in Juvenile Justice: The Influence of Juvenile Mentoring Programs on At Risk Youth.

    ERIC Educational Resources Information Center

    Belshaw, Scott H.; Kritsonis, William Allan

    2007-01-01

    In 1972 the federal government created the Juvenile Justice Delinquency Prevention Act that procured funding for various governmental programs to combat the sudden increase in juvenile crime. A provision of this Act set out the creation of mentoring programs to help decrease the juvenile crime rate and dropout rates in secondary schools. This…

  14. Juvenile Justice: A Century of Change. 1999 National Report Series. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC. Office of Juvenile Justice and Delinquency Prevention.

    This report describes the development of the juvenile justice system in the United States. It uses current data to look at where it is heading, and the recent trend of transferring certain juvenile cases to adult criminal court. Section 1 explains that the juvenile justice system was founded on the concept of rehabilitation through individualized…

  15. SOME CHROMOSOME NUMBERS OF DRAPARNALDIA.

    PubMed

    Carroll, J W; Deason, T R

    1969-03-01

    The variability exhibited by Draparnaldia both in nature and in the laboratory makes it difficult to identify the species. The natural variability of Draparnaldia was amplified by the environmental conditions and the media used in this study. With the hope that chromosome studies would aid in taxonomic characterization by providing additional differentiating criteria, special attention was devoted to adapting techniques which could be used to determine chromosome numbers of Draparnaldia isolates. The chromosome numbers reported herein are as follows: (1) Draparnaldia glomerata, Isolate #1, isolated from Davis Falls, Montevallo, Alabama, was found to have a chromosome number of 13. (2) Draparnaldia Isolate #2, an unidentified species obtained from Anniston, Alabama, was found to have a chromosome number of 13. (3) Draparnaldia acuta, Isolate #3 from Northwood Lake, Northport, Alabama, exhibited 26 chromosomes. (4) Draparnaldia plumosa strain 423 (Indiana Culture Collection), 418/a (Cambridge) was observed to have a chromosome number of 13.

  16. Automated Chromosome Breakage Assessment

    NASA Technical Reports Server (NTRS)

    Castleman, Kenneth

    1985-01-01

    An automated karyotyping machine was built at JPL in 1972. It does computerized karyotyping, but it has some hardware limitations. The image processing hardware that was available at a reasonable price in 1972 was marginal, at best, for this job. In the meantime, NASA has developed an interest in longer term spaceflights and an interest in using chromosome breakage studies as a dosimeter for radiation or perhaps other damage that might occur to the tissues. This uses circulating lymphocytes as a physiological dosimeter looking for chromosome breakage on long-term spaceflights. For that reason, we have reactivated the automated karyotyping work at JPL. An update on that work, and a description of where it appears to be headed is presented.

  17. Chromosome 19 International Workshop

    SciTech Connect

    Pericak-Vance, M.A. . Medical Center); Ropers, H.H. . Dept. of Human Genetics); Carrano, A.J. )

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  18. Chromosomal evolution in Rodentia.

    PubMed

    Romanenko, S A; Perelman, P L; Trifonov, V A; Graphodatsky, A S

    2012-01-01

    Rodentia is the most species-rich mammalian order and includes several important laboratory model species. The amount of new information on karyotypic and phylogenetic relations within and among rodent taxa is rapidly increasing, but a synthesis of these data is currently lacking. Here, we have integrated information drawn from conventional banding studies, recent comparative painting investigations and molecular phylogenetic reconstructions of different rodent taxa. This permitted a revision of several ancestral karyotypic reconstructions, and a more accurate depiction of rodent chromosomal evolution.

  19. Construction of human chromosome 21-specific yeast artificial chromosomes

    SciTech Connect

    McCormick, M.K.; Shero, J.H.; Hieter, P.A.; Antonarakis, S.E. ); Cheung, Meichi; Kan, Yuetwai )

    1989-12-01

    Chromosome 21-specific yeast artificial chromosomes (YACs) have been constructed by a method that performs all steps in agarose, allowing size selection by pulsed-field gel electrophoresis and the use of nanogram to microgram quantities of DNA. The DNA sources used were hybrid cell line WAV-17, containing chromosome 21 as the only human chromosome and flow-sorted chromosome 21. The transformation efficiency of ligation products was similar to that obtained in aqueous transformations and yielded YACs with sizes ranging from 100 kilobases (kb) to > 1 megabase when polyamines were included in the transformation procedure. Twenty-five YACs containing human DNA have been obtained from a mouse-human hybrid, ranging in size from 200 to > 1000 kb, with an average size of 410 kb. Ten of these YACs were localized to subregions of chromosome 21 by hybridization of RNA probes to a panel of somatic cell hybrid DNA. Twenty-one human YACs, ranging in size from 100 to 500 kb, with an average size of 150 kb, were obtained from {approx} 50 ng of flow-sorted chromosome 21 DNA. Three were localized to subregions of chromosome 21. YACs will aid the construction of a physical map of human chromosome 21 and the study of disorders associated with chromosome 21 such as Alzheimer disease and Down syndrome.

  20. Interpreting Chromosome Aberration Spectra

    NASA Technical Reports Server (NTRS)

    Levy, Dan; Reeder, Christopher; Loucas, Bradford; Hlatky, Lynn; Chen, Allen; Cornforth, Michael; Sachs, Rainer

    2007-01-01

    Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

  1. PON1Q192R genetic polymorphism modifies organophosphorous pesticide effects on semen quality and DNA integrity in agricultural workers from southern Mexico

    SciTech Connect

    Perez-Herrera, N.; Polanco-Minaya, H. |; Salazar-Arredondo, E. |; Solis-Heredia, M.J.; Hernandez-Ochoa, I.; Rojas-Garcia, E.; Alvarado-Mejia, J.; Borja-Aburto, V.H.; Quintanilla-Vega, B.

