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Sample records for proximal chromosome 11q

  1. Chromosome 11q13 deletion syndrome

    OpenAIRE

    Kim, Yu-Seon; Kim, Gun-Ha; Byeon, Jung Hye; Eun, So-Hee; Eun, Baik-Lin

    2016-01-01

    Chromosome 11q13 deletion syndrome has been previously reported as either otodental syndrome or oculo-oto-dental syndrome. The otodental syndrome is characterized by dental abnormalities and high-frequency sensorineural hearing loss, and by ocular coloboma in some cases. The underlying genetic defect causing otodental syndrome is a hemizygous microdeletion involving the FGF3 gene on chromosome 11q13.3. Recently, a new form of severe deafness, microtia (small ear) and small teeth, without the ...

  2. An emerging phenotype of proximal 11q deletions.

    Science.gov (United States)

    Melis, Daniela; Genesio, Rita; Cozzolino, Mariarosaria; Del Giudice, Ennio; Mormile, Angela; Imperati, Floriana; Ronga, Valentina; Della Casa, Roberto; Nitsch, Lucio; Andria, Generoso

    2010-01-01

    Few reports of small interstitial chromosome 11q deletions are reported in the literature and no clear genotype-phenotype correlation has been demonstrated. We describe a five years old boy who was referred to our attention because of the presence of ptosis of the left eyelid, iris coloboma and developmental delay. Clinical examination also revealed the presence of dysmorphic features including: low frontal hairline, flat profile, round face, full cheeks, periorbital fullness, hypertelorism, broad nasal bridge, down-turned corners of the mouth. Cytogenetic analysis, performed by array-CGH (resolution 1 Mb), revealed a deletion of chromosome 11q13.5q14.2. The present case represents a further patient described in the literature with a small interstitial deletion of chromosome 11q. Our patient shares the dysmorphic features and the presence of developmental delay with the previously reported patients with overlapping proximal 11q deletion. Considering these clinical and cytogenetic similarities, we suggest the existence of an emerging syndrome associated to proximal 11q deletions. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  3. Jacobsen syndrome: chromosome deletion at 11q23.

    Science.gov (United States)

    Clang, D R; LaBaere, R J

    1998-10-01

    A male infant delivered at term to unrelated parents was found to have multiple dysmorphic facial characteristics, abnormal head shape, anemia, thrombocytopenia, a prominent holosystolic heart murmur with multiple cardiac defects, hypotonia, and was small for his gestational age. Karotype revealed a de novo deletion of the long arm of chromosome 11, del (11)(q23), which has been previously described as Jacobsen syndrome. Recent studies have demonstrated that a folate-sensitive fragile site at 11q, band 23, (11q23) may be responsible for this deletion and possibly other syndromes as well.

  4. Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region

    Directory of Open Access Journals (Sweden)

    Kashork Catherine D

    2008-01-01

    Full Text Available Abstract Background Prader-Willi syndrome (PWS is a neurobehavioral disorder characterized by neonatal hypotonia, childhood obesity, dysmorphic features, hypogonadism, mental retardation, and behavioral problems. Although PWS is most often caused by a paternal interstitial deletion of a 6-Mb region of chromosome 15q11-q13, the identity of the exact protein coding or noncoding RNAs whose deficiency produces the PWS phenotype is uncertain. There are also reports describing a PWS-like phenotype in a subset of patients with full mutations in the FMR1 (fragile X mental retardation 1 gene. Taking advantage of the human genome sequence, we have performed extensive sequence analysis and molecular studies for the PWS candidate region. Results We have characterized transcripts for the first time for two UCSC Genome Browser predicted protein-coding genes, GOLGA8E (golgin subfamily a, 8E and WHDC1L1 (WAS protein homology region containing 1-like 1 and have further characterized two previously reported genes, CYF1P1 and NIPA2; all four genes are in the region close to the proximal/centromeric deletion breakpoint (BP1. GOLGA8E belongs to the golgin subfamily of coiled-coil proteins associated with the Golgi apparatus. Six out of 16 golgin subfamily proteins in the human genome have been mapped in the chromosome 15q11-q13 and 15q24-q26 regions. We have also identified more than 38 copies of GOLGA8E-like sequence in the 15q11-q14 and 15q23-q26 regions which supports the presence of a GOLGA8E-associated low copy repeat (LCR. Analysis of the 15q11-q13 region by PFGE also revealed a polymorphic region between BP1 and BP2. WHDC1L1 is a novel gene with similarity to mouse Whdc1 (WAS protein homology region 2 domain containing 1 and human JMY protein (junction-mediating and regulatory protein. Expression analysis of cultured human cells and brain tissues from PWS patients indicates that CYFIP1 and NIPA2 are biallelically expressed. However, we were not able to

  5. Partial trisomy 11q involving chromosome 1 detected by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, M.; Bereziouk, O.; McCorquodale, D.J. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    Partial trisomy 11q was detected in an infant delivered 3-4 weeks prematurely. The phenotype included slanted palpebral fissures, high arched palate, developmental delay, microcephaly, and cardiac defects, all of which occur in the majority of cases with this syndrome. Other features included a column-shaped skull, preauricular pit, single palmar crease, short, broad great toes, flat occiput, unilateral kidney agenesis, and strabismus. Chromosomes obtained from peripheral blood cells revealed the presence of extra material on the long arm of chromosome 1. The G-banding pattern of this extra material indicated that it might be derived from chromosome 1 or 11. Chromosomal {open_quotes}paints{close_quotes} showed that it was not chromosome 1 material, but was chromosome 11 material extending from band q21 to qter. Partial trisomy 11q arising from translocation of the 11q material to chromosome 2, 3, 4, 5, 6, 9, 10, 13, 17, 21, 22, and X has been reported previously, whereas translocation to chromosome 1 has not. The chromosome to which the 11q material is translocated does not alter the most frequent features of the partial trisomy 11q syndrome, but may influence other less common features.

  6. Localization of Jacobsen Syndrome Breakpoints on a 40-Mb Physical Map of Distal Chromosome 11q

    OpenAIRE

    Tunnacliffe, Alan; Jones, Christopher; Le Paslier, Denis; Todd, Roger; Cherif, Dora; Birdsall, Michelle; Devenish, Louise; Yousry, Cherine; Cotter, Finbarr E.; James, Michael R.

    1999-01-01

    Jacobsen syndrome is a haploinsufficiency disorder caused, most frequently by terminal deletion of part of the long arm of chromosome 11, with breakpoints in 11q23.3–11q24.2. Inheritance of an expanded p(CCG)n trinucleotide repeat at the folate-sensitive fragile site FRA11B has been implicated in the generation of the chromosome breakpoint in several Jacobsen syndrome patients. The majority of such breakpoints, however, map distal to this fragile site and are not linked with its expression. T...

  7. Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality

    Directory of Open Access Journals (Sweden)

    Frenny J. Sheth

    2014-01-01

    Full Text Available Terminal 11q deletion, known as Jacobsen syndrome (JBS, is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11 del(11(q24. Array comparative genomic hybridization (aCGH analysis confirmed partial deletion of 11.8–11.9 Mb at 11q24.1q25 (case 1 and 13.9–14 Mb deletion at 11q23.3q25 together with 7.3–7.6 Mb duplication at 12q24.32q24.33 (case 2. Dysmorphism because of the partial duplication of 12q was not overtly decipherable over the Jacobsen phenotype except for a triangular facial profile. Aberrant chromosome 11 was inherited from phenotypically normal father, carrier of balanced translocation 46,XY,t(11;12(q23.3; q24.32. In the present study, both cases had phenotypes that were milder than the ones described in literature despite having large deletion size. Most prominent features in classical JBS is thrombocytopenia, which was absent in both these cases. Therefore, detailed functional analysis of terminal 11q region is warranted to elucidate etiology of JBS and their clinical presentation.

  8. Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality.

    Science.gov (United States)

    Sheth, Frenny J; Datar, Chaitanya; Andrieux, Joris; Pandit, Anand; Nayak, Darshana; Rahman, Mizanur; Sheth, Jayesh J

    2014-01-01

    Terminal 11q deletion, known as Jacobsen syndrome (JBS), is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11) del(11)(q24). Array comparative genomic hybridization (aCGH) analysis confirmed partial deletion of 11.8-11.9 Mb at 11q24.1q25 (case 1) and 13.9-14 Mb deletion at 11q23.3q25 together with 7.3-7.6 Mb duplication at 12q24.32q24.33 (case 2). Dysmorphism because of the partial duplication of 12q was not overtly decipherable over the Jacobsen phenotype except for a triangular facial profile. Aberrant chromosome 11 was inherited from phenotypically normal father, carrier of balanced translocation 46,XY,t(11;12)(q23.3; q24.32). In the present study, both cases had phenotypes that were milder than the ones described in literature despite having large deletion size. Most prominent features in classical JBS is thrombocytopenia, which was absent in both these cases. Therefore, detailed functional analysis of terminal 11q region is warranted to elucidate etiology of JBS and their clinical presentation.

  9. Alterations of chromosome 11q13 in cervical carcinoma cell lines

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    Popescu, N.C.; Zimonjic, D.B. [National Institutes of Health, Bethesda, MD (United States)

    1996-02-01

    In cervical cancer, evidence for the existence of a tumor-suppressor gene on chromosome 11 has been generated from studies with somatic cell hybrids, chromosome microcell transfer, or deletion analysis of DNA markers. As suggested by somatic cell hybrids analysis, chromosome 11 harbors at least three distinctive tumor-suppressor genes, two on the short arm and one on the long arm. Loss of heterozygosity (LOH) analysis using 16 markers, 10 of which were microsatellite-based, placed the region of a putative tumor-suppressor gene to 11q22-24. Recently, 11q13 was assigned as another possible site on the basis of molecular rearrangements, deletions, and translocations, nonrandomly involving this region in four of eight cervical carcinoma cell lines. Abnormal chromosomes 11 were found in HeLa, SiHa, and Caski lines and in C33A, a human papilloma virus-negative cell line. 18 refs.

  10. Prenatal diagnosis of a large de novo terminal deletion of chromosome 11q.

    Science.gov (United States)

    Boehm, D; Laccone, F; Burfeind, P; Herold, S; Schubert, C; Zoll, B; Männer, J; Pauer, H U; Bartels, I

    2006-03-01

    To describe the prenatal phenotype of the 11q deletion syndrome (Jacobsen syndrome) and present the molecular characterization of the deletion in the case presented. Ultrasound at 18 and 20 weeks of gestation, on a 34-year-old woman who presented for amniocentesis, revealed slow movements, oligohydramnios and dilatation of the cerebral ventricles in the fetus. Maternal and paternal ages were 34 and 38 years, respectively. Prenatal karyotyping of cultured amniotic fluid cells revealed an 11q terminal deletion, 46,XX,del(11)(q23) (Jacobsen syndrome). Real-time quantitative PCR analysis was used to identify and map the breakpoint physically to a 45-kb region located 14.5 Mb from the 11q telomere. Polymorphic DNA marker analysis showed that DNA sequences on the paternally derived chromosome are deleted. At autopsy, facial dysmorphism without major malformations was recorded. Examination of the internal organs disclosed the following abnormalities: a Meckels' diverticulum of 4-mm length, adhesion between the gall bladder and the transverse colon, and bilaterally bilobed lungs without further situs anomalies. Our case demonstrates significant phenotypic variability of Jacobsen syndrome at midtrimester pregnancy; the syndrome may be manifested at this stage only by mild to moderate ventriculomegaly of the brain. 2006 John Wiley & Sons, Ltd.

  11. Localization of Jacobsen syndrome breakpoints on a 40-Mb physical map of distal chromosome 11q.

    Science.gov (United States)

    Tunnacliffe, A; Jones, C; Le Paslier, D; Todd, R; Cherif, D; Birdsall, M; Devenish, L; Yousry, C; Cotter, F E; James, M R

    1999-01-01

    Jacobsen syndrome is a haploinsufficiency disorder caused, most frequently by terminal deletion of part of the long arm of chromosome 11, with breakpoints in 11q23.3-11q24.2. Inheritance of an expanded p(CCG)n trinucleotide repeat at the folate-sensitive fragile site FRA11B has been implicated in the generation of the chromosome breakpoint in several Jacobsen syndrome patients. The majority of such breakpoints, however, map distal to this fragile site and are not linked with its expression. To characterize these distal breakpoints and ultimately to further investigate the mechanisms of chromosome breakage, a 40-Mb YAC contig covering the distal long arm of chromosome 11 was assembled. The utility of the YAC contig was demonstrated in three ways: (1) by rapidly mapping the breakpoints from two new Jacobsen syndrome patients using FISH; (2) by demonstrating conversion to high resolution PAC contigs after direct screening of PAC library filters with a YAC clone containing a Jacobsen syndrome breakpoint; and (3) by placing 23 Jacobsen syndrome breakpoints on the physical map. This analysis has suggested the existence of at least two new Jacobsen syndrome breakpoint cluster regions in distal chromosome 11.

  12. Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees

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    Mulcrone, J.; Marchblanks, R.; Whatley, S.A. [Institute of Psychiatry, London (United Kingdom)] [and others

    1995-04-24

    It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia. The hypothesis of linkage under genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity. 32 refs., 2 figs., 4 tabs.

  13. Constitutional 11q14-q22 chromosome deletion syndrome in a child with neuroblastoma MYCN single copy.

    Science.gov (United States)

    Passariello, Annalisa; De Brasi, Daniele; Defferrari, Raffaella; Genesio, Rita; Tufano, Maria; Mazzocco, Katia; Capasso, Maria; Migliorati, Roberta; Martinsson, Tommy; Siani, Paolo; Nitsch, Lucio; Tonini, Gian Paolo

    2013-11-01

    Constitutional 11q deletion is a chromosome imbalance possibly found in MCA/MR patients analyzed for chromosomal anomalies. Its role in determining the phenotype depends on extension and position of deleted region. Loss of heterozygosity of 11q (region 11q23) is also associated with neuroblastoma, the most frequent extra cranial cancer in children. It represents one of the most frequent cytogenetic abnormalities observed in the tumor of patients with high-risk disease even if germline deletion of 11q in neuroblastoma is rare. Hereby, we describe a 18 months old girl presenting with trigonocephaly and dysmorphic facial features, including hypotelorism, broad depressed nasal bridge, micrognathia, synophrys, epicanthal folds, and with a stage 4 neuroblastoma without MYCN amplification, carrying a germline 11q deletion (11q14.1-q22.3), outside from Jacobsen syndrome and from neuroblastoma 11q critical regions. The role of 11q deletion in determining the clinical phenotype and its association with neuroblastoma development in the patient are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Chromosomal-array analysis reveals partial 11q duplication and partial 12p deletion in a mildly affected case.

    Science.gov (United States)

    Tuğ, Esra; Yirmibeş Karaoğuz, Meral; Kayhan, Gülsüm; Ergün, Mehmet Ali; Perçin, Ferda E

    2014-07-01

    Partial trisomy 11q is a rare syndrome and may be observed due to an intra-chromosomal duplication or an inter-chromosomal insertion. The deletions of the short arm of chromosome 12 are also uncommon structural aberrations. Only a small fraction of structural chromosome anomalies are related to the unbalanced progeny of balanced translocation carrier parents. We here report on a 10-month-old baby boy who shows a very mild phenotype related to unique chromosomal abnormality, partial trisomy of 11q, and partial monosomy of 12p, due to the maternal balanced reciprocal translocation (11;12). The proband showed a 49.64 Mb duplication of 11q14.1-q25 and 0.44 Mb deletion of 12p13.33 in chromosomal array analysis. Since it is known that the duplications may cause a milder phenotype than deletions. Dysmorphic facial features, minor cardiac anomalies, respiratory distress, central nervous system anomalies, and psychomotor delay observed in the patient was similar to the reported pure 11q duplication cases, while behavioral problems observed in pure monosomy 12p cases could not be evaluated due to the young age of the patient. Phenotype-genotype correlation will be discussed in view of all the reported pure partial 11q trisomies and pure partial 12p deletion cases. © 2014 Wiley Periodicals, Inc.

  15. Localization of the gene responsible for familial benign polycythemia to chromosome 11q23.

    Science.gov (United States)

    Vasserman, N N; Karzakova, L M; Tverskaya, S M; Saperov, V N; Muchukova, O M; Pavlova, G P; Efimova, N K; Vankina, N N; Evgrafov, O V

    1999-06-01

    Familial benign polycythemia (FBP) (OMIM 263400) is a rare autosomal recessive condition characterized by erythrocytosis, normal leukocyte and platelet counts, normal uric acid level, and usually increased erythropoietin production. There is a high incidence of this disorder in Chuvashia (Russian Federation), probably due to a founder effect. In an attempt to locate the gene responsible for this disorder, we have carried out linkage studies in 12 Chuvash families, with 35 affected and 32 unaffected members. Linkage to the erythropoietin and erythropoietin receptor loci was excluded, and the FBP gene was assigned to the region of chromosome 11q23 between D11S4142 and D11S1356, with a maximal lod score of 6.61.

  16. Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality

    OpenAIRE

    Sheth, Frenny J; Datar, Chaitanya; Andrieux, Joris; Pandit, Anand; Nayak, Darshana; Rahman, Mizanur; Sheth, Jayesh J

    2014-01-01

    Terminal 11q deletion, known as Jacobsen syndrome (JBS), is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11) del(11)(q24). Array comparative genomic hybridization (aCGH) analysis confirmed partial deletion of 11.8–11.9 Mb at 11q24.1q25 (case 1) and 13.9–14 Mb deletion at 11q23.3q25 together with 7.3–7.6 Mb duplication at 1...

  17. Characterization of a DNA sequence family in the Prader-Willi/Angelman syndrome chromosome region in 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Dittrich, B.; Knoblauch, H.; Buiting, K.; Horsthemke, B. (Universitaetsklinikum Essen (Germany))

    1993-04-01

    IR4-3R (D15S11) is an anonymous DNA sequence from human chromosome 15. Using YAC cloning and restriction enzyme analysis, the authors have found that IR4-3R detects five related DNA sequences, which are spread over 700 kb within the Prader-Willi/Angelman syndrome chromosome region in 15q11-q 13. The RsaI and StyI polymorphisms, which were described previously, are associated with the most proximal copy of IR4-3R and are in strong linkage disequilibrium. IR4-3R represents the third DNA sequence family that has been identified in 15q11-q13. 14 refs., 2 figs., 1 tab.

  18. Angelman syndrome: Validation of molecular cytogenetic analysis of chromosome 15q11-q13 for deletion detection

    Energy Technology Data Exchange (ETDEWEB)

    White, L.; Knoll, J.H.M. [Harvard Medical School, Boston, MA (United States)

    1995-03-13

    In a series of 18 individuals comprising parents of Angelman syndrome (AS) patients and AS patients with large deletions, microdeletions, and no deletions, we utilized fluorescence in situ hybridization (FISH) with genomic phage clones for loci D15S63 and GABRB3 for deletion detection of chromosome 15q11-q13. Utilization of probes at these loci allows detection of common large deletions and permits discrimination of less common small deletions. In all individuals the molecular cytogenetic data were concordant with the DNA deletion analyses. FISH provides an accurate method of deletion detection for chromosome 15q11-q13. 23 refs., 2 figs., 1 tab.

  19. [A case of pervasive developmental disorder with chromosomal translocation (X; 4) (p11; q13)].

    Science.gov (United States)

    Azzoni, A; Raja, M

    2006-01-01

    Chromosomal aberrations, with or without congenital physical abnormalities, have been frequently found associated with neuropsychiatric disorders, including mental retardation, psychosis, autism, and criminal behaviour. The meaning of the association frequently remains unclear. However, consistent findings of association between specific chromosomal abnormalities and clinical phenotype may provide evidence of a causal relationship and shed light on the pathogenesis of obscure disorders. Here, we present the case of a 28 year-old, Caucasian male affected by pervasive developmental disorder, associated with chromosomal translocation 46, XY, t (X; 4) (p11; q13), and abnormal facial features. A few days after birth, the patient was taken away from his parents and adopted for unknown reasons. No information is available about his biological relatives. Mild delay in the development of spoken language was reported. Since early childhood, the patient's behaviour was characterized by troublesome relationship with his parents and his fellows, and persistent violation of norms and rules at home and at school. Consequently, social and school functioning was poor. When he was eight, verbal and motor stereotypy appeared for the first time. As an adolescent, he was more and more aggressive. He exhibited countless episodes of rage and verbal and physical aggressiveness. After he had completed secondary school, his way of life was chaotic. He got into the habit of staying away from home, sleeping in the day and vagabonding at night. He began to abuse alcohol. Grandiosity and persecutory delusions became evident. He claimed to hate the Vatican, the Pope, and the Polish people and to be the Devil, the Antichrist. He feared that his food was poisoned by his mother and refused to eat at home any more. He loved to remain in a cage with two wild dogs, accumulating and keeping bottles full of his urine. He often engaged in violent fights in the street with tramps and foreigners. Finally

  20. A 3 Mb YAC contig in the region of Usher Ib on chromosome 11q

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    Kelley, P.M.; Overbeck, L.; Weston, M. [Boys Town National Research Hospital, Omaha, NE (United States)] [and others

    1994-09-01

    Under syndrome type Ib, a recessive disorder characterized by deafness, retinitis pigmentosa, and vestibular dysfunction has been mapped to chromosome 11q13. A 3 Mb YAC contig has been constructed covering the critical region of Usher Ib and spanning over eight loci: D11S1321, D11S527, D11S533, OMP, D11S906, D11S911, D11S937, and D11S918. This contig was constructed by PCR screening using the above described DNA markers of the CEPH mega YAC library. Additional YACs were identified by data presented in the Genethon physical map. A long-range restriction map has been constructed from both YAC and genomic DNA using STS markers as probes. Cosmid libraries from a subset of YACs have been screened for the location of CpG islands. In addition, potential transcribed regions have been identified by 3{prime} exon trapping of cosmid pools and placed on the YAC physical map.

  1. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B

    1995-01-01

    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...

  2. LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ong, Danny C.T.; Rudduck, Christina; Chin, Koei; Kuo, Wen-Lin; Lie, Daniel K.H.; Chua, Constance L.M.; Wong, Chow Yin; Hong, Ga Sze; Gray, Joe; Lee, Ann S.G.

    2008-05-06

    Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We show here that LARG, from 11q23, has functional characteristics of a tumor suppressor. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, utilizing both loss of heterozygosity (LOH) analysis and microarray comparative genomic hybridization (CGH). LARG (also called ARHGEF12), identified from the analyzed region, was underexpressed in 34% of primary breast carcinomas and 80% of breast cancer cell lines including the MCF-7 line. Multiplex ligation-dependent probe amplification on 30 primary breast cancers and six breast cancer cell lines showed that LARG had the highest frequency of deletion compared to the BCSC-1 and TSLC1 genes, two known candidate tumor suppressor genes from 11q. In vitro analysis of breast cancer cell lines that underexpress LARG showed that LARG could be reactivated by trichostatin A, a histone deacetylase inhibitor, but not by 5-Aza-2{prime}-deoxycytidine, a demethylating agent. Bisulfite sequencing and quantitative high-throughput analysis of DNA methylation confirmed the lack of CpG island methylation in LARG in breast cancer. Restoration of LARG expression in MCF-7 cells by stable transfection resulted in reduced proliferation and colony formation, suggesting that LARG has functional characteristics of a tumor suppressor gene.

  3. A 5-year-old white girl with Prader-Willi syndrome and a submicroscopic deletion of chromosome 15q11q13

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    Butler, M.G. [Vanderbilt Univ. Medical Center, Nashville, TN (United States); Christian, S.L.; Kubota, T.; Ledbetter, D.H. [National Inst. of Health, Bethesda, MD (United States)

    1996-10-16

    We report on a 5-year-old white girl with Prader-Willi syndrome (PWS) and a submicroscopic deletion of 15q11q13 of approximately 100-200 kb in size. High resolution chromosome analysis was normal but fluorescence in situ hybridization (FISH), Southern hybridization, and microsatellite data from the 15q11q13 region demonstrated that the deletion was paternal in origin and included the SNRPN, PAR-5, and PAR-7 genes from the proximal to distal boundaries of the deletion segment. SNRPN and PW71B methylation studies showed an abnormal pattern consistent with the diagnosis of PWS and supported the presence of a paternal deletion of 15q11q13 or an imprinting mutation. Biparental (normal) inheritance of PW71B (D15S63 locus) and a deletion of the SNRPN gene were observed by microsatellite, quantitative Southern hybridization, and/or FISH analyses. Our patient met the diagnostic criteria for PWS, but has no reported behavior problems, hyperphagia, or hypopigmentation. Our patient further supports SNRPN and possibly other genomic sequences which are deleted as the cause of the phenotype recognized in PWS patients. 21 refs., 7 figs.

  4. Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study

    Directory of Open Access Journals (Sweden)

    Close Eimear

    2010-05-01

    Full Text Available Abstract Background Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance. The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. Methods We have evaluated six candidate genes in one of these regions (11q23, namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. Results Promotor SNPs (-607, -137 in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P Conclusion Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.

  5. Is classic pericentric inversion of chromosome 2 inv(2)(p11q13) associated with an increased risk of unbalanced chromosomes?

    Science.gov (United States)

    Ferfouri, Fatma; Clement, Patrice; Gomes, Denise Molina; Minz, Marie; Amar, Edouard; Selva, Jacqueline; Vialard, François

    2009-10-01

    To study pericentric inversion segregation and interchromosomal effect on sperm for men heterozygous for inv(2)(p11q13), to assess the risk of miscarriage. Case report. Department of reproductive biology, cytogenetics, gynecology, and obstetrics. Seven patients heterozygous for inv(2)(p11q13) and five patients with normal karyotype with experience of recurrent spontaneous miscarriage. Fluorescence in situ hybridization on sperm with 2 p and 2q subtelomeric probes to screen for inversion segregation, and X, Y, and 18 centromeric probes to study interchromosomal effects. One thousand sperm were analyzed per experiment and per patient. Rate of unbalanced chromosomes and aneuploid sperm. The inv(2)(p11q13) patients showed a 0.3% rate of sperm with unbalanced chromosomes. For interchromosomal effects, a 0.6% aneuploid sperm rate was observed for patients heterozygous for inv(2)(p11q13). This is similar to the 0.5% rate observed for control patients. Inv(2)(p11q13) seems not to increase miscarriage for couples with men heterozygous for this inversion.

  6. Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study.

    LENUS (Irish Health Repository)

    Brophy, Karen

    2010-01-01

    BACKGROUND: Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. METHODS: We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. RESULTS: Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137\\/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C\\/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. CONCLUSION: Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine\\'s role in maintaining inflammation in active CD.

  7. Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study

    LENUS (Irish Health Repository)

    Brophy, Karen

    2010-05-17

    Abstract Background Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. Methods We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. Results Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137\\/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C\\/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. Conclusion Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine\\'s role in maintaining inflammation in active CD.

  8. Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern.

    Science.gov (United States)

    Tan, Ee-Shien; Yong, Min-Hwee; Lim, Eileen Cp; Li, Zhi-Hui; Brett, Maggie Sy; Tan, Ene-Choo

    2014-01-01

    The 15q11-q13 region contains many low copy repeats and is well known for its genomic instability. Several syndromes are associated with genomic imbalance or copy-number-neutral uniparental disomy. We report on two patients: Patient 1 is a boy with developmental delay and autism; and Patient 2 is a girl with developmental delay, hypotonia and dysmorphism. We performed analyses to delineate their dosage in the 15q region, determine whether the patients' dosage correlates with phenotypic severity, and whether genes in the amplified regions are significantly associated with identified functional networks. For the proximal region of 15q, molecular cytogenetic analysis with Agilent oligonucleotide array showed a copy number of 3 for Patient 1 and a copy number of 4 for Patient 2. Fluorescent in situ hybridization analysis of Patient 2 showed two different populations of cells with different marker chromosomes. Methylation analysis of the amplified region showed that the extra copies of small nuclear ribonucleoprotein polypeptide N gene were of maternal origin. Phenotypic severity did not correlate with the size and dosage of 15q, or whether the amplification is interstitial or in the form of a supernumerary marker. Pathway analysis showed that in Patient 2, the main functional networks that are affected by the genes from the duplicated/triplicated regions are developmental disorder, neurological disease and hereditary disease. The 15q11-q13 gains that were found in both patients could explain their phenotypic presentations. This report expands the cohort of patients for which 15q11-q13 duplications are molecularly characterized.

  9. Evaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Nicholls, R.D.; Gottlieb, W.; Davda, M. (Univ. of Florida, Gainesville (United States)); Russell, L.B.; Rinchik, E.M. (Oak Ridge National Lab., TN (United States)); Horsthemke, B. (Universitatsklinikum Essen, Hufelandstrasse (Germany))

    1993-03-01

    Prader-Willi and Angelman syndromes are complex neurobehavioral contiguous gene syndromes whose expression depends on the unmasking of genomic imprinting for different genetic loci in human chromosome 15q11-q13. The homologous chromosomal region in the mouse genome has been fine-mapped by using interspecific (Mus spretus) crosses and overlapping, radiation-induced deletions to evaluate potential animal models for both imprinted and nonimprinted components of these syndromes. Four evolutionarily conserved sequences from human 15q11-q13, including two cDNAs from fetal brain (DN10, D15S12h; DN34, D15S9h-1), a microdissected clone (MN7; D15F37S1h) expressed in mouse brain, and the gene for the [beta]3 subunit of the [gamma]-aminobutyric acid type A receptor (Gabrb3), were mapped in mouse chromosome 7 by analysis of deletions at the pink-eyed dilution (p) locus. Three of these loci are deleted in pre- and postnatally lethal p-locus mutations, which extend up to 5.5 [plus minus] 1.7 centimorgans (cM) proximal to p; D15S9h-1, which maps 1.1 [plus minus] 0.8 cM distal to p and is the mouse homolog of the human gene D15S9 (which shows a DNA methylation imprint), is not deleted in any of the p-locus deletion series. A transcript from the Gabrb3 gene, but not the transcript detected by MN7 at the D15F37S1h locus, is expressed in mice homozygous for the p[sup 6H] deletion, which have an abnormal neurological phenotype. Furthermore, the Gabrb3 transcript is expressed equally well from the maternal or paternal chromosome 7 and, therefore, its expression is not imprinted in mouse brain. Deletions, at the mouse p locus should serve as intermediate genetic reagents and models with which to analyze the genetics and etiology of individual components of human 15q11-q13 disorders. 32 refs., 5 figs.

  10. Involvement of the chromosomal region 11q13 in renal oncocytoma : Case report and literature review

    NARCIS (Netherlands)

    Neuhaus, C; Dijkhuizen, T; vandenBerg, E; Storkel, S; Stockle, M; Mensch, B; Huber, C; Decker, HJ

    Renal oncocytomas comprise a cytogenetically heterogeneous group of tumors consisting potentially of cytogenetic distinguishable subgroups. Review of the literature revealed loss of chromosome 1 and Y as a possible anomaly for at least one subset of oncocytomas. The frequent finding of

  11. Towards the cloning of imprinted genes in the Prader-Willi/Angelman region of chromosome 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, M.; Sutcliffe, J.S.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct clinical phenotypes resulting from paternal and maternal deficiencies respectively in human chromosome 15q11-q13. The data suggest the presence of oppositely imprinted genes in the region, and the gene for small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) has been identified as a candidate gene for PWS. Previous strategies for positional cloning identified a number of transcripts from the PWS/AS region, and two of them, PAR-5 (D15S226E) and PAR-1 (D15S227E), are paternally expressed in cultured human cells from patients deleted for 15q11-q13 as is SNRPN. Cosmid contig maps have been developed from the following YACs (contained loci in parentheses): 307A12 (D15S13), 457B4 (SNRPN), 132D4 (D15S10), A229A2, and 378A12 (D15S113), to facilitate molecular studies of PWS and AS. Exon trapping has been employed to isolate putative exons from these overlapping cosmids. Two trapped fragments from the D15S113 region and one fragment from the SNRPN region has been isolated. Sequence information is available for all of the fragments. In addition to imprinting analysis in cultured human cells, we have developed a method to detect imprinting in mouse and human using a GC-clamped denaturing gradient gel electrophoresis strategy, in combination with reverse transcription-polymerase chain reaction. The imprinting analyses of putative exons are in progress to investigate their possible candidacy for involvement in PWS or AS phenotypes.

  12. Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1

    OpenAIRE

    Germain, Noelle D; Chen, Pin-Fang; Plocik, Alex M; Glatt-Deeley, Heather; Brown, Judith; Fink, James J; Bolduc, Kaitlyn A; Robinson, Tiwanna M; Levine, Eric S; Reiter, Lawrence T; Graveley, Brenton R; Lalande, Marc; Chamberlain, Stormy J

    2014-01-01

    Background Duplications of the chromosome 15q11-q13.1 region are associated with an estimated 1 to 3% of all autism cases, making this copy number variation (CNV) one of the most frequent chromosome abnormalities associated with autism spectrum disorder (ASD). Several genes located within the 15q11-q13.1 duplication region including ubiquitin protein ligase E3A (UBE3A), the gene disrupted in Angelman syndrome (AS), are involved in neural function and may play important roles in the neurobehav...

  13. Genetic, physical and functional analysis of the ataxia-telangiectasia locus on chromosome 11q22-23

    Energy Technology Data Exchange (ETDEWEB)

    Shiloh, Y.; Ziv, Y.; Savitski, K. [Tel Aviv Univ. (Israel)] [and others

    1994-09-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder featuring cerebellar degeneration, immunodeficiency, chromosomal instability, cancer susceptibility, and radiosensitivity. Four complementation groups have been observed in A-T. The two major groups, A and C, were localized to chromosome 11q22-23, and the other two, D and E, may map to the same chromosomal region. We developed an integrated system of positional and complementation cloning to identify the A-T gene(s). The A-T region was saturated with microsatellite markers by physically mapping markers generated at random by other labs and by identifying new polymorphic CA-repeats in YAC clones obtained from this region. According to recent linkage data based on these markers and linkage disequilibrium analysis in Moroccan Jewish A-T patients, the A-T(A) and A-T(C) mutations are contained within a 2 Mb interval between D11S1819 and D11S1960. This interval was cloned in YAC and cosmid contigs, and transcribed sequences were identified using the following methods: screening of cDNA libraries using cosmid clones; magnetic bead capture using YAC and cosmid clones; direct selection of cDNA clones using YAC clones immobilized on a solid matrix; and 3{prime} exon trapping. Preliminary results indicate that the A-T region is rich in transcribed sequences. Structural and functional analysis of these genes is being carried out by sequence analysis, by physical mapping using the cosmid contigs, and by testing their ability to complement the radiomimetic sensitivity of A-T cells.

  14. Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1

    Science.gov (United States)

    2014-01-01

    Background Duplications of the chromosome 15q11-q13.1 region are associated with an estimated 1 to 3% of all autism cases, making this copy number variation (CNV) one of the most frequent chromosome abnormalities associated with autism spectrum disorder (ASD). Several genes located within the 15q11-q13.1 duplication region including ubiquitin protein ligase E3A (UBE3A), the gene disrupted in Angelman syndrome (AS), are involved in neural function and may play important roles in the neurobehavioral phenotypes associated with chromosome 15q11-q13.1 duplication (Dup15q) syndrome. Methods We have generated induced pluripotent stem cell (iPSC) lines from five different individuals containing CNVs of 15q11-q13.1. The iPSC lines were differentiated into mature, functional neurons. Gene expression across the 15q11-q13.1 locus was compared among the five iPSC lines and corresponding iPSC-derived neurons using quantitative reverse transcription PCR (qRT-PCR). Genome-wide gene expression was compared between neurons derived from three iPSC lines using mRNA-Seq. Results Analysis of 15q11-q13.1 gene expression in neurons derived from Dup15q iPSCs reveals that gene copy number does not consistently predict expression levels in cells with interstitial duplications of 15q11-q13.1. mRNA-Seq experiments show that there is substantial overlap in the genes differentially expressed between 15q11-q13.1 deletion and duplication neurons, Finally, we demonstrate that UBE3A transcripts can be pharmacologically rescued to normal levels in iPSC-derived neurons with a 15q11-q13.1 duplication. Conclusions Chromatin structure may influence gene expression across the 15q11-q13.1 region in neurons. Genome-wide analyses suggest that common neuronal pathways may be disrupted in both the Angelman and Dup15q syndromes. These data demonstrate that our disease-specific stem cell models provide a new tool to decipher the underlying cellular and genetic disease mechanisms of ASD and may also offer a

  15. Submicroscopic interstitial deletion of chromosome 11q22.3 in a girl with mild mental retardation and facial dysmorphism: Case report

    Directory of Open Access Journals (Sweden)

    Zagorac Andreja

    2011-08-01

    Full Text Available Abstract Background Except for terminal deletions that lead to Jacobsen syndrome, interstitial deletions involving the long arm of chromosome 11 are not frequently reported. A clinically distinct phenotype is usually observed in these cases, and no clear genotype-phenotype correlation is proposed. Results Here we present a case study of a 5-year-old girl with de novo submicroscopic deletion of chromosome 11q22.3 with mild mental retardation and facial dysmorphism. A standard cytogenetic analysis did not reveal any structural aberrations. In contrary, array-CGH analysis indicated a small deletion of 11q22.3. Discussion To our knowledge, this is the smallest 11q22.3 deletion reported in literature, containing nine RefSeq genes. Although none of the deleted genes are obvious candidates for the features observed in our patient, genes CUL5 and SLN could play a key role in the features described.

  16. Chromosome 11q13.5 variant associated with childhood eczema: an effect supplementary to filaggrin mutations.

    LENUS (Irish Health Repository)

    O'Regan, Grainne M

    2012-02-01

    BACKGROUND: Atopic eczema is a common inflammatory skin disease with multifactorial etiology. The genetic basis is incompletely understood; however, loss of function mutations in the filaggrin gene (FLG) are the most significant and widely replicated genetic risk factor reported to date. The first genome-wide association study in atopic eczema recently identified 2 novel genetic variants in association with eczema susceptibility: a single nucleotide polymorphism on chromosome 11q13.5 (rs7927894) and a single nucleotide polymorphism (rs877776) within the gene encoding hornerin on chromosome 1q21. OBJECTIVE: To test the association of these 2 novel variants with pediatric eczema and to investigate their interaction with FLG null mutations. METHODS: Case-control study to investigate the association of rs7927894, rs877776 and the 4 most prevalent FLG null mutations with moderate-severe eczema in 511 Irish pediatric cases and 1000 Irish controls. Comprehensive testing for interaction between each of the loci was also performed. RESULTS: The association between rs7927894 and atopic eczema was replicated in this population (P = .0025, chi(2) test; odds ratio, 1.27; 95% CI, 1.09-1.49). The 4 most common FLG null variants were strongly associated with atopic eczema (P = 1.26 x 10(-50); combined odds ratio, 5.81; 95% CI, 4.51-7.49). Interestingly, the rs7927894 association was independent of the well-established FLG risk alleles and may be multiplicative in its effect. There was no significant association between rs877776 and pediatric eczema in this study. CONCLUSION: Single nucleotide polymorphism rs7927894 appears to mark a genuine eczema susceptibility locus that will require further elucidation through fine mapping and functional analysis.

  17. Physical linkage of the fragile site FRA11B and a Jacobsen syndrome chromosome deletion breakpoint in 11q23.3.

    Science.gov (United States)

    Jones, C; Slijepcevic, P; Marsh, S; Baker, E; Langdon, W Y; Richards, R I; Tunnacliffe, A

    1994-12-01

    Autosomal fragile sites, unlike their X-linked counterparts, are not known to be associated with disease. However, one case report has highlighted a possible relationship between the inheritance of a rare folate-sensitive fragile site in band 11q23.3 (FRA11B) and the chromosome 11q23-->qter deletion in Jacobsen (11q-) syndrome. The mother and brother of the reported Jacobsen syndrome child are FRA11B carriers, suggesting that in vivo breakage at the fragile site during early development could have given rise to the chromosome deletion. We have tested this hypothesis by high resolution physical mapping of FRA11B and of the deletion chromosome breakpoint in the Jacobsen syndrome patient. A detailed restriction map of 600 kb of human chromosome band 11q23.3 has been assembled which covers the PBGD, CBL2 and THY1 genes. FISH experiments with YACs and cosmids from this region have localised FRA11B to an interval of approximately 100 kb containing the 5' end of the CBL2 gene, which includes a CCG trinucleotide repeat. This class of repeat is expanded in the four cloned examples of fragile site and therefore the CBL2 repeat is a candidate for the location of FRA11B. Further, it is shown that the chromosomal deletion breakpoint of the Jacobsen syndrome child maps within the same interval as the fragile site. The breakpoint has apparently been repaired and stabilised by the de novo addition of a telomere. These data are consistent with a role for an inherited fragile site in the aetiology of a chromosome deletion syndrome.

  18. Complex Mosaic Ring Chromosome 11 Associated with Hemizygous Loss of 8.6 Mb of 11q24.2qter in Atypical Jacobsen Syndrome.

    Science.gov (United States)

    Galvão Gomes, Alexandra; Paiva Grangeiro, Carlos H; Silva, Luiz R; Oliveira-Gennaro, Flávia G; Pereira, Ciro S; Joaquim, Tatiana M; Panepucci, Rodrigo A; Squire, Jeremy A; Martelli, Lucia

    2017-01-01

    Jacobsen syndrome (JBS) is a contiguous gene deletion syndrome involving terminal chromosome 11q. The haploinsufficiency of multiple genes contributes to the overall clinical phenotype, which can include the variant Paris-Trousseau syndrome, a transient thrombocytopenia related to FLI1 hemizygous deletion. We investigated a boy with features of JBS using classic cytogenetic methods, FISH and high-resolution array CGH. The proband was found to have a mosaic ring chromosome 11 resulting in a hemizygous 11q terminal deletion of 8.6 Mb, leading to a copy number loss of 52 genes. The patient had a hemizygous deletion in the FLI1 gene region without apparent thrombocytopenia, and he developed diabetes mellitus type I, which has not previously been described in the spectrum of disorders associated with JBS. The relationship of some of the genes within the context of the phenotype caused by a partial deletion of 11q has provided insights concerning the developmental anomalies presented in this patient with atypical features of JBS.

  19. Localization of the human phosphatidylinositol-specific phospholipase C {beta}{sub 3} gene (PLCB3) within chromosome band 11q13

    Energy Technology Data Exchange (ETDEWEB)

    Sinke, R.J.; Geurts Van Kessel, A. [Univ. Hospital Nijmegen (Netherlands)

    1995-01-20

    In course of the molecular characterization of a human extragonadal germ cell tumor (EGCT)-associated chromosomal translocation, we identified YACs and cosmids from the 11q13 region. The endclone of one of these YACs appeared to contain a stretch of DNA homologous to part of the human phosphatidylinositol-specific phospholipase C {Beta}{sub 3} gene (PLCB3). Since we considered PLCB3 a candidate gene for these EGCTs, we set out to clone the PLCB3 cDNA, from which the 5{prime} end was still missing, and performed Northern and Southern blot analyses. The localization of PLCB3 to 11q13 was confirmed. In addition, we were able to exclude the gene from involvement in EGCT development. 10 refs., 2 figs.

  20. The analysis of a large Danish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 11q24

    DEFF Research Database (Denmark)

    Rudkjøbing, Laura Aviaja; Eiberg, Hans; Mikkelsen, Hanne Birte

    2015-01-01

    benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family....... Major rearrangements were excluded after karyotyping. The linkage analysis with SNP6 data revealed three candidate areas, on chromosome 2, 6 and 11 respectively, with a LOD score close to two and no negative LOD scores. After extended linkage analysis, the area on chromosome 6 was excluded, leaving...... areas on chromosome 2 and chromosome 11 with the highest possible LOD scores of 2.6. Two other studies have identified 11q24 as a candidate area for colorectal cancer susceptibility and this area is supported by our results....

  1. New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22(q34;p11;q11

    Directory of Open Access Journals (Sweden)

    Abdeljabar El Andaloussi

    2007-01-01

    Full Text Available A Chronic myeloid leukaemia (CML case with a new complex t(9;18;22(q34;p11;q11 of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH. In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.

  2. Prenatal diagnosis of Prader-Willi syndrome and Angelman syndrome for fetuses with suspicious deletion of chromosomal region 15q11-q13.

    Science.gov (United States)

    Chang, Chia-Wei; Hsu, Hui-Kuo; Kao, Chiu-Ching; Huang, Jyun-Yuan; Kuo, Pao-Lin

    2014-04-01

    To identify Prader-Willi syndrome (PWS) and Angelman syndrome (AS) among fetuses with suspicious deletion of the chromosomal region 15q11-q13. In a retrospective study, data were assessed from fetuses missing chromosomal band 15q12 that underwent molecular diagnosis at the National Chen-Kung University Hospital, Tainan, Taiwan, between January 2001 and December 2012. Amniocytes were subjected to molecular testing, including fluorescence in situ hybridization (FISH) analysis, methylation-specific PCR (M-PCR), and methylation-specific multiplex-ligation-dependent probe amplification (MS-MLPA). During the 12-year study period, 26 041 amniocyte samples were analyzed at the study center and 27 (0.1%) were found to have a missing 15q12 band. A further 16 samples with a missing 15q12 band were received from other cytogenetic laboratories; as a result, 43 amniocyte samples lacking chromosomal band 15q12 underwent further molecular testing. Among these samples, 3 fetuses (7.0%) were found to have PWS (n=1) or AS (n=2). A minority of cases with missing 15q12 had deletion of the PWS/AS critical region. This finding draws attention to the subtle structural rearrangements that occur on 15q11-q13 and provides useful information for prenatal diagnosis of PWS and AS. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  3. The Human HNP36 Gene Is Localized to Chromosome 11q13 and Produces Alternative Transcripts That Are Not Mutated in Multiple Endocrine Neoplasia, Type 1 (MEN I) Syndrome

    National Research Council Canada - National Science Library

    Williams, John B; Rexer, Brent; Sirripurapu, Sarada; John, Sutha; Goldstein, Richard; Phillips, John A; Haley, Linda L; Sait, Shiela N.J; Shows, Thomas B; Smith, Carissa M; Gerhard, Daniela S

    1997-01-01

    Multiple endocrine neoplasia, type 1 (MEN I), is an autosomal dominant syndrome of selected endocrine neoplasms whose causative gene, a suspected tumor suppressor, has been localized to chromosome 11q13, but has not been identified...

  4. Prenatal diagnosis of terminal 11q deletion

    OpenAIRE

    Simão, Laurentino; Brito, Filomena; Silva, Marisa; Marques, Bárbara; Furtado, José; Ventura, Catarina; Caetano, Paula; Dias, Ivone; Correia, Hildeberto

    2011-01-01

    The majority of 11q deletion cases described may be included in the “distal 11q deletion syndrome”, or Jacobsen syndrome. This is a rare but clinically recognizable condition with an incidence of 1/ 100,000 births. The most common clinical features are psychomotor delay, characteristic facial dysmorphism and malformations of the heart, kidney, genitalia, central nervous system and skeleton. Patients usually have visible deletions of chromosomal bands 11q23, 11q24, and/or 11q25. Approximately ...

  5. Haplotype analysis of DNA microsatellites tightly linked to the locus of Usher syndrome type I on chromosome 11q

    Energy Technology Data Exchange (ETDEWEB)

    Korostishevsky, M.; Kalinsky, H.; Seroussi, E. [Sackler Faculty of Medicine, Ramat-Aviv (Israel)] [and other

    1994-09-01

    Usher syndrome type I (USHI), an autosomal recessive disorder associated with congenital sensorineural deafness and progressive visual loss, is closely linked to the D11S533 locus. The availability of 7 other polymorphic markers within few centimorgans spanning the disease locus allowed us to identify a unique and single haplotype among all carriers of USHI gene in the Samaritan kindred. Occurrence of recombination in this small chromosomal interval is rare, hindering the detection of the mitotic recombination events needed for analysis by traditional linkage methods. Attempts to order the eight loci by linkage disequilibrium models proved to be problematic. However, our haplotype analysis implied that recombinations which had arisen in past generations may be utilized in fine mapping of the USHI gene and in resolving the conflicting linkage maps previously obtained for this region. We have developed a simple algorithm for predicting the order of the microsatellites on the basis of haplotype resemblance. The following chromosomal map in which the USHI gene is closest to D11S533 (location score of 31.0 by multipoint analysis) is suggested: D11S916, GARP, D11S527, D11S533, OMP, D11S906, D11S911, D11S937. Physical mapping efforts are currently directed to verify and to detail the map of this chromosomal region.

  6. A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    José Ángel Hernández

    Full Text Available To analyze the impact of the 11q deleted (11q- cells in CLL patients on the time to first therapy (TFT and overall survival (OS, 2,493 patients with CLL were studied. 242 patients (9.7% had 11q-. Fluorescence in situ hybridization (FISH studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ≥40% of losses in 11q (11q-H (74%, the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q (11q-L (P<0.0001. In the multivariate analysis, only the presence of 11q-L, mutated IGHV status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached (P = 0.008. The absence of splenomegaly (P = 0.02, low LDH (P = 0.018 or β2M (P = 0.006, and the presence of 11q-L (P = 0.003 were associated with a longer OS. In addition, to detect the presence of mutations in the ATM, TP53, NOTCH1, SF3B1, MYD88, FBXW7, XPO1 and BIRC3 genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q- showed mutations and fewer patients with low frequencies of 11q- had mutations among genes examined (50% vs 94.1%, P = 0.023. In summary, CLL patients with <40% of 11q- had a long TFT and OS that could be associated with the presence of fewer mutated genes.

  7. A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene

    Energy Technology Data Exchange (ETDEWEB)

    Mutirangura, A.; Jayakumar, A.; Sutcliffe, J.S.; Nakao, M.; McKinney, M.J.; Beaudet, A.L.; Chinault, A.C.; Ledbetter, D.H. (Baylor College of Medicine, Houston, TX (United States)); Buiting, K.; Horsthemke, B. (Institut fur Humangenetik (Germany))

    1993-12-01

    Since a previous report of a partial YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13), a complete contig spanning approximately 3.5 Mb has been developed. YACs were isolated from two human genomic libraries by PCR and hybridization screening methods. Twenty-three sequence-tagged sites (STSs) were mapped within the contig, a density of [approximately]1 per 200 kb. Overlaps between YAC clones were identified by Alu-PCR dot-blot analysis and confirmed by STS mapping or hybridization with ends of YAC inserts. The gene encoding small nuclear ribonucleoprotein-associated peptide N (SNRPN), recently identified as a candidate gene for Prader-Willi syndrome, was localized within this contig between markers PW71 and TD3-21. Loci mapped within and immediately flanking the Prader-Willi/Angelman chromosome region contig are ordered as follows: cen-IR39-ML34-IR4-3R-TD189-1-PW71-SNRPN-TD3-21-LS6-1-GABRB3,D15S97-GABRA5-IR10-1-CMW1-tel. This YAC contig will be a useful resource for more detailed physical mapping of the region, for generation of new DNA markers, and for mapping or cloning candidate genes for the Prader-Willi and Angelman syndromes. 36 refs., 2 figs., 2 tabs.

  8. Isolation and characterization of a novel gene close to the human phosphoinositide-specific phospholipase C {beta}3 gene on chromosomal region 11q13

    Energy Technology Data Exchange (ETDEWEB)

    Lagercrantz, J.; Carson, E.; Larsson, C. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1996-02-01

    We describe the isolation, characterization, and genomic structure of a gene, Phospholipase C {beta}3 Neighboring gene (PNG), located on chromosome 11q13. The cDNA was isolated using a cosmid that also contains the phospholipase C{beta}3 gene (PLCB3). PNG does not have any marked similarity to other known genes on the DNA level. However, analysis of hybridization to a panel of somatic cell hybrids indicates the existence of related sequences on chromosomes 2, 4, 7, and 22. PNG showed expression of a 1-kb message in multiple tissues. The predicted protein is 199 amino acids. The gene spans approximately 2.5 kb, divided into four exons and three introns. It is located 4.4 kb upstream of PLCB3, with the 5{prime} ends facing each other. The intergenic region has been completely sequenced, revealing separate CpG islands at both ends of this region. The islands are separated by a stretch of 2 kb, characterized by periodic alteration of the GC content. The 5{prime}-flanking region of PNG does not contain TATA or CCAAT, suggesting a housekeeping promoter structure. 22 refs., 4 figs., 1 tab.

  9. A genomewide exploration suggests a new candidate gene at chromosome 11q23 as the major determinant of plasma homocysteine levels: results from the GAIT project.

    Science.gov (United States)

    Souto, Juan Carlos; Blanco-Vaca, Francisco; Soria, José Manuel; Buil, Alfonso; Almasy, Laura; Ordoñez-Llanos, Jordi; Martín-Campos, Jesús Ma; Lathrop, Mark; Stone, William; Blangero, John; Fontcuberta, Jordi

    2005-06-01

    Homocysteine (Hcy) plasma level is an independent risk marker for venous thrombosis, myocardial infarction, stroke, congestive heart failure, osteoporotic fractures, and Alzheimer disease. Hcy levels are determined by the interaction of genetic and environmental factors. The genetic basis is still poorly understood, since only the MTHFR 677 C-->T polymorphism has been consistently associated with plasma Hcy levels. We conducted a genomewide linkage scan for genes affecting variation in plasma Hcy levels in 398 subjects from 21 extended Spanish families. A variance-components linkage method was used to analyze the data. The strongest linkage signal (LOD score of 3.01; genomewide P = .035) was found on chromosome 11q23, near marker D11S908, where a candidate gene involved in the metabolism of Hcy (the nicotinamide N-methyltransferase gene [NNMT]) is mapped. Haplotype analyses of 10 single-nucleotide polymorphisms within this gene found one haplotype associated with plasma Hcy levels (P = .0003). Our results, to our knowledge, represent the first genomic scan for quantitative variation in Hcy plasma levels. They strongly suggest that the NNMT gene could be a major genetic determinant of plasma Hcy levels in Spanish families. Since this gene encodes an enzyme involved in Hcy synthesis, this finding would be consistent with known biochemical pathways. These data could be relevant in determining the relationships between Hcy level, cardiovascular disease, osteoporosis, and Alzheimer disease.

  10. The human [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster in chromosome 15q11-q13 is rich in highly polymorphic (CA)[sub n] repeats

    Energy Technology Data Exchange (ETDEWEB)

    Glatt, K.; Lalande, M. (Howard Hughes Medical Institute, Boston, MA (United States)); Sinnett, D. (Harvard Medical School, Boston, MA (United States))

    1994-01-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptor [beta]33 (GABRB3) and [alpha]5 (GABRA5) subunit genes have been localized to the Angelman and Prader-Willi syndrome region of chromosome 15q11-q13. GABRB3, which encompasses 250 kb, is located 100 kb proximal of GABRA5, with the two genes arranged in head-to-head transcriptional orientation. In screening 135 kb of cloned DNA within a 260-kb interval extending from within GABRB3 to the 5[prime] end of GABRA5, 10 new (CA), repeats have been identified. Five of these have been analyzed in detail and found to be highly polymorphic, with the polymorphism information content (PIC) ranging from 0.7 to 0.85 and with heterozygosities of 67 to 94%. In the clones from GABRB3/GABRA5 region, therefore, the frequency of (CA)[sub n] with PICs [ge] 0.7 is 1 per 27 kb. Previous estimates of the density of (CA)[sub n] with PICs [ge] 0.7 in the human genome have been approximately 10-fold lower. The GABRB3/GABRA5 region appears, therefore, to be enriched for highly informative (CA)[sub n]. This set of closely spaced, short tandem repeat polymorphisms will be useful in the molecular analyses of Prader-Willi and Angelman syndromes and in high-resolution studies of genetic recombination within this region. 21 refs., 2 figs., 1 tab.

  11. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids

    Energy Technology Data Exchange (ETDEWEB)

    Kedda, M.A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M. (South African Institute for Medical Research, Johannesburg (South Africa) Univ. of Witwatersrand, Johannesburg (South Africa))

    1994-06-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid [open quotes]ty-pos OCA[close quotes] individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and [open quotes]normal[close quotes] chromosomes. No haplotype showed statistically significant association with ty-pos OCA, and thus none could be used to predict the origins of the ty-pos OCA mutations. On the basis of the D15S12 results, there is evidence for multiple ty-pos OCA mutations in southern African negroids. 31 refs., 1 fig., 3 tabs.

  12. Coexistence of neuroblastoma and ganglioneuroma in a girl with a hemizygous deletion of chromosome 11q14.1-23.3.

    Science.gov (United States)

    Shiohama, Tadashi; Fujii, Katsunori; Hino, Moeko; Shimizu, Kenji; Ohashi, Hirofumi; Kambe, Michiyo; Nakatani, Yukio; Mitsunaga, Tetsuya; Yoshida, Hideo; Ochiai, Hidemasa; Shimojo, Naoki

    2016-02-01

    Constitutional 11q interstitial deletion syndrome presents with congenital anomalies including microcephaly with craniostenosis, minor dysmorphic features, vitreoretinopathy, and renal anomalies. This syndrome is occasionally associated with neuroblastoma (NB) as a life-threatening complication, which is important for clinical care. Although the corresponding locus to NB has been predicted to exist in 11q22-23 by previous deletion studies related to NB, the causative haploinsufficient genes have not yet been identified. We herein reported for the first time the simultaneous coexistence of adrenal NB and abdominal prevertebral ganglioneuroma in a 6-year-old girl with a constitutional hemizygous 11q14.1-23.3 deletion. Of the 11 haploinsufficient genes predicted with an in silico database, we focused on NCAM1 and CADM1 as the genes accountable for NB and ganglioneuroma. The deletion range, especially the 11q22.3 involvement, needs to be determined in 11q deletion cases in order to predict susceptibility to peripheral nerve tumors involving NB and ganglioneuroma. © 2015 Wiley Periodicals, Inc.

  13. Chromosomal microarray mapping suggests a role for BSX and Neurogranin in neurocognitive and behavioral defects in the 11q terminal deletion disorder (Jacobsen syndrome).

    Science.gov (United States)

    Coldren, C D; Lai, Z; Shragg, P; Rossi, E; Glidewell, S C; Zuffardi, O; Mattina, T; Ivy, D D; Curfs, L M; Mattson, S N; Riley, E P; Treier, M; Grossfeld, P D

    2009-04-01

    We performed a prospective analysis on 14 11q- patients to determine the relationship between the degree of cognitive impairment and relative deletion size. Seventeen measures of cognitive function were assessed. All nine patients with a deletion of at least 12.1 Mb had severe global cognitive impairment, with full-scale IQ deletions, deletions (11.4, 11.8 Mb) had a selective impairment in freedom from distractability compared to the three patients with smaller deletions (11q that when deleted, cause global and selective deficits in neurocognitive function. These findings have important implications for genetic counseling and potential gene-specific therapies.

  14. A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides.

    Directory of Open Access Journals (Sweden)

    Timothy R Braun

    Full Text Available Recent genome-wide association scans (GWAS and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD. In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638 in our Asian Indian cohort from the Sikh Diabetes Study (SDS comprising 3,781 individuals (2,902 from Punjab and 879 from the US. Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C (p = 2.03×10(-26. Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037 from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG levels in this Asian Indian cohort (rs964184: p = 1.74×10(-17; rs12286037: p = 1.58×10(-2. We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP (UK and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10(-39. Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG and, consequently, diabetes and CAD.

  15. Molecular characterization of complex chromosomal rearrangement: first report of novel t(7;12) (q11;q22) as part of a complex karyotype in de novo AML-M2 case.

    Science.gov (United States)

    Ahmad, Firoz; Dalvi, Rupa; Mandava, Swarna; Das, Bibhu R

    2014-12-01

    The strong association of diagnostic karyotype with clinical outcome has made cytogenetics one of the most valuable diagnostic and prognostic tools for acute myeloid leukemia (AML) till today. Complex chromosomal findings are reported to be seen in nearly 10-15% of adult AMLs and are generally associated with poor outcome. In the current report, we present the results of hematologic, immunophenotypic, cytogenetic, chromosomal microarray and molecular analyses of a 60-year-old female patient diagnosed with AML-M2. Cytogenetic analysis revealed complex chromosomal findings involving seven different chromosomes. However, cytogenetic analyses were not able to precisely unveil all karyotypic changes, hence chromosomal microarray was used for further characterization. The most interesting observation was identification of a t(7;12) (q11;q22) as part of this complex karyotype. To the best of our knowledge, this is the first report of identification of novel t(7;12) (q11;q22) as part of a complex karyotype in de novo AML-M2. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

    Science.gov (United States)

    Rice, Terri; Zheng, Shichun; Decker, Paul A; Walsh, Kyle M; Bracci, Paige; Xiao, Yuanyuan; McCoy, Lucie S; Smirnov, Ivan; Patoka, Joseph S; Hansen, Helen M; Hsuang, George; Wiemels, Joe L; Tihan, Tarik; Pico, Alexander R; Prados, Michael D; Chang, Susan M; Berger, Mitchel S; Caron, Alissa; Fink, Stephanie; Kollmeyer, Thomas; Rynearson, Amanda; Voss, Jesse; Kosel, Matthew L; Fridley, Brooke L; Lachance, Daniel H; Eckel-Passow, Jeanette E; Sicotte, Hugues; O'Neill, Brian Patrick; Giannini, Caterina; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2013-05-01

    Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas. We tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele. The 11q23 glioma risk locus was associated with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29-1.74; P = 1.3X10(-7)) but not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81-1.03; P = 0.14). The associations were independent of the rs55705857 G allele. A variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology.

  17. Chromosome segregation in a man heterozygous for a pericentric inversion, inv(9)(p11q13), analyzed by using sperm karyotyping and two-color fluorescence in situ hybridization on sperm nuclei.

    Science.gov (United States)

    Colls, P; Blanco, J; Martínez-Pasarell, O; Vidal, F; Egozcue, J; Márquez, C; Guitart, M; Templado, C

    1997-06-01

    Analysis of sperm karyotypes and two-color fluorescent in situ hybridization (FISH) on sperm nuclei were carried out in a man heterozygous for the pericentric inversion inv(9)(p11q13). Sperm chromosome complements were obtained after in vitro fusion of zona-free hamster oocytes and donor sperm. A total of 314 sperm complements was analyzed: 153 (48.7%) carried the inverted chromosome 9 and 161 (51.3%) carried the normal one. None of the sperm complements contained a recombinant chromosome 9, suggesting that no chiasmata were formed in the heterochromatic region. The frequency of structural chromosome aberrations unrelated to the inversion (8.3%) and the frequency of conservative aneuploidy (3.2%) were within the limits observed in our control donors. The proportions of X-bearing (47.3%) and Y-bearing sperm (52.7%) were not significantly different from the expected 1:1 ratio. The percentage of disomy for chromosome 21 was analyzed by two-color FISH in 10336 sperm nuclei. The disomy rate for chromosome 21 (0.30%) was not significantly different from that found in our controls. These results suggest that the risk for this man of producing chromosomally abnormal offspring or spontaneous abortions was not increased, and do not support the existence of an interchromosomal effect for chromosome 21.

  18. A new case of de novo 11q duplication in a patient with normal development and intelligence and review of the literature.

    Science.gov (United States)

    Zarate, Yuri A; Kogan, Jillene M; Schorry, Elizabeth K; Smolarek, Teresa A; Hopkin, Robert J

    2007-02-01

    A new case of 11q interstitial duplication is reported in a patient with mild dysmorphic features but normal development. Chromosome analysis revealed a de novo 11q dup(11)(q14.1q21) on G banding and FISH studies. Additional molecular genetic studies revealed a similar but more distal duplication at the level of 11q21q23.1. Previous cases of isolated 11q duplication that overlapped with this case were associated with a wide variety of clinical findings and variable developmental disability. These cases all included additional material not duplicated in this patient. The current case represents the first de novo case of 11q duplication with normal development suggesting that the segment between 11q14.1 and 11q21 contains few genes that are dose sensitive. Review of other cases that have used conventional cytogenetic resolution studies suggests that the band 11q13.5 may contain genes contributing to the developmental disabilities in the cases previously reported with proximal 11q duplication. Differences between conventional cytogenetic techniques and newer molecular genetic studies are expected. These newer techniques will help refine prognosis and counseling for families in the future. (c) 2007 Wiley-Liss, Inc.

  19. 11q-syndrome : Three cases and a review of the literature

    NARCIS (Netherlands)

    Leegte, B; Kerstjens-Frederikse, WS; Deelstra, K; Begeer, JH; Van Essen, AJ

    1999-01-01

    11q-syndrome: three cases and a review of the literature: We report on three children with de novo terminal deletions of the long arm of chromosome 11 (11q-) and breakpoints in 11q23-q24. Eighty-nine other patients with partial monosomy 11q have been reported and were reviewed by us. Salient

  20. CHROMOSOMAL CHANGES IN RENAL ONCOCYTOMAS - EVIDENCE THAT T(5-11)(Q35-Q13) MAY CHARACTERIZE A 2ND SUBGROUP OF ONCOCYTOMAS

    NARCIS (Netherlands)

    VANDENBERG, E; DIJKHUIZEN, T; STORKEL, S; DELARIVIERE, GB; MENSINK, HJA; OOSTERHUIS, JW; DEJONG, B; Dam, A.

    Many of the reported oncocytomas have different chromosome abnormalities, indicating that they comprise a cytogenetically heterogenous group of tumors consisting of potentially cytogenetic subgroups. We have performed cytogenetic studies on nine renal oncocytomas. Clonal abnormalities were present

  1. Alterations of ATM and CADM1 in chromosomal 11q22.3-23.2 region are associated with the development of invasive cervical carcinoma.

    Science.gov (United States)

    Mazumder Indra, Dipanjana; Mitra, Sraboni; Roy, Anup; Mondal, Ranajit Kumar; Basu, Partha Sarathi; Roychoudhury, Susanta; Chakravarty, Runu; Panda, Chinmay Kumar

    2011-12-01

    To understand the importance of chr11q22.3-23.2 region in the development of cervical cancer, we have studied the genetic and epigenetic alterations of the candidate genes ATM, PPP2R1B, SDHD and CADM1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CACX) samples. Our study revealed low expression and high alterations (methylation/deletion) (55-59%) of ATM and CADM1 genes along with poor patient outcome. The alterations of ATM and CADM1 are associated with the progression of tumor from CIN to Stage I/II, thus implying their role in early invasiveness. The two genes, PPP2R1B and SDHD, lying in between ATM and CADM1, have low frequency of alterations, and majority of the alterations are in CACX samples, indicating that their alterations might be associated with disease progression. Expressions (mRNA/protein) of the genes showed concordance with their molecular alterations. Significant co-alteration of ATM and CADM1 points to their synergic action for the development of CACX. Mutation is, however, a rare phenomenon for inactivation of ATM. Association between the alteration of ATM and CHEK1 and poor survival of the patients having co-alterations of ATM and CHEK1 points to the DNA damage response pathway disruption in development of CACX. Thus, our data suggest that inactivation of ATM-CHEK1-associated DNA damage response pathway and CADM1-associated signaling network might have an important role in the development of CACX.

  2. Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

    Directory of Open Access Journals (Sweden)

    Grabe Hans

    2010-06-01

    Full Text Available Abstract Background Obsessive-compulsive disorder (OCD is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome, suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients. Methods We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA. Results No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients. Conclusions Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.

  3. High-resolution mapping of the [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Sinnett, D.; Wagstaff, J.; Woolf, E. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)); Glatt, K. (Children' s Hospital, Boston, MA (United States)); Kirkness, E.J. (National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States))Lalande, M. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Inst., Boston, MA (United States))

    1993-06-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptors are a family of ligand-gated chloride channels constituting the major inhibitory neurotransmitter receptors in the nervous system. In order to determine the genomic organization of the GABA[sub A] receptor [beta]3 subunit gene (GABRB3) and [alpha]5 subunit gene (GABRA5) in chromosome 15q11-q13, the authors have constructed a high-resolution physical map using the combined techniques of field-inversion gel electrophoresis and phage genomic library screening. This map, which covers nearly 1.0 Mb, shows that GABRB3 and GABRA5 are separated by less than 100 kb and are arranged in a head-to-head configuration. GABRB3 encompasses approximately 250 kb, while GABRA5 is contained within 70 kb. This difference in size is due in large part to an intron of 150 kb within GABRB3. The authors have also identified seven putative CpG islands within a 600-kb interval. Chromosomal rearrangement breakpoints -- in one Angelman syndrome (AS) patient with an unbalanced translocation and in another patient with a submicroscopic deletion -- are located within the large GABRB3 intron. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the DNA rearrangements in these AS patients and will be valuable for mapping new genes to the AS chromosomal region. 64 refs., 6 figs., 2 tabs.

  4. Physical mapping studies at D15S10: Implications for candidate gene identification in the Angelman syndrome/Prader-Willi syndrome chromosome region of 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Woodage, T.; Lindeman, R.; Deng, Z.M.; Fimmel, A.; Trent, R.J. (Royal Prince Alfred Hospital, New South Wales (Australia)); Smith, A. (Children' s Hospital, New South Wales (Australia))

    1994-01-01

    The Angelman syndrome (AS) and Prader-Willi syndrome (PWS) loci have been mapped to chromosome 15q11-q13. Chromosomal deletions of differing parental origin in the two syndromes have been interpreted as being due to genetic imprinting. Molecular analysis of patients with varying deletions has localized the AS locus to the interval between D15S113 and GABRB3 and the PWS locus between D15S13 and D15S113. In the present study, DNA cloning and physical mapping techniques have been used to characterize the AS/PWS chromosome region in the vicinity of D15S10, a locus that is telomeric to D15S113 and centromeric to GABRB3. A CpG island near TD3-21 at D15S10 has been cloned, allowing the identification of a widely expressed 4.5-kb transcript and providing a novel DNA marker, OP3, at this locus. OP3 and TD3-21 have been used to construct a long-range physical map extending over approximately 2800 kb. Clusters of rare-cutting restriction sites on this map locate four other CpG islands. Since these CpG islands lie within the minimum deletion intervals for AS and PWS, they mark the possible locations of candidate genes for the two syndromes. 13 refs., 2 figs.

  5. The coding region of TP53INP2, a gene expressed in the developing nervous system, is not altered in a family with autosomal recessive non-progressive infantile ataxia on chromosome 20q11-q13.

    Science.gov (United States)

    Bennetts, Jennifer S; Rendtorff, Nanna D; Simpson, Fiona; Tranebjaerg, Lisbeth; Wicking, Carol

    2007-03-01

    The locus for autosomal recessive infantile cerebellar ataxia (CLA3 or SCAR6) has been mapped to chromosome 20q11-q13 in a single Norwegian pedigree. We identified a relatively uncharacterised mouse gene Tp53inp2, and showed that its human orthologue mapped within this candidate interval. Tp53inp2 appears to encode a mammalian-specific protein with homology to the two Tp53inp1 isoforms that respond to cellular stress and interact with p53. We show that Tp53inp2 expression is highly restricted during mouse embryogenesis, with strong expression in the developing brain and spinal cord, as well as in the sensory and motor neuron tracts of the peripheral nervous system. Given this expression pattern, the neurological phenotype of CLA3 and the chromosomal localisation of TP53INP2, we searched the coding region for mutations in samples from individuals from the CLA3 pedigree. Our failure to detect causative mutations suggests that alterations in the coding region of TP53INP2 are not responsible for ataxia in this family, although we cannot rule out changes in non-coding elements of this gene.

  6. 'Deletion rescue' by mitotic 11q uniparental disomy in a family with recurrence of 11q deletion Jacobsen syndrome.

    Science.gov (United States)

    Johnson, J P; Haag, M; Beischel, L; McCann, C; Phillips, S; Tunby, M; Hansen, J; Schwanke, C; Reynolds, J F

    2014-04-01

    We describe a family with recurrent 11q23-qter deletion Jacobsen syndrome in two affected brothers, with unique mosaic deletion 'rescue' through development of uniparental disomy (UPD) in the mother and one of the brothers. Inheritance studies show that the deleted chromosome is of maternal origin in both boys, and microarray shows a break near the ASAM gene. Parental lymphocyte chromosomes were normal. However, the mother is homozygous in lymphocytes for all loci within the deleted region in her sons, and presumably has UPD for this region. In addition, she is mosaic for the 11q deletion seen in her sons at a level of 20-30% in skin fibroblasts. We hypothesize that one of her #11 chromosomes shows fragility, that breakage at 11q23 occurred with telomeric loss in some cells, but 'rescue' from the deletion occurred in most cells by the development of mitotic UPD. She apparently carries the 11q deletion in her germ line resulting in recurrence of the syndrome. The older son is mosaic for the 11q cell line (70-88%, remainder 46,XY), and segmental UPD11 'rescue' apparently also occurred in his cytogenetically normal cells. This is a novel phenomenon restoring disomy to an individual with a chromosomal deletion. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. A familial pericentric inversion of chromosome 11 associated with a microdeletion of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or eye anomalies.

    Science.gov (United States)

    Balay, Lara; Totten, Ellen; Okada, Luna; Zell, Sidney; Ticho, Benjamin; Israel, Jeannette; Kogan, Jillene

    2016-01-01

    Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L, and ELP4 are previously reported to have downstream transcriptional effects on the expression of PAX6, due to a downstream regulatory region (DRR). Currently, no clear genotype-phenotype correlations have been established allowing for conclusive information regarding the exact location of the PAX6 DRR, though its location has been approximated in mouse models to be within the Elp4 gene. Of the clinical reports currently published examining patients with intact PAX6 genes but harboring deletions identified in genes downstream of PAX6, 100% indicate phenotypes which include aniridia, whereas approximately half report additional eye deformities, autism, or intellectual disability. In this clinical report, we present a 12-year-old male patient, his brother, and mother with pericentric inversions of chromosome 11 associated with submicroscopic interstitial deletions of 11p13 and duplications of 11q22.3. The inversions were identified by standard cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The patient's phenotype includes intellectual disability, speech abnormalities, and autistic behaviors, but interestingly neither the patient, his brother, nor mother have aniridia or other eye anomalies. To the best of our knowledge, these findings in three family members represent the only reported cases with 11p13 deletions downstream of PAX6 not demonstrating phenotypic characteristics of aniridia or abnormal eye development. Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6. © 2015 Wiley Periodicals, Inc.

  8. 11q- syndrome: three cases and a review of the literature.

    Science.gov (United States)

    Leegte, B; Kerstjens-Frederikse, W S; Deelstra, K; Begeer, J H; van Essen, A J

    1999-01-01

    We report on three children with de novo terminal deletions of the long arm of chromosome 11 (11q-) and breakpoints in 11q23-q24. Eighty-nine other patients with partial monosomy 11q have been reported and were reviewed by us. Salient features of 11q- syndrome are psychomotor retardation, trigonocephaly, telecanthus/hypertelorism, broad depressed nasal bridge, micrognathia, low set abnormal ears, cardiac anomalies and hand/foot anomalies. Renal agenesis and anal atresia are reported first here. Supratentorial white matter abnormality on CT and MRI present in our second patient was reported in three patients. Increased mortality is caused by cardiac anomalies. A third of all patients with partial monosomy 11q had thrombocytopenia or pancytopenia and this seems to be related to the absence of band 11q23-q24. Seventy-six percent of patients have de novo deletions with breakpoints in 11q21-q25. There is no obvious correlation between the length of the deleted segment and the severity of the symptoms. In unbalanced chromosomal patterns with deletions of 11q involving bands 11q23-q24 the typical phenotype of 11q- syndrome remains recognizable. Deletions distal to 11q24.1 do not produce the typical 11q- syndrome.

  9. Prenatal diagnosis of mosaicism for 11q terminal deletion.

    Science.gov (United States)

    Valduga, M; Cannard, V Latger; Philippe, C; Romana, S; Miton, A; Droulle, P; Foliguet, B; Lecompte, T; Jonveaux, P

    2007-01-01

    The phenotype of 11q terminal deletion also known as Jacobsen syndrome is a clinically well known entity whose diagnosis in infancy and childhood is based on clinical examination, hematological and cytogenetic findings. Hematological features in Jacobsen syndrome are very similar to those reported in Paris-Trousseau syndrome (PTS) which is also associated with11q terminal deletion. Karyotype analysis shows a variable terminal deletion from 11q23 sub-band extending to the telomere. Most often in patients with Jacobsen syndrome, this chromosomal deletion is present in all metaphases. We report on the identification of a distal 11q deletion in mosaic (20% of deleted cells) in a fetus ascertained after amniocentesis for maternal serum screening test indicative for Down syndrome. The present case is the third prenatal diagnosis of a mosaic for a distal 11q deletion with the lowest mosaicism rate. The 2D-ultrasound examination and cord blood hematological studies were useful to estimate the prognosis at term, considering the contribution of the mosaicism rate to the phenotypic variability in Jacobsen syndrome. The identification of mosaicism for distal 11q deletion is a very rare event in prenatal diagnosis. This case illustrates the complexity in genetic counselling for prenatally ascertained partial monosomy 11qter in mosaic.

  10. Chromosome breakage in Prader-Willi and Angelman syndrome deletions may involve recombination between a repeat at the proximal and distal breakpoints

    Energy Technology Data Exchange (ETDEWEB)

    Amos-Landgraf J.; Nicholls, R.D. [Case Western Reserve Univ., Cleveland, OH (United States); Gottlieb, W. [Univ. of Florida, Gainesville, FL (United States)] [and others

    1994-09-01

    Prader-Willi (PWS) and Angelman (AS) syndromes most commonly arise from large deletions of 15q11-q13. Deletions in PWS are paternal in origin, while those in AS are maternal in origin, clearly demonstrating genomic imprinting in these clinically distinct neurobehavioural disorders. In at least 90% of PWS and AS deletion patients, the same 4 Mb region within 15q11-q13 is deleted with breakpoints clustering in single YAC clones at the proximal and distal ends. To study the mechanism of chromosome breakage in PWS and AS, we have previously isolated 25 independent clones from these three YACs using Alu-vector PCR. Four clones were selected that appear to detect a low copy repeat that is located in the proximal and distal breakpoint regions of chromosome 15q11-q13. Three clones detect the same 4 HindIII bands in genomic DNA, all from 15q11-q13, with differing intensities for the probes located at the proximal or distal breakpoints region, respectively. This suggests that these probes detect related members of a low-copy repeat at either location. Moreover, the 254RL2 probe detects a novel HindIII band in two unrelated PWS deletion patients, suggesting that this may represent a breakpoint fragment, with recombination occurring within a similar interval in both patients. A fourth clone, 318RL3 detects 5 bands in HindIII-digested genomic DNA, all from 15q11-q13. This YAC endclone itself is not deleted in PWS and AS deletion patients, as seen by an invariant strong band. Two other strong bands are variably intact or deleted in different PWS or AS deletion patients, suggesting a relationship of this sequence to the breakpoints. Moreover, PCR using 318RL3 primers from the distal 93C9 YAC led to the isolation of a related clone with 96% identity, demonstrating the existence of a low-copy repeat with members close to the proximal and distal breakpoints. Taken together, our data suggest a complex, low-copy repeat with members at both the proximal and distal boundaries.

  11. The 11q- syndrome with mosaic partial deletion of 11q.

    Science.gov (United States)

    Ishida, Y; Watanabe, N; Ishihara, Y; Matsuda, H

    1992-12-01

    A female child with mosaic partial deletion of 11q is reported. At 1 month of age she was presented with cogenital glaucoma, trigonocephaly and multiple minor anomalies. She exhibited growth retardation and the typical phenotype of 11q- syndrome. G-banding analysis failed to show any abnormality, although subsequent high resolution banding revealed the abnormal karyotype 46,XX,del(11)(q23.3 q24.2)/46,XX,del(11)(q23.3 q25). This case is a second case of mosaic 11q- syndrome and her karyotype suggests that the region of 11q23.3-11q24.2 is critical in 11q-syndrome. Congenital glaucoma has never been reported as a complication of 11q- syndrome.

  12. AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases.

    Science.gov (United States)

    Schoch, Claudia; Schnittger, Susanne; Klaus, Mirjam; Kern, Wolfgang; Hiddemann, Wolfgang; Haferlach, Torsten

    2003-10-01

    Acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene comprise one category of recurring genetic abnormalities in the WHO classification. In an unselected series of 1897 AML cases, 54 patients with an 11q23/MLL rearrangement were identified, resulting in an incidence of 2.8%. The incidence of AML with MLL rearrangement was significantly higher in therapy-related AML (t-AML) than in de novo AML (9.4% vs 2.6%, P FAB) subtypes (P <.0001). Compared with AML with intermediate karyotype, AML with 11q23/MLL rearrangement had a worse outcome, which was rather comparable with AML with unfavorable karyotype. Compared with t-AML, the median overall survival (OS) of de novo AML with MLL rearrangement was significantly better (2.5 vs 10 months, P =.0143). No significant differences in median OS were observed between cases with t(9;11) compared with all other MLL rearrangements (10.0 vs 8.9 months, P =.36). In conclusion, the category AML with 11q23/MLL abnormalities accounts for 2.8% of unselected AML, is closely associated with monocytic differentiation, and has a dismal prognosis. (

  13. de novo interstitial deletions at the 11q23.3-q24.2 region

    OpenAIRE

    Su, Jiasun; Chen, Rongyu; Luo, Jingsi; Fan, Xin; Fu, Chunyun; Wang, Jin; He, Sheng; Hu, Xuyun; Zhang, ShuJie; Yi, Shang; Chen, Shaoke; Shen, Yiping

    2016-01-01

    Background Jacobsen syndrome (JBS) is a contiguous gene deletion syndrome involving 11q terminal deletion. Interstitial deletions at distal 11q are rare and their contributions to the clinical phenotype of JBS are unknown. Case presentation We presented the chromosome microarray (CMA) data and the clinical features of two individuals carrying a non-overlapping de novo deletion each at the 11q23.3-q24.2 region in an effort to analyze the correlation between region of deletion at 11q and phenot...

  14. An Interstitial 15q11-q14 Deletion: Expanded Prader-Willi Syndrome Phenotype

    Science.gov (United States)

    Butler, Merlin G.; Bittel, Douglas C.; Kibiryeva, Nataliya; Cooley, Linda D.; Yu, Shihui

    2009-01-01

    We present an infant girl with a de novo interstitial deletion of the chromosome 15q11-q14 region, larger than the typical deletion seen in Prader-Willi syndrome (PWS). She presented with features seen in PWS including hypotonia, a poor suck, feeding problems and mild micrognathia. She also presented with features not typically seen in PWS such as preauricular ear tags, a high arched palate, edematous feet, coarctation of the aorta, a PDA and a bicuspid aortic valve. G-banded chromosome analysis showed a large de novo deletion of the proximal long arm of chromosome 15 confirmed using FISH probes (D15511 and GABRB3). Methylation testing was abnormal and consistent with the diagnosis of PWS. Because of the large appearing deletion by karyotype analysis, an array comparative genomic hybridization (CGH) was performed. A 12.3 Mb deletion was found which involved the 15q11-q14 region containing approximately 60 protein coding genes. This rare deletion was approximately twice the size of the typical deletion seen in PWS and involved the proximal breakpoint BP1 and the distal breakpoint was located in the 15q14 band between previously recognized breakpoints BP5 and BP6. The deletion extended slightly distal to the AVEN gene including the neighboring CHRM5 gene. There is no evidence that the genes in the 15q14 band are imprinted; therefore, their potential contribution in this patient's expanded Prader-Willi syndrome phenotype must be a consequence of dosage sensitivity of the genes or due to altered expression of intact neighboring genes from a position effect. PMID:20082457

  15. de novo interstitial deletions at the 11q23.3-q24.2 region.

    Science.gov (United States)

    Su, Jiasun; Chen, Rongyu; Luo, Jingsi; Fan, Xin; Fu, Chunyun; Wang, Jin; He, Sheng; Hu, Xuyun; Zhang, ShuJie; Yi, Shang; Chen, Shaoke; Shen, Yiping

    2016-01-01

    Jacobsen syndrome (JBS) is a contiguous gene deletion syndrome involving 11q terminal deletion. Interstitial deletions at distal 11q are rare and their contributions to the clinical phenotype of JBS are unknown. We presented the chromosome microarray (CMA) data and the clinical features of two individuals carrying a non-overlapping de novo deletion each at the 11q23.3-q24.2 region in an effort to analyze the correlation between region of deletion at 11q and phenotype. Both deletions are likely pathogenic for patient's condition. The deletion at 11q23.3q24.1 is associated with short stature, relative microcephaly, failure to thrive, hypotonia and sleeping disorder. The deletion at 11q24.2 involves HEPACAM and our patient's clinical presentation (relative macrocephaly, abnormal MRI, mild developmental delay and seizure) is not inconsistent with Megalencephalic leukoencephalopathy with subcortical cysts 2B. Our finds support the notion that more than one critical region at 11q23.3-qter are responsible for the variable clinical presentation of JBS, thus JBS is a true contiguous gene deletion syndrome where multiple loci contributed to the clinical characteristics of JBS. Small interstitial deletions at 11q23.3-q24.2 and their associated unique features also suggest emerging novel genomic disorders.

  16. Two craniosynostotic patients with 11q deletions, and review of 48 cases

    Energy Technology Data Exchange (ETDEWEB)

    Lewanda, A.F.; Jabs, E.W.; Morsey, S. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others

    1995-11-06

    Many chromosomal abnormalities have craniofacial manifestations. One such abnormality, partial monosomy of chromosome 11q, is associated with metopic synostosis and resultant trigonocephaly. We reviewed 48 published cases of 11q deletions and translocations. Eighty percent were associated with abnormal head shape. Also commonly found were hypertelorism, ptosis of the eyelids, wide or low nasal bridge, apparently low-set malformed ears, down-turned mouth, micro/retrognathia, digital and cardiac anomalies, and psychomotor retardation. We report on two patients referred for abnormal head shape. The first case had brachycephaly, flat occiput, hypertelorism, and maxillary hypoplasia. Karyotype was 46,XY,del(11)(q24.1{yields}qter). The second patient had trigonocephaly, hypotelorism, posteriorly angulated ears, horizontal crease below his lower lip, syndactyly, shawl scrotum, cryptorchidism, and inguinal hernias. Karyotype showed partial trisomy of chromosome 4q as well as partial monosomy of 11q [46,XY,11,+der(11)t(4;11)(q31.3;q25)], a combination not previously reported. Deletions of 11q appear to produce a wide spectrum of abnormalities. 46 refs., 4 figs., 2 tabs.

  17. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...... with the probe L1.26 confirmed the derivation from chromosome 13 and DNA polymorphism analysis showed maternal origin of the ring chromosome. Our results, together with a review of previous reports of cases with ring chromosome 13 with identified breakpoints, could neither support the theory of distinct clinical...

  18. Partial proximal trisomy 10q syndrome: a new case.

    Science.gov (United States)

    Nucaro, A; Faedda, A; Cao, A; Boccone, L

    2002-01-01

    We report a case of partial proximal trisomy of the long arm of chromosome 10 confirmed by fluorescence in situ hibridization (FISH) performed with whole chromosome 10 specific painting and specific yac clones. The phenotypic findings, compared to those found in other published cases with the same karyotype, support the recognition of a distinctive partial proximal trisomy 10q syndrome (10q11-->q22).

  19. Endocrine abnormalities in patients with Jacobsen (11q-) syndrome.

    Science.gov (United States)

    Haghi, Marjan; Dewan, Asheesh; Jones, Kenneth Lee; Reitz, Richard; Jones, Christopher; Grossfeld, Paul

    2004-08-15

    Jacobsen syndrome (JS), a rare disorder with multiple dysmorphic features, is caused by the terminal deletion of chromosome 11q. Short stature has been reported in this syndrome, however very few of these patients have undergone endocrine evaluation. Serum insulin-like growth factor-1 (IGF-1) levels are an indirect indicator of growth hormone activity and are a useful initial screening tool in the assessment of an individual's growth hormone axis. We studied nine children with JS, eight of whom had short stature. Four out of eight children with short stature (50%) had low IGF-1 values, with three low for age and one low for Tanner stage. Four out of six males (67%) had cryptorchidism, a potential sign of hypogonadism. We conclude that low IGF-1 is common in patients with JS and short stature, and that growth hormone status and possibly hypothalamic-pituitary function should be evaluated in this patient population.

  20. Deletion of 11q12.3-11q13.1 in a patient with intellectual disability and childhood facial features resembling Cornelia de Lange syndrome.

    Science.gov (United States)

    Boyle, Martine Isabel; Jespersgaard, Cathrine; Nazaryan, Lusine; Ravn, Kirstine; Brøndum-Nielsen, Karen; Bisgaard, Anne-Marie; Tümer, Zeynep

    2015-11-01

    Deletions within 11q12.3-11q13.1 are very rare and to date only two cases have been described in the literature. In this study we describe a 23-year-old male patient with intellectual disability, behavioral problems, dysmorphic features, dysphagia, gastroesophageal reflux and skeletal abnormalities. Cornelia de Lange syndrome (CdLS, OMIM #122470; #300590; #610759; #300882; #614701) was suggested as a differential diagnosis in childhood although he lacked some of the features typical for this disorder. He does not have a mutation in any of the five known CdLS genes (NIPBL, SMC1A, SMC3, HDAC8, RAD21), but a 1.6Mb deletion at chromosome region 11q12.3-11q13.1 was detected by chromosome microarray. The deletion contains several genes including PPP2R5B, which has been associated with intellectual disability and overgrowth; NRXN2, which has been associated with intellectual disability and autism spectrum disorder; and CDCA5, which is part of the cohesin pathway, as are all the five known CdLS genes. It is therefore possible that deletion of CDCA5 may account for some of the CdLS like features of the present case. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Terminal deletion of 11q with significant late-onset combined immune deficiency.

    Science.gov (United States)

    Seppänen, Mikko; Koillinen, Hannele; Mustjoki, Satu; Tomi, Mölkänen; Sullivan, Kathleen E

    2014-01-01

    We report a 45-year old female adult patient with terminal deletion of chromosome 11q resulting in clinical phenotype of late-onset combined immunodeficiency. We describe the clinical phenotype and discuss the similarities between our patient and those with chromosome 22q11.2 deletion syndrome. Immunological evaluation included immunoglobulin levels, vaccine responses, number and function of T, NK and B cell subsets and comparative genomic hybridization test of blood and fibroblasts. The patient suffered from recurrent pneumococcal pneumonia and genital and cutaneous condylomas. She had a history of learning difficulties, dysmorphic features, autoimmune thyroiditis, chronic thrombocytopenia and severe asthma. We found Paris-Trousseau type thrombocytopenia, B-, T- and NK-lymphopenia, T cell oligoclonality and IgG hypogammaglobulinemia with inability to respond to pneumococcal polysaccharide, tetanus and diphtheria vaccines. A terminal deletion of chromosome 11q compatible with partial Jacobsen syndrome was found. This confirms Jacobsen syndrome as a chromosome deletion syndrome able to cause combined immunodeficiency.

  2. Construction of a YAC contig in the region of three retinal degeneration genes in 11q13

    Energy Technology Data Exchange (ETDEWEB)

    Gerhard, J.; Wang, J. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-09-01

    We have previously isolated a large number of bacteriophage clones specific for human chromosome 11. Seventy-two clones map to distal 11q13, a region haboring a number of human disease genes. Among them are genes for Best macular degeneration (BMD), Usher`s syndrome type 1B, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) and a form of Bardet-Biedl syndrome; all diseases involve retinal degenerations. From the genetic mapping it is clear the BMD and Bardet-Biedl syndrome are located in the proximal portion of the band, while Usher`s syndrome 1B and ADNIV are in the distal portion of 11q13. As the first step towards the cloning of the latter two disease genes, we set out to isolate this region of the chromosome as yeast artificial chromosomes (YACs). The 72 clones, as well as two transcribed genes, were assigned into 4 segregation groups with radiation-reduced somatic cell hybrids. We have shown previously that this high probe density can result in the development of large YAC contigs. We chose to use two complementing strategies to screen three different YAC libraries. The two strategies are: (1) the generation of Alu-primed products from the bacteriophage clones that are then used as probes against filters from individual YAC library pools; (2) the sequencing of the bacteriophage clones, STS development and screening YAC libraries by the method of Green and Olson (1990). The former has the advantage of speed, while the latter of specificity. We have identified a total of 140 YACs from 50 screens. Approximately 50% of the markers are already in small contigs. The largest contig has 10 markers and is {approximately}1 mbp. This approach results in fairly rapid development of YAC contigs without additional application of labor-intensive, locus-specific manipulation. We expect to complete the contig within a year.

  3. Fibroma of tendon sheath with 11q rearrangements.

    Science.gov (United States)

    Nishio, Jun; Iwasaki, Hiroshi; Nagatomo, Masaya; Naito, Masatoshi

    2014-09-01

    Fibroma of tendon sheath is an uncommon, benign fibroblastic tumor that usually occurs in the upper extremities of young and middle-aged adults. A clonal chromosomal aberration, t(2;11)(q31-32;q12), has been described in one case. We herein present a unique cytogenetic finding of fibroma of tendon sheath arising in the first web space of the right hand of a 38-year-old woman. Physical examination showed a 3.5-cm, firm, mobile, non-tender mass. Magnetic resonance imaging showed a well-defined soft tissue mass with iso- to slightly-low signal intensity relative to skeletal muscle on both T1- and T2-weighted sequences. Contrast-enhanced T1-weighted sequences demonstrated moderate patchy enhancement of the mass. A fibroma or giant cell tumor of tendon sheath was suggested, and the lesion was marginally excised. Histological examination confirmed the diagnosis of fibroma of tendon sheath. Cytogenetic analysis revealed a novel t(9;11)(p24;q13-14) translocation among other karyotypic abnormalities. The postoperative course was uneventful, and the patient is doing well without local recurrence two months after surgery. To the best of our knowledge, this is only the second report of fibroma of tendon sheath with clonal chromosomal abnormalities. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Genetic instability and intratumoral heterogeneity in neuroblastoma with MYCN amplification plus 11q deletion.

    Directory of Open Access Journals (Sweden)

    Eva Villamón

    Full Text Available Genetic analysis in neuroblastoma has identified the profound influence of MYCN amplification and 11q deletion in patients' prognosis. These two features of high-risk neuroblastoma usually occur as mutually exclusive genetic markers, although in rare cases both are present in the same tumor. The purpose of this study was to characterize the genetic profile of these uncommon neuroblastomas harboring both these high-risk features.We selected 18 neuroblastomas with MNA plus 11q loss detected by FISH. Chromosomal aberrations were analyzed using Multiplex Ligation-dependent Probe Amplification and Single Nucleotide Polymorphism array techniques.This group of tumors has approximately the same high frequency of aberrations as found earlier for 11q deleted tumors. In some cases, DNA instability generates genetic heterogeneity, and must be taken into account in routine genetic diagnosis.

  5. Molecular cytogenetic characterization of two cases with constitutional distal 11q duplication/triplication.

    Science.gov (United States)

    Burnside, Rachel D; Lose, Edward J; Domínguez, Maria G; Sánchez-Corona, Jose; Rivera, Horacio; Carroll, Andrew J; Mikhail, Fady M

    2009-07-01

    Here, we report two cases with isolated distal 11q rearrangement and multiple congenital anomalies. The first patient is a two-and-a-half year old male referred to our genetics clinic due to dysmorphic features and developmental delay including speech delay. Using conventional and molecular cytogenetic techniques, we demonstrate that he carries a recombinant chromosome with duplication of the 11q23.3q24.2 region resulting from an intrachromosomal insertion in the father. The second patient was originally reported by Partida-Perez, et al. [Partida-Perez et al., 2006] as having a tandem duplication of the 11q23.3 region. We performed array comparative genomic hybridization (aCGH) on this patient in order to map the exact region of the duplication, and demonstrated that the patient actually had a triplication within 11q23.3. We compare the clinical features of our two patients with those previously reported to further delineate the phenotype of isolated distal 11q duplication. Our study also demonstrates the clinical usefulness of whole genome high resolution aCGH analysis as a powerful molecular cytogenetic tool capable of detecting genomic imbalances due to cytogenetically visible but uncertain rearrangements.

  6. Tetrasomy 15q11-q13 Diagnosed by FISH in a Patient with Autistic Disorder

    Directory of Open Access Journals (Sweden)

    Karim Ouldim

    2007-01-01

    Full Text Available We report the case of a Moroccan boy with mental retardation, hyperactivity, epilepsy, developmental problems and behavioural disorders. Cytogenetic analysis showed the presence of a supernumerary marker chromosome. Molecular cytogenetics allowed us to determine the marker as an inverted duplication of chromosome 15. It is the first case of a Moroccan patient with tetrasomy 15q in which fluorescence in situ hybridization (FISH enabled us to specify the diagnosis. Interestingly, this patient has an infantile autism with cytogenetic abnormalities on chromosomal region 15q11-q13 as reported in patients with Autistic Disorder.

  7. Chromosome 5 derived small supernumerary marker: towards a genotype/phenotype correlation of proximal chromosome 5 imbalances.

    Science.gov (United States)

    Melo, Joana Barbosa; Backx, Liesbeth; Vermeesch, Joris R; Santos, Heloisa G; Sousa, Ana C; Kosyakova, Nadezda; Weise, Anja; von Eggeling, Ferdinand; Liehr, Thomas; Carreira, Isabel Marques

    2011-05-01

    Small supernumerary marker chromosomes (sSMC) are a morphological heterogeneous group of additional abnormal chromosomes that cannot be characterized alone by conventional banding cytogenetics. Molecular cytogenetic techniques are valuable tools for the accurate identification of sSMC and a prerequisite for sound genetic counseling based on refined genotype/phenotype correlation. We describe a new case of a retarded patient with an sSMC derived from chromosome 5. The characterization of the sSMC was done by subcentromere-specific multicolor (subcenM) fluorescence in-situ hybridization (FISH) and by full tilling resolution array analysis, after microdissection and amplification of the marker DNA. Uniparental disomy for normal sister chromosomes of the sSMC(5) was excluded. The karyotype was mos47,XX,+r(5)(::p11.1 → q12.1::)[70%]/46,XX[30%], being the trisomic region between 46.15 ∼ 49.56 Mb and 61.25 ∼ 61.335 Mb, a region known to harbor ∼45 annotated genes. Together with a review of the previously described cases of sSMC(5) and duplications involving the 5q proximal region, we can conclude that trisomy of the 5q11 region is associated with learning difficulties and speech delay.

  8. Evidence for autism spectrum disorder in Jacobsen syndrome: identification of a candidate gene in distal 11q.

    Science.gov (United States)

    Akshoomoff, Natacha; Mattson, Sarah N; Grossfeld, Paul D

    2015-02-01

    Jacobsen syndrome, also called the 11q terminal deletion disorder, is a contiguous gene disorder caused by the deletion of the end of the long arm of chromosome 11. Intellectual skills range from low average to severe/profound intellectual disability and usually correlate with deletion size. Comprehensive genotype/phenotype evaluations are limited, and little is known about specific behavioral characteristics associated with 11q terminal deletion disorder. In this prospective study, 17 patients with 11q terminal deletion disorder underwent cognitive and behavioral assessments. Deletion sizes were determined by array comparative genomic hybridization. Deletion sizes ranged from 8.7 to 14.5 Mb across the patients. We found that 8 of 17 patients (47%) exhibited behavioral characteristics consistent with an autism spectrum disorder diagnosis. There was no correlation between deletion size and the presence of autism spectrum disorder, implicating at least one predisposing gene in the distal 8.7 Mb of 11q. The findings from three additional patients with autistic features and "atypical" distal 11q deletions led to the identification of an autism "critical region" in distal 11q containing four annotated genes including ARHGAP32 (also known as RICS), a gene encoding rho GTPase activating protein. Results from this study support early autism spectrum disorder screening for patients with 11q terminal deletion disorder and provide further molecular insights into the pathogenesis of autism spectrum disorder.