    2008-07-15

    Pesticide exposure, including organophosphorous (OP) insecticides, has been associated with poor semen quality, and paraoxonase (PON1), an enzyme involved in OP deactivation, may have a role on their susceptibility, due to PON1 polymorphisms. Our objective was to evaluate the role of PON1Q192R polymorphism on the susceptibility to OP toxicity on semen quality and DNA integrity in agricultural workers. A cross-sectional study was conducted in farmers with Mayan ascendancy from southeastern Mexico chronically exposed to pesticides; mostly OP. Fifty four agricultural workers (18-55 years old) were included, who provided semen and blood samples. Semen quality was evaluated according to WHO, sperm DNA damage by in situ-nick translation (NT-positive cells), PON1Q192R polymorphism by real-time PCR and serum PON1 activity by using phenylacetate and paraoxon. Two OP exposure indexes were created: at the month of sampling and during 3 months before sampling, representing the exposure to spermatids-spermatozoa and to cells at one spermatogenic cycle, respectively. PON1 192R and 192Q allele frequencies were 0.54 and 0.46, respectively. Significant associations were found between OP exposure at the month of sampling and NT-positive cells and sperm viability in homozygote 192RR subjects, and dose-effect relationships were observed between OP exposure during 3 months before sampling and sperm quality parameters and NT-positive cells in homozygote 192RR farmers. This suggests that cells at all stages of spermatogenesis are target of OP, and that there exists an interaction between OP exposure and PON1Q192R polymorphism on these effects; farmers featuring the 192RR genotype were more susceptible to develop reproductive toxic effects by OP exposure.

  2. Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion

    SciTech Connect

    Shashi, V.; Golden, W.L.; Allinson, P.S.

    1996-06-01

    It has been demonstrated in animal studies that, in animals heterozygous for pericentric chromosomal inversions, loop formation is greatly reduced during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the inversion. A recent study in yeast has shown that telomeres, rather than centromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analysis and DNA polymorphisms the nature of meiotic recombination in a three-generation family with a large pericentric X chromosome inversion, inv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegregating with the inversion. On DNA analysis there was no evidence of meiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that the X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result in reduction of recombination between the normal and inverted X chromosomes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by the pericentric inversion. 50 refs., 7 figs., 1 tab.

  3. Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion.

    PubMed Central

    Shashi, V.; Golden, W. L.; Allinson, P. S.; Blanton, S. H.; von Kap-Herr, C.; Kelly, T. E.

    1996-01-01

    It has been demonstrated in animal studies that, in animals heterozygous for pericentric chromosomal inversions, loop formation is greatly reduced during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the inversion. A recent study in yeast has shown that telomeres, rather than centromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analysis and DNA polymorphisms the nature of meiotic recombination in a three-generation family with a large pericentric X chromosome inversion, inv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegregating with the inversion. On DNA analysis there was no evidence of meiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that the X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result in reduction of recombination between the normal and inverted X chromosomes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by the pericentric inversion. Images Figure 2 Figure 5 Figure 6 Figure 7 PMID:8651300

  4. Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion 5(p15.1q35.1).

    PubMed

    Sonoda, T; Kawaguchi, K; Ohba, K; Madokoro, H; Ohdo, S

    1989-06-01

    A male infant with karyotype 46,XY,rec(5),dup q,inv(5)(p15.1 q35.1)pat is presented. The proband showed growth and developmental retardation, complex cardiovascular abnormalities, inguinal hernia and microcephaly in addition to facial appearance and cat-like cry characteristic of the cri-du-chat syndrome. Growth and developmental retardation, and microcephaly noted in this patient were markedly more serious than those observed in patients either with partial monosomy 5p or with partial trisomy 5q alone.

  5. Human 60-kDa SS-A/Ro ribonucleoprotein autoantigen gene (SSA2) localized to 1q31 by fluorescence in situ hybridization

    SciTech Connect

    Chan, E.K.L.; Tan, E.M.; Ward, D.C.

    1994-09-01

    Human autoantibodies to intracellular antigens are often found in patients with systemic rheumatic diseases. Our laboratory and others have reported the cloning of the cDNAs for two protein autoantigens. The 60-kDa protein is a member of the RNA binding protein family containing an RNA binding motif and has been shown to be primarily responsible for direct interaction with hY-RNAs. The assignment of the 60-kDa autoantigen gene (SSA2) to 1q31 may allow further investigation of the genetic basis of human autoimmune diseases in which ss-A/Ro antibodies are observed. 14 refs., 1 fig.

  6. B Chromosomes – A Matter of Chromosome Drive

    PubMed Central

    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. PMID:28261259

  7. Juvenile justice and substance use.

    PubMed

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad range of negative effects, such as smoking, risky sexual behavior, violence, and poor educational, occupational, and psychological outcomes. The high rates of substance use problems among young offenders, says Chassin, suggest a large need for treatment. Although young offenders are usually screened for substance use disorders, Chassin notes the need to improve screening methods and to ensure that screening takes place early enough to allow youths to be diverted out of the justice system into community-based programs when appropriate. Cautioning that no single treatment approach has been proven most effective, Chassin describes current standards of "best practices" in treating substance use disorders, examines the extent to which they are implemented in the juvenile justice system, and describes some promising models of care. She highlights several treatment challenges, including the need for better methods of engaging adolescents and their families in treatment and the need to better address environmental risk factors, such as family substance use and deviant peer networks, and co-occurring conditions, such as learning disabilities and other mental health disorders. Chassin advocates policies that encourage wider use of empirically validated therapies and of documented best practices for treating substance use disorders. High relapse rates among youths successfully treated for substance use disorders also point to a greater need for aftercare services and for managing these disorders as chronic illnesses characterized by relapse and remission. A shortage of aftercare services and a lack of service coordination in the

  8. Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

    PubMed

    Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

    2010-09-01

    We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

  9. Anaesthesia and juvenile Huntington's disease.

    PubMed

    Gupta, K; Leng, C P

    2000-01-01

    Juvenile Huntington's Disease (JHD) is an involuntary movement disorder that comprises both neurological and psychiatric symptoms. Whilst it has many similarities to Huntington's Disease, it is regarded as a separate clinical entity. The anaesthetic plan should be based on careful assessment of the important issues, including the risk of regurgitation and pulmonary aspiration, possible associated autonomic neuropathy, poor respiratory function and the avoidance of precipitating convulsions and clonic spasms. We describe the management of a 12-year-old girl with JHD scheduled for gastroscopy under general anaesthesia necessitating the use of suxamethonium. We suggest an alternative mechanism for the delayed recovery seen in our patient and in other adult case reports.