  9. High rates of de novo 15q11q13 inversions in human spermatozoa

    Directory of Open Access Journals (Sweden)

    Molina Òscar

    2012-02-01

    Full Text Available Abstract Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies. Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 region. Signal associations allowed the discrimination between normal and inverted haplotypes, which were confirmed by laser-scanning confocal microscopy. Two types of inversions were detected which correspond to the segments involved in Class I and II PWS deletions. No significant differences were observed in the mean frequencies of inversions between controls and PWS fathers (3.59% ± 0.46 and 9.51% ± 0.87 vs 3.06% ± 0.33 and 10.07% ± 0.74. Individual comparisons showed significant increases of inversions in four PWS fathers (P Results suggest that the incidence of heterozygous inversion carriers in the general population could reach significant values. This situation could have important implications, as they have been described as predisposing haplotypes for genomic disorders. As a whole, results confirm the high instability of the 15q11-q13 region, which is prone to different types of de novo reorganizations by intrachromatid NAHR.

  10. Pure distal 11q deletion without additional genomic imbalances in a female infant with Jacobsen syndrome and a de novo unbalanced reciprocal translocation.

    Science.gov (United States)

    Chen, C-P; Lin, S-P; Hsu, C-H; Chern, S-R; Su, J-W; Chen, Y-J; Pan, C-W; Wang, W

    2012-01-01

    We report a neonate with pure deletion of distal 11q (11q23.3-->qter) and Jacobsen syndrome. The patient had growth restriction, petechiae, thrombocytopenia, dilation of renal pelvis, congenital heart defects, and seizures. Array comparative genomic hybridization revealed a 15.8-Mb deletion from 11q23.3 to 11q25 without genomic imbalances in other chromosomes. Cytogenetic analysis revealed a karyotype of 46,XX,der(7)(7pter-->7q32),der(11)(11pter--> 11q23.3::7q32-->7qter). The parental karyotypes were normal. This is the first report of pure distal 11q deletion without additional genomic imbalances in a patient with Jacobsen syndrome and a de novo unbalanced reciprocal translocation.

  11. Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts.

    Science.gov (United States)

    Chen, C P; Chern, S R; Tzen, C Y; Lee, M S; Pan, C W; Chang, T Y; Wang, W

    2001-04-01

    In utero diagnosis of de novo distal 11q deletion associated with renal and orofacial malformations has not been previously described. We present a 35-year-old pregnant woman with prenatal sonographic findings of a unilateral duplex renal system, pyelectasis and orofacial clefts at 20 weeks' gestation. Both genetic amniocentesis and postnatal cytogenetic analysis revealed de novo 46,XX,del(11)(q23). After birth, the fetus manifested a dysmorphic phenotype correlated with del(11q) syndrome. Genetic marker analysis showed a paternally derived distal deletion of chromosome 11q and a breakpoint centromeric to D11S1341. The present case represents the earliest prenatal diagnosis of a duplex renal system, pyelectasis and an additional feature of orofacial clefts associated with distal 11q deletion. Prenatal sonographic detection of a duplex renal system, pyelectasis and orofacial clefts should warrant a careful assessment of fetal anatomy and prompt cytogenetic analysis looking for chromosomal aberrations. Copyright 2001 John Wiley & Sons, Ltd.

  12. Assignment of human protein phosphatase 2A regulatory subunit genes B56{alpha}, B56{beta}, B56{gamma}, B56{delta}, and B56{epsilon} (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.1 {r_arrow} p12

    Energy Technology Data Exchange (ETDEWEB)

    McCright, B.; Virshup, D.M.; Brothman, A.R. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)

    1996-08-15

    The activity of the major intracellular protein phosphatase, protein phosphatase 2A WPM, is determined by the nature of the associated regulatory subunit. A new family of human PP2A regulatory subunits has recently been identified. Three of these subunits, B56{beta}, B56{delta}, and B56{epsilon}, are most highly expressed in brain, while the B56{alpha} and B56{gamma} isoforms are highly expressed in cardiac and skeletal muscle. Genes PPP2R5A-PPP2R5E encoding the phosphatase regulatory proteins B56{alpha}, B56{beta}, B56{gamma}, B56{delta}, and B56{epsilon} have now been mapped by fluorescence in situ hybridization to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2-p12, respectively. 16 refs., 1 fig.

  13. Ordered-subset analysis of savant skills in autism for 15q11-q13.

    Science.gov (United States)

    Ma, D Q; Jaworski, J; Menold, M M; Donnelly, S; Abramson, R K; Wright, H H; Delong, G R; Gilbert, J R; Pericak-Vance, M A; Cuccaro, Michael L

    2005-05-05

    Autism is a complex disorder characterized by genetic and phenotypic heterogeneity. Analysis of phenotypically homogeneous subtypes has been used to both confirm and narrow potential autism linkage regions such as the chromosomal region 15q11-q13. Increased evidence for linkage in this region had been found in a subgroup of 21 autism families (total families = 94) stratified based on a savant skill factor (SSF) from the Autism Diagnostic Interview, Revised (ADI-R). We examined the savant phenotypic finding in our sample of 91 multiplex autism families. Using two-point parametric analysis in stratification with a cutoff point of a savant skill score of 0.16, our families failed to demonstrate linkage to 15q11-q13. In addition, ordered subset analysis (OSA) using SSF as a covariate also failed to show evidence for linkage. Our findings do not support savant skills as an informative phenotypic subset for linkage in our sample. Copyright 2005 Wiley-Liss, Inc.

  14. [Deletion 11q23 --> qter (Jacobsen Syndrome) associated with duodenal atresia and annular pancreas].

    Science.gov (United States)

    Fernández González, N; Prieto Espuñes, S; Ibáñez Fernández, A; Fernández Colomer, B; López Sastre, J; Fernández Toral, J

    2002-09-01

    Jacobsen syndrome is a rare chromosomal disorder due to terminal 11q deletion. Prominent features are growth and psychomotor retardation, trigonocephaly and a characteristic facial dysmorphism, but many different abnormalities have been reported. We present the case of a preterm male. Prenatal ultrasonography was suspicious for duodenal atresia. At birth, the boy presented the craniofacial features typical of Jacobsen syndrome, together with diffusely spread petechiae and talipes equinovarus. Hemogram revealed pancytopenia. Ultrasound examination showed left renal agenesis and confirmed the duodenal atresia. Cerebral computed tomography scan, electroencephalogram and cardiac studies showed no abnormalities. Annular pancreas was found during surgery to correct the duodenal atresia. The karyotype was 46,XY,del(11)(q23.2 --> qter), which confirmed Jacobsen syndrome.A wide spectrum of clinical features is described in Jacobsen syndrome, with phenotype-karyotype correlation. This is the first report of duodenal atresia and annular pancreas.

  15. Fine mapping of the human renal oncocytoma-associated translocation (5;11)(q35;q13) breakpoint

    NARCIS (Netherlands)

    Sinke, RJ; Dijkhuizen, T; Janssen, B; Weghuis, DO; Merkx, G; vandenBerg, E; Schuuring, E; Meloni, AM; deJong, B; vanKessel, AG

    1997-01-01

    Recent cytogenetic analysis of a series of human renal oncocytomas revealed the presence of a recurring chromosomal translocation (5;11)(q35;q13) as sole anomaly in a subset of the tumors. The molecular characterization of this translocation was initiated using two primary t(5;11)-positive renal

  16. Supernumerary inv dup (15) in a patient with Angelman syndome and a deletion of 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Spinner, N.B.; Zackai, E. [Children`s Hospital of Philadelphia, PA (United States); Knoll, J.H.M. [Harvard Medical School, Boston, MA (United States)] [and others

    1995-05-22

    We have studied a patient with Angelman syndrome (AS) and a 47,XY,+inv dup(15) (pter{r_arrow}q11::q11{r_arrow}pter) karyotype. Molecular cytogenetic studies demonstrated that one of the apparently normal 15s was deleted at loci D15S9, GABRB3, and D15S12. There were no additional copies of these loci on the inv dup(15). The inv dup(15) contained only the pericentromeric sequence D15Z1. Quantitative DNA analysis confirmed these findings and documented a standard large deletion of sequences from 15q11-q13, as usually seen in patients with AS. DNA methylation testing at D15S63 showed a deletion of the maternally derived chromosome. AS in this patient can be explained by the absence of DNA sequences from chromosome 15q11-q13 on one of the apparently cytogenetically normal 15s, and not by the presence of an inv dup(15). This is the fourth patient with an inv dup(15) and AS or Prader Willi syndrome, who has been studied at the molecular level. In all cases an additional alteration of chromosome 15 was identified, which was hypothesized to be the cause of the disease. Patients with inv dup(15)s may be at increased risk for other chromosome abnormalities involving 15q11-q13. 29 refs., 3 figs.

  17. A de novo subtelomeric monosomy 11q (11q24.2-qter) and trisomy 20q (20q13.3-qter) in a girl with findings compatible with Jacobsen syndrome: case report and review.

    Science.gov (United States)

    Courtens, Winnie; Wauters, Jan; Wojciechowski, Marek; Reyniers, Edwin; Scheers, Stefan; van Luijk, Rob; Rooms, Liesbeth; Kooy, Frank; Wuyts, Wim

    2007-10-01

    We report on a 2-year-old dysmorphic girl with prenatal and postnatal growth deficiency, cardiopathy, left-sided hydronephrosis due to pyelourethral junction stenosis, frequent respiratory infections and psychomotor retardation, in whom a de novo unbalanced submicroscopic translocation (11q;20q) was detected by subtelomeric multiplex ligation-dependent probe amplification and fluorescence in situ hybridization analyses. Additional fluorescence in situ hybridization studies with locus-specific BAC probes and analyses with microsatellite markers revealed that this translocation resulted in a paternal chromosome 11q terminal deletion of approximately 8.9 Mb and a subtelomeric 20q duplication of approximately 3.7 Mb. A subtelomeric 20q trisomy has only been reported in four cases so far. A subtelomeric 11q deletion has been clinically reported in 18 patients. We review the clinical phenotype of these patients. We suggest that patients with a subterminal (11q24.2/25-qter) deletion may present with features of the well-known phenotype of terminal 11q deletion or Jacobsen syndrome.

  18. A de novo 11q23 deletion in a patient presenting with severe ophthalmologic findings, psychomotor retardation and facial dysmorphism.

    Science.gov (United States)

    Şimşek-Kiper, Pelin Özlem; Bayram, Yavuz; Ütine, Gülen Eda; Alanay, Yasemin; Boduroğlu, Koray

    2014-01-01

    Distal 11q deletion, previously known as Jacobsen syndrome, is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical clinical features include facial dysmorphism, mild-to-moderate psychomotor retardation, trigonocephaly, cardiac defects, and thrombocytopenia. There is a significant variability in the range of clinical features. We report herein a five-year-old girl with severe ophthalmological findings, facial dysmorphism, and psychomotor retardation with normal platelet function, in whom a de novo 11q23 deletion was detected, suggesting that distal 11q monosomy should be kept in mind in patients presenting with dysmorphic facial features and psychomotor retardation even in the absence of hematological findings.

  19. Jacobsen distal 11q deletion syndrome with a myelodysplastic change of hemopoietic cells.

    Science.gov (United States)

    Lin, J H; Hou, J W; Teng, R J; Tien, H F; Lin, K H

    1998-02-03

    We describe a male infant with unusual facial appearance, relative pancytopenia, bilateral simian creases, and an accessory nipple. Cytogenetic analysis showed deletion of the long arm of chromosome 11 [46,XY,del(11)(pter-->q23.2:)]. Bone-marrow study showed a myelodysplastic change of hemopoietic cells compatible with peripheral blood findings. Pachygyria of the temporal and frontal lobes was demonstrated by magnetic resonance image (MRI) of the brain. We present our findings in order to contribute to the information on 11q23 deletion.

  20. A 7 Mb region within 11q13 may contain a high penetrance gene for breast cancer.

    Science.gov (United States)

    Rosa-Rosa, Juan Manuel; Pita, Guillermo; González-Neira, Anna; Milne, Roger L; Fernandez, Victoria; Ruivenkamp, Claudia; van Asperen, Christi J; Devilee, Peter; Benitez, Javier

    2009-11-01

    Familial breast cancer represents up to 5% of all breast cancer cases. Recently, our group has performed a new SNP-based linkage study in 19 non-BRCA1/2 families. We found that a single family was linked to regions in two different chromosomes (11q13 and 14q21), and observed a non-parametric LOD score of 11.5 in both regions. In the present study, we ruled out any possible translocation between the chromosomes. We also used both a panel of STRs and an indirect approach based on HapMap data to narrow down these regions from 28 to 7 Mb in chromosome 11 and from 14.5 to 8.5 Mb in chromosome 14. We performed a mutational screening on candidate genes in 11q13 (NUMA1, FGF3, CCND1, RAD9A, RNF121, FADD and hsa-mir-192), and on FOXA1 in 14q21. Although we have not found any deleterious mutations in the coding region of these genes, data from STR markers confirm 11q13 as a candidate region to contain a breast cancer susceptibility gene.

  1. Partial deletion of long arm of chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Golomb, H.M. (Univ. of Chicago, IL); Rowley, J.; Vardiman, J.; Baron, J.; Locker, G.; Krasnow, S.

    1976-07-01

    Two patients with acute promyelocytic leukemia had an identical chromosomal abnormality detected by fluorescence banding. In each case, the clinical course was rapidly fatal, and was characterized by a lack of response to chemotherapy with cytarabine and thioguanine, and was complicated by disseminated intravascular coagulation. Bone marrow cells from each patient contained 46 chromosomes; in each instance, however, one chromosome 17 had a deletion of almost one half of the proximal portion of the long arm (del(17)(q11q21 or 22)).

  2. Distal 11q monosomy syndrome: a report of two Egyptian sibs with normal parental karyotypes confirmed by molecular cytogenetics.

    Science.gov (United States)

    Afifi, H H; Zaki, M S; El-Gerzawy, A M S; Kayed, H F

    2008-01-01

    Jacobsen syndrome is a rare disorder, caused by segmental monosomy for the distal end of the long arm of chromosome 11 with variable phenotypic expressivity. We report on the first male (6 years old) and female (3 years old) sibs with clinical and cytogenetics characterization of Jacobsen syndrome. Their karyotypes showed deletion 11q23.3-qter. Patients presented with growth and psychomotor retardation, facial dysmorphism, eye anomalies, and congenital heart disease (variable degrees of septal defect). Family history revealed a clinically similar brother, who died at 2 months old from cardiac anomalies in the form of single ventricle without being subjected to further investigations. Chromosomal analysis of the parents was normal. Karyotyping for the 2 patients and their parents was confirmed by fluorescence in situ hybridization analysis (FISH) using whole chromosome painting probes for 11 (WCP 11). Relevant investigations for both sibs showed mild thrombocytopenia with normal platelets morphology and striking periventricular demyelination on neuroimaging. Inguinal small testicles as well as focal epileptiform dysfunction were recorded in the male patient only. Abdominal ultrasound, hearing test, and DEXA scan were normal in both patients. Due to of the presence of apparently 3 affected offspring and normal parental karyotypes, an inherited predisposition was highly suspected. The large size of the distal deleted 11q segment in our patients support the recent hypothesis, that Jacobsen syndrome is a chromosomal deletion syndrome with genetic predisposition, due to expansion of p(CCG)n trinucleotide in the folate-sensitive fragile site FRA11B, at breakpoint 11q23.3. In conclusion, identification and further delineation of more similar patients will contribute to understanding the genetic basis of the 11q phenotype.

  3. Variation analysis of the number of copies and methylene patterns in region 15q11-q13

    Directory of Open Access Journals (Sweden)

    Sergio Laurito

    2018-01-01

    Full Text Available Human chromosome 15q11-q13 region is prone to suffer genetic alterations. Some genes of this region have a differential monoallelic imprinting-regulated expression pattern. Defects in imprinting regulation (IE, uniparental disomy (UPD or copy number variation (CNV due to chromosomal breakpoints (BP in 15q11-q13 region, are associated with several diseases. The most frequent are Prader-Willi syndrome, Angelman syndrome and 15q11-q13 microduplication syndrome. In this work, we analyzed DNA samples from 181 patients with phenotypes which were compatible with the above-mentioned diseases, using Methyl specific-multiplex ligation-dependent probe amplification (MS-MLPA. We show that, of the 181 samples, 39 presented alterations detectable by MS-MLPA. Of those alterations, 61.5% (24/39 were deletions, 5.1% (2/39 duplications and 33.3% (13/39 UPD/IE. The CNV cases were 4 times more frequent than UPD/IE (OR= 4; IC 95%: 1.56-10.25, consistent with the literature. Among the CNVs, two atypical cases allow to postulate new possible BP sites that have not been reported previously in the literature.

  4. [Improved identification for 5p deletion syndrome and partial trisomy 11q presented in a fetus by SNP array].

    Science.gov (United States)

    Shi, Shanshan; Pan, Guanyu; Yang, Yandong; Yan, Ruiling; Li, Weijing

    2016-04-01

    To investigate the prenatal application of single nucleotide polymorphism array (SNP array) in the identification of 5p deletion syndrome with partial trisomy 11q. G-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization (FISH) was also utilized to confirm the results. Karyotype of amniocyte showed 46, XY, der(5) (?::p15 → qter). SNP array revealed a 13.907 Mb deletion at 5p15.33p15.2 (chr5: 113576-14020561), overlapping the region of 5p deletion syndrome, and a 18.254 Mb duplication at 11q23.3 q25 (chr11: 116684627-134938470), overlapping no known syndrome. Karyotype of the parents showed a normal 46,XX in mother and 46,XY,t(5;11)(p15;q23) in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result. SNP array could uncover 5p deletion syndrome with partial trisomy 11q unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.

  5. 11q23 deletion syndrome (Jacobsen syndrome) with severe bleeding: a case report

    OpenAIRE

    Ichimiya, Yuko; Wada, Yuka; Kunishima, Shinji; Tsukamoto, Keiko; Kosaki, Rika; Sago, Haruhiko; Ishiguro, Akira; Ito, Yushi

    2018-01-01

    Background 11q23 deletion syndrome, also known as Jacobsen syndrome, is characterized by growth retardation, psychomotor retardation, facial dysmorphism, multiple congenital abnormalities, and thrombocytopenia. In 11q23 deletion syndrome, it is often difficult to anticipate the severity of bleeding. We report a neonatal case of 11q23 deletion syndrome with bleeding that was more severe than predicted by the platelet count. Case presentation We report a case of 11q23 deletion syndrome in an As...

  6. A novel case of bilateral high myopia, cataract, and total retinal detachment associated with interstitial 11q deletion.

    Science.gov (United States)

    Sachdeva, Reecha; Sears, Jonathan E; Rychwalski, Paul J

    2010-06-01

    Jacobsen syndrome, also known as 11q deletion syndrome, is a rare condition characterized by multiple anomalies, including developmental delay, cardiac abnormalities, blood dyscrasias, distal limb abnormalities, craniofacial anomalies, and variable ophthalmic manifestations. The syndrome's phenotype is due to a terminal deletion and is usually severely debilitating, frequently associated with fatality. Interstitial deletions, not involving the terminal end, have been associated with a more variable and less severe phenotype. Herein, we describe a case of interstitial 11q deletion in a 16 year-old female with associated systemic and craniofacial abnormalities as well as a novel combination of ocular findings, specifically strabismus, high myopia, bilateral cataracts, and bilateral total retinal detachments. This case report highlights the necessity for a detailed ophthalmic examination of patients with both interstitial and terminal deletions of the long arm of chromosome 11.

  7. Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q.

    Science.gov (United States)

    Koiffmann, C P; Gonzalez, C H; Vianna-Morgante, A M; Kim, C A; Odone-Filho, V; Wajntal, A

    1995-07-31

    Deletion 11q23-->qter and duplication 12q23-->qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23-->24 in the cause of the neuroblastoma is discussed.

  8. Deletion of 11q12.3-11q13.1 in a patient with intellectual disability and childhood facial features resembling Cornelia de Lange syndrome

    DEFF Research Database (Denmark)

    Boyle, Martine Isabel; Jespersgaard, Cathrine; Nazaryan, Lusine

    2015-01-01

    Deletions within 11q12.3-11q13.1 are very rare and to date only two cases have been described in the literature. In this study we describe a 23-year-old male patient with intellectual disability, behavioral problems, dysmorphic features, dysphagia, gastroesophageal reflux and skeletal abnormalities...

  9. Genome-wide homozygosity mapping localizes a gene for autosomal recessive non-progressive infantile ataxia to 20q11-q13.

    Science.gov (United States)

    Tranebjaerg, Lisbeth; Teslovich, Tanya M; Jones, MaryPat; Barmada, M Michael; Fagerheim, Toril; Dahl, Arve; Escolar, Diana M; Trent, Jeffrey M; Gillanders, Elizabeth M; Stephan, Dietrich A

    2003-08-01

    Autosomal recessive ataxias represent genetic and clinical heterogeneity. Unsteady gait is often accompanied by poor coordination of limbs, speech, and eye movements. To date, seven genes have been identified. In addition, five chromosomal loci have been localized in non-related families. Here, we report homozygosity mapping of a novel locus to a 19.5-cM region on chromosome 20q11-q13 in a large inbred Norwegian family with infantile non-progressive ataxia.

  10. Combined partial trisomy 11q and partial monosomy 10p in a 19-year-old female patient: phenotypic and genotypic findings.

    Science.gov (United States)

    Hagen, Anja; Bigl, Arndt; Wand, Dorothea; Klopocki, Eva; Heller, Raoul; Siekmeyer, Manuela; Siekmeyer, Werner; Kiess, Wieland; Merkenschlager, Andreas

    2011-12-01

    Constitutional partial trisomy 11q in man mostly occurs in combination with partial trisomy 22 due to a balanced parental translocation t(11;22). Occasionally a chromosome other than 22 is involved in the parental translocation with chromosome 11, resulting in partial monosomy for the other participating chromosome. We report of a patient with partial trisomy 11q and partial monosomy 10p [46,XX,der(10)t(10;11)(p15;q22)] due to a paternal balanced translocation [46,XY,t(10;11)(p15;q22)]. Array CGH showed heterozygosity for a deletion of ∼3.46 Mb at 10p15.3p15.2 and gain of ∼32.21 Mb at 11q22.2q25. The patient, a 19-year-old woman, has a multiple congenital anomaly syndrome with severe developmental and growth delay, muscular hypotonia, iris coloboma, abnormal external ears, widely spaced nipples, atrial septum defect, clubfoot, and arthrogryposis multiplex congenita. Despite multiple health problems and numerous hospitalizations due to massive seizures, pulmonary insufficiency and recurrent infections the patient reached adulthood. The clinical features in our patient are compared to other cases reported in the literature of either partial monosomy 10p or partial trisomy 11q. To the best of our knowledge, this is the first report of the combination of partial trisomy 11q and partial monosomy 10p. Comparing the molecular karyotype and the phenotype of our patient to other patients, the clinical features of our patient are more likely due to partial trisomy 11q than to partial monosomy 10p. Copyright © 2011 Wiley Periodicals, Inc.

  11. A der(11)t(4;11)(q21;p15) in a T-ALL/LBL patient.

    Science.gov (United States)

    Colli, Sandra; Furforo, Lilian; Rojo Pisarello, Eduardo; Maidana, Marcela; Martín, Carlos; Bordone, Javier; Slavutsky, Irma

    2016-04-01

    Translocation t(4;11)(q21;p15) is a rare recurrent change associated to T-cell acute leukemia. In most cases, this alteration appears as the only abnormality or as part of a simple karyotype. In this report, we present the first case of T acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) with the unbalanced translocation der(11)t(4;11)(q21;p15) as part of a very complex karyotype with multiple chromosome abnormalities, most of them not previously described in the literature. FISH (fluorescence in situ hybridization) and spectral karyotype (HiSKY) analysis confirmed the presence of complex alterations. The patient, a 16-year-old male, showed poor response to treatment and short survival (11 months). A detailed review of previously reported cases with t(4;11)(q21;p15) is also provided. The description of this type of alterations may contribute to the identification of new molecular mechanism associated to neoplastic development. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Association of Jacobsen syndrome and bipolar affective disorder in a patient with a de novo 11q terminal deletion.

    Science.gov (United States)

    Böhm, D; Hoffmann, K; Laccone, F; Wilken, B; Dechent, P; Frahm, J; Bartels, I; Bohlander, S K

    2006-02-15

    We report on a young woman with Jacobsen syndrome (JBS) who was admitted to our psychiatric department because of a bipolar affective disorder (BPAD). Chromosome analysis was performed due to the fact that she had mental retardation, short stature, and subtle facial anomalies. A deletion of the distal long arm of chromosome 11 was found. A detailed mapping of the deletion breakpoint by quantitative real time PCR revealed a true terminal 11q deletion of approximately 8 Mb corresponding to the karyotype 46,XX,del(11)(q24.2). Polymorphic DNA marker analysis showed that the deletion is located on the paternal chromosome. Additionally, laboratory investigations revealed a low platelet count and magnetic resonance imaging of the brain showed white matter T2 hyperintensities in frontotemporal regions, which are unlikely to result from a demyelinating process as indicated by localized proton magnetic resonance spectroscopy. To our knowledge, this is the first report describing a BPAD in a case with JBS. Copyright (c) 2006 Wiley-Liss, Inc.

  13. De novo reciprocal translocation t(5;11)(q22;p15) associated with hydrops fetalis (reciprocal translocation and hydrops fetalis).

    Science.gov (United States)

    Pala, Halil Gursoy; Artunc-Ulkumen, Burcu; Uyar, Yildiz; Bal, Filiz; Baytur, Yesim Bulbul; Koyuncu, Faik Mumtaz

    2015-02-01

    This is a case of a prenatally diagnosed non-immune hydrops fetalis (NIHF) associated with translocation t(5;11)(q22;p15). An association between NIHF and this translocation has not been reported previously. The patient was referred to the perinatology clinic with hydrops fetalis diagnosis at 23 weeks' gestation. We noted that the fetus had bilateral pleural effusion, ascites, widespread subcutaneous edema, membranous ventricular septal defect, hypoplastic fifth finger middle phalanx, clinodactyly, single umbilical artery. We performed cordocentesis. Chromosomal analysis on blood showed a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 11 with karyotype of 46,XX,t(5;11)(q22;p15). We present prenatal diagnosis of a de novo translocation (5;11) in a hydropic fetus with ultrason abnormalities. In our case, karyotype analysis of the fetus, mother and father provided evidence of a de novo translocation, that might explain the NIHF.

  14. Partial monosomy of 11q22.2q22.3 including the SDHD gene in individuals with developmental delay.

    Science.gov (United States)

    Yelavarthi, Krishna; Cabral, Huong; Wilson, Golder N; Rohena, Luis; Risheg, Hiba; Penton, Andrea; Schleede, Justin; Burnside, Rachel D

    2015-04-01

    Deletions in the middle portion of 11q are not as well described in the literature as terminal 11q deletions that result in Jacobsen syndrome. One confounding factor in the older literature is that the G-banding pattern of 11q13q21 is very similar to 11q21q23. The advent of fluorescence in situ hybridization and later microarray technologies have allowed for a better resolution of many of these deletions, but genotype-phenotype correlations are still difficult since these deletions are rare events. We present five individuals who presented with developmental delays with de novo 11q22.2q23.3 deletions. Deletions were observed by standard G-banded chromosome analysis with clarification of breakpoints and gene content by SNP microarray analysis. Of note, all individuals had identical distal breakpoints. All deletions include SDHD, which is implicated in hereditary paraganglioma/pheochromocytoma, for which the patients will need to be monitored in adulthood. In spite of the large deletions of 8.6 Mb (Patients 1 and 3), 13.98 Mb (Patient 2), and 12.6 Mb (Patients 4 and 5) all patients show somewhat mild intellectual disability and dysmorphism. © 2015 Wiley Periodicals, Inc.

  15. Study of two patients with craniosynostosis and deletions of 11q: One with features of Saethre-Chotzen syndrome and the other with concomitant partial trisomy 4q

    Energy Technology Data Exchange (ETDEWEB)

    Morsey, S. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)]|[Kennedy-Krieger Institute, Baltimore, MD (United States); Lewanda, A.F. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)]|[Children`s National Medical Center, Washington, DC (United States); Reid, C.S. [Cooper Hospitsl/Univ. Medical Center, Camden, NJ (United States)

    1994-09-01

    Partial monosomy 11q is associated with metopic craniosynostosis and trigonocephaly. Prominant features in the over 30 reported cases include downslanting palpebral fissures, epicanthal folds, hypertelorism, ptosis, wide/depressed nasal bridge, low set malformed ears, downturned mouth, micro/retrognathia, digital and cardiac anomalies and psychomotor retardation. We evaluated two patients referred for abnormal head shape. The first carried a diagnosis of Saethre-Chotzen syndrome due to brachycephaly, facial asymmetry, ptosis, cupped ears, sundactyly of 2nd and 3rd digits, developmental delay, and VSD. Karyotype revealed 46,XY,del(11)(q24.1{yields}qter). No abnormality was noted of chromosome 7p, where the Saethre-Chotzen syndrome locus has been mapped. This suggests genetic heterogeneity for this condition. The second patient had no prior diagnosis. He had trigonocephaly, bilateral cryptorchidism and inguinal hernias. He also had hypotelorism, epicanthal folds, synophrys, posteriorly rotated ears, horizontal crease below his lower lip, unilateral single palmar crease, mild soft tissue syndactyly and a shawl scrotum. His karyotype of 46,XY,-11,+der(11)t(4;11)(q31.3;q25) revealed both partial 11q monosomy and partial 4q trisomy (the latter associated with cryptorchidism, horizontal chin crease and single palmar crease). Deletions of 11q appear to produce a wide spectrum of defects, which may even mimic other known craniosynostotic conditions. Study of these patients may lead to the identification of new genes involved in craniofacial morphogenesis.

  16. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

    Directory of Open Access Journals (Sweden)

    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  17. Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q

    Energy Technology Data Exchange (ETDEWEB)

    Koiffmann, C.P.; Vianna-Morgante, A.M.; Wajntal, A. [Univ. of Sao Paulo (Brazil)] [and others

    1995-07-31

    Deletion 11q23{r_arrow}qter and duplication 12q23{r_arrow}qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23{r_arrow}24 in the cause of the neuroblastoma is discussed. 18 refs., 2 figs., 1 tab.

  18. Genetic and physical mapping of two centromere-proximal regions of chromosome IV in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Aleksenko, Alexei Y.; Nielsen, Michael Lynge; Clutterbuck, A.J.

    2001-01-01

    revision of the genetic map of the chromosome, including the position of the centromere, Comparison of physical and genetic maps indicates that meiotic recombination is low in subcentromeric DNA, its frequency being reduced from 1 crossover per 0.8 Mb to approximately 1 crossover per 5 Mb per meiosis...

  19. Identification of a B lymphoid disorder defined by specific morphologic features, a del(11)(q13) and a same breakpoint far from CCND1

    Energy Technology Data Exchange (ETDEWEB)

    Morel, D.; Callet, E.; Reynaud, S. [Laboratoire d`Hematologie, Pierre-Benite (France)] [and others

    1994-09-01

    Chromosome rearrangements in 11q13 have been shown to occur in a variety of diffuse small B-cell lymphomas/leukemias, including, beside mantle cell lymphomas (MCL), some cases of CLL/SLL, PLL, and SLVL. If t(11;14)(q13;q32) may be considered as a hallmark of MCL, less is known about deletions involving 11q13. A series of 13 patients with a diffuse small B-lymphoma/leukemia was examined for morphology (cytology and histology), immunology, cytogenetics and FISH for some of them. According to karyotype findings, 2 groups were identified: Group 1: 9 patients (6M,3F), median age 60 yrs. without 11q anomalies. Apart from trisomy 12 (3 cases), diverse anomalies were identified including chromosomes 1, 2, 7, 8, 12, 17. Cases were classified as CLL (2), SLL/SLP (5), blast-rich immunocytomas (2). Group 2: 4 patients, all males, median age 52 yrs. with breakpoints in 11q13; there were 3 deletions, and a t(11;14) was present in another case. 2 patients presented with refractory disease followed for 23 and 9 months, respectively, without any consistent morphologic change, the chromosomal anomaly being present at diagnosis in 1.3 cases. Cytologically, a nucleolated cell component was the constant and striking feature and FISH study by cos 14, pHS 11, cos 17, cos 105 revealed the same breakpoint located far from CCND1. The fourth case, bearing the t(11;14), was diagnosed as CLL/PLL in cytology, but was histologically consistent with MCL; the breakpoint was located by FISH into the BCL1 locus. Even if this study needs further confirmation, it points at the 11q13 deletion as a genetic event leading to a more aggressive disease, associated with distinct cytologic features differing from MCL and a molecular event probably not involving BCL1/CCND1.

  20. Interstitial 11q deletion derived from a maternal ins(4;11)(p14;q24.2q25): a patient report and review.

    Science.gov (United States)

    Van Zutven, Laura J C M; van Bever, Yolande; Van Nieuwland, Carolien C M; Huijbregts, Gido C M; Van Opstal, Diane; von Bergh, Anne R M; Corel, Linda J A; Tibboel, Dick; Wouters, Cokkie H; Poddighe, Pino J

    2009-07-01

    We present a family with multiple cytogenetic abnormalities, identified through a girl with several dysmorphic features and cardiac problems, suspected for Jacobsen syndrome. Cytogenetic analysis showed a 46,XX,del(11)(qter) karyotype, which was confirmed by fluorescence in situ hybridization (FISH). Cytogenetic investigation of the parents showed a chromosome aberration in both: the father had a t(11;12)(p13;q22) translocation and the mother was carrier of an ins(4;11)(p14;q24q25). FISH analysis with an 11q-subtelomeric probe from the second-generation telomere clone set and BACs from 11q24-q25 suggested a complex maternal rearrangement. However, subsequent array analysis showed a single interstitial deletion in the proband, derived from the maternal insertion. The aberrant karyotypes in both parents implicated an increased risk of unbalanced fetal chromosome composition, thus high risk for a child with multiple congenital abnormalities. Therefore, during the next pregnancy, the couple opted for prenatal diagnosis by means of amniocentesis. An interphase FISH strategy for uncultured amniotic fluid cells predicted two possible unbalanced fetal chromosome constitutions. Karyotyping of cultured amniotic cells confirmed one of the predicted unbalanced cytogenetic options, demonstrating the value of a fast interphase strategy for parents who both are carriers of a chromosomal abnormality. In addition, we present an overview of patients with Jacobsen syndrome and an interstitial 11q deletion reported thus far in literature.

  1. A YAC contig spanning the ataxia-telangiectasia locus (groups A and C) at 11q22-q23

    Energy Technology Data Exchange (ETDEWEB)

    Rotman, G.; Savitsky, K.; Ziv, Y. [Tel Aviv Univ. Ramat Aviv (Israel)] [and others

    1994-11-15

    Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving cerebellar degeneration, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. A-T is heterogeneous, and the majority of A-T cases are associated with two complementation groups, A and C. The ATA and ATC loci are closely linked at chromosome 11q22-q23. Recombination mapping and linkage disequilibrium analysis have confined both loci between the markers D11S1817 and D11S927. Construction of this contig was expedited by prior generation of a region-specific ICRF sublibrary using Alu-PCR products derived from a radiation hybrid. The contig was expanded further by screening the libraries with Alu-PCR products derived from YAC clones and with STSs from YAC ends. YAC clones were aligned by fingerprinting with moderately repetitive probes. 56 refs., 5 figs., 1 tab.

  2. Chromosome

    Science.gov (United States)

    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 ...

  3. Prenatal detection of a rec (21),dup q,inv(21)(p11q22) utilizing FISH

    Energy Technology Data Exchange (ETDEWEB)

    Travers, H.; Weinstein, M.E. [Integrated Genetics, Miami, FL (United States); Lamb, A. [Integrated Genetics, Framingham, MA (United States)] [and others

    1994-09-01

    Region-specific probes to chromosomes 13, 18, 21, X, and Y have been used to determine ploidy level in uncultured anmiocytes. The case described here is the first reported instance of an observed trisomic hybridization pattern in a fetus with a recombinant chromosome 21. The 30-year-old G3P010 patient was referred at 13 weeks gestation due to abnormalities seen on ultrasound (cystic hygroma and edema surrounding the head and body). Amniotic fluid was submitted for aneuploidy detection for chromosomes 13, 18, 21, X & Y by FISH in addition to cytogenetic analysis. Molecular analysis with a chromosome-specific 21q22.3 probe showed a hybridization pattern in which 89% of hybridized nuclei had three signals, consistent with trisomy 21. Cytogenetic analysis showed a male karyotype with a modal number of 46; one no. 21 showed an abnormal G-banding pattern in the short arm. Subsequent metaphase analysis using the 21q22.3 probe showed hybridization to two regions on an F-group sized chromosome. Maternal chromosome analysis revealed a 46,XX,inv(21)(p11q22) karyotype. The abnormal chromosome 21 seen in the amniocyte cell represents a recombinant chromosome which has resulted from a meiotic crossover. This interpretion is consistent with the FISH results which indicate the presence of 3 copies of region 21q22.3. FISH analysis in this case was particularly helpful because of the short arms of chromosome no. 21 are highly polymorphic and this rearrangement was fairly subtle.

  4. Periventricular nodular heterotopia and transverse limb reduction defect in a woman with interstitial 11q24 deletion in the Jacobsen syndrome region.

    Science.gov (United States)

    So, Joyce; Stockley, Tracy; Stavropoulos, Dimitri J

    2014-02-01

    Jacobsen syndrome (JS) is a disorder of developmental delay, growth retardation, thrombocytopenia, dysmorphic features, and cardiac abnormalities, among other congenital anomalies. JS is caused by contiguous gene deletion in distal chromosome 11q, generally varying in size from 7 to 20 Mb. Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder in which neurons are abnormally located in nodules along the edges of the lateral ventricles. PVNH can also be seen with other congenital anomalies, including a recurrent association with distal limb defects. Transverse limb defects have previously been reported in two patients with JS. We report on a patient with a 3.162 Mb interstitial deletion at chromosome region 11q24 overlapping the region commonly affected in JS. The patient had PVNH and a transverse limb reduction defect, with minimal typical findings of JS. This is the first report of PVNH associated with a microdeletion at chromosome 11q and may represent an expansion of the phenotypic spectrum associated with JS. This is the third report of transverse limb reduction defects in association with JS, supporting a widening of the skeletal phenotypic spectrum in JS to include more severe limb anomalies. ETS1 is proposed as a candidate gene for involvement in limb anomalies in JS. © 2013 Wiley Periodicals, Inc.

  5. Repair-mediated duplication by capture of proximal chromosomal DNA has shaped vertebrate genome evolution.

    Directory of Open Access Journals (Sweden)

    John K Pace

    2009-05-01

    Full Text Available DNA double-strand breaks (DSBs are a common form of cellular damage that can lead to cell death if not repaired promptly. Experimental systems have shown that DSB repair in eukaryotic cells is often imperfect and may result in the insertion of extra chromosomal DNA or the duplication of existing DNA at the breakpoint. These events are thought to be a source of genomic instability and human diseases, but it is unclear whether they have contributed significantly to genome evolution. Here we developed an innovative computational pipeline that takes advantage of the repetitive structure of genomes to detect repair-mediated duplication events (RDs that occurred in the germline and created insertions of at least 50 bp of genomic DNA. Using this pipeline we identified over 1,000 probable RDs in the human genome. Of these, 824 were intra-chromosomal, closely linked duplications of up to 619 bp bearing the hallmarks of the synthesis-dependent strand-annealing repair pathway. This mechanism has duplicated hundreds of sequences predicted to be functional in the human genome, including exons, UTRs, intron splice sites and transcription factor binding sites. Dating of the duplication events using comparative genomics and experimental validation revealed that the mechanism has operated continuously but with decreasing intensity throughout primate evolution. The mechanism has produced species-specific duplications in all primate species surveyed and is contributing to genomic variation among humans. Finally, we show that RDs have also occurred, albeit at a lower frequency, in non-primate mammals and other vertebrates, indicating that this mechanism has been an important force shaping vertebrate genome evolution.

  6. Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

    Directory of Open Access Journals (Sweden)

    Lenka Mikalová

    2017-03-01

    Full Text Available Treponema pallidum subsp. endemicum (TEN is the causative agent of endemic syphilis (bejel. An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan.The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE strains, but not to TEN sequences.A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

  7. Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

    Science.gov (United States)

    Mikalová, Lenka; Strouhal, Michal; Oppelt, Jan; Grange, Philippe Alain; Janier, Michel; Benhaddou, Nadjet; Dupin, Nicolas; Šmajs, David

    2017-03-01

    Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan. The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA) strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE) strains, but not to TEN sequences. A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

  8. Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects.

    Science.gov (United States)

    Hassan, Maaz; Butler, Merlin G

    2016-11-01

    We report a 20 year follow up on a Caucasian female, now 26 years of age, with Prader-Willi syndrome (PWS) harboring an atypical 15q11-q13 submicroscopic deletion of 100-200 kb in size first detected in 1996 involving the imprinting center, SNRPN gene and surrounding region. PWS is a rare complex disorder caused by the loss of paternally expressed genes in the 15q11-q13 region. With high resolution chromosomal microarray and methylation - specific MLPA analysis, we updated the genetic findings on our patient and found a 209,819bp deletion including the SNURF-SNRPN gene complex which includes the imprinting center and the SNORD116 region. We compared with four other similarly reported individuals in the literature with atypical submicroscopic deletions within this region but without imprinting center involvement to better characterize the specific genetic lesions causing PWS clinical findings. Clinically, our patient met the diagnostic criteria of PWS including infantile hypotonia, a poor suck with feeding difficulties, global developmental delays and later food foraging, childhood obesity, small hands and skin picking. Small atypical deletions of comparable sizes were seen in the 15q11-q13 region in all five cases and similar behavioral/physical characteristics were found despite an imprinting defect in our patient. These results further support an overlapping critical deletion region involving the non-coding snoRNA SNORD116 in common in the five individuals playing a key role in contributing to the PWS phenotype. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Interstitial deletion of 11q-implicating the KIRREL3 gene in the neurocognitive delay associated with Jacobsen syndrome.

    Science.gov (United States)

    Guerin, Andrea; Stavropoulos, Dimitri J; Diab, Yaser; Chénier, Sébastien; Christensen, Hilary; Kahr, Walter H A; Babul-Hirji, Riyana; Chitayat, David

    2012-10-01

    Jacobsen syndrome (JS) is a rare contiguous gene disorder characterized by a deletion within the distal part of the long arm of chromosome 11 ranging in size from 7 to 20 Mb. The clinical findings include characteristic dysmorphic features, growth and psychomotor delays and developmental anomalies involving the brain, eyes, heart, kidneys, immune, hematologic, endocrine, and gastrointestinal systems. The majority of cases are due to a terminal deletion of 11q; however interstitial deletions have also been reported. We report on a child with clinical manifestations consistent with JS who had a 2.899 Mb interstitial deletion at 11q24.2-q24.3 which is the smallest interstitial deletion reported so far to our knowledge. This deletion includes the KIRREL3 gene, and given our patient's history of neurocognitive delay and autism spectrum disorder, it raises the possibility that this gene is a candidate for the social and expressive language delay observed in our patient. Copyright © 2012 Wiley Periodicals, Inc.

  10. Antenatal diagnosis of deletion chromosome 11(q23-qter) (Jacobsen syndrome).

    Science.gov (United States)

    Foley, Patricia; McAuliffe, Fionnuala; Mullarkey, Marice; Reardon, William

    2007-07-01

    A case of Jacobsen syndrome, suspected antenatally on the grounds of trigonocephaly and hypoplastic left heart syndrome, is presented. Clinicians are reminded that a hypoplastic left heart should not be assumed to be an isolated malformation and that a careful search for associated malformations can facilitate the recognition of an underlying genetic syndrome.

  11. Deletion of (11)(q24.2) in a mother and daughter with similar phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Neavel, C.B.; Soukup, S. [Univ. Affiliated Cincinnati Center for Developmental Disorders, OH (United States)

    1994-12-01

    A del(11) (q24.2) was ascertained in a 2-year-old child and subsequently in her 20-year-old mother. Both mother and daughter had developmental delay, short stature, and {open_quotes}coarse{close_quotes} facial appearance. We compare our patients` manifestations to those associated with the distal 11q2 deletion phenotype ({open_quotes}Jacobsen{close_quotes} syndrome), and to the one other reported case of del(11)(q24.2). Our patients did not resemble this latter case, but had some findings in common with Jacobsen syndrome. We present our findings in order to contribute to the information on 11q2 deletions. 13 refs., 3 figs., 1 tab.

  12. A pericentric inversion in the cattle Y chromosome.

    Science.gov (United States)

    Iannuzzi, L; Di Meo, G P; Perucatti, A; Eggen, A; Incarnato, D; Sarubbi, F; Cribiu, E

    2001-01-01

    Sixteen male Podolian cattle, two sires and their 14 male offspring, were investigated cytogenetically on the basis of a female-like phenotype found in one of them. Eleven male offspring, including the one with female traits, and one of the two sires were found to carry an abnormal Y chromosome which originated from a pericentric inversion of the proximal half of the Yq arm (Yq11-->q12.2), as demonstrated by both banding and FISH mapping techniques with Y-specific molecular markers. Copyright 2002 S. Karger AG, Basel

  13. Prader-Willi, Angelman, and 15q11-q13 duplication syndromes

    Science.gov (United States)

    2015-01-01

    Three distinct neurodevelopmental disorders arise primarily from deletions or duplications that occur at the 15q11-q13 locus: Prader-Willi syndrome (PWS), Angelman syndrome (AS), and 15q11-q13 duplication syndrome (Dup15q syndrome). Each of these disorders results from the loss of function or over-expression of at least one imprinted gene. Here we discuss the clinical background, genetic etiology, diagnostic strategy, and management for each of these three disorders. PMID:26022164

  14. Interstitial deletion 11q. Case report and review of the literature.

    Science.gov (United States)

    De Pater, J M; Ippel, P F; Bijlsma, J B; Van Nieuwenhuizen, O

    1997-01-01

    A mildly retarded male with a unique interstitial deletion 11 (pter-->q22.3::q23.2-->qter) is described. To the best of our knowledge this patient is the first case with this specific type of deletion. The clinical features and cytogenetic findings of this patient are compared with those of previously reported cases with interstitial deletions 11q and patients with terminal deletions involving band 11q24.1 (leading to the so-called Jacobsen syndrome).

  15. 11q23 deletion syndrome (Jacobsen syndrome) with severe bleeding: a case report.

    Science.gov (United States)

    Ichimiya, Yuko; Wada, Yuka; Kunishima, Shinji; Tsukamoto, Keiko; Kosaki, Rika; Sago, Haruhiko; Ishiguro, Akira; Ito, Yushi

    2018-01-08

    11q23 deletion syndrome, also known as Jacobsen syndrome, is characterized by growth retardation, psychomotor retardation, facial dysmorphism, multiple congenital abnormalities, and thrombocytopenia. In 11q23 deletion syndrome, it is often difficult to anticipate the severity of bleeding. We report a neonatal case of 11q23 deletion syndrome with bleeding that was more severe than predicted by the platelet count. We report a case of 11q23 deletion syndrome in an Asian male newborn with severe bleeding just after birth. The diagnosis of 11q23 deletion syndrome was made prenatally by amniocentesis. An array comparative genomic hybridization analysis revealed a deletion of the 13.0 Mb regions ranging from 11q24.1 to the q terminus encoding FLI1. Our patient was delivered by cesarean section and exhibited skull deformities, facial asymmetry, low-set ears, inguinal hernia, flat feet, and crowded toes. He had a low platelet count (45,000/μL) and a coagulation abnormality with a prothrombin time-international normalized ratio of 1.92 and an activated partial thromboplastin time of 158.6 seconds. Bleeding at the site of a peripheral vessel puncture was more severe than expected with thrombocytopenia. The peripheral blood featured two different sizes of platelets containing large α-granules. As a result, he required eight platelet transfusions and two fresh frozen plasma transfusions within 13 days of birth. Massive bleeding was avoided, and cerebral magnetic resonance imaging indicated the occurrence of only petechial hemorrhage. Our patient with 11q deletion including FLI1 avoided massive bleeding and serious sequelae because of careful management after prenatal diagnosis. We suggest that prenatal diagnosis and vigilant perinatal care including a cesarean section are warranted for patients with 11q23 deletion syndrome.

  16. Detection of structural abnormalities in spermatozoa of a translocation carrier t(3;11)(q27.3;q24.3) by triple FISH.

    Science.gov (United States)

    Martini, E; von Bergh, A R; Coonen, E; de Die-Smulders, C E; Hopman, A H; Ramaekers, F C; Geraedts, J P

    1998-02-01

    Structural chromosome abnormalities in spermatozoa represent an important category of paternally transmittable genetic damage. A couple was referred to our centre because of repetitive abortions and the man was found to be a carrier of a reciprocal translocation t(3;11)(q27.3;q24.3). A tailored fluorescence in situ hybridisation (FISH) approach was developed to study the meiotic segregation patterns in spermatozoa from this translocation carrier. A combination of three DNA probes was used, a centromeric probe for chromosome 11, a cosmid probe for chromosome 11q and a YAC probe for chromosome 3q. The frequency of spermatozoa carrying an abnormal chromosome constitution was compared with baseline frequencies in control semen specimens and it was found that a significantly higher percentage of spermatozoa carried an abnormal constitution for the chromosomes involved in the translocation. A normal or balanced chromosome constitution was found in 44.3% of the analysed spermatozoa, while the remainder exhibited an abnormal chromosome constitution reflecting different modes of segregation (15.9% adjacent I segregation, 6.5% adjacent II segregation, 28.9% 3:1 segregation, 0.8% 4:0 segregation, 3.6% aberrant segregation). The frequency of aneuploidy for chromosomes X, Y, 13 and 21 was assessed using specific probes but there was no evidence of interchromosomal effects or variations in the sex ratio in spermatozoa from the translocation carrier. In conclusion, structural aberrations can be reliably assessed in interphase spermatozoa using unique DNA probe cocktails, and this method provides insight into the genetic constitution of germ cells and enables evaluation of potential risks for the offspring.

  17. Molecular cytogenetic characterization of Jacobsen syndrome (11q23.3-q25 deletion) in a fetus associated with double outlet right ventricle, hypoplastic left heart syndrome and ductus venosus agenesis on prenatal ultrasound.

    Science.gov (United States)

    Chen, Chih-Ping; Wang, Liang-Kai; Wu, Pei-Chen; Chang, Tung-Yao; Chern, Schu-Rern; Wu, Peih-Shan; Chen, Yen-Ni; Chen, Shin-Wen; Lee, Chen-Chi; Yang, Chien-Wen; Wang, Wayseen

    2017-02-01

    We present molecular cytogenetic characterization of Jacobsen syndrome (11q23.3-q25 deletion) in a fetus associated with double outlet right ventricle (DORV), hypoplastic left heart syndrome (HLHS), and ductus venosus (DV) agenesis on prenatal ultrasound. A 26-year-old woman underwent prenatal ultrasound examination at 22 weeks of gestation, which revealed intrauterine growth restriction, short femurs, DORV, HLHS, DV agenesis, single umbilical artery, and curly fourth toe of the left foot. The parents elected to terminate the pregnancy, and a 500-g female fetus was delivered at 23 weeks of gestation with facial dysmorphism, bilateral camptodactyly, and hammertoes. The parental karyotypes were normal. Cytogenetic analysis of the cord blood and umbilical cord revealed a karyotype of 46,XX,del(11)(q23). Array comparative genomic hybridization analysis of the DNA extracted from the umbilical cord revealed a 14.38-Mb deletion of 11q23.3-q25 encompassing BSX, ETS1, FLI1, and ARHGAP32. Metaphase fluorescence in situ hybridization analysis using the probes RP11-209L12 (11q25) and RP11-25M7 (11q11) showed a distal 11q deletion in the aberrant chromosome 11 in 17/17 cells examined. Prenatal diagnosis of DORV, HLHS, DV agenesis associated with intrauterine growth restriction and short limbs should include a differential diagnosis of Jacobsen syndrome. Copyright © 2017 Taiwan Association of Obstetrics & Gynecology. Published by Elsevier B.V. All rights reserved.

  18. Chromosomes

    Science.gov (United States)

    ... a new cell, the centromere serves as an attachment site for the two halves of each replicated ... of each chromosome is inherited from the female parent and the other from the male parent. This ...

  19. Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11(q21;q23/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    F. Marchesi

    2011-01-01

    Full Text Available Translocation t(4;11(q21;q23 leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT in first complete remission (CR could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11(q21;q23/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide.

  20. Diagnosis and fine mapping of a deletion in distal 11q in two Chinese patients with developmental delay.

    Science.gov (United States)

    Ji, Taoyun; Wu, Ye; Wang, Huifang; Wang, Jingmin; Jiang, Yuwu

    2010-08-01

    Jacobsen syndrome (JBS) is a haploinsufficiency syndrome caused by partial deletion of the long arm of chromosome 11. It is characterized by developmental delay (DD)/mental retardation (MR), physical growth retardation, facial dysmorphism, visceral malformations and thrombocytopenia. We report two JBS patients from China out of a total of 451 patients with unexplained DD/MR. The genotypes of these patients were compared with earlier reported patients in North America and Europe. Both patients presented with severe DD, microcephaly and facial dysmorphism; one patient had a low birth weight, congenital heart disease and structural brain abnormalities. Neither patient was thrombocytopenic at the time of diagnosis. The two deletions were 4.1 and 12.8 Mb. The 4.1 Mb deletion is the smallest of all pathogenic regions earlier reported in JBS. Therefore, the critical region underlying DD/MR might be located in the distal portion of the chromosomal segment within 4.1 Mb of the telomere. Candidate genes for DD/MR in this region include SNX19, THYN1, OPCML, NCAPD3 and NTM. One of the critical regions for craniofacial abnormalities may be within 130.3-134.4 Mb in chromosome 11q. Further analysis of Chinese JBS patients would elucidate the relation of phenotype to genotype further.

  1. Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH.

    Science.gov (United States)

    Tyson, Christine; Qiao, Ying; Harvard, Chansonette; Liu, Xudong; Bernier, Francois P; McGillivray, Barbara; Farrell, Sandra A; Arbour, Laura; Chudley, Albert E; Clarke, Lorne; Gibson, William; Dyack, Sarah; McLeod, Ross; Costa, Teresa; Vanallen, Margot I; Yong, Siu-Li; Graham, Gail E; Macleod, Patrick; Patel, Millan S; Hurlburt, Jane; Holden, Jeanette Ja; Lewis, Suzanne Me; Rajcan-Separovic, Evica

    2008-11-11

    Jacobsen syndrome is a rare contiguous gene disorder that results from a terminal deletion of the long arm of chromosome 11. It is typically characterized by intellectual disability, a variety of physical anomalies and a distinctive facial appearance. The 11q deletion has traditionally been identified by routine chromosome analysis. Array-based comparative genomic hybridization (array-CGH) has offered new opportunities to identify and refine chromosomal abnormalities in regions known to be associated with clinical syndromes. Using the 1 Mb BAC array (Spectral Genomics), we screened 70 chromosomally normal children with idiopathic intellectual disability (ID) and congenital abnormalities, and identified five cases with submicroscopic abnormalities believed to contribute to their phenotypes. Here, we provide detailed molecular cytogenetic descriptions and clinical presentation of two unrelated subjects with de novo submicroscopic deletions within chromosome bands 11q24-25. In subject 1 the chromosome rearrangement consisted of a 6.18 Mb deletion (from 128.25-134.43 Mb) and an adjacent 5.04 Mb duplication (from 123.15-128.19 Mb), while in subject 2, a 4.74 Mb interstitial deletion was found (from 124.29-129.03 Mb). Higher resolution array analysis (385 K Nimblegen) was used to refine all breakpoints. Deletions of the 11q24-25 region are known to be associated with Jacobsen syndrome (JBS: OMIM 147791). However, neither of the subjects had the typical features of JBS (trigonocephaly, platelet disorder, heart abnormalities). Both subjects had ID, dysmorphic features and additional phenotypic abnormalities: subject 1 had a kidney abnormality, bilateral preauricular pits, pectus excavatum, mild to moderate conductive hearing loss and behavioral concerns; subject 2 had macrocephaly, an abnormal MRI with delayed myelination, fifth finger shortening and squaring of all fingertips, and sensorineural hearing loss. Two individuals with ID who did not have the typical clinical

  2. Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness

    DEFF Research Database (Denmark)

    Ingason, Andrés; Kirov, George; Giegling, Ina

    2011-01-01

    ), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q13 duplications in psychotic illness. Method: The authors scanned 7,582 patients with schizophrenia.......1 that overlaps with the Prader-Willi/Angelman syndrome critical region may be a rare risk factor for schizophrenia and other psychoses. Given that maternal duplications of this region are among the most consistent cytogenetic observations in autism, the findings provide further support for a shared genetic...

  3. Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.

    Science.gov (United States)

    Nurmi, Erika L; Dowd, Michael; Tadevosyan-Leyfer, Ovsanna; Haines, Jonathan L; Folstein, Susan E; Sutcliffe, James S

    2003-07-01

    Autism displays a remarkably high heritability but a complex genetic etiology. One approach to identifying susceptibility loci under these conditions is to define more homogeneous subsets of families on the basis of genetically relevant phenotypic or biological characteristics that vary from case to case. The authors performed a principal components analysis, using items from the Autism Diagnostic Interview, which resulted in six clusters of variables, five of which showed significant sib-sib correlation. The utility of these phenotypic subsets was tested in an exploratory genetic analysis of the autism candidate region on chromosome 15q11-q13. When the Collaborative Linkage Study of Autism sample was divided, on the basis of mean proband score for the "savant skills" cluster, the heterogeneity logarithm of the odds under a recessive model at D15S511, within the GABRB3 gene, increased from 0.6 to 2.6 in the subset of families in which probands had greater savant skills. These data are consistent with the genetic contribution of a 15q locus to autism susceptibility in a subset of affected individuals exhibiting savant skills. Similar types of skills have been noted in individuals with Prader-Willi syndrome, which results from deletions of this chromosomal region.

  4. Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate.

    Science.gov (United States)

    Zou, Ying S; Hoppman, Nicole L; Singh, Zeba N; Sawhney, Sameer; Kotiah, Sandy D; Baer, Maria R

    2017-04-01

    We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a 150 kb genomic region containing three genes, including NUMA1. Mate pair sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in protein homodimerization and heteroassociation) and tyrosine kinase domains of PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17) translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB fusion is the second instance of rearrangement of NUMA1, encoding an element of the mitotic apparatus, in human cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Subtelomeric monosomy 11q and trisomy 16q in siblings and an unrelated child: molecular characterization of two der(11)t(11;16).

    Science.gov (United States)

    Basinko, Audrey; Audebert-Bellanger, Séverine; Douet-Guilbert, Nathalie; Le Franc, Jérémie; Parent, Philippe; Quemener, Sylvia; La Selve, Philippe; Bovo, Clément; Morel, Frédéric; Le Bris, Marie-Josée; De Braekeleer, Marc

    2011-09-01

    We report here three children with a der(11)t(11;16), two sibs (patients 1 and 2) having inherited a recombinant chromosome from a maternal t(11;16)(q24.3;q23.2) and a third unrelated child with a de novo der(11)t(11;16)(q25;q22.1), leading to partial monosomy 11q and trisomy 16q. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones and array-CGH were performed to determine the breakpoints involved in the familial and the de novo rearrangements. The partial 11 monosomy extended from 11q24.3 to 11qter and measured 6.17-6.21 Mb in Patients 1 and 2 while the size of the partial 11q25->qter monosomy was estimated at 1.97-2.11 Mb for Patient 3. The partial 16 trisomy extended from 16q23.2 to 16qter and measured 8.93-8.95 Mb in Patients 1 and 2 while the size of the partial 16q22.1->qter trisomy was 20.82 Mb for Patient 3. Intraventricular hemorrhage and transitional thrombocytopenia were found in both sibs but not in the third patient. The FLI1 gene, which is the most relevant gene for thrombocytopenia in Jacobsen syndrome, was neither deleted in family A nor in Patient 3. We suggest that a positional effect could affect the FLI1 expression for these two sibs. Deafness of our three patients confirmed the association of this anomaly to 11q monosomy and tended to confirm the hypothetic role of DFNB20 in Jacobsen syndrome hearing loss. Both sibs shared most of the features commonly observed in Jacobsen syndrome, but not the third patient. This confirmed that terminal 11q trisomy spanning 1 to 1.97-2.11 Mb is not associated with a typical Jacobsen syndrome. Copyright © 2011 Wiley-Liss, Inc.

  6. A case with 46,XX,del(11)(q23.2) karyotype and poor vision with literature review.

    Science.gov (United States)

    Mahjoubi, F; Razazian, F; Torabi, R

    2014-01-01

    Here we describe clinical and cytogenetic data on a female child whom had been referred to our laboratory suspected to have Turner syndrome since she had webbed neck. Cytogenetic analysis revealed that she had deletion at 11q23.2 to 11q terminal so her karyotype was ascertained as 46,XX,del(11)(q23.2). Her parents had normal karyotypes. In addition to many clinical features of del(11q ) syndrome the case had poor vision which is not common for this syndrome. Clinical features of this case and a few published cases will be reviewed briefly.

  7. Chromatin remodeling of human subtelomeres and TERRA promoters upon cellular senescence: commonalities and differences between chromosomes.

    Science.gov (United States)

    Thijssen, Peter E; Tobi, Elmar W; Balog, Judit; Schouten, Suzanne G; Kremer, Dennis; El Bouazzaoui, Fatiha; Henneman, Peter; Putter, Hein; Eline Slagboom, P; Heijmans, Bastiaan T; van der Maarel, Silvère M

    2013-05-01

    Subtelomeres are patchworks of evolutionary conserved sequence blocks and harbor the transcriptional start sites for telomere repeat containing RNAs (TERRA). Recent studies suggest that the interplay between telomeres and subtelomeric chromatin is required for maintaining telomere function. To further characterize chromatin remodeling of subtelomeres in relation to telomere shortening and cellular senescence, we systematically quantified histone modifications and DNA methylation at the subtelomeres of chromosomes 7q and 11q in primary human WI-38 fibroblasts. Upon senescence, both subtelomeres were characterized by a decrease in markers of constitutive heterochromatin, suggesting relative chromatin relaxation. However, we did not find increased levels of markers of euchromatin or derepression of the 7q VIPR2 gene. The repressed state of the subtelomeres was maintained upon senescence, which could be attributed to a rise in levels of facultative heterochromatin markers at both subtelomeres. While senescence-induced subtelomeric chromatin remodeling was similar for both chromosomes, chromatin remodeling at TERRA promoters displayed chromosome-specific patterns. At the 7q TERRA promoter, chromatin structure was co-regulated with the more proximal subtelomere. In contrast, the 11q TERRA promoter, which was previously shown to be bound by CCCTC-binding factor CTCF, displayed lower levels of markers of constitutive heterochromatin that did not change upon senescence, whereas levels of markers of facultative heterochromatin decreased upon senescence. In line with the chromatin state data, transcription of 11q TERRA but not 7q TERRA was detected. Our study provides a detailed description of human subtelomeric chromatin dynamics and shows distinct regulation of the TERRA promoters of 7q and 11q upon cellular senescence.

  8. Human ciliary neurotrophic factor: Localization to the proximal region of the long arm of chromosome 11 and association with CA/GT dinucleotide repeat

    Energy Technology Data Exchange (ETDEWEB)

    Lev, A.A.; Rosen, D.R.; Kos, C.; Brown, R.H. Jr.; Clifford, E.; Landes, G.; Hauser, S.L.

    1993-05-01

    Ciliary neurotrophic factor (CNTF) promotes survival and differentiation of several types of sensory, motor, sympathetic, and parasympathetic neurons. The authors have used the polymerase chain reaction to amplify, clone, and partially sequence CNTF cDNA from human muscle. Using a rodent-human mapping panel and fluorescence in situ hybridization, they have localized a single copy of the gene for human CNTF to the proximal long arm of chromosome 11. They have also identified a polymorphic tandem CA/GT dinucleotide repeat associated with the human CNTF gene. 14 refs., 1 fig.

  9. Translocations of 11q13 in mantle cell lymphoma fail to disrupt the S mu bp-2 gene.

    Science.gov (United States)

    Gulley, M L; Zhang, Q; Gascoyne, R D; DuPont, B R; Banks, P M; Cho, C G; Huang, J M; Montalvo, E A

    We recently cloned a gene whose protein product binds to the Epstein-Barr virus BZLF1 gene promoter. The same gene has been previously cloned by another group who named it S mu bp-2 because its protein product binds to the S mu motif of the immunoglobulin heavy chain gene where it is postulated to function in immunoglobulin class switching. In the current study, we confirm that the S mu bp-2 gene is located on chromosome 11q13, a locus known to be altered by translocation in 50-70% of mantle cell lymphomas. We used Southern blot analysis to determine whether the S mu bp-2 gene was structurally rearranged in any of 25 mantle cell lymphomas. We found no evidence of rearrangement in any of these lymphomas including 18 that were proven to contain t(11;14) by cytogenetic analysis. These data suggest that structural alteration of the S mu bp-2 gene is not an underlying mechanism of tumorigenesis in mantle cell lymphomas.

  10. Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH

    Directory of Open Access Journals (Sweden)

    VanAllen Margot I

    2008-11-01

    Full Text Available Abstract Background Jacobsen syndrome is a rare contiguous gene disorder that results from a terminal deletion of the long arm of chromosome 11. It is typically characterized by intellectual disability, a variety of physical anomalies and a distinctive facial appearance. The 11q deletion has traditionally been identified by routine chromosome analysis. Array-based comparative genomic hybridization (array-CGH has offered new opportunities to identify and refine chromosomal abnormalities in regions known to be associated with clinical syndromes. Results Using the 1 Mb BAC array (Spectral Genomics, we screened 70 chromosomally normal children with idiopathic intellectual disability (ID and congenital abnormalities, and identified five cases with submicroscopic abnormalities believed to contribute to their phenotypes. Here, we provide detailed molecular cytogenetic descriptions and clinical presentation of two unrelated subjects with de novo submicroscopic deletions within chromosome bands 11q24-25. In subject 1 the chromosome rearrangement consisted of a 6.18 Mb deletion (from 128.25–134.43 Mb and an adjacent 5.04 Mb duplication (from 123.15–128.19 Mb, while in subject 2, a 4.74 Mb interstitial deletion was found (from 124.29–129.03 Mb. Higher resolution array analysis (385 K Nimblegen was used to refine all breakpoints. Deletions of the 11q24-25 region are known to be associated with Jacobsen syndrome (JBS: OMIM 147791. However, neither of the subjects had the typical features of JBS (trigonocephaly, platelet disorder, heart abnormalities. Both subjects had ID, dysmorphic features and additional phenotypic abnormalities: subject 1 had a kidney abnormality, bilateral preauricular pits, pectus excavatum, mild to moderate conductive hearing loss and behavioral concerns; subject 2 had macrocephaly, an abnormal MRI with delayed myelination, fifth finger shortening and squaring of all fingertips, and sensorineural hearing loss. Conclusion Two

  11. Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH

    Science.gov (United States)

    Tyson, Christine; Qiao, Ying; Harvard, Chansonette; Liu, Xudong; Bernier, Francois P; McGillivray, Barbara; Farrell, Sandra A; Arbour, Laura; Chudley, Albert E; Clarke, Lorne; Gibson, William; Dyack, Sarah; McLeod, Ross; Costa, Teresa; VanAllen, Margot I; Yong, Siu-li; Graham, Gail E; MacLeod, Patrick; Patel, Millan S; Hurlburt, Jane; Holden, Jeanette JA; Lewis, Suzanne ME; Rajcan-Separovic, Evica

    2008-01-01

    Background Jacobsen syndrome is a rare contiguous gene disorder that results from a terminal deletion of the long arm of chromosome 11. It is typically characterized by intellectual disability, a variety of physical anomalies and a distinctive facial appearance. The 11q deletion has traditionally been identified by routine chromosome analysis. Array-based comparative genomic hybridization (array-CGH) has offered new opportunities to identify and refine chromosomal abnormalities in regions known to be associated with clinical syndromes. Results Using the 1 Mb BAC array (Spectral Genomics), we screened 70 chromosomally normal children with idiopathic intellectual disability (ID) and congenital abnormalities, and identified five cases with submicroscopic abnormalities believed to contribute to their phenotypes. Here, we provide detailed molecular cytogenetic descriptions and clinical presentation of two unrelated subjects with de novo submicroscopic deletions within chromosome bands 11q24-25. In subject 1 the chromosome rearrangement consisted of a 6.18 Mb deletion (from 128.25–134.43 Mb) and an adjacent 5.04 Mb duplication (from 123.15–128.19 Mb), while in subject 2, a 4.74 Mb interstitial deletion was found (from 124.29–129.03 Mb). Higher resolution array analysis (385 K Nimblegen) was used to refine all breakpoints. Deletions of the 11q24-25 region are known to be associated with Jacobsen syndrome (JBS: OMIM 147791). However, neither of the subjects had the typical features of JBS (trigonocephaly, platelet disorder, heart abnormalities). Both subjects had ID, dysmorphic features and additional phenotypic abnormalities: subject 1 had a kidney abnormality, bilateral preauricular pits, pectus excavatum, mild to moderate conductive hearing loss and behavioral concerns; subject 2 had macrocephaly, an abnormal MRI with delayed myelination, fifth finger shortening and squaring of all fingertips, and sensorineural hearing loss. Conclusion Two individuals with ID who

  12. Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3

    Energy Technology Data Exchange (ETDEWEB)

    Greger, V.; Knoll, J.H.M.; Wagstaff, J.; Lalande, M. [and others

    1997-03-01

    Angelman syndrome (AS) most frequently results from large ({ge}5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located {approximately}25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within {approximately}1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. 47 refs., 3 figs.

  13. Mosaic loss of 15q11q13 in a patient with hypomelanosis of Ito: Is there a role for the P gene?

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrino, J.E.; Schnur, R.E.; Kline, R. [Children`s Hospital of Philadelphia, PA (United States)] [and others

    1994-09-01

    Hypomelanosis of Ito (HMI) is a heterogeneous and clinically variable disorder characterized by specific patterns of hypopigmentation on the limbs and trunk. Many different mosaic chromosomal abnormalities have been reported with this condition leading to the hypothesis that HMI may be a non-specific marker of chromosome mosaicism. We studied a patient with dysmorphia, mental retardation, behavioral disturbances and HMI. Cytogenetic analysis demonstrated that he was mosaic for an unbalanced translocation, 45,XY,-7,-15,+der(7)t(7;15)(q34;q13)/46,XY in both blood and skin rendering him monosomic for 7q34 to qter and 15pter to q13 in the cells containing the translocation. The human homologue (P) of the p gene, the product of the mouse pink-eyed dilution locus, maps to 15q11q13. Loss of this locus is believed to be the cause of the hypopigmentation seen in patients with deletions of 15q11q13 and the Prader-Willi and Angelman syndromes. Mutations within the P gene have also been associated with tyrosinase positive (type II) oculocutaneous albinism. By fluorescence in situ hybridization we demonstrated that our patient is deleted for one copy of the P gene in the cells with the unbalanced translocation as well as for two probes from the Prader-Willi/Angelman critical region. The myl gene, which maps to 15q22, was present on the translocated chromosome as expected. There is a previous report in the literature of an HMI patient who was mosaic for del(15)(q11), although the copy number of the P gene was not specifically determined. Although hypomelanosis of Ito is a heterogeneous disorder, we postulate that in our case, and potentially in others, this phenotype may result from loss of a specific pigmentation gene.

  14. High fluorescence in situ hybridization percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome.

    Science.gov (United States)

    Jain, Preetesh; Keating, Michael; Thompson, Phillip A; Trinh, Long; Wang, Xuemei; Wierda, William; Ferrajoli, Alessandra; Burger, Jan; Kantarjian, Hagop; Estrov, Zeev; Abruzzo, Lynne; O'Brien, Susan

    2015-06-01

    We have analyzed patients with previously untreated chronic lymphocytic leukemia with del11q fluorescence in situ hybridization (FISH) abnormality (n = 196) in this study. Detection of the 11q22.3 used a multicolor FISH technique. Patients with del11q fell into two major FISH subsets-sole del11q (n = 64) and del11q with del13q (n = 132). FISH subsets were compared using the median del11q FISH% (>58%, high vs. ≤58%, low). Overall survival (OS) and time to first treatment (TTFT) were estimated using Kaplan-Meier plots (log rank). Multivariate analysis was performed to assess the association between FISH% of del11q and outcomes. Patients with sole del11q were similar to del11q with del13q in terms of TTFT and OS. Patients with high FISH% of del11q had significantly shorter OS and TTFT as compared with patients with low FISH%, particularly in sole del11q; this negative impact of high FISH% of del11q on OS and TTFT was diminished with coexistent del13q. In multivariate analysis, high FISH% of del11q was a significant predictor for shorter OS and TTFT. A comparison of these del11q subsets with a separate cohort of (n = 673) previously untreated patients with sole del13q showed that the high FISH% del11q cohort had a significantly shorter TTFT and OS. In addition, bulky disease by physical examination or computed tomography imaging was infrequent at presentation in patients with del11q. High FISH% of del11q can reliably discriminate higher risk patients with chronic lymphocytic leukemia. Presence of coexistent del13q should be accounted for while prognosticating patients with del11q. © 2015 Wiley Periodicals, Inc.

  15. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2).

    Science.gov (United States)

    Jiang, Y; Chen, H-C; Su, X; Thompson, P A; Liu, X; Do, K-A; Wierda, W; Keating, M J; Plunkett, W

    2016-09-02

    Approximately 10-20% of chronic lymphocytic leukemia (CLL) patients exhibit del(11q22-23) before treatment, this cohort increases to over 40% upon progression following chemoimmunotherapy. The coding sequence of the DNA damage response gene, ataxia-telangiectasia-mutated (ATM), is contained in this deletion. The residual ATM allele is frequently mutated, suggesting a relationship between gene function and clinical response. To investigate this possibility, we sought to develop and validate an assay for the function of ATM protein in these patients. SMC1 (structural maintenance of chromosomes 1) and KAP1 (KRAB-associated protein 1) were found to be unique substrates of ATM kinase by immunoblot detection following ionizing radiation. Using a pool of eight fluorescence in situ hybridization-negative CLL samples as a standard, the phosphorylation of SMC1 and KAP1 from 46 del (11q22-23) samples was analyzed using normal mixture model-based clustering. This identified 13 samples (28%) that were deficient in ATM function. Targeted sequencing of the ATM gene of these samples, with reference to genomic DNA, revealed 12 somatic mutations and 15 germline mutations in these samples. No strong correlation was observed between ATM mutation and function. Therefore, mutation status may not be taken as an indicator of ATM function. Rather, a direct assay of the kinase activity should be used in the development of therapies.

  16. Testicular microlithiasis in two boys with a chromosomal abnormality

    NARCIS (Netherlands)

    Goede, J.; Hack, W.W.M.; Pierik, F.H.

    2012-01-01

    A nine and 13-year-old boy, previously diagnosed with 18q syndrome and an 11q deletion, respectively were diagnosed with testicular microlithiasis (TM). Both cases demonstrate that TM occurs in patients with various chromosomal abnormalities.

  17. The 11q terminal deletion disorder: a prospective study of 110 cases.

    Science.gov (United States)

    Grossfeld, Paul D; Mattina, Teresa; Lai, Zona; Favier, Remi; Jones, Ken Lyons; Cotter, Finbarr; Jones, Christopher

    2004-08-15

    We performed a prospective study of 110 patients (75 not previously published) with the 11q terminal deletion disorder (previously called Jacobsen syndrome), diagnosed by karyotype. All the patients have multiple dysmorphic features. Nearly all the patients (94%) have Paris-Trousseau syndrome characterized by thrombocytopenia and platelet dysfunction. In total, 56% of the patients have serious congenital heart defects. Cognitive function ranged from normal intelligence to moderate mental retardation. Nearly half of the patients have mild mental retardation with a characteristic neuropsychiatric profile demonstrating near normal receptive language ability, but mild to moderate impairment in expressive language. Ophthalmologic, gastrointestinal, and genitourinary problems were common, as were gross and fine motor delays. Infections of the upper respiratory system were common, but no life-threatening infections were reported. We include a molecular analysis of the deletion breakpoints in 65 patients, from which genetic "critical regions" for 14 clinical phenotypes are defined, as well as for the neuropsychiatric profiles. Based on these findings, we provide a comprehensive set of recommendations for the clinical management of patients with the 11q terminal deletion disorder.

  18. FEVR-like Presentation in an 11q Deletion Syndrome and 16p13.11 Microdeletion.

    Science.gov (United States)

    Garcia, Maria D; Ventura, Camila V; Berrocal, Audina M

    2017-11-17

    A 7-year-old boy was diagnosed and treated for familial exudative vitreoretinopathy. Genetic testing revealed a 16p13.11 microdeletion and unbalanced translocation causing 11q deletion syndrome. This is the first report describing retinal findings associated with this combination of genetic alterations. Patients with 11q deletion syndrome or 16p13 microdeletions should undergo ophthalmologic examination. [J Pediatr Ophthalmol Strabismus. 2017;54:e71-e74.]. Copyright 2017, SLACK Incorporated.

  19. Confirmation of linkage of Best`s macular dystrophy to 11q13, and evidence for genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Mansergh, F.C.; Kenna, P.F.; Farrar, G.J. [Trinity College, Dublin (United Kingdom)] [and others

    1994-09-01

    Best`s macular dystrophy, also known as vitelliform macular degeneration, is an autosomal dominant, early onset form of macular degeneration. The disease is characterized by a roughly circular deposit of lipofuscin beneath the pigment epithelium of the retinal macula. Linkage studies were performed in two families, one Irish and one German, segregating typical Best`s macular dystrophy. In the Irish family (BTMD1), linkage analysis mapped the disease causing gene to chromosome 11q13, in a 10 cM region between the microsatellite markers PYGM and D11S871. Both markers showed different recombinants with the disease phenotype. This is a region that has previously shown linkage in families affected with Best`s macular dystrophy. Lod scores of 9.63, 9.12, 6.92, and 6.83 at zero recombination, were obtained with markers D11S1344, D11S1361, D11S1357 and D11S903, respectively. This data places the disease locus definitvely within the region between PYGM and D11S871. Linkage has been significantly excluded in this region in the German family (FamE), thereby providing evidence for genetic heterogeneity in this disease. The retinal specific gene, rod outer membrane protein 1 (ROM1), which maps to this region, has been screened for mutations in family BTMD1 by SSCPE analysis and by direct sequencing. Some of the promoter region, the three exons, and both introns have been sequenced; however, no mutations were found. It is likely that a gene other than ROM1 within this region may be responsible for causing the disease phenotype.

  20. Sleep problems in individuals with 11q terminal deletion disorder (Jacobsen syndrome).

    Science.gov (United States)

    Maas, A P H M; Grossfeld, P D; Didden, R; Korzilius, H; Braam, W J; Smits, M G; Curfs, L M G

    2008-01-01

    Characteristics of sleep and sleep problems were investigated in 43 individuals with 11q terminal deletion disorder (Jacobsen syndrome). Data were collected using a sleep questionnaire. Ten individuals (23%) had a sleep problem. Settling problems, frequent night waking and early waking occurred in 2 (4%), 7 (16%) and 2 (6%) individuals, respectively. Twenty-two individuals (54%) had a history of sleep problems. Twenty-five individuals (60%) showed restless sleep and 23 individuals (54%) slept in an unusual position. Apart from frequent coughs, no significant relationships were found between the presence of a sleep problem and other variables, such as age, level of ID, breathing problems, heart defects, constipation, daytime activity and behavioral diagnosis, restless sleep and sleeping in an unusual positions.

  1. Localization of the nucleotide excision repair gene ERCC-6 to human chromosome 10q11-q21.

    NARCIS (Netherlands)

    C. Troelstra (Christine); R.M. Landsvater; J. Wiegant; M. van der Ploeg; G. Viel; C.H.C.M. Buys; J.H.J. Hoeijmakers (Jan)

    1992-01-01

    textabstractWe have cloned the human DNA excision repair gene ERCC6 by virtue of its ability to correct the uv sensitivity of Chinese hamster overy cell mutant UV61. This mutant is a member of complementation group 6 of the nucleotide excision repair-deficient rodent mutants. By means of in situ

  2. Molecular characterization of an 11q interstitial deletion in a patient with the clinical features of Jacobsen syndrome.

    Science.gov (United States)

    Wenger, Sharon L; Grossfeld, Paul D; Siu, Benjamin L; Coad, James E; Keller, Frank G; Hummel, Marybeth

    2006-04-01

    The 11q terminal deletion disorder or Jacobsen syndrome is a contiguous gene disorder. It is characterized by psychomotor retardation, cardiac defects, blood dyscrasias (Paris-Trousseau syndrome) and craniofacial anomalies. We report on a female patient with an approximately 10 Mb interstitial deletion with many of the features of Jacobsen syndrome: A congenital heart defect, dysmorphic features, developmental delay, and Paris-Trousseau syndrome. The karyotype of the patient is 46,XX,del(11)(q24.1q24.3). The interstitial deletion was confirmed using FISH probes for distal 11q, and the breakpoints were characterized by microarray analysis. This is the first molecularly characterized interstitial deletion in a patient with the clinical features of Jacobsen syndrome. The deletion includes FLI-1, but not JAM-3, which will help to determine the critical genes involved in this syndrome. Copyright 2006 Wiley-Liss, Inc.

  3. Molecular cloning of a novel human gene encoding a 63-kDa protein and its sublocalization within the 11q13 locus

    Energy Technology Data Exchange (ETDEWEB)

    Perelman, B.; Dafni, N.; Naiman, T. [Tel Aviv Univ., Ramat Aviv (Israel)] [and others

    1997-05-01

    A human cDNA previously isolated by virtue of its ability to complement partially the ultraviolet sensitivity of a xeroderma pigmentosum cell line was further characterized. The transcription unit is expressed as a single 4.0-kb mRNA that encodes a novel 63-kDa cytoplasmic protein, possibly initiating from an internal AUG codon. The gene encoding this protein, named UVRAG, has been extremely well conserved during evolution, implying an important role for this gene product in cell metabolism. The transcribed mRNA is constitutively expressed in a wide variety of human tissues. The protein encoded by this gene is predicted to contain a coiled-coil structure and is likely to be metabolically unstable based on the occurrence of a strong PEST domain. UVRAG was assigned to human chromosome 11 by Southern hybridization to a somatic cell hybrid panel. Fluorescence in situ hybridization coupled with PCR analysis of human/rodent somatic cell hybrids containing segments of human chromosome 11 has localized this gene to a subregion of 11q13 in between the D11S916 and the D11S906 loci. Importantly, this region has been shown to be amplified in a variety of human malignancies, including breast cancer. 28 refs., 7 figs.

  4. Jacobsen syndrome due to an unbalanced translocation between 11q23 and 22q11.2 identified at age 40 years.

    Science.gov (United States)

    Takahashi, Ikuko; Takahashi, Tsutomu; Sawada, Kenichi; Shimojima, Keiko; Yamamoto, Toshiyuki

    2012-01-01

    A woman with psychomotor developmental delay, congenital glaucoma, and distinctive facial features, and a short neck was diagnosed with Jacobsen syndrome (JBS) at age 40 years. A previously reported balanced translocation between chromosome 11 and 22 instead showed an unbalanced translocation by a microarray-based comparative hybridization analysis with the final karyotype of 46,XX,der(11)t(11;22)(q23.3;q11.21),del(22)(q11.21) dn. The breakpoint of chromosome 11 was determined to be at TECTA and not near the apolipoprotein gene cluster site or the fragile site (FRA11B), which are commonly seen in patients with t(11;22) and patients with typical 11q deletions, respectively. Although the phenotypic features of the patient, including psychomotor developmental delay, distinctive features, and mild thrombocytopenia, were consistent with JBS, congenital glaucoma, which is an uncommon finding of JBS, was the most prominent condition during her natural history. Copyright © 2011 Wiley Periodicals, Inc.

  5. The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency

    NARCIS (Netherlands)

    V.A.S.H. Dalm (Virgil); G.J.A. Driessen (Gertjan); B.H. Barendregt (Barbara); P.M. van Hagen (Martin); M. van der Burg (Mirjam)

    2015-01-01

    textabstractBackground: Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case

  6. 11q13 is a Susceptibility Locus for Hormone Receptor Positive Breast Cancer

    DEFF Research Database (Denmark)

    Lambrechts, Diether; Truong, Therese; Justenhoven, Christina

    2012-01-01

    A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10 and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we ge...

  7. Evaluation of Anosognosia in Alzheimer's Disease Using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q).

    Science.gov (United States)

    Maki, Yohko; Yamaguchi, Tomoharu; Yamaguchi, Haruyasu

    2013-01-01

    The objective is to propose a brief method to evaluate anosognosia in Alzheimer's disease (AD) using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), a short informant-based screening questionnaire for identifying dementia. The participants were 107 elderly individuals: 13 with a Clinical Dementia Rating (CDR) of 0.5, 73 with mild AD of CDR 1, and 21 with moderate AD of CDR 2. The patients and caregivers answered the SED-11Q independently, and the degree of discrepancy indicated the severity of anosognosia. THE SCORES WERE AS FOLLOWS: caregiver scores were 2.46 ± 1.85 (mean ± SD) in CDR 0.5, 6.36 ± 3.02 in CDR 1, and 9.00 ± 1.14 in CDR 2; patient scores were 2.00 ± 1.78, 2.55 ± 2.33, and 1.33 ± 2.46, respectively. Discrepancy was 0.46 ± 1.61, 3.81 ± 3.95, and 7.67 ± 2.87, respectively, and the caregiver assessments were significantly higher than the patient assessments in CDR 1 and CDR 2 (p SED-11Q for anosognosia was validated with the standardized Anosognosia Questionnaire for Dementia (AD-Q). The caregiver scores were moderately correlated with behavioral and psychological symptoms of dementia scores (r = 0.524), and the patient scores were moderately correlated with depression scores (r = 0.561). The SED-11Q serves a dual purpose: caregiver assessment is useful for the screening of dementia, and any discrepancy between the patient and the caregiver assessment is considered as an indication of the severity of anosognosia; this can be informative for caregivers and essential for successful care.

  8. Evaluation of Anosognosia in Alzheimer's Disease Using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q

    Directory of Open Access Journals (Sweden)

    Yohko Maki

    2013-10-01

    Full Text Available Aims: The objective is to propose a brief method to evaluate anosognosia in Alzheimer's disease (AD using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q, a short informant-based screening questionnaire for identifying dementia. Methods: The participants were 107 elderly individuals: 13 with a Clinical Dementia Rating (CDR of 0.5, 73 with mild AD of CDR 1, and 21 with moderate AD of CDR 2. The patients and caregivers answered the SED-11Q independently, and the degree of discrepancy indicated the severity of anosognosia. Results: The scores were as follows: caregiver scores were 2.46 ± 1.85 (mean ± SD in CDR 0.5, 6.36 ± 3.02 in CDR 1, and 9.00 ± 1.14 in CDR 2; patient scores were 2.00 ± 1.78, 2.55 ± 2.33, and 1.33 ± 2.46, respectively. Discrepancy was 0.46 ± 1.61, 3.81 ± 3.95, and 7.67 ± 2.87, respectively, and the caregiver assessments were significantly higher than the patient assessments in CDR 1 and CDR 2 (p Conclusion: The SED-11Q serves a dual purpose: caregiver assessment is useful for the screening of dementia, and any discrepancy between the patient and the caregiver assessment is considered as an indication of the severity of anosognosia; this can be informative for caregivers and essential for successful care.

  9. Leukoencephalopathy associated with 11q24 deletion involving the gene encoding hepatic and glial cell adhesion molecule in two patients.

    Science.gov (United States)

    Yamamoto, Toshiyuki; Shimada, Shino; Shimojima, Keiko; Sangu, Noriko; Ninomiya, Shinsuke; Kubota, Masaya

    2015-09-01

    Leukoencephalopathies are heterogeneous entities with white matter abnormalities. Mutations of the gene encoding hepatic and glial cell adhesion molecule (HEPACAM) located on 11q24 are related to one of the leukoencephalopathies: megalencephalic leukoencephalopathy with subcortical cysts type 2 (MLC2). Genomic copy number aberrations were analyzed by microarray comparative hybridization for two patients. One patient who presented with abnormal intensity of the white matter had been previously been diagnosed with the typical genotype and phenotype of Jacobsen syndrome due to an 11q subtelomere deletion, which was further characterized here. In a second patient who exhibited the characteristic finding of leukoencephalopathy, an interstitial deletion of 11q24 was also identified. HEPACAM was involved in both deletions. We therefore suggest that haploinsufficiency of HEPACAM, a gene previously associated with the features of MLC2 and located on the overlapping deletion region between the two patients, might be related to the observed white matter abnormalities. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Symptoms of Early Dementia-11 Questionnaire (SED-11Q): A Brief Informant-Operated Screening for Dementia.

    Science.gov (United States)

    Maki, Yohko; Yamaguchi, Tomoharu; Yamaguchi, Haruyasu

    2013-01-01

    The aim of this study was to develop a brief informant-based questionnaire, namely the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), for the screening of early dementia. 459 elderly individuals participated, including 39 with mild cognitive impairment in the Clinical Dementia Rating scale (CDR) 0.5, 233 with mild dementia in CDR 1, 106 with moderate dementia in CDR 2, and 81 normal controls in CDR 0. Informants were required to fill out a 13-item questionnaire. Two items were excluded after analyzing sensitivities and specificities. The final version of the SED-11Q assesses memory, daily functioning, social communication, and personality changes. Receiver operator characteristic curves assessed the utility to discriminate between CDR 0 (no dementia) and CDR 1 (mild dementia). The statistically optimal cutoff value of 2/3, which indicated a sensitivity of 0.84 and a specificity of 0.90, can be applied in the clinical setting. In the community setting, a cutoff value of 3/4, which indicated a sensitivity of 0.76 and a specificity of 0.96, is recommended to avoid false positives. The SED-11Q reliably differentiated nondemented from demented individuals when completed by an informant, and thus is practical as a rapid screening tool in general practice, as well as in the community setting, to decide whether to seek further diagnostic confirmation.

  11. Clinical and molecular-cytogenetic evaluation of a family with partial Jacobsen syndrome without thrombocytopenia caused by an approximately 5 Mb deletion del(11)(q24.3).

    Science.gov (United States)

    Bernaciak, Joanna; Szczałuba, Krzysztof; Derwińska, Katarzyna; Wiśniowiecka-Kowalnik, Barbara; Bocian, Ewa; Sasiadek, Maria Małgorzata; Makowska, Izabela; Stankiewicz, Paweł; Smigiel, Robert

    2008-10-01

    Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between approximately 7 and 20 Mb. Typical JBS features include developmental delay/mental retardation, short stature, congenital heart defects, thrombocytopenia, and characteristic dysmorphic facial features. We report on a family in which a 4-year-old girl as well as her mother and maternal uncle present with subtle features of JBS. Notably, neither thrombocytopenia nor congenital anomalies were detected in this family. Cytogenetic analyses revealed normal karyotypes. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an approximately 5 Mb deletion of the terminal part of chromosome 11q in all the three affected family members. The deletion breakpoint was mapped between 129,511,419 and 129,519,794 bp. This is the smallest deletion reported in a JBS patient. Interestingly, the FLI1 (friend leukemia virus integration 1) hematopoiesis factor gene located approximately 6.5 Mb from 11qter and usually deleted in patients with JBS, is intact. Our data support previous hypotheses that FLI1 haploinsufficiency is responsible for thrombocytopenia in patients with JBS. Copyright 2008 Wiley-Liss, Inc.

  12. The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency.

    Science.gov (United States)

    Dalm, Virgil A S H; Driessen, Gertjan J A; Barendregt, Barbara H; van Hagen, Petrus M; van der Burg, Mirjam

    2015-11-01

    Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency. To evaluate the presence of immunodeficiency in a series of 6 patients with JS. Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry. Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found. Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS.

  13. Identification of a yeast artificial chromosome that spans the human papillary renal cell carcinoma-associated t(X;1) breakpoint in Xp11.2

    NARCIS (Netherlands)

    Suijkerbuijk, R F; Meloni, A M; Sinke, R J; de Leeuw, B; Wilbrink, M; Janssen, H A; Geraghty, M T; Monaco, A P; Sandberg, A A; Geurts van Kessel, A

    1993-01-01

    Recently, a specific chromosome abnormality, t(X;1)(p11;q21), was described for a subgroup of human papillary renal cell carcinomas. The translocation breakpoint in Xp11 is located in the same region as that in t(X;18)(p11;q11)-positive synovial sarcoma. We used fluorescence in situ hybridization

  14. Fasiyal anomalilerin eşlik ettiği bir holoprozensefali olgusu: 11q delesyon sendromu

    OpenAIRE

    Petik, Bülent; Baykara, Murat; Yılmaz, Mehmet

    2011-01-01

    Holoprozensefali terimi, prozensefalonun farklı safhalardaki ayrılma ve farklılaşma yetersizlikleri ile karakterize bir grup hastalığı tanımlar. Holoprozensefaliye kraniyofasiyal ve ekstrakraniyal (polidaktili, renal displazi, omfalosel, hidrops vb.) anomaliler eşlik edebilir. Bu olgularda genellikle kromozomal anomaliler de vardır. Bu makalede belirgin kulak ve yüz anomalilerin eşlik ettiği nadir bir 11q mozaisizmli holoprozensefali olgusunun bulguları sunuldu

  15. Single-molecule sequencing and Hi-C-based proximity-guided assembly of amaranth (Amaranthus hypochondriacus) chromosomes provide insights into genome evolution.

    Science.gov (United States)

    Lightfoot, D J; Jarvis, D E; Ramaraj, T; Lee, R; Jellen, E N; Maughan, P J

    2017-08-31

    Amaranth (Amaranthus hypochondriacus) was a food staple among the ancient civilizations of Central and South America that has recently received increased attention due to the high nutritional value of the seeds, with the potential to help alleviate malnutrition and food security concerns, particularly in arid and semiarid regions of the developing world. Here, we present a reference-quality assembly of the amaranth genome which will assist the agronomic development of the species. Utilizing single-molecule, real-time sequencing (Pacific Biosciences) and chromatin interaction mapping (Hi-C) to close assembly gaps and scaffold contigs, respectively, we improved our previously reported Illumina-based assembly to produce a chromosome-scale assembly with a scaffold N50 of 24.4 Mb. The 16 largest scaffolds contain 98% of the assembly and likely represent the haploid chromosomes (n = 16). To demonstrate the accuracy and utility of this approach, we produced physical and genetic maps and identified candidate genes for the betalain pigmentation pathway. The chromosome-scale assembly facilitated a genome-wide syntenic comparison of amaranth with other Amaranthaceae species, revealing chromosome loss and fusion events in amaranth that explain the reduction from the ancestral haploid chromosome number (n = 18) for a tetraploid member of the Amaranthaceae. The assembly method reported here minimizes cost by relying primarily on short-read technology and is one of the first reported uses of in vivo Hi-C for assembly of a plant genome. Our analyses implicate chromosome loss and fusion as major evolutionary events in the 2n = 32 amaranths and clearly establish the homoeologous relationship among most of the subgenome chromosomes, which will facilitate future investigations of intragenomic changes that occurred post polyploidization.

  16. Cytogenetic manifestation of chromosome 11 duplication/amplification in acute myeloid leukemia.

    Science.gov (United States)

    Sárová, Iveta; Brezinová, Jana; Zemanová, Zuzana; Izáková, Silvia; Lizcová, Libuse; Malinová, Eva; Berková, Adéla; Cermák, Jaroslav; Maaloufová, Jacqueline; Nováková, Ludmila; Michalová, Kyra

    2010-06-01

    Gene amplification is a frequent genetic abnormality in solid tumors, and many oncogenes are activated in this way. In acute myeloid leukemia (AML), a frequent target of gene amplification is chromosome 11, particularly chromosome region 11q23, including the MLL (myeloid/lymphoid leukemia) gene. However, the number of other amplicons from the long arm of chromosome 11 has also been described. Duplication/amplification of chromosome 11 was found by cytogenetic methods in 10 of 119 newly diagnosed patients with AML. The amplification was presented as: amplification including only the 5' segment of the MLL gene (1 patient), trisomy 11 (3 patients), partial trisomy 11q (2 patients), isochromosome 11q (1 patient), and multiple amplification of specific regions (3 patients). In two cases, amplification involved parts of not only long arm but also of short arm of the chromosome 11: 11p15 and 11p11.1 to 11p13. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13).

    Science.gov (United States)

    Panagopoulos, Ioannis; Gorunova, Ludmila; Davidson, Ben; Heim, Sverre

    2015-02-28

    Multicystic mesothelioma is a rare disease of unknown etiology and pathogenesis. Nothing has been known about the cytogenetic and molecular genetic features of these tumors. Here we present the first cytogenetically analyzed multicystic mesothelioma with the karyotype 46,XX,t(7;17)(p13;q23),t(8;11)(q23;p13). RNA-sequencing showed that the t(7;17)(p13;q23) generated a chimeric TNS3-MAP3K3 gene, which codes for a chimeric protein kinase, as well as the reciprocal MAP3K3-TNS3 in which the region of TNS3 coding for the SH2_Tensin_like region and the tensin phosphotyrosine-binding domain is under the control of the MAP3K3 promoter. The other translocation, t(8;11)(q23;p13), generated a chimeric ZFPM2-ELF5 gene which codes for a chimeric transcription factor in which the first 40 amino acids of ELF5 are replaced by the first 100 amino acids of ZFPM2. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcripts. The finding of acquired clonal chromosome abnormalities in cells cultured from the lesion and the presence of the TNS3-MAP3K3 chimeric protein kinase and the ZFPM2-ELF5 chimeric transcription factor confirm the neoplastic nature of multicystic mesothelioma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Peripheral blood complete remission after splenic irradiation in Mantle-Cell Lymphoma with 11q22-23 deletion and ATM inactivation

    Directory of Open Access Journals (Sweden)

    Galliano Marco

    2006-09-01

    Full Text Available Abstract Mantle Cell Lymphoma (MCL is a well-known histological and clinical subtype of B-cell non-Hodgkin's Lymphomas. It is usually characterized by an aggressive disease course, presenting with advanced stage disease at diagnosis and with low response rates to therapy. However few cases of indolent course MCL have been described. We herein report a case of MCL with splenomegaly and peripheral blood involvement as main clinical features. The patient underwent moderate dose splenic radiation therapy and achieved spleen downsizing and peripheral blood complete remission. Splenic irradiation has been extensively used in the past as palliative treatment in several lymphoproliferative disorders and a systemic effect and sometimes peripheral blood complete remissions have been observed. Mainly advocated mechanisms responsible for this phenomenon are considered direct radiation-induced apoptotic cell death, immune modulation via proportional changes of lymphocyte subsets due to known differences in intrinsic radiosensitivity and a radiation-induced cytokine release. The peculiar intrinsic radiosensitivity pattern of lymphoid cells could probably be explained by well-defined individual genetic and molecular features. In this context, among NHLs, MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated inactivation. While the ATM gene is thought to play a key-role in detecting radiation-induced DNA damage (expecially Double Strand Breaks, recent in vitro data support the hypothesis that ATM loss may actually contribute to the radiosensitivity of MCL cells. ATM status was retrospectively investigated in our patient, with the tool of Fluorescence In Situ Hybridization, showing a complete inactivation of a single ATM allele secondary to the deletion of chromosomal region 11q22-23. The presence of this kind of cytogenetic aberration may be regarded in the future as a potential predictive marker of radiation response.

  19. Localization of a gene for autosomal dominant Larsen syndrome to chromosome region 3p21.1-14.1 in the proximity of, but distinct from the COL7A1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Vujic, M.; Hallstensson, K.; Wahlstroem, J. [East Hospital, Gothenburg (Sweden)] [and others

    1995-11-01

    Larsen syndrome (LS) is a skeletal dysplasia (osteochondrodysplasia) in which multiple dislocations of the large joints are the major feature. Nosology in this group of diseases, which constitutes 8% of Mendelian disorders in man, is primarily based on clinical and radiographic features. Hopes for more accurate classification grounds are currently being met by progress in elucidation of underlying genetic defects. We have performed linkage analysis in a large Swedish kindred with autosomal dominant LS and found the gene (LAR1) to be strongly linked to chromosome 3p markers (Z{sub max} = 13.4 at {theta} = .00). Recombination analysis indicates that the LAR1 locus is located in a region defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to chromosome region 3p21.1-14.1. Linkage and recombination analysis of a COL7A1 PvuII intragenic polymorphism versus LS and chromosome 3 markers indicate that COL7A1 is located close to, but distinct from, the LAR1 locus. 33 refs., 6 figs., 3 tabs.