  10. [Juvenile monomelic amyotrophy: Hirayama disease].

    PubMed

    Drozdowski, W; Baniukiewicz, E; Lewonowska, M

    1998-01-01

    We present three patients with unilateral upper limb weakness (with muscular atrophy)-two of them with distal and one with proximal localization. The disease onset was between 18th end 35-th year of life; the disease course was biphasic (i.e. progressive within first 1 to 3 years, and stabilized during following 4-24 years). The laboratory investigations permitted to diagnose juvenile monomelic amyotrophy, an entity that is very rare outside Japan. Electromyography revealed neurogenic involvement with spinal features also in clinically unaffected muscles. We suggest that these results may support the hypothesis of this disease being a benign variant of spinal muscular atrophy.

  11. Juvenile Competency to Stand Trial.

    PubMed

    Stepanyan, Sofia T; Sidhu, Shawn S; Bath, Eraka

    2016-01-01

    Competency to stand trial is interpreted as a protected due process right for all defendants and is defined as a defendant's fundamental knowledge and understanding of the criminal charges being filed, roles and procedures within the courtroom, and a general ability to work with the defense counsel. Questions of competency are most often raised by the judge, defense, or the prosecution, and competency evaluations are most often completed by psychiatrists or psychologists with forensic training or work experience. Mental illness, intellectual disability, developmental disorders, and developmental immaturity are the 4 main factors considered in most juvenile competency evaluations.

  12. Predictors of support for juvenile sex offender registration: educated individuals recognize the flaws of juvenile registration.

    PubMed

    Stevenson, Margaret C; Smith, Amy C; Sekely, Ady; Farnum, Katlyn S

    2013-01-01

    We investigated demographic predictors of support for juvenile sex offender registration policies, including education level, gender, political orientation, and age. Participants were 168 individuals recruited from public places in a Midwest community (45% women; M age = 42). In line with hypotheses, as education level increased, support for juvenile registration decreased, as did the belief that juvenile registration protects the community. In addition, as education level increased, belief that the juvenile understood his actions decreased, as did support for juvenile registration when it is framed as ineffective at reducing sex crime. These beliefs mediated the relationship between education level and diminished support for juvenile registration. Implications of these results for the advancement of effective juvenile sex offender policy are discussed.

  13. Juvenile Offenders and Victims: 2006 National Report

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    2006-01-01

    This report presents comprehensive information on juvenile crime, violence, and victimization and on the juvenile justice system. This report brings together the latest available statistics from a variety of sources and includes numerous tables, graphs, and maps, accompanied by analyses in clear, nontechnical language. The report offers Congress,…

  14. Juvenile Offenders and Victims: 1999 National Report.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    This report offers the Congress, state legislators, and other state and local policymakers, professors and teachers, juvenile justice professionals, and concerned citizens solid answers to the most frequently asked questions about the nature of juvenile crime and victimization and about the justice system's response. Citing FBI and other data…

  15. Genetic and clinical evaluation of juvenile retinoschisis

    PubMed Central

    Kim, Judy E.; Ruttum, Mark S.; Koeberl, Matthew J.; Hassemer, Eryn L.; Sidjanin, D. J.

    2014-01-01

    Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.1 Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants. PMID:19393523

  16. Genetic and clinical evaluation of juvenile retinoschisis.

    PubMed

    Kim, Judy E; Ruttum, Mark S; Koeberl, Matthew J; Hassemer, Eryn L; Sidjanin, D J

    2009-04-01

    Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.(1) Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants.

  17. Juvenile Anorexia Nervosa: Family Therapy's Natural Niche

    ERIC Educational Resources Information Center

    Fishman, H. Charles

    2006-01-01

    Juvenile Anorexia Nervosa (AN) is a severe problem both in terms of presenting symptomatology and its tendency toward chronicity. Researchers have consistently shown that family-based approaches are superior to individual approaches for the treatment of juvenile AN. This article addresses the capacity deficit of trained family therapists to treat…

  18. Juveniles' Motivations for Remaining in Prostitution

    ERIC Educational Resources Information Center

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

  19. Juvenile Obesity, Physical Activity, and Lifestyle Changes.

    ERIC Educational Resources Information Center

    Bar-Or, Oded

    2000-01-01

    Because many obese children become obese adults, the recent rapid increase in juvenile obesity poses a major public health challenge. Enhanced physical activity is a cornerstone in a multidisciplinary approach to preventing and treating juvenile obesity. Giving exercise recommendations focused for obese youth is critical. Cutting down on sedentary…

  20. Families, Juvenile Justice and Children's Mental Health.

    ERIC Educational Resources Information Center

    McManus, Marilyn C., Ed.

    1997-01-01

    The theme issue of this bulletin is a discussion of youth with emotional disturbances who are in the juvenile justice system and how to meet their needs. Articles include: (1) "Responding to the Mental Health Needs of Youth in the Juvenile Justice System" (Susan Rotenberg); (2) "Prevalence of Mental Disorders among Youth in the…

  1. Assessing Reoffense Risk with Juvenile Sexual Offenders.

    ERIC Educational Resources Information Center

    Kahn, Timothy J.; Chambers, Heather J.

    1991-01-01

    Summarizes a two-year study of juvenile sexual offenders in Washington. Evaluates both community- and institution-based treatment programs. Offers a demographic profile of the typical juvenile sexual offender and the recidivism data from a mean 20-month follow-up period. Surprisingly few variables were found to have a significant relationship to…

  2. Juvenile dispersal in Calomys venustus (Muridae: Sigmodontinae)

    NASA Astrophysics Data System (ADS)

    Priotto, José; Steinmann, Andrea; Provensal, Cecilia; Polop, Jaime

    2004-05-01

    Both spacing behaviour and dispersal movement are viewed as hierarchical processes in which the effects may be expressed at spatial scale. This research was carried out to examine the hypothesis that the presence of parents promotes the dispersal of juveniles from their natal nest and their father or mother home-range, in Calomys venustus.The study was carried out in four 0.25 ha fences (two controls and two experimentals), in a natural pasture. This study had two periods: Father Removal (FR) (August and December 1997; year one) and Mother Removal (MR) (August 1998 and January 1999; year two). For the FR treatment fathers were removed after juveniles were born, but in the MR treatment mothers were removed after the juveniles were weaned. The effect of parents on the dispersal distance of juveniles was analysed with respect to their natal nest and their mother and father home-range. Dispersal distance from the nest of C. venustus was independent of either male or female parent. Juveniles were more dispersing in relation to the centre of activity of their mothers than to that of their fathers, and females were more dispersing than males. Female juveniles overlap their home-range with their parents less than male juveniles do. The differences observed between female and male juveniles would be related to their different sexual maturation times, as well as to the female territoriality.

  3. Systemic juvenile xanthogranuloma with fatal outcome.

    PubMed

    Azorín, Daniel; Torrelo, Antonio; Lassaletta, Alvaro; de Prada, Inmaculada; Colmenero, Isabel; Contra, Trinidad; González-Mediero, Imelda

    2009-01-01

    Juvenile xanthogranuloma is a benign and self-limited disease which usually appears in the skin of children. Visceral involvement has been rarely reported, as has fatal outcome in some affected individuals. We report a case of systemic juvenile xanthogranuloma in a female newborn with mainly skin, bone marrow, and liver involvement, leading to death at the age of 2 months.

  4. Changes in Juvenile Justice in China.

    ERIC Educational Resources Information Center

    Wong, Dennis S. W.

    2001-01-01

    Discusses rising juvenile and youth crime in China, highlighting the essence of Chinese Marxist criminological thought and changing conceptions of delinquency from the postrevolutionary period to the present; examining official responses to delinquency and the recent development of juvenile justice; and suggesting that current delinquency control…

  5. Moral Development of Solo Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Van Vugt, Eveline; Stams, Geert Jan; Dekovic, Maja; Brugman, Daan; Rutten, Esther; Hendriks, Jan

    2008-01-01

    This study compared the moral development of solo juvenile male sex offenders (n = 20) and juvenile male non-offenders (n = 76), aged 13-19 years, from lower socioeconomic and educational backgrounds. The Moral Orientation Measure (MOM) was used to assess punishment- and victim-based moral orientation in sexual and non-sexual situations. Moral…

  6. Factors Affecting Attitudes toward Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Sahlstrom, Kimberly J.; Jeglic, Elizabeth L.

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment…

  7. Juvenile Offender Comprehensive Reentry Substance Abuse Treatment

    ERIC Educational Resources Information Center

    Watson, Donnie W.

    2004-01-01

    The literature provides ample evidence of the relationship of substance abuse to crime. Research over the last 20 years has established a strong correlation between substance abuse and juvenile delinquency (held, 1998). Currently, there are more than 350,000 juveniles on probation and in continuing care programs in the U.S. who have substance…

  8. Intelligence Score Profiles of Female Juvenile Offenders

    ERIC Educational Resources Information Center

    Werner, Shelby Spare; Hart, Kathleen J.; Ficke, Susan L.

    2016-01-01

    Previous studies have found that male juvenile offenders typically obtain low scores on measures of intelligence, often with a pattern of higher scores on measures of nonverbal relative to verbal tasks. The research on the intelligence performance of female juvenile offenders is limited. This study explored the Wechsler Intelligence Scale for…

  9. Psychiatric Disorder in a Juvenile Assessment Center

    ERIC Educational Resources Information Center

    McReynolds, Larkin S.; Wasserman, Gail A.; DeComo, Robert E.; John, Reni; Keating, Joseph M.; Nolen, Scott

    2008-01-01

    Juvenile assessment centers (JACs) were developed to address service fragmentation and promote the sharing of information among agencies providing services to youth involved with the juvenile justice system. To date, there are no reports that describe the diagnostic profiles of the youth served by such centers. The authors hypothesize that the…

  10. Utilizing Adventure Education to Rehabilitate Juvenile Delinquents.

    ERIC Educational Resources Information Center

    Golins, Gerald L.

    The use of adventure based education is a new and relatively unresearched but apparently successful practice in the rehabilitation of juvenile delinquents. Courses offered by schools, state social service systems, juvenile courts, youth service bureaus, and other agencies are generally patterned after the standard Outward Bound course and involve…

  11. Juvenile hormone regulation of Drosophila aging

    PubMed Central

    2013-01-01

    Background Juvenile hormone (JH) has been demonstrated to control adult lifespan in a number of non-model insects where surgical removal of the corpora allata eliminates the hormone’s source. In contrast, little is known about how juvenile hormone affects adult Drosophila melanogaster. Previous work suggests that insulin signaling may modulate Drosophila aging in part through its impact on juvenile hormone titer, but no data yet address whether reduction of juvenile hormone is sufficient to control Drosophila life span. Here we adapt a genetic approach to knock out the corpora allata in adult Drosophila melanogaster and characterize adult life history phenotypes produced by reduction of juvenile hormone. With this system we test potential explanations for how juvenile hormone modulates aging. Results A tissue specific driver inducing an inhibitor of a protein phosphatase was used to ablate the corpora allata while permitting normal development of adult flies. Corpora allata knockout adults had greatly reduced fecundity, inhibited oogenesis, impaired adult fat body development and extended lifespan. Treating these adults with the juvenile hormone analog methoprene restored all traits toward wildtype. Knockout females remained relatively long-lived even when crossed into a genotype that blocked all egg production. Dietary restriction further extended the lifespan of knockout females. In an analysis of expression profiles of knockout females in fertile and sterile backgrounds, about 100 genes changed in response to loss of juvenile hormone independent of reproductive state. Conclusions Reduced juvenile hormone alone is sufficient to extend the lifespan of Drosophila melanogaster. Reduced juvenile hormone limits reproduction by inhibiting the production of yolked eggs, and this may arise because juvenile hormone is required for the post-eclosion development of the vitellogenin-producing adult fat body. Our data do not support a mechanism for juvenile hormone control