  20. Testicular microlithiasis in two boys with a chromosomal abnormality

    Directory of Open Access Journals (Sweden)

    Joery Goede

    2012-01-01

    Full Text Available A nine and 13-year-old boy, previously diagnosed with 18q syndrome and an 11q deletion, respectively were diagnosed with testicular microlithiasis (TM. Both cases demonstrate that TM occurs in patients with various chromosomal abnormalities

  1. [Clinical characteristics of acute myeloid leukemia with t (16;21) (p11;q22):nine cases report and literature review].

    Science.gov (United States)

    Ouyang, M; Xu, L P; Wang, Y; Zhu, H H; Qin, Y Z; Lai, Y Y; Liu, Y R; Jiang, B; Huang, X J; Jiang, H

    2016-03-01

    To analyze the biological and clinical characteristics of acute myeloid leukemia (AML) with t (16;21) (p11;q22), and the curative effect and prognosis. A retrospective study was conducted in nine cases with AML with t(16;21) (p11;q22) from January, 2009 to December, 2014 in People's Hospital of Peking University. Of 1 372 AML patients, 9 cases with t(16;21) (p11;q22), 4 males and 5 females, were identified. According to the FAB classification, 1 case was classified as M1, 5 as M2, 1 as M4, 2 as M5. Three patients have morphological cavity at the time of diagnosis. Immunophenotypic features showed the positive CD117, CD13, CD33 and CD34, especially CD56. 5 cases were identified as complex karyotype abnormalities, besides from t (16;21) (p11;q22). All cases could be detected TLS/FUS-ERG fusion genes. 9 cases acquired complete remission (CR) after chemotherapy. 2 cases were only treated with chemotherapy and relapsed after 5 months and 16 months, and died at 10 months and 27 months after diagnosis. 7 of 9 cases accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) after chemotherapy, the median survival for 21 months (11-46 months). Summarized the 42 cases of adult AML with t (16;21) (p11;q22) from literature, 27 cases with chemotherapy alone, 15 cases underwent HSCT, the median survival for 10 (95% CI 1-17) months and 18(95% CI 2-76) months, respectively. The difference was statistically significant (P<0.001). AML with t (16;21) (p11;q22) was rare, it has a special form and distinct immunophenotypic characteristics and poor prognosis, allo-HSCT could improve the prognosis and should be considered after CR.

  2. 11q terminal deletion and combined immunodeficiency (Jacobsen syndrome): Case report and literature review on immunodeficiency in Jacobsen syndrome.

    Science.gov (United States)

    Blazina, Štefan; Ihan, Alojz; Lovrečić, Luca; Hovnik, Tinka

    2016-12-01

    Antibody deficiency is common finding in patients with Jacobsen syndrome (JS). In addition, there have been few reports of T-cell defects in this condition, possibly because most of the reported patients have not been specifically evaluated for T-cell function. In this article, we present a child with an 11q deletion and combined immunodeficiency and we perform a literature overview on immunodeficiency in JS. Our patient presented with recurrent bacterial and prolonged viral infections involving the respiratory system, as well as other classic features of the syndrome. In addition to low IgM, IgG4, and B-cells, also low recent thymic emigrants, helper and naïve T-cells were found. We propose that patients with Jacobsen syndrome need thorough immunological evaluations as T-cell dysfunction might be more prevalent than previously reported. Patients with infections consistent with T-cell defects should be classified as having combined immunodeficiency. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Partial deletion of the long arm of chromosome 11: ten Japanese children.

    Science.gov (United States)

    Ono, J; Hasegawa, T; Sugama, S; Sagehashi, N; Hase, Y; Oku, K; Endo, Y; Ohdo, S; Ishikiriyama, S; Tsukamoto, H; Okada, S

    1996-12-01

    The clinical features of partial deletion 11q were correlated with the size of the deleted region. Ten Japanese children with partial deletion of 11q were investigated. They were divided into three groups. Three patients in the first group had interstitial deletions and preserved subband q24.1. Six patients in the second group demonstrated terminal deletion of 11q including subband q24.1, with typical features of 11q- syndrome (Jacobsen syndrome). The third group included only one patient, who had terminal deletion of 11q without characteristics of typical 11q- syndrome. Prominent features of patients in the first group included severe mental and motor developmental delay, seizures, cleft lip and palate, and ophthalmological findings. Patients in the second group showed mild to moderate developmental delays without deterioration. Abnormalities in neuroimages, high intensity in the cerebral white matter in T2-weighted magnetic resonance (MR) images, and recurrent infections were not observed after the age of 7 years. The subject in the third group, with the smallest amount of deleted chromosome, did not show developmental delays, suggesting that some unknown genes related to developmental delays may be located adjacent to subband q24.1. Variation in the deleted parts of 11q resulted in different clinical features in each group.

  4. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

    DEFF Research Database (Denmark)

    French, Juliet D; Ghoussaini, Maya; Edwards, Stacey L

    2013-01-01

    Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causativ...

  5. Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage.

    Science.gov (United States)

    Jones, C; Müllenbach, R; Grossfeld, P; Auer, R; Favier, R; Chien, K; James, M; Tunnacliffe, A; Cotter, F

    2000-05-01

    Folate-sensitive fragile sites are associated with the expansion and hypermethylation of CCG-repeats. The fragile site in 11q23.3, FRA11B, has been shown to cause chromosome deletions in vivo, its expression being associated with Jacobsen (11q-) syndrome. However, the majority of Jacobsen deletions are distal to FRA11B and are not related to its expression. To test the hypothesis that other unidentified fragile sites might be located in 11q23.3-24 and may cause these deletions, we have identified and characterised CCG-trinucleotide repeats within a 40 Mb YAC contig spanning distal chromosome 11q. Only eight CCG-repeats were identified within the entire YAC contig (not including FRA11B ), six of which map to the region of 11q23.3-24 that includes Jacobsen deletions. We have previously collated the deletion mapping data of 24 Jacobsen patients with the physical map of chromosome 11q, and accurately localised six breakpoints to short intervals corresponding to individual YAC clones. We now show that in each of these cases, YAC clones found to contain a deletion breakpoint also contain a CCG-repeat. The improved analysis of one of these deletions, together with those of several new Jacobsen cases, further strengthens this association by localising five breakpoints to individual PAC clones containing CCG-repeats. These data provide strong evidence for the non-random clustering of chromosome deletion breakpoints with CCG-repeats, and suggests that they may play an important role in a common mechanism of chromosome breakage.

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

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.; Mertz, A.; Rappold, G. [Univ. of Heidelberg (Germany)] [and others

    1995-09-01

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

  7. Linkage analysis between manic-depressive illness and markers on the long arm of chromosome 11

    Energy Technology Data Exchange (ETDEWEB)

    Ewald, H.; Mors, O. [Institute of Basic Psychiatric Research, Copenhagen (Denmark); Eiberg, H. [Univ. of Copenhagen (Denmark)] [and others

    1995-10-09

    The long arm of chromosome 11 is one of the most interesting regions in the search for major genes involved in the etiology of manic-depressive illness. Several candidate genes have been identified, including the gene encoding the dopamine D2 receptor, the M1 muscarinic receptor, and porfobillinogen deaminase. Furthermore, different families with co-segregation of psychiatric illness and structural chromosome abnormalities involving regions 11q21, 11q22.3, and 11q25 have been reported. Using narrow as well as broad phenotypic models, conservative genetic parameters, models with dominant or recessive modes of inheritance, and various methods to reduce misclassification, the present study did not find evidence for a major gene causing manic-depressive illness on the long arm of chromosome 11. In the broader phenotypic models multi-point analyses excluded at least 11q14 to 11q23.3, approximately 60 cM, even in one large family. Assuming homogeneity, close linkage to DRD2 was excluded for all dominant models, and also in the affecteds-only analyses in the large family alone. 38 refs., 3 figs., 1 tab.

  8. Proximal Hypospadias

    Science.gov (United States)

    Kraft, Kate H.; Shukla, Aseem R.; Canning, Douglas A.

    2011-01-01

    Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. The spectrum of abnormalities may also include ventral curvature of the penis, a dorsally redundant prepuce, and atrophic corpus spongiosum. Due to the severity of these abnormalities, proximal hypospadias often requires more extensive reconstruction in order to achieve an anatomically and functionally successful result. We review the spectrum of proximal hypospadias etiology, presentation, correction, and possible associated complications. PMID:21516286

  9. The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

    DEFF Research Database (Denmark)

    Wang, Yifan; Bernhardy, Andrea J; Cruz, Cristina

    2016-01-01

    and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR......Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression...... carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance...

  10. Haplotype dependent association of rs7927894 (11q13.5) with atopic dermatitis and chronic allergic rhinitis: A study in ECAP cohort.

    Science.gov (United States)

    Ponińska, Joanna Kinga; Samoliński, Bolesław; Tomaszewska, Aneta; Raciborski, Filip; Samel-Kowalik, Piotr; Walkiewicz, Artur; Lipiec, Agnieszka; Piekarska, Barbara; Krzych-Fałta, Edyta; Namysłowski, Andrzej; Kostrzewa, Grażyna; Pawlik, Andrzej; Jasek, Monika; Wiśniewski, Andrzej; Kuśnierczyk, Piotr; Majewski, Sławomir; Płoski, Rafał

    2017-01-01

    The T allele of rs7927894 (at 11q13.5) was associated with atopic dermatitis and other allergic diseases. Our purpose was to replicate the association with allergic phenotypes and explore the role of rs7927894 in predisposing to persistent allergic rhinitis and atopic asthma. We also wanted to explore if other SNPs at 11q13.5 contributed to effect of rs7927894. We studied patients with atopic dermatitis (N = 270), atopic asthma (N = 486), persistent allergic rhinitis (N = 589) and controls matched for age, sex and region (N = 540, N = 372 and N = 1178, respectively). We found that rs7927894 T was associated with atopic dermatitis (OR = 1.39, CI: 1.12-1.73, P = 0.003) and independently with persistent allergic rhinitis (OR = 1.24, CI:1.07-1.43, P = 0.0043, Pcorrected = 0.013) but not atopic asthma. Analysis of additional tagging SNPs (rs7930763, rs2513517, rs7125552) showed that effect of rs7927894 T was limited to haplotypes encoding G at rs7125552. In conclusion, rs7927894 T is associated not only with atopic dermatitis but also persistent allergic rhinitis. Since these effects are haplotype dependent rs7927894 alone does not account for the association between 11q13.5 and atopic dermatitis/persistent allergic rhinitis.

  11. Amplicon mapping and expression profiling identify the fas-associated death domain gene as a new driver in the 11q13.3 amplicon in Laryngeal/Pharyngeal cancer

    NARCIS (Netherlands)

    Gibcus, J.H.; Menkema, L.; Mastik, M.F.; Hermsen, M.A.; de Bock, G.H.; van Velthuysen, M.L.; Takes, R.P.; Kok, K.; Alvarez Marcos, C.A.; van der Laan, B.F.; van den Brekel, M.W.; Langendijk, J.A.; Kluin, P.M.; van der Wal, J.E.; Schuuring, E.

    2007-01-01

    Purpose: Amplification of the 11q13 region is a frequent event in human cancer, The highest incidence (36%) is found in head and neck squamous cell carcinomas. Recently, we reported that the amplicon size in 30 laryngeal and pharyngeal carcinomas with 11q13 amplification is determined by unique

  12. Comparative analysis of vertebrate EIF2AK2 (PKR genes and assignment of the equine gene to ECA15q24–q25 and the bovine gene to BTA11q12–q15

    Directory of Open Access Journals (Sweden)

    Zharkikh Andrey A

    2006-09-01

    Full Text Available Abstract The structures of the canine, rabbit, bovine and equine EIF2AK2 genes were determined. Each of these genes has a 5' non-coding exon as well as 15 coding exons. All of the canine, bovine and equine EIF2AK2 introns have consensus donor and acceptor splice sites. In the equine EIF2AK2 gene, a unique single nucleotide polymorphism that encoded a Tyr329Cys substitution was detected. Regulatory elements predicted in the promoter region were conserved in ungulates, primates, rodents, Afrotheria (elephant and Insectifora (shrew. Western clawed frog and fugu EIF2AK2 gene sequences were detected in the USCS Genome Browser and compared to those of other vertebrate EIF2AK2 genes. A comparison of EIF2AK2 protein domains in vertebrates indicates that the kinase catalytic domains were evolutionarily more conserved than the nucleic acid-binding motifs. Nucleotide substitution rates were uniform among the vertebrate sequences with the exception of the zebrafish and goldfish EIF2AK2 genes, which showed substitution rates about 20% higher than those of other vertebrates. FISH was used to physically assign the horse and cattle genes to chromosome locations, ECA15q24–q25 and BTA11q12–15, respectively. Comparative mapping data confirmed conservation of synteny between ungulates, humans and rodents.

  13. Pericentric inversion of the Y chromosome of infertile male.

    Science.gov (United States)

    Tomomasa, H; Adachi, Y; Iwabuchi, M; Oshio, S; Umeda, T; Iino, Y; Takano, T; Nakahori, Y

    2000-01-01

    The authors report a case with pericentric inversion of the Y chromosome associated with asthenonecrozoospermia. The conventional karyotype was 46, X, inv (Y) (p11q11). Polymerase chain reaction (PCR) analysis revealed the deletion of DYZ3, DYS139, and RBM1. Three-color fluorescent in situ hybridization (FISH) analysis of the sperm chromosomes showed normal ratio between X- and Y-bearing sperm. In this case, the frequencies of aneuploidy of the sperm are not significantly higher compared with those from the normal volunteers. Cytogenetic analysis is recommended when the patients with pericentric inversion of the Y chromosome are attending an infertility clinic.

  14. Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ruey-Bing; Fuelle, H.J.; Garbers, D.L. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

    1996-02-01

    We recently cloned three membrane guanylyl cyclases, designated GC-D, CG-E, and GC-F, from rat olfactory tissue and eye. Amino acid sequence homology suggests that they may compose a new gene subfamily of guanylyl cyclase receptors specifically expressed in sensory tissues. Their chromosomal localization was determined by mouse interspecific backcross analysis. The GC-D, CG-E, and GC-F genes (Gucy2d, Gucy2e, and Gucy2f) are dispersed through the mouse genome in that they map to chromosomes 7, 11, and X, respectively. Close proximity of the mouse GC-D gene to Omp (olfactory marker protein) and Hbb (hemoglobin {beta}-chain complex) suggests that the human homolog gene maps to 11p15.4 or 11q13.4-q14.1. The human GC-F gene was localized to the long arm of chromosome Xq22 by fluorescence in situ hybridization. The genomic organization of the mouse GC-E, and GC-F genomic clones contain identical exon-intron boundaries within their extracellular and cytoplasmic domains, demonstrating the conservation of the gene structures. With respect to human genetic diseases, GC-E mapped to mouse chromosome 11 within a syntenic region on human chromosome 17p13 that has been linked with loci for autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. No apparent disease loci have been yet linked to the locations of the GC-D or GC-F genes. 39 refs., 3 figs., 2 tabs.

  15. A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

    Directory of Open Access Journals (Sweden)

    Joyce Siew Yong Low

    Full Text Available Nasopharyngeal carcinoma (NPC is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV. CNV is an inherent structural variation that has been found to be involved in cancer predisposition.A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256 were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677 and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124.Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR = 7.27; 95% CI = 2.96-17.88 overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11 overlapping MICA/HCP5/HCG26 genes.Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

  16. A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

    Science.gov (United States)

    Low, Joyce Siew Yong; Chin, Yoon Ming; Mushiroda, Taisei; Kubo, Michiaki; Govindasamy, Gopala Krishnan; Pua, Kin Choo; Yap, Yoke Yeow; Yap, Lee Fah; Subramaniam, Selva Kumar; Ong, Cheng Ai; Tan, Tee Yong; Khoo, Alan Soo Beng; Ng, Ching Ching

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition. A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124). Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes. Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

  17. Molecular cytogenetic detection of chromosome 15 deletions in patients with Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, D.E.; Weksberg, R.; Shuman, C. [Hospital for Sick Children, Toronto (Canada)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct genetic disorders involving alterations of chromosome 15q11-q13. Approximately 75% of individuals with PWS and AS have deletions within 15q11-q13 by molecular analysis. We have evaluated fluorescence in situ hybridization (FISH) for the clinical laboratory detection of del(15)(q11q13) using the cosmid probes D15S11 and GABRB3 (ONCOR, Gaithersburg, NY). 4/4 PWS and 1/1 AS patients previously identified as having cytogenetic deletions were deleted for both probes. In a prospectively ascertained series of 54 patient samples referred to rule out either PWS or AS, 8 were deleted for D15S11 and GABRB3. In addition, an atypical deletion patient with PWS was also identified who was found to be deleted for GABRB3 but not D15S11. The SNRPN locus was also deleted in this patient. Only 4 of the 9 patient samples having molecular cytogenetic deletions were clearly deleted by high resolution banding (HRB) analysis. The microscopic and submicroscopic deletions have been confirmed by dinucleotide (CA) repeat analysis. Microsatellite polymorphism analysis was also used to demonstrate that five non-deletion patients in this series had biparental inheritance of chromosome 15, including region q11-q13. Deletions were not detected by either HRB, FISH or microsatellite polymorphism analysis in samples obtained from parents of the deletion patients. Methylation studies of chromosome 15q11-q13 are in progress for this series of PWS and AS families. FISH analysis of chromosome 15q11-q13 in patients with PWS and AS is a rapid, sensitive and reliable method for deletion detection.

  18. Chromosome Abnormalities

    Science.gov (United States)

    ... XX), and males have an X and a Y chromosome (XY). The mother and father each contribute one ... chromosome has attached to another at the centromere. Inversions: A portion of the chromosome has broken off, turned upside down, and reattached. ...

  19. Evidence-based mini-review: the role of alkylating agents in the initial treatment of chronic lymphocytic leukemia patients with the 11q deletion.

    Science.gov (United States)

    Ding, Wei; Ferrajoli, Alessandra

    2010-01-01

    A 55-year-old man presented with fever, night sweats, and weight loss of about 20 lbs. in the prior 6 months. Physical examination revealed multiple cervical, axillary, and inguinal lymphadenopathy. The spleen was enlarged. A complete blood count revealed leukocytosis with absolute lymphocytosis: 30,000/μL. Peripheral blood-flow cytometric analysis showed a clonal lymphocyte population with immunophenotypes positive for CD5, CD20(dim), and monotypic kappa light chain. Fluorescence in situ hybridization (FISH) analysis revealed del(11q22.3), but negative for t(11:14). What should be used to treat his chronic lymphocytic leukemia (CLL) disease?

  20. Permanent Neonatal Diabetes in a Patient with a KCNJ11/Q52R Mutation Accompanied by Intermittent Hypoglycemia and Liver Failure

    Directory of Open Access Journals (Sweden)

    Majzoub JosephA

    2009-09-01

    Full Text Available The most common monogenic cause of neonatal diabetes is mutation in KCNJ11, which encodes a potassium channel in pancreatic beta cells. Some mutations in this gene, including Q52R, have been described in association with neurological deficits, but never with hepatic involvement. We report the second case of neonatal diabetes in a patient with a KCNJ11 Q52R mutation. This patient's clinical course did not include obvious neurological deficits despite the presence of prematurity, but did include transient hyperbilirubinemia, and recurrent hypoglycemia. The phenotypic spectrum of KCNJ11 mutations is variable and is likely influenced by additional genetic and environmental factors.

  1. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3

    Science.gov (United States)

    Purdue, Mark P.; Johansson, Mattias; Zelenika, Diana; Toro, Jorge R.; Scelo, Ghislaine; Moore, Lee E.; Prokhortchouk, Egor; Wu, Xifeng; Kiemeney, Lambertus A; Gaborieau, Valerie; Jacobs, Kevin B; Chow, Wong-Ho; Zaridze, David; Matveev, Vsevolod; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Péter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S.; Davis, Faith G.; Schwartz, Kendra L.; Banks, Rosamonde E; Selby, Peter J; Harnden, Patricia; Berg, Christine D.; Hsing, Ann W.; Grubb, Robert L.; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Françoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J.; Ramón Quirós, José; Sanchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Peeters, Petra HM; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Börje; Overvad, Kim; Tjønneland, Anne; Romieu, Isabelle; Riboli, Elio; Mukeria, Anush; Shangina, Oxana; Stevens, Victoria L; Thun, Michael J; Diver, W. Ryan; Gapstur, Susan M; Pharoah, Paul D; Easton, Douglas F; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Njølstad, Inger; Tell, Grethe; Stoltenberg, Camilla; Kumar, Rajiv; Koppova, Kvetoslava; Cussenot, Olivier; Benhamou, Simone; Oosterwijk, Egbert; Vermeulen, Sita H.; Aben, Katja K.H.; van der Marel, Saskia L.; Ye, Yuanqing; Wood, Christopher G.; Pu, Xia; Mazur, Alexander M; Bulygina, Eugenia S; Chekanov, Nikolai N; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Blanche, Hélène; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F.; Skryabin, Konstantin G; McKay, James D; Rothman, Nathaniel; Chanock, Stephen J.; Lathrop, Mark; Brennan, Paul

    2011-01-01

    We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 cases and 8,505 controls of European background from 11 studies, and followed up 6 SNPs in three replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r2 = 0.99 in controls), rs11894252 (P = 1.8×10−8) and rs7579899 (P = 2.3×10−9), map to EPAS1 on 2p21, which encodes hypoxia-inducible- factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13, contains no characterized genes (P = 7.8×10−14). In addition, we observed a promising association on 12q24.31 for rs4765623 which maps to the scavenger receptor class B, member 1 (SCARB1) gene (P = 2.6×10−8). Our study reports novel genomic regions associated with RCC risk that may lead to new etiological insights. PMID:21131975

  2. Ring chromosome 13 syndrome characterized by high resolution array based comparative genomic hybridization in patient with 47, XYY syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Fu Fang

    2011-03-01

    Full Text Available Abstract Introduction The co-occurrence of ring chromosome 13 syndrome and 47, XYY syndrome in the same individual is rare. To the best of our knowledge, this is the first report of the co-existence of this kind of chromosome aberrations. At present, the deletion 13q syndrome is divided into three groups based on the deletion's location relative to chromosomal band 13q32. Group 1 (proximal to q32 and group 2 (including q32 have shown distinctive phenotypes including mental retardation and growth deficiency. Group 3 (q33-34 deletion is defined by the presence of mental retardation but there is usually an absence of major malformations. Case presentation We describe a 10-month-old Chinese Han boy presenting with severe mental retardation, profound congenital bilateral hearing loss with a terminal 13q33.2 deletion and multiple malformations. Routine chromosome analysis disclosed a de novo complex karyotype 47, XYY, r(13(p11q34. Further investigation by high resolution array-based comparative genomic hybridization delineated an 8.5 Mb terminal deletion on the long arm of chromosome 13(13q33.2→q34. Conclusion The co-occurrence of double syndromes in the same individual is rare and its clinical presentation is variable depending on the predominating abnormality or a combination of the effect of both. Hearing impairment is suggested as another new clinical feature to 13qter deletion. This case report will contribute to more accurate genetic counselling and provide further insight to the syndrome.

  3. Marker chromosomes.

    Science.gov (United States)

    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.

  4. Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11

    Directory of Open Access Journals (Sweden)

    Bader Scott

    2005-07-01

    Full Text Available Abstract Background Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11. Results In a first step, we performed high-resolution arrayCGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene. Conclusion Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.

  5. Different mechanisms causing loss of mismatched human leukocyte antigens in relapsing t(6;11)(q27;q23) acute myeloid leukemia after haploidentical transplantation.

    Science.gov (United States)

    Tamaki, Hiroya; Fujioka, Tatsuya; Ikegame, Kazuhiro; Yoshihara, Satoshi; Kaida, Katsuji; Taniguchi, Kyoko; Kato, Ruri; Tokugawa, Taduko; Nakata, Jun; Inoue, Takayuki; Yano, Aya; Eguchi, Ryoji; Okada, Masaya; Maruya, Etsuko; Saji, Hiroh; Ogawa, Hiroyasu

    2012-12-01

    Mismatched human leukocyte antigens (HLAs) on leukemic cells can be targeted by donor T cells in HLA-mismatched/haploidentical stem cell transplantation. In two cases of acute myeloid leukemia with t(6;11)(q27;q23) abnormality presented here, flow cytometry analysis showed a lack of HLA-A unshared between recipients and donors in relapsing leukemic cells after HLA-haploidentical transplantation. However, high-resolution HLA genotyping showed that one case lacked a corresponding HLA haplotype, whereas the other preserved it. These cases suggest that leukemic cells, which lacked mismatched HLA expression, might have an advantage in selective expansion under donor T-cell immune surveillance after HLA-haploidentical transplantation. Most importantly, down-regulation of unshared HLA expression potentially occurs by genetic alterations other than loss of HLA alleles. © 2012 John Wiley & Sons A/S.

  6. Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2.

    Science.gov (United States)

    Jones, C; Penny, L; Mattina, T; Yu, S; Baker, E; Voullaire, L; Langdon, W Y; Sutherland, G R; Richards, R I; Tunnacliffe, A

    1995-07-13

    The fragile site FRA11B has been localized to the p(CCG)n repeat of the CBL2 proto-oncogene. A proportion of Jacobsen (11q-) syndrome patients inherited a chromosome carrying a CBL2 p(CCG)n expansion, which was truncated close to FRA11B. These results have broad implications for the role of p(CCG)n repeat expansion in the aetiology of genetic disease involving chromosome rearrangements.

  7. Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Michaela Aubele

    2002-01-01

    Full Text Available Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH. Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow‐up period of 99 months (max. 193 months by CGH to determine the prognostic value of chromosomal gains and losses. The mean number of chromosomal imbalances per tumor was 6.5±0.7 (range 2 to 18. The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (p≤0.05 was found between DNA‐diploid and non‐diploid tumors (gain on chromosome 17. Differences were also noted between tumors progressing to distant metastases within the period of follow‐up and those which do not (gains on 11q13 and 12q24; loss on 12q. Significant univariate correlations (p≤0.05 with the metastasis‐free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non‐diploid and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24. In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis‐free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status. The prognostic value of chromosomal alterations – some of them by inverse correlation – suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients.

  8. Polytene chromosome map and inversion polymorphism in Drosophila mediopunctata

    Directory of Open Access Journals (Sweden)

    Ananina Galina

    2002-01-01

    Full Text Available Drosophila mediopunctata belongs to the tripunctata group, and is one of the commonest Drosophila species collected in some places in Brazil, especially in the winter. A standard map of the polytene chromosomes is presented. The breakpoints of the naturally occurring chromosomal rearrangements are marked on the map. The distribution of breaking points through the chromosomes of D. mediopunctata is apparently non-random. Chromosomes X, II and IV show inversion polymorphisms. Chromosome II is the most polymorphic, with 17 inversions, 8 inversions in the distal region and 9 in the proximal region. Chromosome X has four different gene arrangements, while chromosome IV has only two.

  9. Combined fluorescent-chromogenic in situ hybridization for identification and laser microdissection of interphase chromosomes.

    Directory of Open Access Journals (Sweden)

    Nerea Paz

    Full Text Available Chromosome territories constitute the most conspicuous feature of nuclear architecture, and they exhibit non-random distribution patterns in the interphase nucleus. We observed that in cell nuclei from humans with Down Syndrome two chromosomes 21 frequently localize proximal to one another and distant from the third chromosome. To systematically investigate whether the proximally positioned chromosomes were always the same in all cells, we developed an approach consisting of sequential FISH and CISH combined with laser-microdissection of chromosomes from the interphase nucleus and followed by subsequent chromosome identification by microsatellite allele genotyping. This approach identified proximally positioned chromosomes from cultured cells, and the analysis showed that the identity of the chromosomes proximally positioned varies. However, the data suggest that there may be a tendency of the same chromosomes to be positioned close to each other in the interphase nucleus of trisomic cells. The protocol described here represents a powerful new method for genome analysis.

  10. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  11. ATM modulates the loading of recombination proteins onto a chromosomal translocation breakpoint hotspot.

    Directory of Open Access Journals (Sweden)

    Jiying Sun

    Full Text Available Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots.

  12. Twin Pregnancy Obtention of Patient with Nonmosaic Klinefelter's Syndrome and His Wife with Chromosome 9 Inversion by ICSI Treatment.

    Science.gov (United States)

    Zhang, Changjun; Peng, Haiying; Hu, Yueyue

    2013-07-01

    A 24-year-old man was diagnosed with klinefelter's syndrome (KS) and his wife was found to have an inversion on chromosome 9-46, XX, inv (9) (p11q21)- because of infertility. Intracytoplasmic sperm injection (ICSI) was performed for fertilization after fluorescence in-situ hybridization (FISH) was used to analyze the aneuploidy rate of the X and Y chromosomes of the ejaculated sperms of the patient, and 99 sperms were haploid among 100 sperms that were to be analyzed. A twin pregnancy was achieved. The chromosomes of the two fetuses were identified as 46, XY and 46, XY, inv (9)(p11q21) after a prenatal diagnosis at 18 weeks gestation. Two healthy twins were born through caesarean section at 32 weeks gestation because of premature rupture of membranes (PROM).

  13. Interphase chromosomes

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Interphase chromosomes. Genomes within interphase nuclei occupy discrete, three-dimensional regions known as 'chromosome territories' (Bridger and Bickmore, 1998, Cremer and Cremer, 2001, Parada and Misteli, 2002). The non-randomness of CT organization within an ...

  14. Modeling Chromosomes

    Science.gov (United States)

    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…

  15. De novo interstitial duplication of 15q11.2-q13.1 with complex maternal uniparental trisomy for the 15q11-q13 region in a patient with Prader-Willi syndrome.

    Science.gov (United States)

    Burrage, Lindsay C; Person, Richard E; Flores, Angela; Villanos, Maria Theresa M; Bi, Weimin; Wiszniewska, Joanna; Bacino, Carlos A

    2012-10-01

    Prader-Willi syndrome is caused by the lack of paternal contribution for the imprinted 15q11-q13 region that originates through a number of mechanisms such as paternal deletion of 15q11-q13, maternal uniparental disomy, or by an imprinting defect due to epimutations in the paternal imprinting center. In the present report, we describe a female patient with complex maternal uniparental trisomy for the 15q11-q13 Prader-Willi syndrome critical region due to a de novo interstitial duplication of 15q11-q13 region that is present in one of the maternal homologs. As a result, the patient has three maternally derived copies of the Prader-Willi syndrome critical region and absence of paternal 15 contribution and thus, presents with a Prader-Willi syndrome phenotype with risk for developing additional phenotypes (e.g., autism and psychiatric phenotypes) characteristic of maternally derived duplications of this region. We suggest that this is a rather unique mechanism leading to Prader-Willi syndrome that has not been previously reported. Copyright © 2012 Wiley Periodicals, Inc.

  16. CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes.

    Science.gov (United States)

    Reindl, Carola; Quentmeier, Hilmar; Petropoulos, Konstantin; Greif, Philipp A; Benthaus, Tobias; Argiropoulos, Bob; Mellert, Gudrun; Vempati, Sridhar; Duyster, Justus; Buske, Christian; Bohlander, Stefan K; Humphries, Keith R; Hiddemann, Wolfgang; Spiekermann, Karsten

    2009-04-01

    CBL is a negative regulator of activated receptor tyrosine kinases (RTK). In this study, we determined the frequency of CBL mutations in acute leukemias and evaluated the oncogenic potential of mutant CBL. The cDNA of 300 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL) patients and 82 human leukemic cell lines was screened for aberrations in the linker and RING finger domain of CBL. The oncogenic potential of identified mutants was evaluated in hematopoietic cells. We identified 3 of 279 AML/MDS patients expressing CBL exon 8/9 deletion mutants. Three of four cases at diagnosis expressed deleted transcripts missing exon 8 or exon 8/9. In remission samples a weak or no expression of mutant CBL was detected. No aberrations were found in normal hematopoietic tissues. One of 116 sequenced AML/MDS cases carried a R420G missense mutation. All AML/MDS patients with identified CBL mutants belonged to the core binding factor and 11q deletion AML subtypes. Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. Expression of CBLDeltaexon8 and CBLDeltaexon8+9 in FLT3-WT-Ba/F3 cells induced growth factor-independent proliferation associated with autophosphorylation of FLT3 and activated the downstream targets signal transducer and activator of transcription 5 (STAT5) and protein kinase B (AKT). FLT3 ligand-dependent hyperproliferation of CBL mutant cells could be abrogated by treatment with the FLT3 PTK inhibitor PKC412 (midostaurin). CBL exon8/9 mutants occur in genetically defined AML/MDS subtypes and transform hematopoietic cells by constitutively activating the FLT3 pathway. This phenotype resembles the one of mutated RTKs and suggests that CBL mutant AML patients might benefit from treatment with FLT3 PTK inhibitors.

  17. Jacobsen syndrome: report of a patient with severe eye anomalies, growth hormone deficiency, and hypothyroidism associated with deletion 11 (q23q25) and review of 52 cases.

    OpenAIRE

    Pivnick, E K; Velagaleti, G V; Wilroy, R S; Smith, M E; Rose, S R; Tipton, R E; Tharapel, A T

    1996-01-01

    We have evaluated a patient with Jacobsen syndrome. The patient presented with growth retardation, hypotonia, trigonocephaly, telecanthus, downward slanting palpebral fissures, bilateral inferior colobomas (of the iris, choroid, and retina), hydrocephalus, central nervous system (CNS) abnormalities, and an endocardial cushion defect, features commonly seen in Jacobsen syndrome. Endocrine evaluation showed growth hormone deficiency and central hypothyroidism. Chromosome analysis showed a 46,XX...

  18. Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader-Willi syndrome and Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Delach, J.A.; Rosengren, S.S.; Kaplan, L.; Greenstein, R.M.; Cassidy, S.B.; Benn, P.A.

    1994-08-01

    The development of probes containing segments of DNA from chromosome region 15q11-q13 provides the opportunity to confirm the diagnosis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) by fluorescence in situ hybridization (FISH). We have evaluated FISH studies and high resolution chromosome banding studies in 14 patients referred to confirm or rule out AS. In four patients (three from the PWS category and 1 from the AS group) chromosome analysis suggested that a deletion was present but FISH failed to confirm the finding. In one AS group patient, FISH identified a deletion not detectable by high resolution banding. Review of the clinical findings in the discrepant cases suggested that FISH results were correct and high resolution findings were erroneous. Studies with a chromosome 15 alpha satellite probe (D15Z) on both normal and abnormal individuals suggested that incorrect interpretation of chromosome banding may occasionally be attributable to alpha satellite polymorphism but other variation of 15q11-q13 chromosome bands also contributes to misinterpretation. We conclude that patients who have been reported to have a cytogenetic deletion of 15q11-q13 and who have clinical findings inconsistent with PWS and AS should be re-evaluated by molecular genetic techniques. 31 refs., 3 figs., 2 tabs.

  19. Genomic imprinting and human chromosome 15

    Directory of Open Access Journals (Sweden)

    GABRIELA M. REPETTO

    2001-01-01

    Full Text Available Genomic imprinting is a reversible phenomenon that affects the expression of genes depending on their parental origin. The best characterized human disorders resulting from an alteration of the imprinting process are Angelman and Prader-Willi syndromes. They are due to the lack of active maternal or paternal genes, respectively, from chromosome region 15q11q13. Most cases arise via interstitial deletions. We review evidence that other common cytogenetic alterations of this region, interstitial and supernumerary duplications, could be the reciprocal products of the deletions and are also affected by the imprinting phenomenon, given the predominance of maternally-derived duplications in patients ascertained due to developmental delays or autistic features.

  20. Establishment of Sequence-Tagged Sites on 15q11-q13 by Alu-Vector PCR Cloning of Yac-Generated Fragments

    Directory of Open Access Journals (Sweden)

    W. S. Kim

    1996-01-01

    Full Text Available Angelman syndrome (AS is caused by the loss of function of undefined gene(s on human chromosome 15. The majority of subjects have deletions involving maternally-derived chromosome 15q II-q 13, and the shortest region of deletion overlap (SRO has been localized to the region between D15S10 and D15S113. In this study, yeast artificial chromosomes (YACs, 6G-D4, 9H-D2 and 37D-F9, mapping within the AS SRO, were isolated from the ICI Y AC library. Alu-vector PCR products were amplified from the YACs and from YACs A229A2 and A33FI 0 which had been obtained from the St. Louis Y AC library. The PCR products were cloned and sequenced, and three new sequence-tagged sites were generated within the AS SRO, facilitating the characterization of gene(s involved in the Angelman syndrome.

  1. Non-disjunction of chromosome 18

    DEFF Research Database (Denmark)

    Bugge, M; Collins, A; Petersen, M B

    1998-01-01

    A sample of 100 trisomy 18 conceptuses analysed separately and together with a published sample of 61 conceptuses confirms that an error in maternal meiosis II (MII) is the most frequent cause of non-disjunction for chromosome 18. This is unlike all other human trisomies that have been studied......, which show a higher frequency in maternal meiosis I (MI). Maternal MI trisomy 18 shows a low frequency of recombination in proximal p and medial q, but not the reduction in proximal q observed in chromosome 21 MI non-disjunction. Maternal MII non-disjunction does not fit the entanglement model...... that predicts increased recombination, especially near the centromere. Whereas recent data on MII trisomy 21 show the predicted increase in recombination proximally, maternal MII trisomy 18 has non-significantly reduced recombination. Therefore, chromosome-specific factors must complicate the simple model...

  2. t(4;11 (q21;q23 in acute myeloid leukemia-M0 following treatment [EW92 Protocol] for Ewing's sarcoma Leucemia mielóide aguda-M0 com t(4;11 (q21;q23 após tratamento para sarcoma de Ewing com o protocolo EW92

    Directory of Open Access Journals (Sweden)

    Terezinha J. Marques Salles

    2004-01-01

    Full Text Available We report on a 7-year-old girl with Ewing's Sarcoma (ES who developed a poorly differentiated acute myeloid leukemia (AML-M0 20 months after beginning the EW92 protocol for the treatment of the primary tumor. She received a total dose of 1500 mg of etoposide, a tumor cumulative radiation dose of 35Gy and granulocyte colony-stimulating factor (G-CSF was as predicted in the protocol regimen. At onset of secondary malignancy her laboratorial analysis revealed immature blast cells characterized by CD34+/CD33-/a-MPO+ and a t(4;11(q21;q23 abnormality. This serious complication of ES treatment, which associates etoposide, irradiation and G-CSF schedule, should be weighed against its therapeutic benefits.Nós descrevemos o caso clínico de uma criança do sexo feminino, com 7 anos de idade, portadora de sarcoma de Ewing, que evoluiu com leucemia aguda mielóide pouco diferenciada (LMA-M0 após vinte meses de tratamento utilizando o protocolo EW92. Ela recebeu uma dose total de 1.500 mg de etoposídio, irradiação tumoral na dose total de 35G, e fator de estimulação de colônia granulocítica (G-CSF conforme programação do protocolo terapêutico. Os exames laboratoriais, por ocasião do diagnóstico da segunda malignidade, mostraram células blásticas imaturas caracterizadas pela expressão de CD34+/CD33-/aMPO+ e a translocação t(4;11 (q 21;q23. A exclusão do G-CSF nos esquemas terapêuticos que associam etoposídio e irradiação tumoral se justifica devido a esta séria complicação no tratamento do sarcoma de Ewing.

  3. Epilepsy and electroencephalographic findings in pericentric inversion of chromosome 12.

    Science.gov (United States)

    Grosso, Salvatore; Pucci, Lucia; Farnetani, MariAngela; Di Bartolo, Rosanna Maria; Galimberti, Daniela; Mostardini, Rosa; Anichini, Cecilia; Balestri, Martina; Morgese, Guido; Balestri, Paolo

    2004-08-01

    Epilepsy, together with mental retardation, represents a common manifestation of chromosomal aberrations. Specific electroencephalographic (EEG) and epileptic patterns have been described in several chromosomal disorders, such as Angelman's syndrome, Miller-Dieker syndrome, Wolf-Hirschhorn syndrome, and ring 20 syndrome. A peculiar electroclinical pattern has also been identified in trisomy 12p syndrome. We report three patients with a pericentric inversion of chromosome 12, with breakpoints localized to p11-q13 and affected by epilepsy or EEG anomalies. Two suffered from epilepsy, which, in the clinical course, was mainly characterized by complex partial seizures with a semiology related to the temporal lobe. In one patient, myoclonic absences, head drop, and massive jerky attacks were also present. In both patients, generalized 3 Hz bursts were registered, together with multifocal and focal paroxysmal activity, which were most prominent in the temporoparietal and temporal areas, respectively. In the other patient, who had no epilepsy, EEG showed bioccipital paroxysmal activity. In all patients, the clinical picture was characterized by the presence of moderate mental retardation and behavioral disorders. The incidence of epilepsy or EEG anomalies among patients with a pericentric inversion of chromosome 12 remains to be ascertained. However, the present study confirms that chromosome 12 anomalies can be associated with epilepsy. Although myoclonic absence-like episodes can occasionally be part of the epileptic phenotype, the electroclinical pattern in pericentric inversion of chromosome 12 seems to be more polymorphic when compared with that observed in trisomy 12p syndrome.

  4. Multiset proximity spaces

    Directory of Open Access Journals (Sweden)

    A. Kandil

    2016-10-01

    Full Text Available A multiset is a collection of objects in which repetition of elements is essential. This paper is an attempt to explore the theoretical aspects of multiset by extending the notions of compact, proximity relation and proximal neighborhood to the multiset context. Examples of new multiset topologies, open multiset cover, compact multiset and many identities involving the concept of multiset have been introduced. Further, an integral examples of multiset proximity relations are obtained. A multiset topology induced by a multiset proximity relation on a multiset M has been presented. Also the concept of multiset δ- neighborhood in the multiset proximity space which furnishes an alternative approach to the study of multiset proximity spaces has been mentioned. Finally, some results on this new approach have been obtained and one of the most important results is: every T4- multiset space is semi-compatible with multiset proximity relation δ on M (Theorem 5.10.

  5. [Disorders of sex development and proximal hypospadias].

    Science.gov (United States)

    Oswald, J

    2016-01-01

    Children with ambiguous genitalia due to different chromosome or gonadal sex are a particular challenge concerning the diagnostic and therapeutic implications. Proximal hypospadias patients with normal gonadal development should be distinguished from children with DSD (disorders of sex development) to guarantee normal gender identity and the best possible surgical therapy. This paper focuses on the terminology, embryology, and pathophysiology of the different manifestations of DSD. The state of knowledge about this disease pattern with particular emphasis on proximal hypospadias based on national and international scientific discussions is presented. The different clinical pictures as well as therapeutic options of DSD with a special focus on recent literature and giving particular attention to patients with proximal hypospadias are presented. Because of the complexity of patients suffering from disorders of sex development an interdisciplinary DSD healthcare team including a paediatric endocrinologist as well as paediatric urologist should be provided. These specialists enable an accurate diagnosis in severe hypospadias patients without reference to DSD diseases patterns.

  6. Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: data from children with Prader-Willi syndrome chromosome 15 q11-q13 deletion and boys with Fragile X syndrome.

    Science.gov (United States)

    Woodcock, Kate A; Oliver, Chris; Humphreys, Glyn W

    2009-03-01

    Prader-Willi syndrome (PWS) and Fragile X syndrome (FraX) are associated with distinctive cognitive and behavioural profiles. We examined whether repetitive behaviours in the two syndromes were associated with deficits in specific executive functions. PWS, FraX, and typically developing (TD) children were assessed for executive functioning using the Test of Everyday Attention for Children and an adapted Simon spatial interference task. Relative to the TD children, children with PWS and FraX showed greater costs of attention switching on the Simon task, but after controlling for intellectual ability, these switching deficits were only significant in the PWS group. Children with PWS and FraX also showed significantly increased preference for routine and differing profiles of other specific types of repetitive behaviours. A measure of switch cost from the Simon task was positively correlated to scores on preference for routine questionnaire items and was strongly associated with scores on other items relating to a preference for predictability. It is proposed that a deficit in attention switching is a component of the endophenotypes of both PWS and FraX and is associated with specific behaviours. This proposal is discussed in the context of neurocognitive pathways between genes and behaviour.

  7. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

    Full Text Available Abstract Background The Characidium (a Neotropical fish group have a conserved diploid number (2n = 50, but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR. In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.

  8. Synthetic chromosomes.

    Science.gov (United States)

    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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Proximal Probes Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Proximal Probes Facility consists of laboratories for microscopy, spectroscopy, and probing of nanostructured materials and their functional properties. At the...

  10. Three rearrangements of chromosome 5 in a patient with myelodysplastic syndrome: an atypical deletion 5q, a complex intrachromosomal rearrangement of chromosome 5, and a paracentric inversion of chromosome 5.

    Science.gov (United States)

    Douet-Guilbert, Nathalie; Basinko, Audrey; Eveillard, Jean-Richard; Morel, Frédéric; Le Bris, Marie-Josée; Guéganic, Nadia; Bovo, Clément; Herry, Angèle; Berthou, Christian; De Braekeleer, Marc

    2010-12-01

    We report the case of a 74-year-old man who sought care for de novo myelodysplastic syndrome (RAEB-1). Conventional cytogenetic techniques showed a karyotype with two different deletions of the long arm of chromosome 5 distributed in three clones: 46,XY,del(1)(p34),del(5)(q14q23)[2]/46,XY,del(1)(p34),del(5)(q14q34)[10]/46,idem,inv(5)(q?11q?34)[7]. Precise characterization of the breakpoints, delineation of the deleted regions, identification of the complex intrachromosomal rearrangement of chromosome 5, and sequential accumulation of chromosomal abnormalities were elucidated by several fluorescence in situ hybridization analyses. We also assessed the clinical, biological, and cytogenetic evolution under lenalidomide treatment and after its interruption. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3.

    Science.gov (United States)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B; Pastinen, Tomi; Droit, Arnaud; Lemaçon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J; Bobolis, Kristie; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caligo, Maria A; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Gareth Evans, D; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A; Garber, Judy; Gayther, Simon A; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hays, John L; Hogervorst, Frans B L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y; Kets, Carolien M; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maïté; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Oosterwijk, Jan C; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Rodriguez, Gustavo C; Rookus, Matti A; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D; Singer, Christian F; Slavin, Thomas P; Snape, Katie; Sokolowska, Johanna; Sønderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Yen; Tea, Muy-Kheng; Teixeira, Manuel R; Teulé, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M W; van der Luijt, Rob B; van Engelen, Klaartje; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Nord, Silje; Easton, Douglas F; Antoniou, Antonis C; Simard, Jacques

    2017-01-01

    Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

  12. 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

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Takako; Yamanouchi, Yasuko; Mori, Yosuke [Teikyo Univ. School of Medicine, Tokyo (Japan)] [and others

    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.

  13. Chromosome structure and function

    Energy Technology Data Exchange (ETDEWEB)

    Risley, M.S.

    1986-01-01

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

  14. Twin Pregnancy Obtention of Patient with Nonmosaic Klinefelter’s Syndrome and His Wife with Chromosome 9 Inversion by ICSI Treatment

    Directory of Open Access Journals (Sweden)

    Yueyue Hu

    2013-01-01

    Full Text Available A 24-year-old man was diagnosed with klinefelter’s syndrome (KS and his wife wasfound to have an inversion on chromosome 9-46, XX, inv (9 (p11q21- because of infertility.Intracytoplasmic sperm injection (ICSI was performed for fertilization after fluorescencein-situ hybridization (FISH was used to analyze the aneuploidy rate of the Xand Y chromosomes of the ejaculated sperms of the patient, and 99 sperms were haploidamong 100 sperms that were to be analyzed. A twin pregnancy was achieved. The chromosomesof the two fetuses were identified as 46, XY and 46, XY, inv (9(p11q21 after aprenatal diagnosis at 18 weeks gestation. Two healthy twins were born through caesareansection at 32 weeks gestation because of premature rupture of membranes (PROM.

  15. SMC complexes differentially compact mitotic chromosomes according to genomic context.

    Science.gov (United States)

    Schalbetter, Stephanie Andrea; Goloborodko, Anton; Fudenberg, Geoffrey; Belton, Jon-Matthew; Miles, Catrina; Yu, Miao; Dekker, Job; Mirny, Leonid; Baxter, Jonathan

    2017-09-01

    Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes.

  16. Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome

    Directory of Open Access Journals (Sweden)

    Peitsidis Panagiotis

    2009-12-01

    Full Text Available Abstract Background Jacobsen syndrome (JBS is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS. Results We report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High resolution SNP oligonucleotide microarray analysis revealed a terminal deletion of 11.4 Mb in size, in the area 11q24.1-11qter. This specific deletion encompasses around 170 genes. Other molecular techniques such as fluorescence in situ hybridization and multiplex ligation-dependent probe amplification were used to confirm the array-result. Discussion Our results suggest that the identification and detailed analysis of similar patients with abnormal platelet function and otherwise mild clinical features will contribute to identification of more patients with 11q deletion and JBS.

  17. Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome).

    Science.gov (United States)

    Manolakos, Emmanouil; Orru, Sandro; Neroutsou, Rosita; Kefalas, Konstantinos; Louizou, Eirini; Papoulidis, Ioannis; Thomaidis, Loretta; Peitsidis, Panagiotis; Sotiriou, Sotirios; Kitsos, George; Tsoplou, Panagiota; Petersen, Michael B; Metaxotou, Aikaterini

    2009-12-09

    Jacobsen syndrome (JBS) is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS. We report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High resolution SNP oligonucleotide microarray analysis revealed a terminal deletion of 11.4 Mb in size, in the area 11q24.1-11qter. This specific deletion encompasses around 170 genes. Other molecular techniques such as fluorescence in situ hybridization and multiplex ligation-dependent probe amplification were used to confirm the array-result. Our results suggest that the identification and detailed analysis of similar patients with abnormal platelet function and otherwise mild clinical features will contribute to identification of more patients with 11q deletion and JBS.

  18. Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia.