  12. Measuring Transit Signal Recovery in the Kepler Pipeline. III. Completeness of the Q1-Q17 DR24 Planet Candidate Catalogue with Important Caveats for Occurrence Rate Calculations

    NASA Astrophysics Data System (ADS)

    Christiansen, Jessie L.; Clarke, Bruce D.; Burke, Christopher J.; Jenkins, Jon M.; Bryson, Stephen T.; Coughlin, Jeffrey L.; Mullally, Fergal; Thompson, Susan E.; Twicken, Joseph D.; Batalha, Natalie M.; Haas, Michael R.; Catanzarite, Joseph; Campbell, Jennifer R.; Kamal Uddin, AKM; Zamudio, Khadeejah; Smith, Jeffrey C.; Henze, Christopher E.

    2016-09-01

    With each new version of the Kepler pipeline and resulting planet candidate catalog, an updated measurement of the underlying planet population can only be recovered with a corresponding measurement of the Kepler pipeline detection efficiency. Here we present measurements of the sensitivity of the pipeline (version 9.2) used to generate the Q1-Q17 DR24 planet candidate catalog. We measure this by injecting simulated transiting planets into the pixel-level data of 159,013 targets across the entire Kepler focal plane, and examining the recovery rate. Unlike previous versions of the Kepler pipeline, we find a strong period dependence in the measured detection efficiency, with longer (>40 day) periods having a significantly lower detectability than shorter periods, introduced in part by an incorrectly implemented veto. Consequently, the sensitivity of the 9.2 pipeline cannot be cast as a simple one-dimensional function of the signal strength of the candidate planet signal, as was possible for previous versions of the pipeline. We report on the implications for occurrence rate calculations based on the Q1-Q17 DR24 planet candidate catalog, and offer important caveats and recommendations for performing such calculations. As before, we make available the entire table of injected planet parameters and whether they were recovered by the pipeline, enabling readers to derive the pipeline detection sensitivity in the planet and/or stellar parameter space of their choice.

  13. Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation

    SciTech Connect

    Scott, J.A.; Wenger, S.L.; Chakravarti, A.

    1995-03-13

    A 9-year-old, mildly mentally retarded girl presented with phenotypic manifestations of Down syndrome. G-banded chromosomal analyses of peripheral blood lymphocytes from the patient and her parents, and skin fibroblasts from the patient, did not detect any abnormality. Molecular analysis of 15 highly polymorphic chromosome 21 dinucleotide repeat markers demonstrated a partial duplication of the Down syndrome critical region (D21S55, subband 21q22.2) of maternal origin in the patient. The segmental trisomy was confirmed by FISH analysis using the cosmid probe D21S55. Further analysis demonstrated that the trisomy was due to segregation of an apparently balanced cryptic translocation from the mother. The patient`s karyotype is 46,XX,-12,tder(12)t(12;21)(p13.1;q22.2)mat. 21 refs., 3 figs., 1 tab.

  14. Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21

    SciTech Connect

    Shugart, Yin Y.; Banerjee, P.; Knowles, J.A.

    1995-08-01

    The inherited retinal degenerations known as retinitis pigmentosa (RP) can be caused by mutations at many different loci and can be inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait. Two forms of autosomal recessive (arRP) have been reported to cosegregate with mutations in the rhodopsin gene and the beta-subunit of rod phosphodiesterase on chromosome 4p. Genetic linkage has been reported on chromosomes 6p and 1q. In a large Dominican family, we reported an arRp gene near the region of the peripherin/RDS gene. Four recombinations were detected between the disease locus and an intragenic marker derived from peripherin/RDS. 26 refs., 2 figs., 1 tab.

  15. Polymer Models of Interphase Chromosomes

    NASA Astrophysics Data System (ADS)

    Martin, Joshua; Kondev, Jané; Bressen, Debra; Haber, James

    2006-03-01

    Experiments during interphase, the growth phase of the cell cycle in eukaryotic cells, have shown that parts of chromosomes are tethered to the nuclear periphery[1]. Using a simple polymer model of interphase chromosomes that includes tethering, we compute the probability distribution for the distance between two marked points on the chromosome. These calculations are inspired by recent experiments with two or more fluorescent markers placed along the chromosome[2]. We demonstrate how experiments of this kind, in conjunction with simpe polymer models, can be used to systematically dissect the spatial organization of interphase chromosomes in the nucleus of living cells. This comparison of theory with experiments has lead to the conclusion that the structure of chromosome III in yeast is consistent with a 10nm-fiber model of chromatin. [1]Wallace F. Marshall. Current Biology, 12, 2002. [2] Kerstin Bystricky, Patrick Heun, Lutz Gehlen, Jörg Langowski and Susan M. Gasser. PNAS, 101(47) 2004

  16. Family transitions and juvenile delinquency.

    PubMed

    Schroeder, Ryan D; Osgood, Aurea K; Oghia, Michael J

    2010-01-01

    There is a large body of research that shows children from non-intact homes show higher rates of juvenile delinquency than children from intact homes, partially due to weaker parental control and supervision in non-intact homes. What has not been adequately addressed in the research is the influence of changes in family structure among individual adolescents over time on delinquent offending. Using the first and third waves of the National Youth Study, we assess the effect of family structure changes on changes in delinquent offending between waves through the intermediate process of changes in family time and parental attachment. Although prior research has documented adolescents in broken homes are more delinquent than youth in intact homes, the process of family dissolution is not associated with concurrent increases in offending. In contrast, family formation through marriage or cohabitation is associated with simultaneous increases in offending. Changes in family time and parental attachment account for a portion of the family formation effect on delinquency, and prior parental attachment and juvenile offending significantly condition the effect of family formation on offending.

  17. Juvenile delinquency and adolescent fatherhood.

    PubMed

    Khurana, Atika; Gavazzi, Stephen M

    2011-08-01

    This study examined ecological risk factors associated with teen paternity in a sample of 2,931 male adolescents coming to the attention of juvenile courts across five midwestern counties. In contrast to previous studies documenting significantly higher rates of teen paternity among African American youth, we found that the European American court-involved youth in our sample were as likely to be teen fathers as their African American counterparts. However, an in-depth examination of the social ecologies of these court-involved youth revealed significant racial differences (regardless of the paternity status), with African American males reporting more prior offenses, delinquent peer associations, traumatic pasts, risky sexual behaviors, and educational risks as compared to European American youth, who reported greater involvement in substance use. Furthermore, logistic regression analyses revealed that after controlling for age and racial background, youth who reported greater exposure to trauma and prior offenses had significantly greater odds of having fathered a child. Surprisingly, youth who were teen fathers reported lower rates of behavioral problems as compared to their nonfathering peers. Given the cross-sectional nature of our data, interpretation of this result is limited. Overall, our findings underscore the need for developing a comprehensive understanding of the ecological risk and protective factors present in the lives of teen fathers coming in contact with the juvenile justice system, as an essential first step in designing effective and relevant intervention programs and services for this at-risk population.

  18. Histone acetylation in insect chromosomes.

    PubMed

    Allfrey, V G; Pogo, B G; Littau, V C; Gershey, E L; Mirsky, A E

    1968-01-19

    Acetylation of histones takes place along the salivary gland chromosomes of Chironomus thummi when RNA synthesis is active. It can be observed but not measured quantitatively by autoradiography of chromosome squashes. The "fixatives" commonly used in preparing squashes of insect chromosomes preferentially extract the highly acetylated "arginine-rich" histone fractions; the use of such fixatives may explain the reported absence of histone acetylation in Drosophila melanogaster.

  19. Complex chromosomal rearrangement and associated counseling issues in a family with Pelizaeus-Merzbacher disease.

    PubMed

    Woodward, Karen; Cundall, Maria; Palmer, Rodger; Surtees, Robert; Winter, Robin M; Malcolm, Sue

    2003-04-01

    We report cytogenetic and molecular findings in a family in which Pelizaeus-Merzbacher disease has arisen by a sub-microscopic duplication of the proteolipid protein (PLP1) gene involving the insertion of approximately 600 kb from Xq22 into Xq26.3. The duplication arose in an asymptomatic mother on a paternally derived X chromosome and was inherited by her son, the proband, who is affected with Pelizaeus-Merzbacher disease. The mother also carries a large interstitial deletion of approximately 70 Mb extending from Xq21.1 to Xq27.3, which is present in a mosaic form. In lymphocytes, the mother has no normal cells, having one population with three copies of the PLP1gene (one normal X and one duplication X chromosome) and the other population having only one copy of the PLP1 gene (one normal X and one deleted X chromosome). Her karyotype is 46,XX.ish dup (X) (Xpter --> Xq26.3::Xq22 --> Xq22::Xq26.3 --> Xqter)(PLP++)/46,X,del(X)(q21.1q27.3).ish del(X)(q21.1q27.3)(PLP-). Both ends of the deletion have been mapped by fluorescence in situ hybridization using selected DNA clones and neither involves the PLP1 gene or are in the vicinity of the duplication breakpoints. Prenatal diagnosis was carried out in a recent pregnancy and the complex counseling issues associated with these chromosomal rearrangements are discussed.

  20. The XXXXY Chromosome Anomaly

    PubMed Central

    Zaleski, Witold A.; Houston, C. Stuart; Pozsonyi, J.; Ying, K. L.

    1966-01-01

    The majority of abnormal sex chromosome complexes in the male have been considered to be variants of Klinefelter's syndrome but an exception should probably be made in the case of the XXXXY individual who has distinctive phenotypic features. Clinical, radiological and cytological data on three new cases of XXXXY syndrome are presented and 30 cases from the literature are reviewed. In many cases the published clinical and radiological data were supplemented and re-evaluated. Mental retardation, usually severe, was present in all cases. Typical facies was observed in many; clinodactyly of the fifth finger was seen in nearly all. Radiological examination revealed abnormalities in the elbows and wrists in all the 19 personally evaluated cases, and other skeletal anomalies were very frequent. Cryptorchism is very common and absence of Leydig's cells may differentiate the XXXXY chromosome anomaly from polysomic variants of Klinefelter's syndrome. The relationship of this syndrome to Klinefelter's syndrome and to Down's syndrome is discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15 PMID:4222822

  1. Chromosome Connections: Compelling Clues to Common Ancestry

    ERIC Educational Resources Information Center

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  2. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    PubMed

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  3. Distance between homologous chromosomes results from chromosome positioning constraints.

    PubMed

    Heride, Claire; Ricoul, Michelle; Kiêu, Kien; von Hase, Johann; Guillemot, Vincent; Cremer, Christoph; Dubrana, Karine; Sabatier, Laure

    2010-12-01

    The organization of chromosomes is important for various biological processes and is involved in the formation of rearrangements often observed in cancer. In mammals, chromosomes are organized in territories that are radially positioned in the nucleus. However, it remains unclear whether chromosomes are organized relative to each other. Here, we examine the nuclear arrangement of 10 chromosomes in human epithelial cancer cells by three-dimensional FISH analysis. We show that their radial position correlates with the ratio of their gene density to chromosome size. We also observe that inter-homologue distances are generally larger than inter-heterologue distances. Using numerical simulations taking radial position constraints into account, we demonstrate that, for some chromosomes, radial position is enough to justify the inter-homologue distance, whereas for others additional constraints are involved. Among these constraints, we propose that nucleolar organizer regions participate in the internal positioning of the acrocentric chromosome HSA21, possibly through interactions with nucleoli. Maintaining distance between homologous chromosomes in human cells could participate in regulating genome stability and gene expression, both mechanisms that are key players in tumorigenesis.