    Science.gov (United States)

    Dewald, G W; Pierre, R V; Phyliky, R L

    1982-01-01

    Structural abnormalities of the X chromosome are rarely found in neoplastic disorders. We describe three patients with a history of idiopathic acquired sideroblastic anemia (IASA); each one had an abnormal clone of cells in the bone marrow, characterized by a structurally abnormal X chromosome. In two of these patients, the predominant karyotype was 47,X,2idic(X)(q13); in the other patient, it was 46,X,t(X;11)(q13;p15). Inasmuch as all three of these cases involved chromosome band Xq13, as did two previously published cases, we suggest that band Xq13 may be more prone to structural rearrangement than other X chromosome bands in hematologic disorders. The common Xq13 chromosome breakpoint and clinical presentation (IASA) among these three patients and the occurrence of an X-linked type of sideroblastic anemia may suggest that an association exists between X chromosome abnormalities and IASA. Perhaps alteration of a gene or chromosome structure in or near band Xq13 predisposes to development of IASA. The fact that two of these patients had preleukemia and the third had overt acute leukemia may imply that patients with IASA and X chromosome abnormalities have a poor prognosis. Cases of IASA without associated X chromosome abnormalities are known; thus, if an association between IASA and an abnormal X chromosome does exist, most likely it involves only some patients with IASA.

  19. FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, I.; Chadwick, D.; Chitayat, D. [Hospital for Sick Children and Univ. of Toronto, Ontario (Canada)

    1996-03-29

    We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3. In a series of 118 samples from patients referred for PWS or AS, 29 had deletions by FISH analysis. These included two brothers with a paternally transmitted deletion detectable with the probe for SNRPN only. G-banding analysis was less sensitive for deletion detection but useful in demonstrating other cytogenetic alterations in four cases. Methylation and CA-repeat analyses of 15q11-q13 were used to validate the FISH results. Clinical findings of patients with deletions were variable, ranging from newborns with hypotonia as the only presenting feature to children who were classically affected. We conclude that FISH analysis is a rapid and reliable method for detection of deletions within 15q11-q13 and whenever a deletion is found, FISH analysis of parental chromosomes should also be considered. 41 refs., 4 figs., 2 tabs.

  20. Clonal analysis of stable chromosome rearrangements in Bloom's syndrome fibroblasts.

    Science.gov (United States)

    Hoehn, H; Salk, D

    1984-04-01

    In situ cytogenetic analysis was performed on colonies derived from single cells of cultured skin fibroblast-like strains from two patients with Bloom's syndrome (GM 1492 and GM 2520). Metaphases in all of the colonies displayed structural chromosome rearrangements. Among 212 metaphases from 24 colonies of GM 1492, only 16% were pseudodiploid, and there was a high incidence of de novo rearrangements within individual colonies. There were two "families" of 16 and five colonies, respectively, each containing identical or related aneusomies, and these could be arranged into pedigrees showing clonal evolution. The heterochromatic region of chromosome #1 and the telomeric regions of chromosome arms 2q, 3q, 4p, and 11q were most frequently involved in the rearrangements. In contrast, strain GM 2520 showed less intraclonal variation, was primarily pseudodiploid, and displayed only three clonal types, one of which had extensive subclonal variation (19 of 24 clones). A remarkable finding in GM 2520 was that, in some clones, extra copies of specific chromosome segments were present as translocations. These results caution against the use of strain GM 1492 as a prototype Bloom's syndrome strain for cell biological studies.

  1. Insect sex chromosomes, XI. 3H-TdR induces random aberrations in the X chromosome(s) of Gryllotalpa fossor (Orthoptera).

    Science.gov (United States)

    Sarkar, S; Rao, S R

    1992-06-01

    The pattern of titrated thymidine (3H-TdR), a direct precursor of DNA, induced aberrations on the X chromosome of Gryllotalpa fossor was examined. 3H-TdR produced aberrations randomly distributed over the entire length of the X chromosome; breaks were observed in both the eu- and the heterochromatic arms of the X chromosome in both the sexes. Since the eu- and the heterochromatic arms cannot be distinguished cytologically in this insect, the presence of aberrations on both arms of the same X chromosome in the male and damage to both X chromosomes in the female indicate that both euchromatic and heterochromatic regions (facultative or constitutive) are equally liable to aberrations induced by H-TdR. This is in contrast to the non-random induction of aberrations by 3H-UdR, which causes chromosome damage due to the proximity of the labeled RNA to the DNA template during transcription.

  2. Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kushner Brian

    2009-02-01

    Full Text Available Abstract Background Neuroblastoma (NB tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods Thirty-five NB tumours from patients diagnosed at Results All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36, 23% 11q and/or 14q LOH (27% and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 P P = 0.0054, 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 P P = 0.005 was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 Conclusion Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour.

  3. Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19

    Science.gov (United States)

    Meilleur, K.G.; Traoré, M.; Sangaré, M.; Britton, A.; Landouré, G.; Coulibaly, S.; Niaré, B.; Mochel, F.; La Pean, A.; Rafferty, I.; Watts, C.; Littleton-Kearney, M. T.; Blackstone, C.; Singleton, A.; Fischbeck, K.H.

    2010-01-01

    We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43. PMID:20039086

  4. Capacitive proximity sensor

    Science.gov (United States)

    Kronberg, James W.

    1994-01-01

    A proximity sensor based on a closed field circuit. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change.

  5. Neighborhoods and manageable proximity

    Directory of Open Access Journals (Sweden)

    Stavros Stavrides

    2011-08-01

    Full Text Available The theatricality of urban encounters is above all a theatricality of distances which allow for the encounter. The absolute “strangeness” of the crowd (Simmel 1997: 74 expressed, in its purest form, in the absolute proximity of a crowded subway train, does not generally allow for any movements of approach, but only for nervous hostile reactions and submissive hypnotic gestures. Neither forced intersections in the course of pedestrians or vehicles, nor the instantaneous crossing of distances by the technology of live broadcasting and remote control give birth to places of encounter. In the forced proximity of the metropolitan crowd which haunted the city of the 19th and 20th century, as well as in the forced proximity of the tele-presence which haunts the dystopic prospect of the future “omnipolis” (Virilio 1997: 74, the necessary distance, which is the stage of an encounter between different instances of otherness, is dissipated.

  6. The Karyotype of Microsternarchus aff. bilineatus: A First Case of Y Chromosome Degeneration in Gymnotiformes.

    Science.gov (United States)

    Batista, Jéssica Almeida; Cardoso, Adauto Lima; Milhomem-Paixão, Susana Suely Rodrigues; Ready, Jonathan Stuart; Pieczarka, Julio Cesar; Nagamachi, Cleusa Yoshiko

    2017-06-01

    Various species and lineages that until recently were identified as Microsternarchus bilineatus (Hypopomidae, Gymnotiformes) have a widespread distribution in the Amazon and Orinoco River basins and across the Guiana shield. Recent molecular studies show five distinct lineages for Microsternarchus from different localities. These results suggest that this previously monotypic genus actually consists of more than one species. Here, we describe the karyotype of M. aff. bilineatus from the Cururutuia River (Bragança, Pará, Brazil). The diploid number of 48 chromosomes (14 meta-submetacentric/34 subtelo-acrocentric) is found for males and females, with an XX/XY sex chromosome system. The nucleolar organizer region is found in the short arm of pair 9. Constitutive heterochromatin occurs in the pericentromeric region of all chromosomes, in the distal region of 3p, 5p, 7p, 8q, 9q, 16q, and Xq, in the interstitial region in 2p, 10q, 11q, and 12q and all along 4p, and in a large block of the Y chromosome. These results indicate extensive karyotype divergence between this population and samples from Igarapé Tarumã Grande (Negro River, Amazonas, Brazil) studied by other researchers. Moreover, despite the diversity of sex chromosome systems found in Gymnotiformes, the XX/XY sex chromosome system of M. aff. bilineatus is the first case of Y chromosome degeneration in this order. The present data are valuable to help understand karyotype evolution in Hypopomidae.

  7. Atrofia muscular proximal familiar

    Directory of Open Access Journals (Sweden)

    José Antonio Levy

    1962-09-01

    Full Text Available Os autores relatam dois casos de atrofia muscular proximal familiar, moléstia caracterizada por déficit motor e atrofias musculares de distribuição proximal, secundárias a lesão de neurônios periféricos. Assim, como em outros casos descritos na literatura, foi feito inicialmente o diagnóstico de distrofia muscular progressiva. O diagnóstico correto foi conseguido com auxílio da eletromiografia e da biopsia muscular.

  8. Modeling Three-Dimensional Chromosome Structures Using Gene Expression Data.

    Science.gov (United States)

    Xiao, Guanghua; Wang, Xinlei; Khodursky, Arkady B

    2011-03-01

    Recent genomic studies have shown that significant chromosomal spatial correlation exists in gene expression of many organisms. Interestingly, coexpression has been observed among genes separated by a fixed interval in specific regions of a chromosome chain, which is likely caused by three-dimensional (3D) chromosome folding structures. Modeling such spatial correlation explicitly may lead to essential understandings of 3D chromosome structures and their roles in transcriptional regulation. In this paper, we explore chromosomal spatial correlation induced by 3D chromosome structures, and propose a hierarchical Bayesian method based on helical structures to formally model and incorporate the correlation into the analysis of gene expression microarray data. It is the first study to quantify and infer 3D chromosome structures in vivo using expression microarrays. Simulation studies show computing feasibility of the proposed method and that, under the assumption of helical chromosome structures, it can lead to precise estimation of structural parameters and gene expression levels. Real data applications demonstrate an intriguing biological phenomenon that functionally associated genes, which are far apart along the chromosome chain, are brought into physical proximity by chromosomal folding in 3D space to facilitate their coexpression. It leads to important biological insight into relationship between chromosome structure and function.

  9. The developmental spectrum of proximal radioulnar synostosis

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Alison M. [University of Manitoba, Winnipeg Regional Health Association Program of Genetics and Metabolism, Winnipeg, MB (Canada); University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, WRHA Program of Genetics and Metabolism, Departments of Paediatrics and Child Health, Biochemistry and Medical Genetics, Winnipeg, MB (Canada); Kibria, Lisa [University of Manitoba, Department of School of Medical Rehabilitation, Winnipeg, MB (Canada); Reed, Martin H. [University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, Department of Diagnostic Imaging, Winnipeg, MB (Canada)

    2010-01-15

    Proximal radioulnar synostosis is a rare upper limb malformation. The elbow is first identifiable at 35 days (after conception), at which stage the cartilaginous anlagen of the humerus, radius and ulna are continuous. Subsequently, longitudinal segmentation produces separation of the distal radius and ulna. However, temporarily, the proximal ends are united and continue to share a common perichondrium. We investigated the hypothesis that posterior congenital dislocation of the radial head and proximal radioulnar fusion are different clinical manifestations of the same primary developmental abnormality. Records were searched for ''proximal radioulnar fusion/posterior radial head dislocation'' in patients followed at the local Children's Hospital and Rehabilitation Centre for Children. Relevant radiographic, demographic and clinical data were recorded. Ethics approval was obtained through the University Research Ethics Board. In total, 28 patients met the inclusion criteria. The majority of patients (16) had bilateral involvement; eight with posterior dislocation of the radial head only; five had posterior radial head dislocation with radioulnar fusion and two had radioulnar fusion without dislocation. One patient had bilateral proximal radioulnar fusion and posterior dislocation of the left radial head. Nine patients had only left-sided involvement, and three had only right-sided involvement.The degree of proximal fusion varied, with some patients showing 'complete' proximal fusion and others showing fusion that occurred slightly distal to the radial head: 'partially separated.' Associated disorders in our cohort included Poland syndrome (two patients), Cornelia de Lange syndrome, chromosome anomalies (including tetrasomy X) and Cenani Lenz syndactyly. The suggestion of a developmental relationship between posterior dislocation of the radial head and proximal radioulnar fusion is supported by the fact that both anomalies

  10. [Experimental proximal carpectomy. Biodynamics].

    Science.gov (United States)

    Kuhlmann, J N

    1992-01-01

    Proximal carpectomy was performed in 10 fresh cadavre wrists. Dynamic x-rays were taken and the forces necessary to obtain different movements before and after the operation were measured. Comparison of these parameters clearly defines the advantages and limitations of carpectomy and indicates the reasons.

  11. Proximate Analysis of Coal

    Science.gov (United States)

    Donahue, Craig J.; Rais, Elizabeth A.

    2009-01-01

    This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…

  12. Proximal Tibial Bone Graft

    Science.gov (United States)

    ... the Big Toe Ailments of the Smaller Toes Diabetic Foot Treatments Currently selected Injections and other Procedures Treatments ... from which the bone was taken if the foot/ankle surgeries done at the same time allow for it. ... problems after a PTBG include infection, fracture of the proximal tibia and pain related ...

  13. Chromosome 15 anomalies and the Prader-Willi syndrome: cytogenetic analysis.

    Science.gov (United States)

    Mattei, M G; Souiah, N; Mattei, J F

    1984-01-01

    The behaviour of chromosome 15 is very different from that of the other acrocentric chromosomes. The cytogenetic characteristics of rearrangements associated with Prader-Willi syndrome (PWS) are analyzed as similar rearrangements irrespective of the associated phenotype (reciprocal translocations of chromosome 15, small bisatellited additional chromosomes, Robertsonian translocations, interstitial deletions, pericentric inversions). This study suggests that: (1) The proximal ( 15q ) region and PWS seem to be indissociable ; (2) chromosome 15 has an indisputable cytogenetic originality which could be related to its histochemical properties. Chromosome 15 constitutive heterochromatin usually contains much 5-methylcytosine-rich DNA and a large amount of each of the four satellite DNAs. Furthermore the existence in the proximal ( 15q ) region of one or several palindromic sequences could be postulated to explain the great lability of this region of chromosome 15.

  14. The Precarious Prokaryotic Chromosome

    Science.gov (United States)

    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

  15. Phenotypic consequences of a mosaic marker chromosome identified by fluorescence in situ hybridization (FISH) as being derived from chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Ray, J.H.; Zhou, X.; Pletcher, B.A. [Cornell Univ. Medical College, Manhasset, NY (United States)] [and others

    1994-09-01

    De novo marker chromosomes are detected in 1 in 2500 amniotic fluid samples and are associated with a 10-15% risk for phenotypic abnormality. FISH can be utilized as a research tool to identify the origins of marker chromosomes. The phenotypic consequences of a marker chromosome derived from the short arm of chromosome 16 are described. A 26-year-old woman underwent amniocentesis at 28 weeks gestation because of a prenatally diagnosed tetralogy of Fallot. Follow-up ultrasounds also showed ventriculomegaly and cleft lip and palate. 32 of 45 cells had the karyotype 47,XY,+mar; the remaining cells were 46,XY. The de novo marker chromosome was C-band positive and non-satellited and failed to stain with distamycin A/DAPI. At birth the ultrasound findings were confirmed and dysmorphic features and cryptorchidism were noted. Although a newborn blood sample contained only normal cells, mosaicism was confirmed in 2 skin biopsies. FISH using whole-chromosome painting and alpha-satellite DNA probes showed that the marker chromosome had originated from chromosome 16. As proximal 16q is distamycin A/DAPI positive, the marker is apparently derived from proximal 16p. At 15 months of age, this child is hypotonic, globally delayed and is gavage-fed. His physical examination is significant for microbrachycephaly, a round face, sparse scalp hair, ocular hypertelorism, exotropia, a flat, wide nasal bridge and tip, mild micrognathia, and tapered fingers with lymphedema of hands and feet. Inguinal hernias have been repaired. His features are consistent with those described for patients trisomic for most or all of the short arm of chromosome 16. Marker chromosomes derived from the short arm of chromosome 16 appear to have phenotypic consequences. As the origin of more marker chromosomes are identified using FISH, their karyotype/phenotype correlations will become more apparent, which will permit more accurate genetic counseling.

  16. Intrachromosomal exchange aberrations predicted on the basis of globular interphase chromosome model

    Energy Technology Data Exchange (ETDEWEB)

    Andreev, S.G.; Eidelman, Yu.A

    2002-07-01

    One of the key questions in understanding mechanisms of chromosome aberration production is how does interphase chromosome structure affect aberration formation. To explore this a modelling approach is presented which combines Monte Carlo simulation of both a particle track and interphase chromosome structure. The structural state of interphase chromosome influences a dose-effect relationship for intrachromosomal exchange aberrations (intrachanges). It is shown that intrachanges are induced frequently by both X rays and a particles if the chromosome is in the condensed globular but not in the decondensed coiled state. Truly simple intra-arm intrachanges induced by X rays are dose squared in coiled chromosomes, but exhibit linear dose dependence in globular chromosomes. Experimental data on interarm intrachanges obtained by dual arm chromosome painting are analysed by means of the technique presented. Results of analysis support the conclusion about the arms proximity of chromosome 1 in human lymphocytes. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.B.; May, K.M.; Blackston, R.D.; Muralidharan, K. [Emory Univ., Atlanta, GA (United States)] [and others

    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.

  18. Proximal femoral fractures

    DEFF Research Database (Denmark)

    Palm, Henrik; Teixidor, Jordi

    2015-01-01

    -displaced femoral neck fractures and prosthesis for displaced among the elderly; and sliding hip screw for stabile- and intramedullary nails for unstable- and sub-trochanteric fractures) but they are based on a variety of criteria and definitions - and often leave wide space for the individual surgeons' subjective...... guidelines for hip fracture surgery and discuss a method for future pathway/guideline implementation and evaluation. METHODS: By a PubMed search in March 2015 six studies of surgical treatment pathways covering all types of proximal femoral fractures with publication after 1995 were identified. Also we...... searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...

  19. Proximal humeral fractures

    OpenAIRE

    Mauro, Craig S.

    2011-01-01

    Proximal humeral fractures may present with many different configurations in patients with varying co-morbities and expectations. As a result, the treating physician must understand the fracture pattern, the quality of the bone, other patient-related factors, and the expanding range of reconstructive options to achieve the best functional outcome and to minimize complications. Current treatment options range from non-operative treatment with physical therapy to fracture fixation using percuta...

  20. Paternal uniparental disomy of chromosome 14: confirmation of a clinically-recognizable phenotype.

    Science.gov (United States)

    Stevenson, David A; Brothman, Arthur R; Chen, Zhong; Bayrak-Toydemir, Pinar; Longo, Nicola

    2004-09-15

    We report on a girl with a dicentric chromosome 14 [45,XX,inv(9)(p11q13),dic(14;14)(p11.1;p11.1)] with paternal uniparental disomy (UPD) for chromosome 14. Clinical findings include severe hypotonia, thoracic dystrophy, diastasis recti, swallowing difficulties with aspiration, developmental delay, and multiple minor anomalies. UPD for chromosome 14 has been documented with paternal UPD much less commonly than with maternal UPD. There have been ten cases of paternal UPD for chromosome 14 and one case of segmental paternal isodisomy of chromosome 14. Many of the findings are nonspecific, but the radiographic rib findings (referred to as the "coat-hanger" sign) are characteristic for this condition. UPD 14 studies should be performed in children thought to have Jeune asphyxiating thoracic dystrophy or other related osteochondrodysplasias when the diagnosis is in question. Our patient and the previously reported cases support a discrete recognizable phenotype for paternal UPD for chromosome 14. Copyright 2004 Wiley-Liss, Inc.

  1. Sex chromosomes and sex chromosome abnormalities.

    Science.gov (United States)

    Li, Xu

    2011-12-01

    This article focuses on constitutional sex chromosome abnormalities detected by conventional cytogenetics and fluorescence in situ hybridization. The author discusses the two general classifications of abnormalities: numerical and structural. Also included are descriptions of unique aspects of X and Y chromosomes, technological advances in detection, and future perspectives.

  2. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J

    1983-01-01

    The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...

  3. Chromosome Disorder Outreach

    Science.gov (United States)

    ... Visit our Photo Gallery Education, Advocacy, Information & Support Chromosome Disorder Outreach, Inc is a non-profit organization. ... Inc. All Rights Reserved You are donating to : Chromosome Disorder Outreach, Inc, a 501c non-profit organization. ...

  4. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Final report, January 1--December 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1998-03-01

    It has been clear for the last 15 years that cloning translocation breakpoints in both AML de novo and t-AML would provide the DNA probes required to determine whether the breakpoints in cytogenetically apparently similar translocations were identical at the level of DNA. Therefore the author has pursued an analysis of rearrangements in both types of leukemia simultaneously. She has also cloned and sequenced several translocations in acute lymphoblastic leukemia and in chronic lymphatic leukemia. Recently she cloned the breakpoint in a number of translocations involving chromosome bands 11q23 and 21q22. She has cloned the gene which she called MLL, that is located in 11q23 that is involved in the 6;11, 9;11, and 11;19 translocations that are seen in AML de novo as well as in t-AML. She has evidence that the breakpoint in 11q23 and in the t(9;11) is relatively similar in de novo and secondary AML. In addition, she has cloned the gene at the breakpoint in chromosome 21 in the t(3;21). These studies have provided DNA probes that will be very important for diagnosis and for monitoring the patient`s response to treatment.

  5. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in

  6. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

    Banding techniques were carried out on metaphase chromosomes of zebrafish (Danio rerio) embryos. The karyotypes with the longest chromosomes consist of 12 metacentrics, 26 submetacentrics, and 12 subtelocentrics (2n = 50). All centromeres are C-band positive. Eight chromosomes have a pericentric

  7. High resolution chromosome analysis and fluorescence in situ hybridization in patients referred for Prader-Willi or Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-08

    Laboratory testing is helpful in the evaluation of patients suspected to have either Prader-Willi syndrome (PWS) or Angelman syndrome (AS) because most of the patients have recognizable cytogenetic deletions of 15q11q13. Maternal uniparental disomy of chromosome 15, identified by molecular genetic techniques, is found in about 20 to 25% of PWS patients. Paternal uniparental disomy of chromosome 15 is seen in 2 to 3% of AS patients. Thus, PWS and AS represent the first examples in humans of genetic imprinting or the differential expression of genetic information depending on the parental origin. Herein, I report our experience with FISH and high resolution chromosome analysis in patients referred to confirm or rule out PWS or AS. 10 refs., 1 tab.

  8. Korean patients with chronic lymphocytic leukemia show the similar types of chromosomal aberrations as those in Europe and North America.

    Science.gov (United States)

    Chang, Yoon Hwan; Park, Junwan; Kim, Hee Chan; Chun, Hong Ku; Kim, Young Ree; Kim, Myungshin; Han, Kyungja; Lee, Je-Hwan; Lee, Kyoo-Hyung; Cho, Han Ik; Lee, Yun Song; Lee, Dong Soon

    2006-06-01

    Chronic lymphocytic leukemia (CLL) is frequent in the West, but rare in Korea. In this study, the frequency of chromosome aberration in Korean CLL patients was examined by applying interphase fluorescence in situ hybridization (FISH). Conventional cytogenetic test and FISH were performed on bone marrow aspirates obtained from 16 CLL patients. By applying DNA probes (Vysis, Downers Grove, IL, USA), the deletion in 11q22-23, 13q14, 13q34, and 17p13, and trisomy 12 were examined. With FISH, molecular cytogenetic aberration was detected in 10 of 16 patients [63%, 95% confidence interval (CI) 39-86], whereas with conventional cytogenetic test, chromosomal aberration was detected only in 2 out of 13 cases (15%, 95% CI 0-35). In total, the cases with one or more chromosomal aberrations were 11 out of 16 cases (69%, 95% CI 46-92). The most frequently detected aberration was the 13q14 deletion (69%, 95% CI 44-94), followed by trisomy 12 (19%, 95% CI 0-38) and 11q22 deletion (14%, 95% CI 0-33). No deletion in 17p13 was observed. In conclusion, CLL in Korean is a heterogeneous genetic disorder, showing similar genetic changes in Europe and North America.

  9. Mapping strategies: Chromosome 16 workshop

    Energy Technology Data Exchange (ETDEWEB)

    1989-01-01

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

  10. Proximal dup(10q): Case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Barritt, J.A.; Teague, K.E.; Bodurtha, J.N. [Virginia Commonwealth Univ., Richmond, VA (United States)] [and others

    1994-09-01

    We report a case of a proximal dir dup(10q) in a female with multiple congenital anomalies. During infancy she was noted to gave growth retardation, microcephaly, microphthalmia, coloboma, a long, beaked nose, posteriorly rotated ears with simple helices, full bowed lips, widely-spaced nipples, broad first toes, hypermobile and proximally placed thumbs, a heart murmur, PDA, and coarctation of the aorta. Additional findings at age 13 included a full columella, short philtrum, thin limbs, bilateral blindness, and mental retardation, as well as continued growth retardation. Her medical history included precocious puberty at age 8 and a diagnosis of hyperactivity. Using FISH with multiple probes combined with GTG-banding, the aberrant chromosome was determined to be a dir dup(10)(q21{r_arrow}q22). Parental chromosomes were normal and the family history was unremarkable. The parental origin of the dir dup(10) is being assessed using DNA markers. Five similar cases of proximal dup(10q) have been reported previously. Consistent characteristics include low birth weight, developmental and psychomotor delay, growth retardation, and microcephaly. Also found in most cases were short prominent philtrum, bowed mouth, PDA, thin limbs, coloboma, micropthalmia, deep set eyes, and other ocular anomalies. Our case is unique in that she has a long, beaked nose, precocious puberty, and hyperactivity. Future studies such as this, using molecular cytogenetic techniques to better define the chromatin involved in proximal dup(10q), may lead to its recognition as a distinct clinical phenotype.

  11. Origin and Evolution of the Neo-Sex Chromosomes in Pamphagidae Grasshoppers through Chromosome Fusion and Following Heteromorphization

    Science.gov (United States)

    Bugrov, Alexander Gennadievich; Buleu, Olesya Georgievna; Bogomolov, Anton Gennadievich; Rubtsov, Nikolay Borisovich

    2017-01-01

    In most phylogenetic lineages, the evolution of sex chromosomes is accompanied by their heteromorphization and degradation of one of them. The neo-sex chromosomes are useful model for studying early stages of these processes. Recently two lineages of the neo-sex chromosomes on different stages of heteromorphization was discovered in Pamphagidae family. The neo-sex chromosome heteromorphization was analyzed by generation of DNA probes derived from the neo-Xs and neo-Ys followed with chromosome painting in nineteen species of Pamphagidae family. The homologous regions of the neo-sex chromosomes were determined in closely related species with the painting procedure and image analysis with application of the Visualization of the Specific Signal in Silico software package. Results of these analyses and distribution of C-positive regions in the neo-sex chromosomes revealed details of the heteromorphization of the neo-sex chromosomes in species from both phylogenetic lineages of Pamphagidae grasshoppers. The hypothetical mechanism of the neo-Y degradation was suggested. It includes expansion of different repeats from the proximal neo-Y chromosome region by inversions, spreading them towards distal region. Amplification of these repeats leads to formation of C-positive regions and elimination of the C-negative regions located between them. PMID:29137168

  12. [Detection of complex chromosomal aberrations in patients with multiple myeloma using multiplex fluorescence in situ hybridization].

    Science.gov (United States)

    Jiang, Yuan-qiang; Chen, Li-juan; Zhu, Yu; Qiu, Hai-rong; Wang, Rong; Xu, Jia-ren; Lu, Hua; Li, Jian-yong

    2010-08-01

    To explore the value of multiplex fluorescence in situ hybridization (M-FISH) in the detection of the complex chromosomal aberrations (CCAs) in multiple myeloma (MM). M-FISH was used in 10 MM patients with CCAs detected by conventional cytogenetics (CC) using R-banding to refine the rearrangement of CCAs and identify the characteristics of marker chromosome. M-FISH confirmed the 29 structural aberrations shown by CC analysis, and also confirmed the specific source of 21 types of chromosomal aberration, which were not detected by CC analysis. Among them, t(2;15)(q33;q22), t(6;7)(q23;q34), t(8;11) (q24;q23), t(1;14)(q10;q32) and t(X;1)(q26;q25) were new chromosomal aberrations. The median survival time of 9 MM patients with CCAs was 23 months and evidently shorter than that of MM patients without CCAs, with the mean survival time being 34 months. M-FISH could refine CCAs in MM patients, find or correct the missed or misidentified abnormalities analyzed by CC. It has provided one of the essential methods for the research of chromosomal aberrations in MM.

  13. Breakpoint of a Y chromosome pericentric inversion in the DAZ gene area. A case report.

    Science.gov (United States)

    Causio, F; Canale, D; Schonauer, L M; Fischetto, R; Leonetti, T; Archidiacono, N

    2000-07-01

    The presence of a spermatogenesis locus (gene or gene complex) in the euchromatic region of the long arm of the Y chromosome (Yq11), defined as azoospermia factor on the basis of gross structural rearrangement, was detected. The gene family responsible for different spermatogenetic defects is "deleted in azoospermia" (DAZ). A 34-year-old man had oligozoospermia, and a cytogenetic analysis carried out on peripheral lymphocytes with G banding revealed a 46,X, inv(Y)(p11q11)karyotype. The relation between the chromosomal breakpoint and the DAZ gene was more precisely defined by a fluorescent in situ hybridization technique. We revealed two signals for the DAZ gene, weaker than normal, one on the short arm and the other on the long arm of the Y chromosome, indicating that the breakpoint was located at the DAZ gene level. This is the first report documenting a chromosomal pericentric inversion with disruption in the DAZ gene area. We hope to obtain information on whether the disruption affects a functional zone of the gene and correlates with oligospermia at the chromosomal level.

  14. The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial

    Science.gov (United States)

    Marks, David I.; Moorman, Anthony V.; Chilton, Lucy; Paietta, Elisabeth; Enshaie, Amir; DeWald, Gordon; Harrison, Christine J.; Fielding, Adele K.; Foroni, Letizia; Goldstone, Anthony H.; Litzow, Mark R.; Luger, Selina M.; McMillan, Andrew K.; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Wiernik, Peter; Lazarus, Hillard M.

    2013-01-01

    The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10NEG). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)-negative patients. Complete remission was achieved in 77 (93%) patients but only 35% survived 5 years (95% CI: 25–45%); the relapse rate was 45% (95% CI: 33–58%). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56% and 67% respectively, only 2/31 patients relapsed. This compares with a 24% survival rate and 59% relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71% of patients aged <25 years surviving. Younger patients had lower relapse rates (19%) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov PMID:23349309

  15. Some Properties of Fuzzy Soft Proximity Spaces

    Science.gov (United States)

    Demir, İzzettin; Özbakır, Oya Bedre

    2015-01-01

    We study the fuzzy soft proximity spaces in Katsaras's sense. First, we show how a fuzzy soft topology is derived from a fuzzy soft proximity. Also, we define the notion of fuzzy soft δ-neighborhood in the fuzzy soft proximity space which offers an alternative approach to the study of fuzzy soft proximity spaces. Later, we obtain the initial fuzzy soft proximity determined by a family of fuzzy soft proximities. Finally, we investigate relationship between fuzzy soft proximities and proximities. PMID:25793224

  16. PROXIMITY MANAGEMENT IN CRISIS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Ion Dorin BUMBENECI

    2010-01-01

    Full Text Available The purpose of this study is to evaluate the level of assimilation for the terms "Proximity Management" and "Proximity Manager", both in the specialized literature and in practice. The study has two parts: the theoretical research of the two terms, and an evaluation of the use of Proximity management in 32 companies in Gorj, Romania. The object of the evaluation resides in 27 companies with less than 50 employees and 5 companies with more than 50 employees.

  17. Sex Chromosome Drive

    OpenAIRE

    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 t...

  18. Chromosomal Evolution in Chiroptera

    Directory of Open Access Journals (Sweden)

    Cibele G. Sotero-Caio

    2017-10-01

    Full Text Available Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62. As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae, focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems.

  19. Chromosome analyses in dogs.

    Science.gov (United States)

    Reimann-Berg, N; Bullerdiek, J; Murua Escobar, H; Nolte, I

    2012-01-01

    Cytogenetics is the study of normal and abnormal chromosomes. Every species is characterized by a given number of chromosomes that can be recognized by their specific shape. The chromosomes are arranged according to standard classification schemes for the respective species. While pre- and postnatal chromosome analyses investigate the constitutional karyotype, tumor cytogenetics is focused on the detection of clonal acquired, tumor-associated chromosome aberrations. Cytogenetic investigations in dogs are of great value especially for breeders dealing with fertility problems within their pedigrees, for veterinarians and last but not least for the dog owners. Dogs and humans share a variety of genetic diseases, including cancer. Thus, the dog has become an increasingly important model for genetic diseases. However, cytogenetic analyses of canine cells are complicated by the complex karyotype of the dog. Only just 15 years ago, a standard classification scheme for the complete canine karyotype was established. For chromosome analyses of canine cells the same steps of chromosome preparation are used as in human cytogenetics. There are few reports about cytogenetic changes in non-neoplastic cells, involving predominantly the sex chromosomes. Cytogenetic analyses of different entities of canine tumors revealed that, comparable to human tumors, tumors of the dog are often characterized by clonal chromosome aberrations, which might be used as diagnostic and prognostic markers. The integration of modern techniques (molecular genetic approaches, adaptive computer programs) will facilitate and complete conventional cytogenetic studies. However, conventional cytogenetics is still non-replaceable.

  20. Genome structure and primitive sex chromosome revealed in Populus

    Energy Technology Data Exchange (ETDEWEB)

    Tuskan, Gerald A [ORNL; Yin, Tongming [ORNL; Gunter, Lee E [ORNL; Blaudez, D [UMR, France

    2008-01-01

    We constructed a comprehensive genetic map for Populus and ordered 332 Mb of sequence scaffolds along the 19 haploid chromosomes in order to compare chromosomal regions among diverse members of the genus. These efforts lead us to conclude that chromosome XIX in Populus is evolving into a sex chromosome. Consistent segregation distortion in favor of the sub-genera Tacamahaca alleles provided evidence of divergent selection among species, particularly at the proximal end of chromosome XIX. A large microsatellite marker (SSR) cluster was detected in the distorted region even though the genome-wide distribute SSR sites was uniform across the physical map. The differences between the genetic map and physical sequence data suggested recombination suppression was occurring in the distorted region. A gender-determination locus and an overabundance of NBS-LRR genes were also co-located to the distorted region and were put forth as the cause for divergent selection and recombination suppression. This hypothesis was verified by using fine-scale mapping of an integrated scaffold in the vicinity of the gender-determination locus. As such it appears that chromosome XIX in Populus is in the process of evolving from an autosome into a sex chromosome and that NBS-LRR genes may play important role in the chromosomal diversification process in Populus.

  1. Distribution of X-ray induced chromosome rearrangement breaks along the polytene chromosomes of Anopheles messeae

    Energy Technology Data Exchange (ETDEWEB)

    Pleshkova, G.N. (Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki)

    1983-09-01

    Distribution of chromosomal aberrations localization along polytene chromosomes (aoutosomes) of salivary glands of malarial mosquito. Anopheles messeae is presented. Induced aberrations in F/sub 1/ posterity from X-ray irradiated fecundated females are studied. Points of breaks of inversions and translocations are localized separately. There are no considerable differences in the distribution character of two types of aberrations. Over the length of autosomes the breaks are more frequent in distal halves, their frequency in proximal parts anally in near centromeric regions of chromosomes is reduced. Concentration of breaks in certain ''hot points'' of the chromosomes is pointed out. Comparison of distribution of actual and expected frequencies of break points according to chi/sup 2/ criterion revealed highly fiducial discrepancies, testifying to uneven participation of different regions of chromosomes in aberration formation. Similarities and differences of the data obtained from analogous ones, demonstrated in Drosophila, as well as possible reasons for the distribution unevennes are discussed. On the basis of analysis of intrinsic and literature data a supposition is made that the ''hot points'' (break concentrations) can be considered as localizaion markers of intercalary heterochromatin.

  2. Bloom syndrome and maternal uniparental disomy for chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. (Children' s Hospital, Camperdown, New South Wales (New Zealand)); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. (Wellington Hospital (New Zealand)); Graham, D. (Waikato Hospital, Hamilton (New Zealand)); Rogan, P.K. (Pennsylvania State Univ., Hershey, PA (United States)) (and others)

    1994-07-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.

  3. The human Y chromosome: a masculine chromosome

    NARCIS (Netherlands)

    Noordam, Michiel J.; Repping, Sjoerd

    2006-01-01

    Once considered to be a genetic wasteland of no scientific interest beyond sex determination, the human Y chromosome has made a significant comeback in the past few decades and is currently implicated in multiple diseases, including spermatogenic failure - absent or very low levels of sperm

  4. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation

    Directory of Open Access Journals (Sweden)

    Kiefer Y

    2012-03-01

    Full Text Available Yvonne Kiefer1, Christoph Schulte2, Markus Tiemann2, Joern Bullerdiek11Center for Human Genetics, University of Bremen, Bremen, Germany; 2Hematopathology Hamburg, Hamburg, GermanyAbstract: Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected. In some of these aberrations the molecular target has been identified as eg, ataxia telangiectasia mutated (ATM in case of deletions of chromosomal region 11q22~23 and the genes encoding microRNAs miR-15a/16-1 as likely targets of deletions of chromosomal band 13q14.3. Of note, these aberrations do not characterize independent subgroups but often coexist within the metaphases of one tumor. Generally, complex aberrations are associated with a worse prognosis than simple karyotypic alterations. Due to smaller sizes of the missing segment the detection of recurrent deletions is not always possible by means of classical cytogenetics but requires more advanced techniques as in particular fluorescence in situ hybridization (FISH. Nevertheless, at this time it is not recommended to replace classical cytogenetics by FISH because this would miss additional information given by complex or secondary karyotypic alterations. However, the results of cytogenetic analyses allow the stratification of prognostic and predictive groups of the disease. Of these, the group characterized by deletions involving TP53 is clinically most relevant. In the future refined methods as eg, array-based comparative genomic hybridization will supplement the existing techniques to characterize CLL. Keywords: chronic lymphocytic leukemia, chromosomal abnormality, miRNA deregulation

  5. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review

    Directory of Open Access Journals (Sweden)

    Bani Bandana Ganguly

    2016-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q, monosomy 5/7, trisomy 8/19, i(17q, and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p, der(12 dic(12;?19, +15, −18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q/-17, der(12p, del(5q26, del(7q36, and del(20q11 indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  6. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review.

    Science.gov (United States)

    Ganguly, Bani Bandana; Dolai, Tuphan Kanti; De, Rajib; Kadam, Nitin N

    2016-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q), monosomy 5/7, trisomy 8/19, i(17q), and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p), der(12) dic(12;?19), +15, -18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q)/-17, der(12p), del(5q26), del(7q36), and del(20q11) indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  7. Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11

    Energy Technology Data Exchange (ETDEWEB)

    Kimberling, W.; Kenyon, J.B.; Grunkemeyers, J.A. (Boys Town National Research Hospital, Omaha, NE (United States)); Moeller, C.G. (Linkoping Univ. Hospital (Sweden)); Davenport, S. (Sensory Genetics/Development, Bloomington, MN (United States)); Priluck, I.A. (Creighton Univ. School of Medicine, Omaha, NE (United States)); Beighton, H.; Greenberg, J. (Univ. of Cape Town Medical School, (South Africa)); Reardon, W. (Institute of Child Health, London (United Kingdom)); Weston, M.D.

    1992-12-01

    Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to chromosome 14q, and this second localization established the existence of a new and independent locus for Usher syndrome. 31 refs., 2 figs., 3 tabs.

  8. Chromosomal mosaicism goes global

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2008-11-01

    Full Text Available Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy. It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.

  9. Report on the third international workshop on chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Povey, S.; White, J.A. [Univ. College London (United Kingdom); Armour, J. [Univ. of Leicester (United Kingdom)] [and others

    1994-04-01

    The Third International Workshop on human chromosome 9 was held at Queens` College, Cambridge 9-11 April, 1994. The meeting was attended by 74 participants from 12 countries. On the morning of 12 April a satellite meeting was held on Tuberous Sclerosis, and because of its relevance to chromosome 9 a summary of this meeting is also presented within this report. The division consisted of a group with global interests, four regional groups 9p, 9q11-q21, 9q22-q33 and 9q33-qter, a group interested in mapping putative suppressor genes in ovarian and bladder cancer and a comparative mapping group. There was also discussion of resources, both physical and informatic. The amount of information on chromosome 9 has increased greatly in the past two years and it is clear that the integration of different types of information and the display of such information is an urgent problem. At this meeting two possible systems were explored, SIGMA and 1db. As described in the global group report an attempt was made to enter all mapping information into SIGMA, a program developed by Michael Cinkosky at Los Alamos. Within the text of this report a name without a date refers to an abstract at this meeting. A name with a date refers to a publication listed in the references and these are in general confined to very recent or {open_quote}in press{close_quote} references. A verbal communication at the meeting is identified as a personal communication. For authoritative referencing of published information and also for all primer sequences (except a few actually listed in the abstracts) the reader should consult GDB. The proceedings of the two previous workshops have been published and are listed in the references. It was decided that a fourth workshop would be held in about a year`s time. Dr. Margaret Pericak-Vance offered to host this at Duke University, North Carolina.

  10. Fractures of the proximal humerus

    DEFF Research Database (Denmark)

    Brorson, Stig

    2013-01-01

    . The bandages were further supported by splints made of wood or coarse grass. Healing was expected in forty days. Different fracture patterns have been discussed and classified since Ancient Greece. Current classification of proximal humeral fractures mainly relies on the classifications proposed by Charles......, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis......Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate...

  11. The infrastructure of psychological proximity

    DEFF Research Database (Denmark)

    Nickelsen, Niels Christian Mossfeldt

    2015-01-01

    ). The experience of psychological proximity between patient and nurse is provided through confidence, continuity and the practical set-up. This constitutes an important enactment of skillfulness, which may render telemedicine a convincing health service in the future. Methodology: The study draws on a pilot...... (Langstrup & Winthereik 2008). This study contributes by showing the infrastructure of psychological proximity, which is provided by way of device, confidence, continuity and accountability....

  12. Microsatellite instability in cancer of the proximal colon

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, S.N.; Bren, G.; Schaid, D. (Mayo Clinic and Foundation, Rochester, MN (United States))

    1993-05-07

    Colorectal tumor DNA was examined for somatic instability at (CA)[sub n] repeats on human chromosomes 5q, 15q, 17p, and 18q. Differences between tumor and normal DNA were detected in 25 of the 90 (28 percent) tumors examined. This instability appeared as either a substantial change in repeat length (often heterogeneous in nature) or a minor change (typically two base pairs). Microsatellite instability was significantly correlated with the tumor's location in the proximal colon (P = 0.003), with increased patient survival (P = 0.02), and, inversely, with loss of heterozygosity for chromosomes 5q, 17p, and 18q. These data suggest that some colorectal cancers may arise through a mechanism that does not necessarily involve loss of heterozygosity. 23 refs., 2 figs., 3 tabs.

  13. Chromosomal Abnormalties with Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available The correlation between specific chromosome abnormalties and various epilepsies was investigated by a study of 76 patients’ records obtained by questionnaires distributed to members of Kyoto Multi-institutional Study Group of Pediatric Neurology.

  14. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

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

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.B.; Muraldharan, K.; Pettay, D. [Emory Univ. School of Medicine, Atlanta, GA (United States)] [and others

    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.

  16. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)

    2016-01-01

    markdownabstractIn mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution.

  17. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  18. Evolutionary breakpoint analysis on Y chromosomes of higher primates provides insight into human Y evolution.

    Science.gov (United States)

    Wimmer, R; Kirsch, S; Rappold, G A; Schempp, W

    2005-01-01

    Comparative FISH mapping of PAC clones covering almost 3 Mb of the human AZFa region in Yq11.21 to metaphases of human and great apes unravels breakpoints that were involved in species-specific Y chromosome evolution. An astonishing clustering of evolutionary breakpoints was detected in the very proximal region on the long arm of the human Y chromosome in Yq11.21. These breakpoints were involved in deletions, one specific for the human and another for the orang-utan Y chromosome, in a duplicative translocation/transposition specific for bonobo and chimpanzee Y chromosomes and in a pericentric inversion specific for the gorilla Y chromosome. In addition, our comparative results allow the deduction of a model for the human Y chromosome evolution. Copyright (c) 2005 S. Karger AG, Basel.

  19. Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes.

    Science.gov (United States)

    Benedetti, Fabrizio; Dorier, Julien; Burnier, Yannis; Stasiak, Andrzej

    2014-03-01

    Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.

  20. Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

    Science.gov (United States)

    Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

    2016-01-01

    Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

  1. The orphan nuclear receptor ROR{alpha} (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Giguere, V. [McGill Univ., Montreal (Canada); Beatty, B.; Squire, J. [Hospital for Sick Children, Toronto (Canada)] [and others

    1995-08-10

    ROR{alpha} is a novel member of the steroid/thyroid/retinoid receptor superfamily with unique DNA-binding properties. We have mapped the RORA gene by fluorescence in situ hybridization to human chromosome 15q21-q22. To map the mouse Rora gene, a partial mouse cDNA clone was isolated from brain. Using interspecific backcross analysis, we have mapped the Rora gene to mouse chromosome 9. This places the human RORA gene in the proximity of the PML gene, which is involved in a reciprocal chromosomal translocation t(15:17) with the RARA gene in patients with acute promyelocytic leukemia. 13 refs., 2 figs.

  2. Cubesat Proximity Operations Demonstration (CPOD)

    Science.gov (United States)

    Villa, Marco; Martinez, Andres; Petro, Andrew

    2015-01-01

    The CubeSat Proximity Operations Demonstration (CPOD) project will demonstrate rendezvous, proximity operations and docking (RPOD) using two 3-unit (3U) CubeSats. Each CubeSat is a satellite with the dimensions 4 inches x 4 inches x 13 inches (10 centimeters x 10 centimeters x 33 centimeters) and weighing approximately 11 pounds (5 kilograms). This flight demonstration will validate and characterize many new miniature low-power proximity operations technologies applicable to future missions. This mission will advance the state of the art in nanosatellite attitude determination,navigation and control systems, in addition to demonstrating relative navigation capabilities.The two CPOD satellites are scheduled to be launched together to low-Earth orbit no earlier than Dec. 1, 2015.

  3. X chromosome activity in mouse XX primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Susana M Chuva de Sousa Lopes

    2008-02-01

    Full Text Available In the early epiblast of female mice, one of the two X chromosomes is randomly inactivated by a Xist-dependent mechanism, involving the recruitment of Ezh2-Eed and the subsequent trimethylation of histone 3 on lysine 27 (H3K27me3. We demonstrate that this random inactivation process applies also to the primordial germ cell (PGC precursors, located in the proximal region of the epiblast. PGC specification occurs at about embryonic day (E7.5, in the extraembryonic mesoderm, after which the germ cells enter the endoderm of the invaginating hindgut. As they migrate towards the site of the future gonads, the XX PGCs gradually lose the H3K27me3 accumulation on the silent X chromosome. However, using a GFP transgene inserted into the X chromosome, we observed that the XX gonadal environment (independently of the gender is important for the substantial reactivation of the inactive X chromosome between E11.5 and E13.5, but is not required for X-chromosome reactivation during the derivation of pluripotent embryonic germ cells. We describe in detail one of the key events during female PGC development, the epigenetic reprogramming of the X chromosome, and demonstrate the role of the XX somatic genital ridge in this process.

  4. [Y chromosome and spermatogenesis].

    Science.gov (United States)

    Ravel, C; Siffroi, J-P

    2009-01-01

    Human Y chromosome evolution has progressively been directed towards a role in sex determination and reproduction. Cytogenetically visible structural abnormalities have determined long arm chromosomal regions which define the AZF factor that contains genes implicated in the spermatogenic process. By using molecular tools, the AZF factor has been subdivided into three loci, AZFa, b and c, the deletion of which leads to specific spermatogenesis impairments due to the loss of particular genes. Most AZF genes are specifically expressed in testis but their functions are far to be known precisely. Partial deletions of AZF regions have been described. Some of them have allowed to define more precise genotype-phenotype relationships whereas others are considered as variants in relation to Y chromosome polymorphism.

  5. Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures

    Directory of Open Access Journals (Sweden)

    Kesterson Robert A

    2003-04-01

    Full Text Available Abstract Background Chromosomal abnormalities affecting human chromosome 15q11-q13 underlie multiple genomic disorders caused by deletion, duplication and triplication of intervals in this region. These events are mediated by highly homologous segments of DNA, or duplicons, that facilitate mispairing and unequal cross-over in meiosis. The gene encoding an amyloid precursor protein-binding protein (APBA2 was previously mapped to the distal portion of the interval commonly deleted in Prader-Willi and Angelman syndromes and duplicated in cases of autism. Results We show that this gene actually maps to a more telomeric location and is partially duplicated within the broader region. Two highly homologous copies of an interval containing a large 5' exon and downstream sequence are located ~5 Mb distal to the intact locus. The duplicated copies, containing the first coding exon of APBA2, can be distinguished by single nucleotide sequence differences and are transcriptionally inactive. Adjacent to APBA2 maps a gene termed KIAA0574. The protein encoded by this gene is weakly homologous to a protein termed X123 that in turn maps adjacent to APBA1 on 9q21.12; APBA1 is highly homologous to APBA2 in the C-terminal region and is distinguished from APBA2 by the N-terminal region encoded by this duplicated exon. Conclusion The duplication of APBA2 sequences in this region adds to a complex picture of different low copy repeats present across this region and elsewhere on the chromosome.

  6. Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?

    Energy Technology Data Exchange (ETDEWEB)

    Bottani, A.; Robinson, W.P.; DeLoizer-Blanchet, C.D.; Engel, E.; Morris, M.A.; Schmitt, Thun-Hohenstein, L.; Schinzel, A. [Univ. of Zuerich (Switzerland)

    1994-05-15

    The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age-dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region q11-q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late-onset mild seizures; as they grow older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients. 25 refs., 2 figs., 1 tab.