  4. Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

    PubMed

    Surapolchai, Pacharapan; Ha, Shau-Yin; Chan, Godfrey Chi-Fung; Lukito, Johannes B; Wan, Thomas S K; So, Chi-Chiu; Chiang, Alan Kwok-Shing

    2013-03-01

    Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

  5. Huntington's disease. Part 2: treatment and management issues in juvenile HD.

    PubMed

    Aubeeluck, Aimee; Brewer, Helen

    Juvenile Huntington's disease (JHD) is a rare condition, with only about 5-10% of Huntington's disease cases occurring in individuals under the age of 20 years. Symptoms of JHD include, for example, rigidity, stiffness, awkwardness in walking, and speech difficulty. JHD is caused by an inherited gene mutation that is localized to the short arm of chromosome 4. There is no cure for the condition, and it is currently managed through symptomatic treatment and supportive care. Being an inherited condition, those involved in the care of a child with JHD need to be aware of the impact that the disorder will have on the whole family.

  6. Different segregation patterns in five carriers due to a pericentric inversion of chromosome 1.

    PubMed

    Luo, Yuqin; Xu, Chenming; Sun, Yixi; Wang, Liya; Chen, Songchang; Jin, Fan

    2014-12-01

    Pericentric inversion can produce recombinant gametes; however, meiotic segregation studies on the relationship between the frequency of recombinants and the inverted segment size are rare. Triple-color fluorescence in situ hybridization (FISH) was performed to analyze the meiotic behavior in five inv(1) carriers with different breakpoints. Recombination gametes were absent in Patient 1, whereas the percentages of the recombinants in Patients 2, 3, 4, and 5 were of 9.2%, 15.3%, 17.3%, and 40.9%, respectively. A significant difference was present for the frequencies of the recombinant spermatozoa among the five patients (p < 0.001). For each patient, the frequency of the two types of recombinant gametes (dup(1p)/del(1q) or del(1p)/dup(1q)) did not exhibit a significant difference in comparison with the expected 1:1 ratio (p > 0.05). The meiotic segregation of nine inv(1) carriers (including those presented in this paper) is now available. A significant correlation was discovered between the rate of recombination and the proportion of the chromosome implicated in the inversion (R = 0.9435, p < 0.001). The frequency of the recombinant gametes was directly related to the proportion of the chromosome that was inverted. Sperm-FISH allowed an additional comprehension of the patterns of meiotic segregation and provided accurate genetic counseling.

  7. Development of a sequential multicolor-FISH approach with 13 chromosome-specific painting probes for the rapid identification of river buffalo (Bubalus bubalis, 2n = 50) chromosomes.

    PubMed

    Pauciullo, Alfredo; Perucatti, Angela; Iannuzzi, Alessandra; Incarnato, Domenico; Genualdo, Viviana; Di Berardino, Dino; Iannuzzi, Leopoldo

    2014-08-01

    The development of new molecular techniques (array CGH, M-FISH, SKY-FISH, etc.) has led to great advancements in the entire field of molecular cytogenetics. However, the application of these methods is still very limited in farm animals. In the present study, we report, for the first time, the production of 13 river buffalo (Bubalus bubalis, 2n = 50) chromosome-specific painting probes, generated via chromosome microdissection and the DOP-PCR procedure. A sequential multicolor-FISH approach is also proposed on the same slide for the rapid identification of river buffalo chromosome/arms, namely, 1p-1q, 2p-2q, 3p-3q, 4p-4q, 5p-5q, 18, X, and Y, using both conventional and late-replicating banded chromosome preparations counterstained by DAPI. The provided 'bank' of chromosome-specific painting probes is useful for any further cytogenetic investigation not only for the buffalo breeds, but also for other species of the family Bovidae, such as cattle, sheep, and goats, for chromosome abnormality diagnosis, and, more generally, for evolutionary studies.

  8. Juvenile Offenders with Mental Health Needs: Reducing Recidivism Using Wraparound

    ERIC Educational Resources Information Center

    Pullmann, Michael D.; Kerbs, Jodi; Koroloff, Nancy; Veach-White, Ernie; Gaylor, Rita; Sieler, Dede

    2006-01-01

    The rate of youth with mental health needs is disproportionately high in juvenile justice. Wraparound planning involves families and providers in coordinating juvenile justice, mental health, and other services and supports. This study compares data from two groups of juvenile offenders with mental health problems: 106 youth in a juvenile justice…

  9. Challenging the Myths: 1999 National Report Series. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    This bulletin, extracted from "Juvenile Offenders and Victims: 1999 National Report," examines juvenile crime statistics, demonstrating that the predictions in the early 1990s of the emergence of juvenile superpredators (juveniles for whom violence is a way of life) is not supported by current data. Research indicates that levels of…

  10. Profile of Incarcerated Juveniles: Comparison of Male and Female Offenders

    ERIC Educational Resources Information Center

    Martin, Don; Martin, Magy; Dell, Rex; Davis, Candice; Guerrieri, Karen

    2008-01-01

    Effective methods of identifying potential juvenile offenders are critical when developing prevention programs within both state and national juvenile justice systems. The characteristics of juvenile offenders in a large juvenile justice system are examined in this study. Participants live in a Midwestern city with a high rate of crime as…

  11. An Analysis of Juvenile Court Laws in Mississippi.

    ERIC Educational Resources Information Center

    Carter, Walter S., III

    Statutory laws, case laws, and model laws have been provided in this report as a basis for comparing Mississippi's juvenile laws with other juvenile laws. Since legislation concerning juvenile courts is vast, complete legislation is only provided for the State of Mississippi and two model juvenile court acts. Discussion, however, is provided which…

  12. 8 CFR 1236.3 - Detention and release of juveniles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Detention and release of juveniles. 1236.3... ORDERED REMOVED Detention of Aliens Prior to Order of Removal § 1236.3 Detention and release of juveniles. (a) Juveniles. A juvenile is defined as an alien under the age of 18 years. (b) Release....

  13. The contribution of both oxygen and nitrogen intermediates to the intracellular killing mechanisms of C1q-opsonized Listeria monocytogenes by the macrophage-like IC-21 cell line.

    PubMed

    Alvarez-Domínguez, C; Carrasco-Marín, E; López-Mato, P; Leyva-Cobián, F

    2000-09-01

    Listeria monocytogenes is a facultative intracellular pathogen which is internalized by host mammalian cells upon binding to their surface. Further listerial growth occurs in the cytosol after escape from the phagosomal-endosomal compartment. We have previously reported that C1q is able to potentiate L. monocytogenes phagocytosis upon bacterial opsonization by ingestion through C1q-binding structures. In this report, we analysed the post-phagocytic events upon internalization of C1q-opsonized L. monocytogenes and found an induction of macrophage (Mphi)-like IC-21 cell bactericidal mechanisms displayed by the production of oxygen and nitrogen metabolites. Both types of molecules are effective in L. monocytogenes killing. Further analysis of the cellular responses promoted by interaction of C1q with its surface binding structures, leads us to consider C1q as a collaborative molecule involved in Mphi activation. Upon interaction with surface binding structures, C1q was able to trigger and/or amplify the production of reactive oxygen and nitrogen intermediates induced by stimuli such as interferon-gamma and L. monocytogenes phagocytosis.

  14. Juvenile Huntington disease in Argentina.

    PubMed

    Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis; Sanguinetti, Ana; Cordi, Lorena; Binelli, Adrian; Persi, Gabriel; Squitieri, Ferdinando

    2016-01-01

    We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.

  15. [Environmental factors in juvenile delinquency].

    PubMed

    Barbagallo, A; Bellia, A; Benvenuto, G; Contiguglia, M A; Cosentino, F

    1975-09-12

    Experimental data are cited for the proposition that the complicated aspects of juvenile delinquency can only be understood and explained by adopting a simultaneous psychological and sociological approach. It is also shown that the manifestations of delinquency, though not its actual presence, may be influenced by sex and a depressed city or rural background. Environmental factors serving as stimulating features and hereditary (i.e. predisposing) factors undoubtedly contribute to the formation of the Ego. The former, however, are elaborated by their receipient and are not sufficient to explain a certain type of behaviour. The influence of cultural models should not be underestimated. These, where predominant, tend to render normative what may be considered as deviant.

  16. [Physiotherapy for juvenile idiopathic arthritis].

    PubMed

    Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

    2012-07-01

    Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

  17. Advances in plant chromosome genomics.

    PubMed

    Doležel, Jaroslav; Vrána, Jan; Cápal, Petr; Kubaláková, Marie; Burešová, Veronika; Simková, Hana

    2014-01-01

    Next generation sequencing (NGS) is revolutionizing genomics and is providing novel insights into genome organization, evolution and function. The number of plant genomes targeted for sequencing is rising. For the moment, however, the acquisition of full genome sequences in large genome species remains difficult, largely because the short reads produced by NGS platforms are inadequate to cope with repeat-rich DNA, which forms a large part of these genomes. The problem of sequence redundancy is compounded in polyploids, which dominate the plant kingdom. An approach to overcoming some of these difficulties is to reduce the full nuclear genome to its individual chromosomes using flow-sorting. The DNA acquired in this way has proven to be suitable for many applications, including PCR-based physical mapping, in situ hybridization, forming DNA arrays, the development of DNA markers, the construction of BAC libraries and positional cloning. Coupling chromosome sorting with NGS offers opportunities for the study of genome organization at the single chromosomal level, for comparative analyses between related species and for the validation of whole genome assemblies. Apart from the primary aim of reducing the complexity of the template, taking a chromosome-based approach enables independent teams to work in parallel, each tasked with the analysis of a different chromosome(s). Given that the number of plant species tractable for chromosome sorting is increasing, the likelihood is that chromosome genomics - the marriage of cytology and genomics - will make a significant contribution to the field of plant genetics.

  18. Visualization of early chromosome condensation

    PubMed Central

    Kireeva, Natashe; Lakonishok, Margot; Kireev, Igor; Hirano, Tatsuya; Belmont, Andrew S.

    2004-01-01

    Current models of mitotic chromosome structure are based largely on the examination of maximally condensed metaphase chromosomes. Here, we test these models by correlating the distribution of two scaffold components with the appearance of prophase chromosome folding intermediates. We confirm an axial distribution of topoisomerase IIα and the condensin subunit, structural maintenance of chromosomes 2 (SMC2), in unextracted metaphase chromosomes, with SMC2 localizing to a 150–200-nm-diameter central core. In contrast to predictions of radial loop/scaffold models, this axial distribution does not appear until late prophase, after formation of uniformly condensed middle prophase chromosomes. Instead, SMC2 associates throughout early and middle prophase chromatids, frequently forming foci over the chromosome exterior. Early prophase condensation occurs through folding of large-scale chromatin fibers into condensed masses. These resolve into linear, 200–300-nm-diameter middle prophase chromatids that double in diameter by late prophase. We propose a unified model of chromosome structure in which hierarchical levels of chromatin folding are stabilized late in mitosis by an axial “glue.” PMID:15353545

  19. Cohesin in determining chromosome architecture

    SciTech Connect

    Haering, Christian H.; Jessberger, Rolf

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  20. Organization of the bacterial chromosome.

    PubMed Central

    Krawiec, S; Riley, M

    1990-01-01

    Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction between a large plasmid and a second chromosome is discussed. Recent information on repeated sequences and chromosomal rearrangements is presented. The growing understanding of limitations on the rearrangements that can be tolerated by bacteria and those that cannot is summarized, and the sensitive region flanking the terminator loci is described. Sources and types of genetic variation in bacteria are listed, from simple single nucleotide mutations to intragenic and intergenic recombinations. A model depicting the dynamics of the evolution and genetic activity of the bacterial chromosome is described which entails acquisition by recombination of clonal segments within the chromosome. The model is consistent with the existence of only a few genetic types of E. coli worldwide. Finally, there is a summary of recent reports on lateral genetic exchange across great taxonomic distances, yet another source of genetic variation and innovation. PMID:2087223