  7. Breakpoint localization of the marker chromosome associated with the cat eye syndrome.

    Science.gov (United States)

    Duncan, A M; Hough, C A; White, B N; McDermid, H E

    1986-01-01

    We investigated the breakpoints involved in the generation of the supernumerary bisatellited chromosome associated with the Cat Eye syndrome. In situ hybridization of DNA probes from band 22q11 revealed that, for two individuals with the Cat Eye syndrome, both breakpoints for the bisatellited chromosome were distal to the DNA sequence corresponding to probe D22S9 and proximal to the immunoglobulin C lambda genes and to at least one subgroup of the V lambda genes. PMID:3088989

  8. Breakpoint localization of the marker chromosome associated with the cat eye syndrome.

    OpenAIRE

    Duncan, A M; Hough, C A; White, B N; McDermid, H E

    1986-01-01

    We investigated the breakpoints involved in the generation of the supernumerary bisatellited chromosome associated with the Cat Eye syndrome. In situ hybridization of DNA probes from band 22q11 revealed that, for two individuals with the Cat Eye syndrome, both breakpoints for the bisatellited chromosome were distal to the DNA sequence corresponding to probe D22S9 and proximal to the immunoglobulin C lambda genes and to at least one subgroup of the V lambda genes.

  9. Giemsa C-banding of Barley Chromosomes. I: Banding Pattern Polymorphism

    DEFF Research Database (Denmark)

    Linde-Laursen, Ib

    1978-01-01

    Twenty barley (Hordeum vulgare) lines studied had a common basic chromosome banding pattern. Most bands ranged from medium to very small in size. The most conspicuous banding occurred at or near the centromeres, in the proximal, intercalary parts of most chromosome arms and beside the secondary c...... 7. Seventeen differently banded karyotypes were found. Some banding pattern polymorphisms can be used in cytological and cytogenetic studies....

  10. SHORT COMMUNICATION PROXIMATE COMPOSITION, MINERAL ...

    African Journals Online (AJOL)

    Preferred Customer

    SHORT COMMUNICATION. PROXIMATE COMPOSITION, MINERAL CONTENT AND ANTINUTRITIONAL. FACTORS OF SOME CAPSICUM (Capsicum annum) VARIETIES GROWN IN. ETHIOPIA. Esayas K.1, Shimelis A.2, Ashebir F.3, Negussie R.3, Tilahun B.4 and Gulelat D.4*. 1Hawassa University, Department of Food ...

  11. Intrachromosomal amplification of chromosome 21 (iAMP21 detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    Directory of Open Access Journals (Sweden)

    Daniela Ribeiro Ney Garcia

    2013-01-01

    Full Text Available Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described.

  12. Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    Science.gov (United States)

    Garcia, Daniela Ribeiro Ney; Arancibia, Alejandro Mauricio; Ribeiro, Raul C.; Land, Marcelo Gerardin Poirot; Silva, Maria Luiza Macedo

    2013-01-01

    Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22)/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described. PMID:24255623

  13. New Y chromosomes and early stages of sex chromosome ...

    Indian Academy of Sciences (India)

    2010-09-06

    Sep 6, 2010 ... [Traut W. 2010 New Y chromosomes and early stages of sex chromosome differentiation: sex determination in Megaselia. J. Genet. 89, ..... Schultheis C., Böhne A., Schartl M., Volff J. and Galiana-Arnoux D. 2009 Sex determination diversity and sex chromosome evolution in poeciliid fish. Sex. Dev. 3, 68–77 ...

  14. Cattle rob(1;29) originating from complex chromosome rearrangements as revealed by both banding and FISH-mapping techniques.

    Science.gov (United States)

    Di Meo, G P; Perucatti, A; Chaves, R; Adega, F; De Lorenzi, L; Molteni, L; De Giovanni, A; Incarnato, D; Guedes-Pinto, H; Eggen, A; Iannuzzi, L

    2006-01-01

    Sixteen carriers of rob(1;29) (one of which was homozygous) from six different breeds (four Italian and two Portuguese), two heterozygous carriers of rob(26;29), three river buffaloes and two sheep were cytogenetically investigated in this study by using banding and FISH-mapping techniques (the latter only in cattle and river buffalo). Single- and dual- colour FISH were used with bovine probes containing both INRA143 (mapping proximally to BTA29) and bovine satellite (SAT) DNA SAT I, SAT III and SAT IV (mapping at the centromeric regions of cattle chromosomes). The combined use of these probes, the comparison of rob(1;29) with the dicentric rob(26;29) and with both river buffalo and sheep chromosomes (biarmed pairs) allowed us to hypothezise that rob(1;29) originated from complex chromosomal rearrangements through at least three sequential events: (a) centric fusion with the formation of a dicentric chromosome; (b) formation of a monocentric chromosome with loss of SAT I from both BTA1 and BTA29, most of SAT IV from BTA29 and, probably, some repeats of SAT III from BTA1; (c) double pericentric inversion or, more probably, a chromosome transposition of a small chromosome segment containing INRA143 from proximal p-arms to proximal q-arm of the translocated chromosome.

  15. An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as risk factors for autistic disorder.

    Science.gov (United States)

    Ashley-Koch, A E; Mei, H; Jaworski, J; Ma, D Q; Ritchie, M D; Menold, M M; Delong, G R; Abramson, R K; Wright, H H; Hussman, J P; Cuccaro, M L; Gilbert, J R; Martin, E R; Pericak-Vance, M A

    2006-05-01

    Gene-gene interactions are likely involved in many complex genetic disorders and new statistical approaches for detecting such interactions are needed. We propose a multi-analytic paradigm, relying on convergence of evidence across multiple analysis tools. Our paradigm tests for main and interactive effects, through allele, genotype and haplotype association. We applied our paradigm to genotype data from three GABAA receptor subunit genes (GABRB3, GABRA5, and GABRG3) on chromosome 15 in 470 Caucasian autism families. Previously implicated in autism, we hypothesized these genes interact to contribute to risk. We detected no evidence of main effects by allelic (PDT, FBAT) or genotypic (genotype-PDT) association at individual markers. However, three two-marker haplotypes in GABRG3 were significant (HBAT). We detected no significant multi-locus associations using genotype-PDT analysis or the EMDR data reduction program. However, consistent with the haplotype findings, the best single locus EMDR model selected a GABRG3 marker. Further, the best pairwise genotype-PDT result involved GABRB3 and GABRG3, and all multi-locus EMDR models also selected GABRB3 and GABRG3 markers. GABA receptor subunit genes do not significantly interact to contribute to autism risk in our overall data set. However, the consistency of results across analyses suggests that we have defined a useful framework for evaluating gene-gene interactions.

  16. Know Your Chromosomes

    Indian Academy of Sciences (India)

    The organization of chromosomes, the structure and function of genes and the role of genetic mutations in diseases continue to be an area of intense scientific investigation. The size of an ... 39 years, while Mendel formulated his laws of inheritance 130 years ago ..... Harper International edition, Harper and Row, New York.

  17. Chromosomal abnormalities and autism

    African Journals Online (AJOL)

    Farida El-Baz

    2015-06-19

    Jun 19, 2015 ... Abstract Background: Autism is a neurodevelopmental disorder characterized by clinical, etio- logic and genetic heterogeneity. Many surveys revealed cytogenetically visible chromosomal abnor- malities in 7.4% of autistic patients documented as well as several submicroscopic variants. This study had ...

  18. Know Your Chromosomes

    Indian Academy of Sciences (India)

    a gene located on the X chromosome is expressed in males more often than in females? For most genes ..... Disease results in light sensitive skin lesions, fragile skin due to deficiency of uroporphyrinogen dicarboxylase, an enzyme involved in biosynthesis of ... Aufwomall'SctlSSlve protein. PX MPl Zellweger syndrome (ZS).

  19. The Y Chromosome

    Science.gov (United States)

    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…

  20. Know Your Chromosomes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 3. Know Your Chromosomes The Strong Holds of Family Trees. Vani Brahmachari. Series Article Volume 1 Issue 3 March 1996 pp 30-38. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Know Your Chromosomes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 1. Know Your Chromosomes Nature's Way of Packing Genes. Vani Brahmachari. Series Article Volume 1 Issue 1 January 1996 pp 40-47. Fulltext. Click here to view fulltext PDF. Permanent link:

  2. Quest for the sex chromosomes in Squalius pyrenaicus (Teleostei, Cyprinidae

    Directory of Open Access Journals (Sweden)

    Carla Sofia A. Pereira

    2015-10-01

    Full Text Available In teleosts, evolutionary proximity does not dictate similarity in the sex determining systems. Hybridization, even among closely related species, often results in a huge shock. A good example of such deviation is the cyprinid species complex of Squalius alburnoides with unique characteristics that make this a very interesting model of study regarding the differentiation of sex chromosomes in a hybrid context. This complex endemic to the Iberian Peninsula resulted from the hybridization of Squalius pyrenaicus females (P genome with males from an unknown species closely related to Anaecypris hispanica (A genome. The complex comprises males and females with different levels of ploidy and genome combinations (genomotypes intertwined by altered modes of reproduction, ranging from normal meiosis to meiotic hybridogenesis. Sex ratio in nature is clearly biased towards the prevalence of triploid females but the complex also comprises an allegedly all-male lineage. Overall, sex chromosomes are very similar with X and Z having euchromatic regions while Y and W are completely heterochromatic. The accumulation of heterochromatin and the potential loss of genes on Y and W chromosomes are considered convergent traits in the process of sex chromosome differentiation. Bearing in mind S. pyrenaicus as the maternal lineage of S. alburnoides and the possibility of a ZW sex determining system in this complex, GISH (genomic in situ hybridization experiments were performed in 6 specimens (3 males, 3 females; Cheleiros tributary, Portugal trying to identify polymorphisms that could be associated with differentiating sex chromosomes in S. pyrenaicus. No differences could be found suggesting that either sex determining genes are scattered throughout the genome of this species or that, if present, sex chromosomes remain in a relatively undifferentiated state (morphological and structural. This investigation requires higher resolution cytogenetic tools like repetitive

  3. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...

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

    Directory of Open Access Journals (Sweden)

    Vázquez Guelaguetza

    2003-03-01

    Full Text Available Abstract 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.

  5. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  6. [Dicentric Y chromosome].

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Furforo, L. [Hospital Materno Infantil Ramon Sarda, Buenos Aires (Argentina)]|[Instituto Nacional de Genetica Medica, Buenos Aires (Argentina); Rittler, M. [Hospital Materno Infantil Ramon Sarda, Buenos Aires (Argentina); Slavutsky, I.R. [Academia Nacional de Medicina, Buenos Aires (Argentina)

    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.

  8. Photoactivated In Vivo Proximity Labeling.

    Science.gov (United States)

    Beck, David B; Bonasio, Roberto

    2017-06-19

    Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  9. Prox-1 Automated Proximity Operations

    Science.gov (United States)

    2016-01-13

    on demonstrating the functionality required to meet minimum mission success criteria. The minimum mission includes on- orbit spacecraft checkout of...also includes deployment of LightSail-B from the P-POD, and imaging of LightSail-B for 20 minutes as it recedes from Prox-1. small satellite ; proximity...criteria. The minimum mission includes on- orbit spacecraft checkout of all spacecraft subsystems, including flight qualification of the following new

  10. A new region of conservation is defined between human and mouse X chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Dinulos, M.B.; Disteche, C.M. [Univ. of Washington, Seattle, WA (United States); Bassi, M.T. [Univ. of Siena (Italy)] [and others

    1996-07-01

    Comparative mapping of the X chromosome in eutherian mammals have revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. Recently, we and others mapped the murine homologue of CLCN4 (Chloride channel 4) to band F4 of the X chromosome in Mus spretus but to chromosome 7 in laboratory strains. We now report the mapping of the murine homologues of APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), two genes that are located on the human X chromosome at band p22.3 and in close proximity to CLCN4. Interestingly, Oa1 and Apxl map to bands F2-F3 in both M. spretus and the laboratory strain C57BL/6J, defining a new rearrangement between human and mouse X chromosomes. 17 refs., 2 figs., 1 tab.

  11. Absence of lambda immunoglobulin sequences on the supernumerary chromosome of the "cat eye" syndrome.

    Science.gov (United States)

    Hough, C A; White, B N; Holden, J J

    1995-09-11

    The supernumerary bisatellited chromosome causing the "cat eye" syndrome (CES) is of chromosome 22 origin and consists of an inverted duplication of the 22pter-->22q11.2 region. To determine the extent of involvement of band q11.2 on the bisatellited chromosome, copy number assessment of sequences homologous to cloned lambda immunoglobulin (lambda Ig) gene region probes was carried out on DNA from individuals with CES using densitometric analysis of Southern blots. None of the 10 lambda Ig sequences studied was found in increased copy number in DNA from any of the 10 CES individuals tested, indicating that these sequences are not present on the supernumerary chromosome. The breakpoints involved in the generation of the bisatellited supernumerary chromosome associated with CES are therefore proximal to the lambda Ig gene region.

  12. The chromosome cycle of prokaryotes

    Science.gov (United States)

    Kuzminov, Andrei

    2013-01-01

    Summary In both eukaryotes and prokaryotes, chromosomal DNA undergoes replication, condensation-decondensation and segregation, sequentially, in some fixed order. Other conditions, like sister-chromatid cohesion (SCC), may span several chromosomal events. One set of these chromosomal transactions within a single cell cycle constitutes the “chromosome cycle”. For many years it was generally assumed that the prokaryotic chromosome cycle follows major phases of the eukaryotic one: -replication-condensation-segregation-(cell division)-decondensation-, with SCC of unspecified length. Eventually it became evident that, in contrast to the strictly consecutive chromosome cycle of eukaryotes, all stages of the prokaryotic chromosome cycle run concurrently. Thus, prokaryotes practice “progressive” chromosome segregation separated from replication by a brief SCC, and all three transactions move along the chromosome at the same fast rate. In other words, in addition to replication forks, there are “segregation forks” in prokaryotic chromosomes. Moreover, the bulk of prokaryotic DNA outside the replication-segregation transition stays compacted. I consider possible origins of this concurrent replication-segregation and outline the “nucleoid administration” system that organizes the dynamic part of the prokaryotic chromosome cycle. PMID:23962352

  13. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    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.

  14. The X chromosome in space.

    Science.gov (United States)

    Jégu, Teddy; Aeby, Eric; Lee, Jeannie T

    2017-06-01

    Extensive 3D folding is required to package a genome into the tiny nuclear space, and this packaging must be compatible with proper gene expression. Thus, in the well-hierarchized nucleus, chromosomes occupy discrete territories and adopt specific 3D organizational structures that facilitate interactions between regulatory elements for gene expression. The mammalian X chromosome exemplifies this structure-function relationship. Recent studies have shown that, upon X-chromosome inactivation, active and inactive X chromosomes localize to different subnuclear positions and adopt distinct chromosomal architectures that reflect their activity states. Here, we review the roles of long non-coding RNAs, chromosomal organizational structures and the subnuclear localization of chromosomes as they relate to X-linked gene expression.

  15. Prenatal diagnosis of chromosome 15 abnormalities in the Prader-Willi/Angelman syndrome region by traditional and molecular cytogenetics

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fejel, S.; Magenis, R.E.; Leff, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1995-02-13

    With improvements in culturing and banding techniques, amniotic fluid studies now achieve a level of resolution at which the Prader-Willi syndrome (PWS) and Angelman syndrome (AS) region may be questioned. Chromosome 15 heteromorphisms, detected with Q- and R-banding and used in conjunction with PWS/AS region-specific probes, can confirm a chromosome deletion and establish origin to predict the clinical outcome. We report four de novo cases of an abnormal-appearing chromosome 15 in amniotic fluid samples referred for advanced maternal age or a history of a previous chromosomally abnormal child. The chromosomes were characterized using G-, Q-, and R-banding, as well as isotopic and fluorescent in situ hybridization of DNA probes specific for the proximal chromosome 15 long arm. In two cases, one chromosome 15 homolog showed a consistent deletion of the ONCOR PWS/AS region A and B. In the other two cases, one of which involved an inversion with one breakpoint in the PWS/AS region, all of the proximal chromosome 15 long arm DNA probes used in the in situ hybridization were present on both homologs. Clinical follow-up was not available on these samples, as in all cases the parents chose to terminate the pregnancies. These cases demonstrate the ability to prenatally diagnose chromosome 15 abnormalities associated with PWS/AS. In addition, they highlight the need for a better understanding of this region for accurate prenatal diagnosis. 41 refs., 5 figs.

  16. Interstitial duplication of proximal 22q: phenotypic overlap with cat eye syndrome.

    Science.gov (United States)

    Knoll, J H; Asamoah, A; Pletcher, B A; Wagstaff, J

    1995-01-16

    We describe a child with downslanting palpebral fissures, preauricular malfunctions, congenital heart defect (total anomalous pulmonary venous return), unilateral absence of a kidney, and developmental delay with an apparent interstitial duplication of proximal 22q. Fluorescent in situ hybridization (FISH) analysis showed duplication of the IGLC locus, and C-banding of the duplicated region was negative. The duplication appears to involve 22q11.2-q12. Although the child has neither colobomas nor microphthalmia, he shows phenotypic overlap with the cat eye syndrome, which is caused by a supernumerary bisatellited chromosome arising from inverted duplication of the short arm and proximal long arm of chromosome 22. Further molecular studies of this patient should help to define the regions responsible for the manifestations of cat eye syndrome.

  17. Localisation of a dystrophin-related autosomal gene to 6q24 in man, and to mouse chromosome 10 in the region of the dystrophia muscularis (dy) locus.

    Science.gov (United States)

    Buckle, V J; Guenet, J L; Simon-Chazottes, D; Love, D R; Davies, K E

    1990-08-01

    We have localised a dystrophin-related autosomal gene called DMDL (Duchenne muscular dystrophy-like) to human chromosome 61q24 by in situ hybridisation. Using restriction fragment length polymorphism analysis in two mouse species, we have localised the homologous gene Dmdl in the mouse to chromosome 10 proximal to the Myb oncogene. A neuromuscular disease locus dystrophia muscularis (dy) has previously been assigned to this region of mouse chromosome 10.

  18. PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS

    African Journals Online (AJOL)

    DR. AMINU

    PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS. 1 Alhassan, A. J. 1M .S. Sule, 1J. ... ABSTRACT. This study determined the proximate and mineral element composition of whole white grubs using standard methods of analysis. Proximate ... days, before pulverized to powder and kept in plastic container.

  19. Y chromosome gr/gr deletions are a risk factor for low semen quality

    NARCIS (Netherlands)

    Visser, L.; Westerveld, G. H.; Korver, C. M.; van Daalen, S. K. M.; Hovingh, S. E.; Rozen, S.; van der Veen, F.; Repping, S.

    2009-01-01

    Subfertility affects one in eight couples. In up to 50% of cases, the male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are established causes of low semen quality. Whether a recently identified

  20. A Novel Pseudo-Dicentric Variant of 16p11.2-q11.2 Contains Euchromatin from 16p11.2-p11.1 and Resembles Pathogenic Duplications of Proximal 16q

    DEFF Research Database (Denmark)

    Barber, J C K; Brasch-Andersen, Charlotte; Maloney, V K

    2012-01-01

    An unusually large G-light band between 2 G-dark bands in the proximal long arm of chromosome 16 was found in a boy of 5 years of age ascertained with growth retardation, microcephaly, and dysmorphic features. Dual color bacterial artificial chromosome fluorescence in situ hybridization (BAC FISH...

  1. Partial trisomy of chromosome 22 resulting from a supernumerary marker chromosome 22 in a child with features of cat eye syndrome.

    Science.gov (United States)

    Bélien, Valérie; Gérard-Blanluet, Marion; Serero, Stéphane; Le Dû, Nathalie; Baumann, Clarisse; Jacquemont, Marie-Line; Dupont, Céline; Krabchi, Kada; Drunat, Séverine; Elbez, Annie; Janaud, Jean-Claude; Benzacken, Brigitte; Verloes, Alain; Tabet, Anne-Claude; Aboura, Azzedine

    2008-07-15

    Small supernumerary marker chromosomes are present in about 0.05% of the human population. In approximately 28% of persons with these markers (excluding the approximately 60% derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. We report on a 3-month-old girl with intrauterine growth retardation, craniofacial features, hypotonia, partial coloboma of iris and total anomalous pulmonary venous return. Cytogenetic analysis showed the presence of a supernumerary marker chromosome, identified by fluorescence in situ hybridization as part of chromosome 22, and conferring a proximal partial trisomy 22q22.21, not encompassing the DiGeorge critical region (RP11-154H4 + , TBX1-). This observation adds new information relevant to cat eye syndrome and partial trisomy of 22q. 2008 Wiley-Liss, Inc.

  2. Finger Proximal Interphalangeal Joint Dislocation.

    Science.gov (United States)

    Ramponi, Denise; Cerepani, Mary Jo

    2015-01-01

    Finger dislocations are common injuries that are often managed by emergency nurse practitioners. A systematic physical examination following these injuries is imperative to avoid complications. Radiographic views, including the anteroposterior, lateral, and oblique views, are imperative to evaluate these finger dislocations. A dorsal dislocation of the proximal interphalangeal (PIP) joint is the most common finger dislocation type often easily reduced. A volar PIP dislocation can often be difficult to reduce and may result in finger deformity. Finger dislocations should be reduced promptly. Referral to an orthopedic hand specialist is required if the dislocation is unable to be reduced or if the finger joint is unstable following reduction attempts.

  3. Equilibrium properties of proximity effect

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, D.; Pothier, H.; Gueron, S.; Birge, N.O.; Devoret, M.

    1996-12-31

    The proximity effect in diffusive normal-superconducting (NS) nano-structures is described by the Usadel equations for the electron pair correlations. We show that these equations obey a variational principle with a potential which generalizes the Ginzburg-Landau energy functional. We discuss simple examples of NS circuits using this formalism. In order to test the theoretical predictions of the Usadel equations, we have measured the density of states as a function of energy on a long N wire in contact with a S wire at one end, at different distances from the NS interface. (authors). 12 refs.

  4. Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma

    Directory of Open Access Journals (Sweden)

    García José

    2005-07-01

    Full Text Available Abstract Background Chromosomal Comparative Genomic Hybridization (CGH has been applied to all stages of cervical carcinoma progression, defining a specific pattern of chromosomal imbalances in this tumor. However, given its limited spatial resolution, chromosomal CGH has offered only general information regarding the possible genetic targets of DNA copy number changes. Methods In order to further define specific DNA copy number changes in cervical cancer, we analyzed 20 cervical samples (3 pre-malignant lesions, 10 invasive tumors, and 7 cell lines, using the GenoSensor microarray CGH system to define particular genetic targets that suffer copy number changes. Results The most common DNA gains detected by array CGH in the invasive samples were located at the RBP1-RBP2 (3q21-q22 genes, the sub-telomeric clone C84C11/T3 (5ptel, D5S23 (5p15.2 and the DAB2 gene (5p13 in 58.8% of the samples. The most common losses were found at the FHIT gene (3p14.2 in 47% of the samples, followed by deletions at D8S504 (8p23.3, CTDP1-SHGC- 145820 (18qtel, KIT (4q11-q12, D1S427-FAF1 (1p32.3, D9S325 (9qtel, EIF4E (eukaryotic translation initiation factor 4E, 4q24, RB1 (13q14, and DXS7132 (Xq12 present in 5/17 (29.4% of the samples. Conclusion Our results confirm the presence of a specific pattern of chromosomal imbalances in cervical carcinoma and define specific targets that are suffering DNA copy number changes in this neoplasm.

  5. Method for obtaining Chromosomes Method for obtaining Chromosomes

    Directory of Open Access Journals (Sweden)

    Bogart James P.

    1973-09-01

    Full Text Available It is very easy to obtain chromosomes from anuran amphibians.Amphibians have very large chromosomes which can easily be seen with an ordinary microscope. The method used has been tested in the laboratory and also at collecting sites. All that is required are a few chemicals and simple equipment.It is very easy to obtain chromosomes from anuran amphibians.Amphibians have very large chromosomes which can easily be seen with an ordinary microscope. The method used has been tested in the laboratory and also at collecting sites. All that is required are a few chemicals and simple equipment.

  6. Y chromosome morphology of cattle.

    Science.gov (United States)

    Potter, W L; Upton, P C

    1979-11-01

    Metaphase chromosomes from cultured lymphocytes were prepared from 246 bulls including Bos indicus, Bos taurus. Bos (Bibos) banteng, Sanga and interspecific and intra-specific breed crosses. Morphology and karyotype position of the Y chromosome for each bull were noted. Karyotype position of the Y chromosome varied between bulls from 25th to 29th pair and the Y chromosomes of Bos indicus and breeds derived from Bos indicus bulls were acrocentric while those of Bos taurus, Sanga and breeds derived from these bulls were metacentric/submetacentric. Two forms of Y chromosome were noted in the Droughtmaster breed. C-banding patterns of the acrocentric Y chromosome were characteristic and enabled easy identification.

  7. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  8. The gene for Nijmegen breakage syndrome (V2) is not located on chromosome 11

    Energy Technology Data Exchange (ETDEWEB)

    Kenshi Komatsu; Shinya Matsuura; Hiroshi Tauchi; Satoru Endo [Hiroshima Univ. (Japan)] [and others

    1996-04-01

    Ataxia telanglectasia (AT) is an autosomal recessive disorder characterized by oculocutaneous telangiectasia and cerebellar ataxia. Individuals with this disorder display immunological impairments, hypersensitivity to ionizing radiation, and a predisposition to cancer. There has been reported genetic heterogeneity in AT, which appeared to include four genetic complementation groups in classical AT - i.e., A, B/C, D, E - and two variants, so-called Nijmegen breakage syndrome (NBS), V1 and V2. Among the four groups of classical AT, no significant differences in clinical appearance have been seen. Familial linkage analyses have produced evidence that genes for all four complementation groups in classical AT reside in a narrow region on chromosome 11q22-23. On the other hand, NBS patients have neither cerebellar ataxia nor telanglectasia but do display microcephaly and a developmental delay. However, patients share features with AT, such as high radiosensitivity, radioresistant DNA synthesis (RDS), and chromosome instability, suggesting that the same pathway (or part thereof) is impaired in both syndromes. The underlying gene for NBS has not yet been identified, and its location in the human genome is still unknown. 15 refs., 3 figs.

  9. Construction of a DNA library representing 15q11-13 by subtraction of two flow sorted marker chromosome-specific libraries

    Energy Technology Data Exchange (ETDEWEB)

    Blennow, E.; Werelius, B.; Nordenskjoeld, M. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1994-09-01

    Constitutional extra {open_quotes}marker chromosomes{close_quotes} are found in {approx}0.5/1000 of newborns. Of these, 50% are inverted duplications of the pericentromeric region of chromosome 15, including two variants; (1) inv dup(15)(pter{yields}q11:q11{yields}pter) and (2) inv dup(15) (pter{yields}q12-13::q12-13{yields}pter). Variant (1) is found in phenotypically normal individuals, whereas variant (2) will produce a typical clinical picture including mental retardation, autism, hyperactivity and discrete dysmorphic features. Fluorescence in situ hybridization (FISH) using single copy probes from the Prader-Willi region confirms these observations as well as chromosome painting using a flow-sorted marker chromosome-specific library from a variant (1) marker, hybridized to the chromosomes of a patient with a variant (2) marker chromosome. Followingly, a flow-sorted biotinylated variant (1) library was subtracted from a non-labeled variant (2) library using magnetic beads and subsequent amplification by degenerate oligonucleotide-primed PCR (DOP-PCR). The successful result was demonstrated by using the amplified material for chromosome painting on chromosome slides from variant (1) and variant (2) patients. We have constructed a library from 15q11-13. This region contains genes producing a specific abnormal phenotype when found in a tri- or tetrasomic state. The region also contains the genes responsible for the Prader-Willi and Angelman syndromes when the paternal/maternal copy is missing, respectively. It is therefore a region where parental imprinting plays an important role. The isolated library may be used to isolate single copy clones which will allow further investigations of this region.

  10. X Chromosome Evolution in Cetartiodactyla.

    Science.gov (United States)

    Proskuryakova, Anastasia A; Kulemzina, Anastasia I; Perelman, Polina L; Makunin, Alexey I; Larkin, Denis M; Farré, Marta; Kukekova, Anna V; Lynn Johnson, Jennifer; Lemskaya, Natalya A; Beklemisheva, Violetta R; Roelke-Parker, Melody E; Bellizzi, June; Ryder, Oliver A; O'Brien, Stephen J; Graphodatsky, Alexander S

    2017-08-31

    The phenomenon of a remarkable conservation of the X chromosome in eutherian mammals has been first described by Susumu Ohno in 1964. A notable exception is the cetartiodactyl X chromosome, which varies widely in morphology and G-banding pattern between species. It is hypothesized that this sex chromosome has undergone multiple rearrangements that changed the centromere position and the order of syntenic segments over the last 80 million years of Cetartiodactyla speciation. To investigate its evolution we have selected 26 evolutionarily conserved bacterial artificial chromosome (BAC) clones from the cattle CHORI-240 library evenly distributed along the cattle X chromosome. High-resolution BAC maps of the X chromosome on a representative range of cetartiodactyl species from different branches: pig (Suidae), alpaca (Camelidae), gray whale (Cetacea), hippopotamus (Hippopotamidae), Java mouse-deer (Tragulidae), pronghorn (Antilocapridae), Siberian musk deer (Moschidae), and giraffe (Giraffidae) were obtained by fluorescent in situ hybridization. To trace the X chromosome evolution during fast radiation in specious families, we performed mapping in several cervids (moose, Siberian roe deer, fallow deer, and Pere David's deer) and bovid (muskox, goat, sheep, sable antelope, and cattle) species. We have identified three major conserved synteny blocks and rearrangements in different cetartiodactyl lineages and found that the recently described phenomenon of the evolutionary new centromere emergence has taken place in the X chromosome evolution of Cetartiodactyla at least five times. We propose the structure of the putative ancestral cetartiodactyl X chromosome by reconstructing the order of syntenic segments and centromere position for key groups.

  11. Fragile sites, dysfunctional telomere and chromosome fusions: What is 5S rDNA role?

    Science.gov (United States)

    Barros, Alain Victor; Wolski, Michele Andressa Vier; Nogaroto, Viviane; Almeida, Mara Cristina; Moreira-Filho, Orlando; Vicari, Marcelo Ricardo

    2017-04-15

    Repetitive DNA regions are known as fragile chromosomal sites which present a high flexibility and low stability. Our focus was characterize fragile sites in 5S rDNA regions. The Ancistrus sp. species shows a diploid number of 50 and an indicative Robertsonian fusion at chromosomal pair 1. Two sequences of 5S rDNA were identified: 5S.1 rDNA and 5S.2 rDNA. The first sequence gathers the necessary structures to gene expression and shows a functional secondary structure prediction. Otherwise, the 5S.2 rDNA sequence does not contain the upstream sequences that are required to expression, furthermore its structure prediction reveals a nonfunctional ribosomal RNA. The chromosomal mapping revealed several 5S.1 and 5S.2 rDNA clusters. In addition, the 5S.2 rDNA clusters were found in acrocentric and metacentric chromosomes proximal regions. The pair 1 5S.2 rDNA cluster is co-located with interstitial telomeric sites (ITS). Our results indicate that its clusters are hotspots to chromosomal breaks. During the meiotic prophase bouquet arrangement, double strand breaks (DSBs) at proximal 5S.2 rDNA of acrocentric chromosomes could lead to homologous and non-homologous repair mechanisms as Robertsonian fusions. Still, ITS sites provides chromosomal instability, resulting in telomeric recombination via TRF2 shelterin protein and a series of breakage-fusion-bridge cycles. Our proposal is that 5S rDNA derived sequences, act as chromosomal fragile sites in association with some chromosomal rearrangements of Loricariidae. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ahlbom, B.E.; Anneren, G. [Univ. Hospital, Uppsala (Sweden); Sidenvall, R. [Central Hospital of Hudiksvall (Sweden)

    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.

  13. Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19.

    Directory of Open Access Journals (Sweden)

    Marco Di Stefano

    Full Text Available The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact poses the more general question of whether it is at all feasible that the numerous genes that are coregulated on a given chromosome, especially those at large genomic distances, might become proximate inside the nucleus. This problem is studied here using steered molecular dynamics simulations in order to enforce the colocalization of thousands of knowledge-based gene sequences on a model for the gene-rich human chromosome 19. Remarkably, it is found that most (≈ 88% gene pairs can be brought simultaneously into contact. This is made possible by the low degree of intra-chromosome entanglement and the large number of cliques in the gene coregulatory network. A clique is a set of genes coregulated all together as a group. The constrained conformations for the model chromosome 19 are further shown to be organized in spatial macrodomains that are similar to those inferred from recent HiC measurements. The findings indicate that gene coregulation and colocalization are largely compatible and that this relationship can be exploited to draft the overall spatial organization of the chromosome in vivo. The more general validity and implications of these findings could be investigated by applying to other eukaryotic chromosomes the general and transferable computational strategy introduced here.

  14. A homologous subfamily of satellite III DNA on human chromosomes 14 and 22.

    Science.gov (United States)

    Choo, K H; Earle, E; McQuillan, C

    1990-10-11

    We describe a new subfamily of human satellite III DNA that is represented on two different acrocentric chromosomes. This DNA is composed of a tandemly repeated array of diverged 5-base-pair monomer units of the sequence GGAAT or GGAGT. These monomers are organised into a 1.37-kilobase higher-order structure that is itself tandemly reiterated. Using a panel of somatic cell hybrids containing specific human chromosomes, this higher-order structure is demonstrated on chromosomes 14 and 22, but not on the remaining acrocentric chromosomes. In situ hybridisation studies have localised the sequence to the proximal p-arm region of these chromosomes. Analysis by pulsed-field gel electrophoresis (PFGE) reveals that 70-110 copies of the higher-order structure are tandemly organised on a chromosome into a major domain which appears to be flanked on both sides by non-tandemly repeated genomic DNA. In addition, some of the satellite III sequences are interspersed over a number of other PFGE fragments. This study provides fundamental knowledge on the structure and evolution of the acrocentric chromosomes, and should extend our understanding of the complex process of interchromosomal interaction which may be responsible for Robertsonian translocation and meiotic nondisjunction involving these chromosomes.

  15. Know Your Chromosomes Hybrid Cells and Human Chromosomes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 6. Know Your Chromosomes Hybrid Cells and Human Chromosomes. Vani Brahmachari. Series Article Volume 1 Issue 6 June 1996 pp 41-49. Fulltext. Click here to view fulltext PDF. Permanent link:

  16. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    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…

  17. Complications in proximal humeral fractures.

    Science.gov (United States)

    Calori, Giorgio Maria; Colombo, Massimiliano; Bucci, Miguel Simon; Fadigati, Piero; Colombo, Alessandra Ines Maria; Mazzola, Simone; Cefalo, Vittorio; Mazza, Emilio

    2016-10-01

    Necrosis of the humeral head, infections and non-unions are among the most dangerous and difficult-to-treat complications of proximal humeral fractures. The aim of this work was to analyse in detail non-unions and post-traumatic bone defects and to suggest an algorithm of care. Treatment options are based not only on the radiological frame, but also according to a detailed analysis of the patient, who is classified using a risk factor analysis. This method enables the surgeon to choose the most suitable treatment for the patient, thereby facilitating return of function in the shortest possible time. The treatment of such serious complications requires the surgeon to be knowledgeable about the following possible solutions: increased mechanical stability; biological stimulation; and reconstructive techniques in two steps, with application of biotechnologies and prosthetic substitution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Chromosomal rearrangements occurred repeatedly and ...

    African Journals Online (AJOL)

    All examined Paroedura showed NORs on the smallest chromosome pair; moreover, six of the eleven examined species show a 2n = 36 karyotype, with a pair of metacentrics and 17 telocentric pair. The remaining species exhibited karyotypes with a diploid chromosome number ranging from 2n = 31 to 2n = 38. We assume ...

  19. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    many membrane-associated activities, such as ion channels, transmembrane transporters, and electron transport chain proteins. Thus, it appears that whilst there are many "housekeeping systems" encoded in chromosome 1, there are far fewer core functions found in chromosome 2. However, the presence...

  20. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    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.

  1. Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated with 22q11 deletion syndrome breakpoints.

    Science.gov (United States)

    McTaggart, K E; Budarf, M L; Driscoll, D A; Emanuel, B S; Ferreira, P; McDermid, H E

    1998-01-01

    The supernumerary cat eye syndrome (CES) chromosome is dicentric, containing two copies of 22pter-->q11.2. We have found that the duplication breakpoints are clustered in two intervals. The more proximal, most common interval is the 450-650 kb region between D22S427 and D22S36, which corresponds to the proximal deletion breakpoint interval found in the 22q11 deletion syndrome (DiGeorge/velocardiofacial syndrome). The more distal duplication breakpoint interval falls between CRKL and D22S112, which overlaps with the common distal deletion interval of the 22q11 deletion syndrome. We have therefore classified CES chromosomes into two types based on the location of the two breakpoints required to generate them. The smaller type I CES chromosomes are symmetrical, with both breakpoints located within the proximal interval. The larger type II CES chromosomes are either asymmetrical, with one breakpoint located in each of the two intervals, or symmetrical, with both breakpoints located in the distal interval. The co-localization of the breakpoints of these different syndromes, plus the presence of low-copy repeats adjacent to each interval, suggests the existence of several specific regions of chromosomal instability in 22q11.2 which are involved in the production of both deletions and duplications. Since the phenotype associated with the larger duplication does not appear to be more severe than that of the smaller duplication, determination of the type of CES chromosome does not currently have prognostic value.

  2. Slit scan flow cytometry of isolated chromosomes following fluorescence hybridization: an approach of online screening for specific chromosomes and chromosome translocations

    NARCIS (Netherlands)

    Hausmann, M.; Dudin, G.; Aten, J. A.; Heilig, R.; Diaz, E.; Cremer, C.

    1991-01-01

    The recently developed methods of non radioactive in situ hybridization of chromosomes offer new aspects for chromosome analysis. Fluorescent labelling of hybridized chromosomes or chromosomal subregions allows to facilitate considerably the detection of specific chromosomal abnormalities. For many

  3. Proximity sensor technology for manipulator end effectors

    Science.gov (United States)

    Johnston, A. R.

    1975-01-01

    Optical proximity sensing techniques which could be used to help control the critical grasping phase of a remote manipulation are described. The proximity sensors described use a triangulation geometry to detect a surface located in a pre-determined region. The design of the proximity sensors themselves is discussed, as well as their application to manipulator control with a local control loop, and possibilities for future development are discussed.

  4. Proximate composition and antinutrient content of pumpkin ...

    African Journals Online (AJOL)

    Proximate composition and antinutrient content of pumpkin ( Cucurbita pepo ) and sorghum ( Sorghum bicolor ) flour blends fermented with Lactobacillus plantarum , Aspergillus niger and Bacillus subtilis.

  5. Chromosomal Evolution in Lower Vertebrates: Sex Chromosomes in Neotropical Fishes

    Directory of Open Access Journals (Sweden)

    Marcelo de Bello Cioffi

    2017-10-01

    Full Text Available Abstract: Fishes exhibit the greatest diversity of species among vertebrates, offering a number of relevant models for genetic and evolutionary studies. The investigation of sex chromosome differentiation is a very active and striking research area of fish cytogenetics, as fishes represent one of the most vital model groups. Neotropical fish species show an amazing variety of sex chromosome systems, where different stages of differentiation can be found, ranging from homomorphic to highly differentiated sex chromosomes. Here, we draw attention on the impact of recent developments in molecular cytogenetic analyses that helped to elucidate many unknown questions about fish sex chromosome evolution, using excellent characiform models occurring in the Neotropical region, namely the Erythrinidae family and the Triportheus genus. While in Erythrinidae distinct XY and/or multiple XY-derived sex chromosome systems have independently evolved at least four different times, representatives of Triportheus show an opposite scenario, i.e., highly conserved ZZ/ZW system with a monophyletic origin. In both cases, recent molecular approaches, such as mapping of repetitive DNA classes, comparative genomic hybridization (CGH, and whole chromosome painting (WCP, allowed us to unmask several new features linked to the molecular composition and differentiation processes of sex chromosomes in fishes.

  6. Field-flow fractionation of chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Giddings, J.C.

    1990-09-01

    Research continued on field flow fractionation of chromosomes. Progress in the past year can be organized into three main categories: (1) chromosome sample preparation; (2) preliminary chromosome fractionation; (3) fractionation of a polystyrene aggregate model which approximates the chromosome shape. We have been successful in isolating metaphase chromosomes from the Chinese hamster. We also received a human chromosome sample from Dr. Carolyn Bell-Prince of Los Alamos National Laboratory. Results are discussed. 2 figs.

  7. Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium

    Directory of Open Access Journals (Sweden)

    Bajpai Manisha

    2012-11-01

    Full Text Available Abstract Barrett’s esophagus (BE is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC. BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD. The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence. However the genetic basis of this process is poorly understood. It is conceived that preclinical models of BE may facilitate discovery of molecular markers due to ease of longitudinal sampling. Clinical markers to stratify the patients at higher risk are vital to institute appropriate therapeutic intervention since EAC has very poor prognosis. We developed a dynamic in-vitro BE carcinogenesis (BEC model by exposing naïve Barrett’s epithelium cell line (BAR-T to acid and bile at pH4 (B4, 5min/day for a year. The BEC model acquired malignant characteristics after chronic repeated exposure to B4 similar to the sequential progression of BE to EAC in vivo. Aim To study cytogenetic changes during progressive transformation in the BEC model. Results We observed that the BAR-T cells progressively acquired several chromosomal abnormalities in the BEC model. Evidence of chromosomal loss (-Y rearrangements [t(10;16 and dup (11q] and clonal selection appeared during the early stages of the BEC model. Clonal selection resulted in a stabilized monoclonal population of cells that had a changed morphology and formed colony in soft agar. BAR-T cells grown in parallel without any exposure did not show any of these abnormalities. Conclusions Prolonged acid and bile exposure induced chromosomal aberrations and clonal selection in benign BAR-T cells. Since aneuploidy preceded morphological/dysplastic changes in the BEC model, chromosomal aberrations may be an early predictor of BE progression. The [t(10;16 and dup(11q] aberrations identified in this study harbor several genes associated with

  8. Clinical and molecular characterization of patients with Jacobsen syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Penny, L.A.; Aquila, M.; Iones, O.W. [Univ. of California San Diego, La Jolla, CA (United States)] [and others

    1994-09-01

    Jacobsen (11q-) syndrome is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical features include mental retardation, trigonocephaly, facial dysmorphism, cardiac defects and thrombocytopenia, among others. We studied 14 Jacobsen syndrome patients with de novo terminal deletions of 11q. The deletions were characterized in a loss of heterozygosity analysis using polymorphic dinucleotide repeats. There was no preference in the parental origin of the deleted chromosome. Seven patients with the largest deletions, extending from 11q23.3-qter, appear to share the same breakpoint, between D11S924 and D11S1341. Terminal deletions extending proximal to this common breakpoint may be lethal. The remaining seven patients had various smaller deletions of 11q23.3, 11q24 or 11q25. Three patients with small terminal deletions had several major features of Jacobsen syndrome, including facial dysmorphism, cardiac defects and thrombocytopenia, suggesting that the genes responsible for these features lie near the end of the chromosome. These three patients did not have trigonocephaly, suggesting that, if hemizygosity for a single gene is responsible, it may lie proximal to D11S934.

  9. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  10. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  11. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  12. Prenatally diagnosed de novo complex chromosome rearrangements: Two new cases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, C.; Grubs, R.E.; Jewett, T. [and others

    1994-09-01

    Complex chromosome rearrangements (CCR) are rare structural rearrangements involving at least three chromosomes with three or more breakpoints. Although there have been numerous reports of individuals with CCR, most have been ascertained through the presence of multiple congenital anomalies, recurrent pregnancy loss, or infertility. Few cases have been ascertained prenatally. We present two new cases of prenatally ascertained CCR. In the first case, an amniocentesis revealed an apparently balanced de novo rearrangement in which chromosomes 5, 6 and 11 were involved in a three-way translocation: 46,XY,t(6;5)(5;11)(q23;p14.3;q15;p13). The pregnancy was unevenful. Recently, at the age of 9 months, a physical and developmental evaluation were normal but, height, weight, and head circumference were below the 5th percentile. In the second case an amniocentesis revealed an unbalanced de novo rearrangement involving separate translocations and an interstitial deletion: 46,XY,del(6)(q25.3q27),t(3;8)(p13;q21.3),t(6;18)(p11.2;q11.2). A meconium plug was present at birth and at 6 months of age surgery for Hirschsprung`s disease was required. Currently, at 10 months of age, the patient has hypotonia and developmental delay. The paucity of information regarding prenatally diagnosed CCR poses a problem in counseling families. Of the four prenatally diagnosed balanced de novo CCR cases, three had abnormal outcomes. In a review of the literature, approximately 70% of the postnatally ascertained balanced de novo CCR cases were associated with congenital anomalies, growth retardation and/or mental retardation. More information regarding the outcome of prenatally ascertained balanced de novo CCR is required for accurate risk assessment.

  13. Functional outcome following proximal humeral interlocking system plating for displaced proximal humeral fractures

    OpenAIRE

    Thyagarajan David; Haridas Samarth; Jones Denise; Dent Colin; Evans Richard; Williams Rhys

    2009-01-01

    Aim: To assess the functional outcome following internal fixation with the PHILOS (proximal humeral interlocking system) for displaced proximal humeral fractures. Patients and Methods: We reviewed 30 consecutive patients treated surgically with the proximal humeral locking plate for a displaced proximal humeral fracture. Functional outcome was determined using the American Shoulder and Elbow Society (ASES) score and Constant Murley score. Results: Average age of the patients was 58 years...

  14. Best Proximity Points for a New Class of Generalized Proximal Mappings

    Directory of Open Access Journals (Sweden)

    Tayyab Kamran

    2017-03-01

    Full Text Available The best proximity points are usually used to find the optimal approximate solution of the operator equation Tx = x, when T has no fixed point. In this paper, we prove some best proximity point theorems for nonself multivalued operators, following the foot steps of Basha and Shahzad [Best proximity point theorems for generalized proximal contractions, Fixed Point Theory Appl., 2012, 2012:42].

  15. Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification.

    Science.gov (United States)

    Starke, Heike; Nietzel, Angela; Weise, Anja; Heller, Anita; Mrasek, Kristin; Belitz, Britta; Kelbova, Christine; Volleth, Marianne; Albrecht, Beate; Mitulla, Beate; Trappe, Ralf; Bartels, Iris; Adolph, Sabine; Dufke, Andreas; Singer, Sylke; Stumm, Markus; Wegner, Rolf-Dieter; Seidel, Jörg; Schmidt, Angela; Kuechler, Alma; Schreyer, Isolde; Claussen, Uwe; von Eggeling, Ferdinand; Liehr, Thomas

    2003-12-01

    Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the approximately 60% SMC derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. The clinical outcome of an SMC is difficult to predict as they can have different phenotypic consequences because of (1). differences in euchromatic DNA-content, (2). different degrees of mosaicism, and/or (3). uniparental disomy (UPD) of the chromosomes homologous to the SMC. Here, we present 35 SMCs, which are derived from all human chromosomes, apart from chromosome 6, as demonstrated by the appropriate molecular cytogenetic approaches, such as centromere-specific multicolor fluoresence in situ hybridization (cenM-FISH), multicolor banding (MCB), and subcentromere-specific multicolor FISH (subcenM-FISH). In nine cases without an aberrant phenotype, neither partial proximal trisomies nor UPD could be detected. Abnormal clinical findings, such as psychomotoric retardation and/or craniofacial dysmorphisms, were associated with seven of the cases in which subcentromeric single-copy probes were proven to be present in three copies. Conversely, in eight cases with a normal phenotype, proximal euchromatic material was detected as partial trisomy. UPD was studied in 12 cases and subsequently detected in two of the cases with SMC (partial UPD 4p and maternal UPD 22 in a der(22)-syndrome patient), indicating that SMC carriers have an enhanced risk for UPD. At present, small proximal trisomies of 1p, 1q, 2p, 6p, 6q, 7q, 9p, and 12q seem to lead to clinical manifestations, whereas partial proximal trisomies of 2q, 3p, 3q, 5q, 7p, 8p, 17p, and 18p may not be associated with significant clinical symptoms. With respect to clinical outcome, a classification of SMCs is proposed that considers molecular genetic and molecular cytogenetic characteristics as demonstrated by presently available methods.

  16. X Chromosome Evolution in Cetartiodactyla

    Science.gov (United States)

    Proskuryakova, Anastasia A.; Kulemzina, Anastasia I.; Makunin, Alexey I.; Kukekova, Anna V.; Lynn Johnson, Jennifer; Lemskaya, Natalya A.; Beklemisheva, Violetta R.; Roelke-Parker, Melody E.; Bellizzi, June; Ryder, Oliver A.; O’Brien, Stephen J.; Graphodatsky, Alexander S.

    2017-01-01

    The phenomenon of a remarkable conservation of the X chromosome in eutherian mammals has been first described by Susumu Ohno in 1964. A notable exception is the cetartiodactyl X chromosome, which varies widely in morphology and G-banding pattern between species. It is hypothesized that this sex chromosome has undergone multiple rearrangements that changed the centromere position and the order of syntenic segments over the last 80 million years of Cetartiodactyla speciation. To investigate its evolution we have selected 26 evolutionarily conserved bacterial artificial chromosome (BAC) clones from the cattle CHORI-240 library evenly distributed along the cattle X chromosome. High-resolution BAC maps of the X chromosome on a representative range of cetartiodactyl species from different branches: pig (Suidae), alpaca (Camelidae), gray whale (Cetacea), hippopotamus (Hippopotamidae), Java mouse-deer (Tragulidae), pronghorn (Antilocapridae), Siberian musk deer (Moschidae), and giraffe (Giraffidae) were obtained by fluorescent in situ hybridization. To trace the X chromosome evolution during fast radiation in specious families, we performed mapping in several cervids (moose, Siberian roe deer, fallow deer, and Pere David’s deer) and bovid (muskox, goat, sheep, sable antelope, and cattle) species. We have identified three major conserved synteny blocks and rearrangements in different cetartiodactyl lineages and found that the recently described phenomenon of the evolutionary new centromere emergence has taken place in the X chromosome evolution of Cetartiodactyla at least five times. We propose the structure of the putative ancestral cetartiodactyl X chromosome by reconstructing the order of syntenic segments and centromere position for key groups. PMID:28858207

  17. Preliminary phytochemical screening, proximate and elemental ...

    African Journals Online (AJOL)

    The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the following proximate ...

  18. Bimalleolar ankle fracture with proximal fibular fracture

    NARCIS (Netherlands)

    Colenbrander, R. J.; Struijs, P. A. A.; Ultee, J. M.

    2005-01-01

    A 56-year-old female patient suffered a bimalleolar ankle fracture with an additional proximal fibular fracture. This is an unusual fracture type, seldom reported in literature. It was operatively treated by open reduction and internal fixation of the lateral malleolar fracture. The proximal fibular

  19. Grouping by Proximity in Haptic Contour Detection

    Science.gov (United States)

    Overvliet, Krista E.; Krampe, Ralf Th.; Wagemans, Johan

    2013-01-01

    We investigated the applicability of the Gestalt principle of perceptual grouping by proximity in the haptic modality. To do so, we investigated the influence of element proximity on haptic contour detection. In the course of four sessions ten participants performed a haptic contour detection task in which they freely explored a haptic random dot display that contained a contour in 50% of the trials. A contour was defined by a higher density of elements (raised dots), relative to the background surface. Proximity of the contour elements as well as the average proximity of background elements was systematically varied. We hypothesized that if proximity of contour elements influences haptic contour detection, detection will be more likely when contour elements are in closer proximity. This should be irrespective of the ratio with the proximity of the background elements. Results showed indeed that the closer the contour elements were, the higher the detection rates. Moreover, this was the case independent of the contour/background ratio. We conclude that the Gestalt law of proximity applies to haptic contour detection. PMID:23762364

  20. Proximate analysis on four edible mushrooms ADEDAYO ...

    African Journals Online (AJOL)

    Michael Horsfall

    Vol. 15 (1) 9 - 11. Full-text Available Online at www.bioline.org.br/ja. Proximate analysis on four edible mushrooms. ADEDAYO, MAJEKODUNMI RACHEL. Nigerian Stored Product Research Institute, P.M.B.3032, Kano. ABSTRACT: Proximate study was conducted on four edible mushrooms commonly found in farmlands in.

  1. Proximate Sources of Collective Teacher Efficacy

    Science.gov (United States)

    Adams, Curt M.; Forsyth, Patrick B.

    2006-01-01

    Purpose: Recent scholarship has augmented Bandura's theory underlying efficacy formation by pointing to more proximate sources of efficacy information involved in forming collective teacher efficacy. These proximate sources of efficacy information theoretically shape a teacher's perception of the teaching context, operationalizing the difficulty…

  2. Phytochemical screening, proximate analysis and anticonvulsant ...

    African Journals Online (AJOL)

    Spigelia anthelmia is used traditionally in Southern Nigeria for the treatment of infant convulsion and epilepsy. This study investigated the phytochemical constituents, proximate analysis and anticonvulsant effect of the methanolic extract of Spigelia anthelmia. Phytochemical evaluation and proximate analysis was carried ...

  3. Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast.

    Directory of Open Access Journals (Sweden)

    Tracey Beyer

    2016-10-01

    Full Text Available DNA replication errors at certain sites in the genome initiate chromosome instability that ultimately leads to stable genomic rearrangements. Where instability begins is often unclear. And, early instability may form unstable chromosome intermediates whose transient nature also hinders mechanistic understanding. We report here a budding yeast model that reveals the genetic ontogeny of genome rearrangements, from initial replication error to unstable chromosome formation to their resolution. Remarkably, the initial error often arises in or near the telomere, and frequently forms unstable chromosomes. Early unstable chromosomes may then resolve to an internal "collection site" where a dicentric forms and resolves to an isochromosome (other outcomes are possible at each step. The initial telomere-proximal unstable chromosome is increased in mutants in telomerase subunits, Tel1, and even Rad9, with no known telomere-specific function. Defects in Tel1 and in Rrm3, a checkpoint protein kinase with a role in telomere maintenance and a DNA helicase, respectively, synergize dramatically to generate unstable chromosomes, further illustrating the consequence of replication error in the telomere. Collectively, our results suggest telomeric replication errors may be a common cause of seemingly unrelated genomic rearrangements located hundreds of kilobases away.

  4. Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast

    Science.gov (United States)

    Weinert, Ted

    2016-01-01

    DNA replication errors at certain sites in the genome initiate chromosome instability that ultimately leads to stable genomic rearrangements. Where instability begins is often unclear. And, early instability may form unstable chromosome intermediates whose transient nature also hinders mechanistic understanding. We report here a budding yeast model that reveals the genetic ontogeny of genome rearrangements, from initial replication error to unstable chromosome formation to their resolution. Remarkably, the initial error often arises in or near the telomere, and frequently forms unstable chromosomes. Early unstable chromosomes may then resolve to an internal "collection site" where a dicentric forms and resolves to an isochromosome (other outcomes are possible at each step). The initial telomere-proximal unstable chromosome is increased in mutants in telomerase subunits, Tel1, and even Rad9, with no known telomere-specific function. Defects in Tel1 and in Rrm3, a checkpoint protein kinase with a role in telomere maintenance and a DNA helicase, respectively, synergize dramatically to generate unstable chromosomes, further illustrating the consequence of replication error in the telomere. Collectively, our results suggest telomeric replication errors may be a common cause of seemingly unrelated genomic rearrangements located hundreds of kilobases away. PMID:27716774

  5. Chromosomal manipulation by site-specific recombinases and fluorescent protein-based vectors.

    Directory of Open Access Journals (Sweden)

    Munehiro Uemura

    Full Text Available Feasibility of chromosomal manipulation in mammalian cells was first reported 15 years ago. Although this technique is useful for precise understanding of gene regulation in the chromosomal context, a limited number of laboratories have used it in actual practice because of associated technical difficulties. To overcome the practical hurdles, we developed a Cre-mediated chromosomal recombination system using fluorescent proteins and various site-specific recombinases. These techniques enabled quick construction of targeting vectors, easy identification of chromosome-rearranged cells, and rearrangement leaving minimum artificial elements at junctions. Applying this system to a human cell line, we successfully recapitulated two types of pathogenic chromosomal translocations in human diseases: MYC/IgH and BCR/ABL1. By inducing recombination between two loxP sites targeted into the same chromosome, we could mark cells harboring deletion or duplication of the inter-loxP segments with different colors of fluorescence. In addition, we demonstrated that the intrachromosomal recombination frequency is inversely proportional to the distance between two recombination sites, implicating a future application of this frequency as a proximity sensor. Our method of chromosomal manipulation can be employed for particular cell types in which gene targeting is possible (e.g. embryonic stem cells. Experimental use of this system would open up new horizons in genome biology, including the establishment of cellular and animal models of diseases caused by translocations and copy-number variations.

  6. Chromosome topology guides the Drosophila Dosage Compensation Complex for target gene activation.

    Science.gov (United States)

    Schauer, Tamás; Ghavi-Helm, Yad; Sexton, Tom; Albig, Christian; Regnard, Catherine; Cavalli, Giacomo; Furlong, Eileen Em; Becker, Peter B

    2017-08-09

    X chromosome dosage compensation in Drosophila requires chromosome-wide coordination of gene activation. The male-specific lethal dosage compensation complex (DCC) identifies and binds to X-chromosomal high-affinity sites (HAS) from which it boosts transcription. A sub-class of HAS, PionX sites, represent first contacts on the X. Here, we explored the chromosomal interactions of representative PionX sites by high-resolution 4C and determined the global chromosome conformation by Hi-C in sex-sorted embryos. Male and female X chromosomes display similar nuclear architecture, concordant with clustered, constitutively active genes. PionX sites, like HAS, are evenly distributed in the active compartment and engage in short- and long-range interactions beyond compartment boundaries. Long-range, inter-domain interactions between DCC binding sites are stronger in males, suggesting that the complex refines chromatin organization. By de novo induction of DCC in female cells, we monitored the extent of activation surrounding PionX sites. This revealed a remarkable range of DCC action not only in linear proximity, but also at megabase distance if close in space, suggesting that DCC profits from pre-existing chromosome folding to activate genes. © 2017 The Authors.

  7. SMC Progressively Aligns Chromosomal Arms in Caulobacter crescentus but Is Antagonized by Convergent Transcription

    Directory of Open Access Journals (Sweden)

    Ngat T. Tran

    2017-08-01

    Full Text Available The structural maintenance of chromosomes (SMC complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the mechanism of SMC-mediated alignment of chromosomal arms remains elusive. Here, using genome-wide methods and microscopy of single cells, we show that Caulobacter SMC is recruited to the centromeric parS site and that SMC-mediated arm alignment depends on the chromosome-partitioning protein ParB. We provide evidence that SMC likely tethers the parS-proximal regions of the chromosomal arms together, promoting arm alignment. Furthermore, we show that highly transcribed genes near parS that are oriented against SMC translocation disrupt arm alignment, suggesting that head-on transcription interferes with SMC translocation. Our results demonstrate a tight interdependence of bacterial chromosome organization and global patterns of transcription.

  8. Intramedullary compression device for proximal ulna fracture.

    Science.gov (United States)

    Hong, Choon Chiet; Han, Fucai; Decruz, Joshua; Pannirselvam, Vinodhkumar; Murphy, Diarmuid

    2015-02-01

    Proximal ulna fractures account for 20% of all proximal forearm fractures. Many treatment options are available for such fractures, such as cast immobilisation, plate and screw fixation, tension band wiring and intramedullary screw fixation, depending on the fracture pattern. Due to the subcutaneous nature of the proximal forearm, it is vulnerable to open injuries over the dorsal aspect of the proximal ulna. This may in turn prove challenging, as it is critical to obtain adequate soft tissue coverage to reduce the risk of implant exposure and bony infections. We herein describe a patient with a Gustillo III-B open fracture of the proximal ulna, treated with minimally invasive intramedullary screw fixation using a 6.0-mm cannulated headless titanium compression screw (FusiFIX, Péronnas, France).

  9. Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.

    Science.gov (United States)

    Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R

    2009-10-01

    Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.

  10. Condensation patterns of prophase/prometaphase chromosome are correlated with H4K5 histone acetylation and genomic DNA contents in plants.

    Science.gov (United States)

    Feitoza, Lidiane; Costa, Lucas; Guerra, Marcelo

    2017-01-01

    Mitotic prophase chromosome condensation plays an essential role in nuclear division being therefore regulated by highly conserved mechanisms. However, degrees of chromatin condensation in prophase-prometaphase cells may vary along the chromosomes resulting in specific condensation patterns. We examined different condensation patterns (CPs) of prophase and prometaphase chromosomes and investigated their relationship with genome size and distribution of histone H4 acetylated at lysine 5 (H4K5ac) in 17 plant species. Our results showed that most species with small genomes (2C condensing terminal regions that were highly enriched in H4K5ac, and early condensing regions with apparently non-acetylated proximal chromatin. The species with large genomes (Allium cepa, Callisia repens, Araucaria angustifolia and Nothoscordum pulchellum) displayed uniformly condensed and acetylated prophase/prometaphase chromosomes. Three species with small genomes (Eleocharis geniculata, Rhynchospora pubera, and R. tenuis) displayed CP and H4K5ac labeling patterns similar to species with large genomes, whereas a forth species (Emilia sonchifolia) exhibited a gradual chromosome labeling, being more acetylated in the terminal regions and less acetylated in the proximal ones. The nucleolus organizer chromatin was the only chromosomal region that in prometaphase or metaphase could be hyperacetylated, hypoacetylated or non-acetylated, depending on the species. Our data indicate that the CP of a plant chromosome complement is influenced but not exclusively determined by nuclear and chromosomal DNA contents, whereas the CP of individual chromosomes is clearly correlated with H4K5ac distribution.

  11. Amphiphysin (Amph) maps to the proximal region of mouse chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, N.A.; Gilbert, D.J.; Copeland, N.G. [NCl-Frederick Cancer Research and Development Center, MD (United States)] [and others

    1995-07-20

    Amphiphysin is a protein concentrated in neuronal synapses and peripherally associated with neurotransmitter vesicles. It is expressed in many neurons of the central and peripheral nervous systems, in the adrenal medulla, in the anterior and posterior pituitary, in cell lines of the endocrine pancreas, and in spermatocytes. Its subcellular localization and tissue distribution indicate a potential involvement in mechanisms of regulated exocytosis. A role in the dynamic organization of the membrane-associated cytoskeleton is suggested by structural homology to the products of two yeast genes, RVS161 and RVS167, whose mutation results in an abnormal actin distribution, disturbs budding morphology, and impairs cell entry into stationary phase. Limited stretches of sequence similarity, including an SH3 domain, are also shared with other actin-binding proteins. Amphiphysin is the dominant autoantigen in paraneoplastic Stiff-Man syndrome, a neurological autoimmune disorder characterized by progressive rigidity of the body musculature with superimposed painful spasms. 8 refs., 1 fig.

  12. Are There Knots in Chromosomes?

    Directory of Open Access Journals (Sweden)

    Jonathan T. Siebert

    2017-08-01

    Full Text Available Recent developments have for the first time allowed the determination of three-dimensional structures of individual chromosomes and genomes in nuclei of single haploid mouse embryonic stem (ES cells based on Hi–C chromosome conformation contact data. Although these first structures have a relatively low resolution, they provide the first experimental data that can be used to study chromosome and intact genome folding. Here we further analyze these structures and provide the first evidence that G1 phase chromosomes are knotted, consistent with the fact that plots of contact probability vs sequence separation show a power law dependence that is intermediate between that of a fractal globule and an equilibrium structure.

  13. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  14. Dynamic organization of mitotic chromosomes.

    Science.gov (United States)

    Kinoshita, Kazuhisa; Hirano, Tatsuya

    2017-06-01

    The assembly of rod-shaped chromosomes during mitosis is an essential prerequisite for faithful segregation of genetic information into daughter cells. Despite the long history of chromosome research, it is only recently that we have acquired powerful approaches and crucial tools that help to unlock the secret of this seemingly complex process. In particular, in vitro assays, mammalian genetics, Hi-C analyses and computer simulations have provided valuable information during the past two years. These studies are now beginning to elucidate how the core components of mitotic chromosomes, namely, histones, topoisomerase IIα and condensins, cooperate with each other to convert very long stretches of DNA into rod-shaped chromosomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved linkage groups on mouse chromosomes 3 and 8

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, C.M.; Frankel, W.N. [Jackson Lab., Bar Harbor, ME (United States); Richards, J.E. [Univ. of Michigan Medical School, Ann Arbor, MI (United States)] [and others

    1997-05-01

    Npy1r and Npy2r, the genes encoding mouse type 1 and type 2 neuropeptide Y receptors, have been mapped by interspecific backcross analysis. Previous studies have localized the human genes encoding these receptors to chromosome 4q31-q32. We have now assigned Npy1r and Npy2r to conserved linkage groups on mouse Chr 8 and Chr 3, respectively, which correspond to the distal region of human chromosome 4q. Using yeast artificial chromosomes, we have estimated the distance between the human genes to be approximately 6 cM. Although ancient tandem duplication events may account for some closely spaced G-protein-coupled receptor genes, the large genetic distance between the human type 1 and type 2 neuropeptide Y receptor genes raises questions about whether this mechanism accounts for their proximity. 20 refs., 1 fig.

  16. Origin and domestication of papaya Yh chromosome

    Science.gov (United States)

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previo...

  17. Proximal Alternating Direction Method with Relaxed Proximal Parameters for the Least Squares Covariance Adjustment Problem

    Directory of Open Access Journals (Sweden)

    Minghua Xu

    2014-01-01

    Full Text Available We consider the problem of seeking a symmetric positive semidefinite matrix in a closed convex set to approximate a given matrix. This problem may arise in several areas of numerical linear algebra or come from finance industry or statistics and thus has many applications. For solving this class of matrix optimization problems, many methods have been proposed in the literature. The proximal alternating direction method is one of those methods which can be easily applied to solve these matrix optimization problems. Generally, the proximal parameters of the proximal alternating direction method are greater than zero. In this paper, we conclude that the restriction on the proximal parameters can be relaxed for solving this kind of matrix optimization problems. Numerical experiments also show that the proximal alternating direction method with the relaxed proximal parameters is convergent and generally has a better performance than the classical proximal alternating direction method.

  18. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  19. Chromosomal characterization of armored catfish Harttia longipinna (Siluriformes, Loricariidae): first report of B chromosomes in the genus.

    Science.gov (United States)

    Blanco, Daniel Rodrigues; Vicari, Marcelo Ricardo; Artoni, Roberto Ferreira; Traldi, Josiane Baccarin; Moreira-Filho, Orlando

    2012-09-01

    The B chromosomes are accessory elements that are widely distributed among eukaryotic genomes and often show non-Mendelian inheritance. They are considered dispensable for the growth, development, and reproduction of organisms. Some studies have suggested that these elements may affect sex determination. Harttia is a small armored catfish genus that shows sexual dimorphism, including hypertrophied odontodes on the pectoral fin spines and along the margins of the snout in mature males. They exhibit considerable karyotypic diversity with diploid number (2n) variation and heteromorphic sex system in H. carvalhoi. To date, no occurrences of B chromosomes in the Harttia genus were detected and no relation to sexual differentiation in Neotropical fish has been determined. To determine the validity of this claim, the present paper characterized specimens of Harttia longipinna by classical and molecular cytogenetic methods. The 2n found was 58 (16m + 12sm + 16st + 14a), but of the 50 specimens analyzed (30 male and 20 female), 23 specimens (16 males and seven females) show an intra-individual from 0 to 2 micro B chromosomes. The B chromosomes were completely heterochromatic. The single NORs were shown in the first acrocentric pair with silver staining and 18S rDNA probing. FISH performed with 5S rDNA probe showed a single cistron in the proximal region of the short arm of a small metacentric pair. Thus, the cytogenetic data obtained in this study of H. longipinna highlight the karyotypic diversity found within the genus Harttia, and represent the first description of B chromosomes for this genus.

  20. The Life Saving Effects of Hospital Proximity

    DEFF Research Database (Denmark)

    Bertoli, Paola; Grembi, Veronica

    We assess the lifesaving effect of hospital proximity using data on fatality rates of road-traffic accidents. While most of the literature on this topic is based on changes in distance to the nearest hospital triggered by hospital closures and use OLS estimates, our identification comes from......) increases the fatality rate by 13.84% on the sample average. This is equal to a 0.92 additional death per every 100 accidents. We show that OLS estimates provide a downward biased measure of the real effect of hospital proximity because they do not fully solve spatial sorting problems. Proximity matters...

  1. De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions

    NARCIS (Netherlands)

    Fregeau, B.; Kim, B.J.; Hernandez-Garcia, A.; Jordan, V.K.; Cho, M.T.; Schnur, R.E.; Monaghan, K.G.; Juusola, J.; Rosenfeld, J.A.; Bhoj, E.; Zackai, E.H.; Sacharow, S.; Baranano, K.; Bosch, D.G.M.; Vries, B.B.A. de; Lindstrom, K.; Schroeder, A.; James, P.; Kulch, P.; Lalani, S.R.; Haelst, M.M. van; Gassen, K.L. van; Binsbergen, E. van; Barkovich, A.J.; Scott, D.A.; Sherr, E.H.

    2016-01-01

    Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region.

  2. Imprinted chromosomal domains revealed by allele-specific replication timing of the GABRB3 and GABRA5 genes

    Energy Technology Data Exchange (ETDEWEB)

    LaSalle, J.; Flint, A.; Lalande, M. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    The GABRB3 and GABRA5 genes are organized as a cluster in chromosome 15q11-q13. The genes are separated by around 100 kb and arranged in opposite transcriptional orientations. The GABA{sub A} receptor cluster lies near the Angelman and Prader-Willi loci and displays asynchronous DNA replication, suggesting that this region is subject to parental imprinting. In order to further study the association between DNA replication and imprinting, allele-specific replication was assayed by fluorescence in situ hybridization with {lambda}-phage probes from the GABRB3/A5 region and a D15Z1 satellite probe to identify the parental origin of each chromosome. The replication kinetics of each allele was determined by using a flow sorter to fractionate mitogen-stimulated lymphocytes on the basis of cell cycle progression prior to FISH analysis. These kinetic studies reveal a 50-150 kb chromosomal domain extending from the middle of the GABRB3/A5 intergenic region into the GABRA5 5{prime}-UTR which displays maternal replication in early S with paternal replication delayed until the end of S. In contrast, genomic regions on either side of this maternal early replication domain exhibit the opposite pattern with paternal before maternal replication and both alleles replicating in the latter half of S. These results indicate that the GABRB3/A5 region is divided into domains in which replication timing is determined by parental origin. In addition to a loss of asynchronous replication, organization into replication timing domains is also lost in lymphocytes from maternal and paternal uniparental disomy 15 patients suggesting that a chromosome contribution from both parents is required for the establishment of the imprinted replication domains.

  3. Mitotic and Meiotic Behavior of B Chromosomes in Crenicichla lepidota: New Report in the Family Cichlidae.

    Science.gov (United States)

    Pires, Larissa B; Sampaio, Tatiane R; Dias, Ana Lucia

    2015-01-01

    B chromosomes are additional genetic elements to the standard complement. They display distinctive features and have been found in 15% of eukaryote species. In this study, we analyzed 4 populations of Crenicichla lepidota from hydrographic system of Laguna dos Patos/RS (Brazil). All specimens showed 2n = 48 with 6m + 42st - a, FN = 54, with a secondary constriction on the first pair of the complement. Among the 18 samples analyzed, 6 individuals belonging to the Gasômetro and Saco da Alemoa populations presented 1-3 small-sized heterochromatic B chromosomes, with intra- and interindividual variation. Simple AgNORs coincident with 18S rDNA and CMA3 positive/DAPI negative sites were present in all populations. The extra chromosomes did not exhibit any 18S rDNA sites. The meiotic analyses showed heteropycnotic regions in leptotene and zygotene stages, which may be related to the presence of B chromosomes. During pachytene were found 24 bivalents and 1 spatially separated, as well as during metaphases I and diplotene, indicating that there is no association between B chromosomes and those of the A complement. During diakinesis, an unusual meiotic configuration was observed, revealing a proximity between the bivalent and chromosome B (univalent), that might be the result of a heterochromatin affinity between these chromosomes. In anaphase I, late migration of B chromosomes was detected. The low frequency of B chromosomes in the Cichlidae family and in Crenicichla suggests its recent origin in this group and may be ascribable to animal exposure to deleterious effects under certain environmental conditions. Moreover, this is the first report in C. lepidota. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Chromosomal evolution of the PKD1 gene family in primates

    Directory of Open Access Journals (Sweden)

    Krawczak Michael

    2008-09-01

    Full Text Available Abstract Background The autosomal dominant polycystic kidney disease (ADPKD is mostly caused by mutations in the PKD1 (polycystic kidney disease 1 gene located in 16p13.3. Moreover, there are six pseudogenes of PKD1 that are located proximal to the master gene in 16p13.1. In contrast, no pseudogene could be detected in the mouse genome, only a single copy gene on chromosome 17. The question arises how the human situation originated phylogenetically. To address this question we applied comparative FISH-mapping of a human PKD1-containing genomic BAC clone and a PKD1-cDNA clone to chromosomes of a variety of primate species and the dog as a non-primate outgroup species. Results Comparative FISH with the PKD1-cDNA clone clearly shows that in all primate species studied distinct single signals map in subtelomeric chromosomal positions orthologous to the short arm of human chromosome 16 harbouring the master PKD1 gene. Only in human and African great apes, but not in orangutan, FISH with both BAC and cDNA clones reveals additional signal clusters located proximal of and clearly separated from the PKD1 master genes indicating the chromosomal position of PKD1 pseudogenes in 16p of these species, respectively. Indeed, this is in accordance with sequencing data in human, chimpanzee and orangutan. Apart from the master PKD1 gene, six pseudogenes are identified in both, human and chimpanzee, while only a single-copy gene is present in the whole-genome sequence of orangutan. The phylogenetic reconstruction of the PKD1-tree reveals that all human pseudogenes are closely related to the human PKD1 gene, and all chimpanzee pseudogenes are closely related to the chimpanzee PKD1 gene. However, our statistical analyses provide strong indication that gene conversion events may have occurred within the PKD1 family members of human and chimpanzee, respectively. Conclusion PKD1 must have undergone amplification very recently in hominid evolution. Duplicative

  5. Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene.

    Science.gov (United States)

    Mollereau, C; Simons, M J; Soularue, P; Liners, F; Vassart, G; Meunier, J C; Parmentier, M

    1996-08-06

    Nociceptin (orphanin FQ), the newly discovered natural agonist of opioid receptor-like (ORL1) receptor, is a neuropeptide that is endowed with pronociceptive activity in vivo. Nociceptin is derived from a larger precursor, prepronociceptin (PPNOC), whose human, mouse, and rat genes we have now isolated. The PPNOC gene is highly conserved in the three species and displays organizational features that are strikingly similar to those of the genes of preproenkephalin, preprodynorphin, and preproopiomelanocortin, the precursors to endogenous opioid peptides, suggesting the four genes belong to the same family-i.e., have a common evolutionary origin. The PPNOC gene encodes a single copy of nociceptin as well as of other peptides whose sequence is strictly conserved across murine and human species; hence it is likely to be neurophysiologically significant. Northern blot analysis shows that the PPNOC gene is predominantly transcribed in the central nervous system (brain and spinal cord) and, albeit weakly, in the ovary, the sole peripheral organ expressing the gene. By using a radiation hybrid cell line panel, the PPNOC gene was mapped to the short arm of human chromosome 8 (8p21), between sequence-tagged site markers WI-5833 and WI-1172, in close proximity of the locus encoding the neurofilament light chain NEFL. Analysis of yeast artificial chromosome clones belonging to the WC8.4 contig covering the 8p21 region did not allow to detect the presence of the gene on these yeast artificial chromosomes, suggesting a gap in the coverage within this contig.

  6. Proximity and Collaboration in European Nanotechnology

    NARCIS (Netherlands)

    Cunningham, S.W.; Werker, C.

    2011-01-01

    Collaborations are particularly important for the development and deployment of technology. We analyze the influence of organizational, technological and geographical proximity on European nanotechnology collaborations with the help of a publication dataset and additional geographical information.

  7. Promoting proximal formative assessment with relational discourse

    Science.gov (United States)

    Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.

    2012-02-01

    The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.

  8. Ammonia transport in the proximal tubule.

    Science.gov (United States)

    Hamm, L L; Simon, E E

    1990-01-01

    The transport of ammonia in the proximal tubule is a complex interaction of a number of processes. Ammonia transport in the proximal tubule is clearly bidirectional; ammonia is secreted into the early proximal tubule lumen, but later in the proximal tubule, efflux out of the lumen may result in net ammonia reabsorption. Two mechanisms of ammonia transport have clearly been established: NH3 diffusion and NH4+ transport on the Na(+)-H+ exchanger. The relative contribution of these pathways to ammonia transport is still unsettled. Other pathways for ammonia transport, particularly NH4+ efflux out of the lumen, may be important as well. A variety of factors may modulate ammonia transport: plasma, cell and luminal pH, luminal flow rate, luminal potassium, and angiotensin II. Each of these factors also alters ammonia production rates and in most circumstances, ammonia transport appears to follow ammonia production rates.

  9. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    DWB) for raw and fried samples, respectively, but decreased to 295.20 ... Key words: Rhynchophorus phoenicis, Oryctes monoceros, proximate composition, cholesterol, heat treatment. INTRODUCTION. Insects have played ...

  10. COMPARATIVE ANALYSIS OF PROXIMATE COMPOSITIONS OF ...

    African Journals Online (AJOL)

    Babatunde Emmanuel

    2011-10-06

    Oct 6, 2011 ... Fish allows for protein improved nutrition in that it has a high biological value in terms of high ... marine algae upon which the fish feed [11]. ... Proximate composition of catfish Clarias gariepinus and Tarpon atlanticus were.

  11. Phytochemical screening, proximate analysis and acute toxicity ...

    African Journals Online (AJOL)

    Phytochemical screening, proximate analysis and acute toxicity studies were carried out on the leaf extract of Cola lepidota, in accordance with established standard procedures. The proximate analysis reveals a moisture content of 27.43 ± 3.11 % w/w, total ash value 9.32 ± 0.27 % w/w, acid insoluble ash 3.12 ± 1.05 % w/w ...

  12. Proximate, Mineral and Phytochemical Composition of Dioscorea ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: Proximate, mineral and phytochemical composition of Dioscorea dumetorum tubers was investigated using standard procedures. Proximate analysis included in g% dry weight: crude protein (6.44 ± 0.32), crude fat (0.75 ± 0.04), crude fibre (15.00 ± 0.56), total ash. (3.45 ± 0.20) and a moisture content of 70.04 ...

  13. Painful Spastic Hip Dislocation: Proximal Femoral Resection

    OpenAIRE

    Albiñana, Javier; Gonzalez-Moran, Gaspar

    2002-01-01

    The dislocated hip in a non-ambulatory child with spastic paresis tends to be a painful interference to sleep, sitting upright, and perineal care. Proximal femoral resection-interposition arthroplasty is one method of treatment for this condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of 30 months. Clinical improvement was observed in all except one case, with respect to pain relief and sitting tolerance. Some proximal migration was observed in three cases, despit...

  14. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.

    2008-01-01

    OBJECTIVE: To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. METHODS: From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome

  15. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.

    Objective To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. Methods From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome

  16. Proximity sensor system development. CRADA final report

    Energy Technology Data Exchange (ETDEWEB)

    Haley, D.C. [Oak Ridge National Lab., TN (United States); Pigoski, T.M. [Merrit Systems, Inc. (United States)

    1998-01-01

    Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors.

  17. Transformations through Proximity Flying: A Phenomenological Investigation

    Science.gov (United States)

    Holmbom, Maria; Brymer, Eric; Schweitzer, Robert D.

    2017-01-01

    Participation in extreme sports has been linked to personal transformations in everyday life. Descriptions of lived experience resulting from transformative experiences are limited. Proximity flying, a relatively new discipline involving BASE jumping with a wingsuit where participants fly close to solid structures, is arguably one of the most extreme of extreme sports. The aim of this paper, part of a larger phenomenological study on the lived experience of proximity flying, is to explicate the ways in which participating in proximity flying influences the everyday lives of participants. Interpretative phenomenological analysis was used to explicate the lived experience of six proximity pilots. An analysis of interview transcripts revealed three significant themes describing the lived experience of participants. First, experiences of change were described as positive and skills developed through proximity flying were transferable into everyday life. Second, transformative experiences were considered fundamental to participants’ perspectives on life. Third, experience of transformation influenced their sense of personal identity and facilitated flourishing in other aspects of everyday life. Participants were clear that their experiences in proximity flying facilitated a profound process of transformation which manifest as changes in everyday capabilities and behaviors, values and sense of identity. PMID:29104552

  18. Radiation-induced chromosomal instability

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, S. [GSI, Biophysics, Darmstadt (Germany)

    1999-03-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/{mu}m) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  19. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

  20. New Advances in Chromosome Architecture.

    Science.gov (United States)

    Leake, Mark C

    2016-01-01

    Our knowledge of the "architecture" of chromosomes has grown enormously in the past decade. This new insight has been enabled largely through advances in interdisciplinary research methods at the cutting-edge interface of the life and physical sciences. Importantly this has involved several state-of-the-art biophysical tools used in conjunction with molecular biology approaches which enable investigation of chromosome structure and function in living cells. Also, there are new and emerging interfacial science tools which enable significant improvements to the spatial and temporal resolution of quantitative measurements, such as in vivo super-resolution and powerful new single-molecule biophysics methods, which facilitate probing of dynamic chromosome processes hitherto impossible. And there are also important advances in the methods of theoretical biophysics which have enabled advances in predictive modeling of this high quality experimental data from molecular and physical biology to generate new understanding of the modes of operation of chromosomes, both in eukaryotic and prokaryotic cells. Here, I discuss these advances, and take stock on the current state of our knowledge of chromosome architecture and speculate where future advances may lead.

  1. Mechanisms for Complex Chromosomal Insertions.

    Science.gov (United States)

    Gu, Shen; Szafranski, Przemyslaw; Akdemir, Zeynep Coban; Yuan, Bo; Cooper, Mitchell L; Magriñá, Maria A; Bacino, Carlos A; Lalani, Seema R; Breman, Amy M; Smith, Janice L; Patel, Ankita; Song, Rodger H; Bi, Weimin; Cheung, Sau Wai; Carvalho, Claudia M B; Stankiewicz, Paweł; Lupski, James R

    2016-11-01

    Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s) with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs) at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs.

  2. Mechanisms for Complex Chromosomal Insertions.

    Directory of Open Access Journals (Sweden)

    Shen Gu

    2016-11-01

    Full Text Available Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH and fluorescence in situ hybridization (FISH. Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs.

  3. Dean flow fractionation of chromosomes

    Science.gov (United States)

    Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.

    2016-03-01

    Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.

  4. Dynamics of rye chromosome 1R regions with high or low crossover frequency in homology search and synapsis development.

    Directory of Open Access Journals (Sweden)

    Nohelia T Valenzuela

    Full Text Available In many organisms, homologous pairing and synapsis depend on the meiotic recombination machinery that repairs double-strand DNA breaks (DSBs produced at the onset of meiosis. The culmination of recombination via crossover gives rise to chiasmata, which locate distally in many plant species such as rye, Secale cereale. Although, synapsis initiates close to the chromosome ends, a direct effect of regions with high crossover frequency on partner identification and synapsis initiation has not been demonstrated. Here, we analyze the dynamics of distal and proximal regions of a rye chromosome introgressed into wheat to define their role on meiotic homology search and synapsis. We have used lines with a pair of two-armed chromosome 1R of rye, or a pair of telocentrics of its long arm (1RL, which were homozygous for the standard 1RL structure, homozygous for an inversion of 1RL that changes chiasma location from distal to proximal, or heterozygous for the inversion. Physical mapping of recombination produced in the ditelocentric heterozygote (1RL/1RL(inv showed that 70% of crossovers in the arm were confined to a terminal segment representing 10% of the 1RL length. The dynamics of the arms 1RL and 1RL(inv during zygotene demonstrates that crossover-rich regions are more active in recognizing the homologous partner and developing synapsis than crossover-poor regions. When the crossover-rich regions are positioned in the vicinity of chromosome ends, their association is facilitated by telomere clustering; when they are positioned centrally in one of the two-armed chromosomes and distally in the homolog, their association is probably derived from chromosome elongation. On the other hand, chromosome movements that disassemble the bouquet may facilitate chromosome pairing correction by dissolution of improper chromosome associations. Taken together, these data support that repair of DSBs via crossover is essential in both the search of the homologous partner

  5. [Homologue pairing: initiation sites and effects on crossing over and chromosome disjunction in Drosophila melanogaster].

    Science.gov (United States)

    Chubykin, V L

    1996-01-01

    The role of homologue pairing and chromocentral association of chromosomes in recombination and segregation during cell division is discussed. Peculiarities of mitotic and meiotic chromosome pairing in Drosophila males and females are considered. On the basis of our own and published data, the presence and localization of sites of homologue pairing initiation in euchromatin are substantiated. The effects of transfer of initiation sites along a chromosome (exemplified by inversions) on chromosome pairing (asynapsis), crossing over (intrachromosomal, interchromosomal, and centromeric effects), and segregation are discussed. To record the effects of pairing sites on crossing over, a method of comparing crossing-over frequencies in an inverted region with those in a region of the same size and position with regard to the centromere on cytological maps was proposed. Chromosomes orient toward opposite division poles during paracentromeric heterochromatin pairing. This occurs after successful euchromatin pairing, during which the chromocentral circular structure is reorganized. If heterochromatin pairing is disrupted because of structural or locus mutations, nonexchange bivalents segregate randomly. In this case, chromosome coordination may occur due to proximal chiasmata or chromocentral associations between homologues.

  6. Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer.

    Science.gov (United States)

    Jorissen, Robert N; Christie, Michael; Mouradov, Dmitri; Sakthianandeswaren, Anuratha; Li, Shan; Love, Christopher; Xu, Zheng-Zhou; Molloy, Peter L; Jones, Ian T; McLaughlin, Stephen; Ward, Robyn L; Hawkins, Nicholas J; Ruszkiewicz, Andrew R; Moore, James; Burgess, Antony W; Busam, Dana; Zhao, Qi; Strausberg, Robert L; Lipton, Lara; Desai, Jayesh; Gibbs, Peter; Sieber, Oliver M

    2015-09-15

    APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.

  7. Treatment of three- and four-part proximal humeral fractures with locking proximal humerus plate.

    Science.gov (United States)

    Sun, Jing-Cheng; Li, Yu-Lin; Ning, Guang-Zhi; Wu, Qiang; Feng, Shi-Qing

    2013-08-01

    The purpose of this study was to evaluate the effectiveness and complications of the locking proximal humerus plate to treat proximal humerus fractures. A retrospective clinical trial. Department of Orthopaedics, Tianjin Medical University General Hospital. Sixty-eight consecutive patients with three- or four-part fractures of the proximal humerus were treated with locking proximal humerus plates. The deltopectoral anterolateral acromial approach was used to the proximal humerus; open reduction and locking proximal humerus plate were applied. Constant Score was used to measure the shoulder functional recovery, and Visual Analog Scale (VAS) was used to measure subjective evaluation of pain. The radiology was observed. After average 26.7 months, the average Constant Score was 72.6 ± 13.2 points and the average VAS was 1.2 ± 0.8 points. All the complications such as screw perforation into the glenohumeral joint, screws loosening, soft tissue infections, avascular necrosis and delayed union occurred in eight cases (11.8 %). The effectiveness of the locking proximal humerus plate was similar to other published literatures on treating fractures of the proximal humerus; however, a lower complications rate in short follow-up time was observed in this study. It may potentially provide a favorable option for treating three- or four-part fractures of the proximal humerus. Dealing with each particular fracture pattern, surgeons should have a decision of appropriate way to internal fixation.

  8. Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

    Directory of Open Access Journals (Sweden)

    Hirai Hirohisa

    2010-07-01

    Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the

  9. Chromosomal Evolution in Lower Vertebrates: Sex Chromosomes in Neotropical Fishes

    Czech Academy of Sciences Publication Activity Database

    Cioffi, M. de B.; Yano, C. F.; Sember, Alexandr; Bertollo, L.A.C.

    2017-01-01

    Roč. 8, č. 10 (2017), č. článku 258. ISSN 2073-4425 R&D Projects: GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : alternative evolutionary models * simple and multiple sex chromosomes * independent and common origins Subject RIV: EG - Zoology Impact factor: 3.600, year: 2016

  10. Comparative mapping of mouse chromosome 4 and human chromosome 9: Lv, Orm, and Hxb are closely linked on mouse chromosome 4.

    Science.gov (United States)

    Pilz, A; Moseley, H; Peters, J; Abbott, C

    1992-01-01

    The genes for orosomucoid (ORM-1 and ORM-2), delta-aminolevulinate dehydratase (ALAD), and hexabrachion or tenascin (HXB) all map to the q31-qter region of human Chromosome (Chr) 9. The mouse homolog of each of these genes has been mapped to Chr4, but hexabrachion has not previously been mapped by linkage analysis. We have now ordered Orm-1, Lv (the mouse homolog of ALAD), and Hxb in an interspecific backcross panel, by use of tyrosinase related protein-1, Tyrp-1, whose human homolog maps to 9p13-pter (Abbott et al., Genomics 1991) as a reference locus. No recombinants were identified in 124 animals between Lv and Orm-1. Hxb was found to be 1.6 cM distal to Lv and Orm-1, and 4.8 cM proximal to Tyrp-1, or b. These data therefore contribute to our knowledge of the conserved synteny between HSA 9q and MMU 4.

  11. Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7

    DEFF Research Database (Denmark)

    Ebert, Grit; Steininger, Anne; Weißmann, Robert

    2014-01-01

    such as the Williams-Beuren syndrome. Despite these adverse effects, SDs have become fixed in the human genome. Focusing on chromosome 7, which is particularly rich in interstitial SDs, we have investigated the distribution of SDs in the context of evolution and the three dimensional organisation of the chromosome...... sites during primate evolution, we can show by means of public data on long distance chromatin interactions that these three intervals, and consequently the paralogous SDs mapping to them, have retained their spatial proximity in the nucleus. Focusing on SD clusters implicated in the aetiology...... chromosome 7, either by promoting regional SD insertion or by contributing to the establishment of higher order chromatin organisation themselves. The latter could compensate for the high risk of structural rearrangements and thus may have contributed to their evolutionary fixation in the human genome....

  12. The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

    Directory of Open Access Journals (Sweden)

    Veronica eKrenn

    2015-10-01

    Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

  13. Polymorphic organization of constitutive heterochromatin in Equus asinus (2n = 62) chromosome 1.

    Science.gov (United States)

    Raimondi, Elena; Piras, Francesca M; Nergadze, Solomon G; Di Meo, Giulia Pia; Ruiz-Herrera, Aurora; Ponsà, Montserrat; Ianuzzi, Leopoldo; Giulotto, Elena

    2011-06-01

    In the karyotype of Equus asinus (domestic donkey, 2n = 62), non-centromeric heterochromatic bands have been described in subcentromeric and telomeric positions. In particular, chromosome 1 is characterised by heterochromatic bands in the proximal region of the long arm and in the short arm; it has been shown that these regions are polymorphic in size. Here we investigated the variation in the intensity and distribution of fluorescence signals observed on donkey chromosome 1 after in situ hybridization with two DNA probes containing fragments from the two major equine satellite DNA families. Our results show that, in Equus asinus chromosome 1, the amount and distribution of large clusters of satellite DNA can define at least nine polymorphic variants of the constitutive heterochromatin that cannot be detected by C-banding alone. © 2011 The Authors.

  14. Heterogeneity of pericentric inversions of the human y chromosome.

    Science.gov (United States)

    Knebel, S; Pasantes, J J; Thi, D A D; Schaller, F; Schempp, W

    2011-01-01

    Pericentric inversions of the human Y chromosome (inv(Y)) are the result of breakpoints in Yp and Yq. Whether these breakpoints occur recurrently on specific hotspots or appear at different locations along the repeat structure of the human Y chromosome is an open question. Employing FISH for a better definition and refinement of the inversion breakpoints in 9 cases of inv(Y) chromosomes, with seemingly unvarying metacentric appearance after banding analysis, unequivocally resulted in heterogeneity of the pericentric inversions of the human Y chromosome. While in all 9 inv(Y) cases the inversion breakpoints in the short arm fall in a gene-poor region of X-transposed sequences proximal to PAR1 and SRY in Yp11.2, there are clearly 3 different inversion breakpoints in the long arm. Inv(Y)-types I and II are familial cases showing inversion breakpoints that map in Yq11.23 or in Yq11.223, outside the ampliconic fertility gene cluster of DAZ and CDY in AZFc. Inv(Y)-type III shows an inversion breakpoint in Yq11.223 that splits the DAZ and CDY fertility gene-cluster in AZFc. This inversion type is representative of both familial cases and cases with spermatogenetic impairment. In a further familial case of inv(Y), with almost acrocentric morphology, the breakpoints are within the TSPY and RBMY repeat in Yp and within the heterochromatin in Yq. Therefore, the presence of specific inversion breakpoints leading to impaired fertility in certain inv(Y) cases remains an open question. Copyright © 2011 S. Karger AG, Basel.

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

    Energy Technology Data Exchange (ETDEWEB)

    Testa, J.R.; Zhou, J.Y.; Bell, D.W.; Yen, T.J. [Fox Chase Cancer Center, Philadelphia, PA (United States)

    1994-10-01

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

  16. Locking plate fixation for proximal humerus fractures.

    LENUS (Irish Health Repository)

    Burke, Neil G

    2012-02-01

    Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head.

  17. Mapping of the {alpha}{sub 4} subunit gene (GABRA4) to human chromosome 4 defines an {alpha}{sub 2}-{alpha}{sub 4}-{beta}{sub 1}-{gamma}{sub 1} gene cluster: Further evidence that modern GABA{sub a} receptor gene clusters are derived from an ancestral cluster

    Energy Technology Data Exchange (ETDEWEB)

    McLean, P.J.; Farb, D.H.; Russek, S.J. [Boston Univ. School of Medicine, MA (United States)] [and others

    1995-04-10

    We demonstrated previously that an {alpha}{sub 1}-{beta}{sub 2}-{gamma}{sub 2} gene cluster of the {gamma}-aminobutyric acid (GABA{sub A}) receptor is located on human chromosome 5q34-q35 and that an ancestral {alpha}-{beta}-{gamma} gene cluster probably spawned clusters on chromosomes 4, 5, and 15. Here, we report that the {alpha}{sub 4} gene (GABRA4) maps to human chromosome 4p14-q12, defining a cluster comprising the {alpha}{sub 2}, {alpha}{sub 4}, {beta}{sub 1}, and {gamma}{sub 1} genes. The existence of an {alpha}{sub 2}-{alpha}{sub 4}-{beta}{sub 1}-{gamma}{sub 2} cluster on chromosome 4 and an {alpha}{sub 1}-{alpha}{sub 6}-{beta}{sub 2}-{gamma}{sub 2} cluster on chromosome 5 provides further evidence that the number of ancestral GABA{sub A} receptor subunit genes has been expanded by duplication within an ancestral gene cluster. Moreover, if duplication of the {alpha} gene occurred before duplication of the ancestral gene cluster, then a heretofore undiscovered subtype of a subunit should be located on human chromosome 15q11-q13 within an {alpha}{sub 5}-{alpha}{sub x}-{beta}{sub 3}-{gamma}{sub 3} gene cluster at the locus for Angelman and Prader-Willi syndromes. 34 refs., 6 figs., 1 tab.

  18. Algorithm for sorting chromosomal aberrations

    DEFF Research Database (Denmark)

    Vogel, Ida; Lund, Najaaraq; Rasmussen, Steen

    2017-01-01

    Prenatal diagnostic methods and screening procedures change rapidly in these years. Years ago only karyotyping was performed prenatally, and we monitored only Down syndrome(1) . Since then the diagnostic possibilities have increased to QF-PCR, FISH, MLPA and chromosomal microarray....

  19. Chromosomal Abnormalities Associated With Omphalocele

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-03-01

    Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

  20. Interpreting chromosomal abnormalities using Prolog.

    Science.gov (United States)

    Cooper, G; Friedman, J M

    1990-04-01

    This paper describes an expert system for interpreting the standard notation used to represent human chromosomal abnormalities, namely, the International System for Human Cytogenetic Nomenclature. Written in Prolog, this program is very powerful, easy to maintain, and portable. The system can be used as a front end to any database that employs cytogenetic notation, such as a patient registry.

  1. CHROMOSOMAL MULTIPLICITY IN BURKHOLDERIA CEPACIA

    Science.gov (United States)

    We have used CHEF gel electrophoresis to screen preparations of large DNA from different Burkholderia cepacia isolates for the presence of DNA species corresponding to the linearized forms of the three chromosomes of 3.4,2.5, and 0.9 Mb identified in B. cepacia strain 17616. DNA ...

  2. The chicken (Gallus gallus) Z chromosome contains at least three nonlinear evolutionary strata.

    Science.gov (United States)

    Nam, Kiwoong; Ellegren, Hans

    2008-10-01

    Birds have female heterogamety with Z and W sex chromosomes. These evolved from different autosomal precursor chromosomes than the mammalian X and Y. However, previous work has suggested that the pattern and process of sex chromosome evolution show many similarities across distantly related organisms. Here we show that stepwise restriction of recombination between the protosex chromosomes of birds has resulted in regions of the chicken Z chromosome showing discrete levels of divergence from W homologs (gametologs). The 12 genes analyzed fall into three levels of estimated divergence values, with the most recent divergence (d(S) = 0.18-0.21) displayed by 6 genes in a region on the Z chromosome corresponding to the interval 1-11 Mb of the assembled genome sequence. Another 4 genes show intermediate divergence (d(S) = 0.27-0.38) and are located in the interval 16-53 Mb. Two genes (at positions 42 and 50 Mb) with higher d(S) values are located proximal to the most distal of the 4 genes with intermediate divergence, suggesting an inversion event. The distribution of genes and their divergence indicate at least three evolutionary strata, with estimated times for cessation of recombination between Z and W of 132-150 (stratum 1), 71-99 (stratum 2), and 47-57 (stratum 3) million years ago. An inversion event, or some other form of intrachromosomal rearrangement, subsequent to the formation of strata 1 and 2 has scrambled the gene order to give rise to the nonlinear arrangement of evolutionary strata currently seen on the chicken Z chromosome. These observations suggest that the progressive restriction of recombination is an integral feature of sex chromosome evolution and occurs also in systems of female heterogamety.

  3. Detection of paternal uniparental disomy 9 in a neonate with prenatally detected mosaicism for a small supernumerary marker chromosome 9 and a supernumerary ring chromosome 9.

    Science.gov (United States)

    Chen, Chih-Ping; Chen, Ming; Wang, Liang-Kai; Chern, Schu-Rern; Wu, Peih-Shan; Chen, Shin-Wen; Lai, Shih-Ting; Chang, Shun-Ping; Yang, Chien-Wen; Pan, Chen-Wen; Wang, Wayseen

    2017-08-01

    We present the association of paternal uniparental disomy (UPD) 9 with mosaicism for a small supernumerary marker chromosome 9 [sSMC(9)] and a supernumerary ring chromosome 9 [r(9)]. A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+mar [25]/48,XY,+mar,+r(9) [4]/47,XY,+r(9) [1]/46,XY [6]. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) of cultured amniocytes revealed a result of de novo 9p13.1q21.11 (38,792,472-71,026,063) × 2.64. The marker chromosome was determined to be an sSMC(9) by spectral karyotyping and aCGH. A phenotypically normal baby was delivered at 38 weeks of gestation. During pediatric follow-ups at age two years, the neonate manifested normal psychomotor and growth development. Cytogenetic analysis, metaphase fluorescence in situ hybridization (FISH), single nucleotide polymorphism (SNP) aCGH and polymorphic DNA marker analysis were performed on the peripheral blood of the neonate. The neonate's blood had the following results. Metaphase FISH confirmed coexistence of the sSMC(9) and the supernumerary r(9). The karyotype was 47,XY,+sSMC(9) [14]/48,XY, +sSMC(9),+r(9) [10]/47,XY,+r(9) [6]/46,XY [10]. SNP aCGH revealed arr 9p22.3q21.11 (14,234,165-71,035,608) × 2-3, arr 9p24.3p22.3 (216,123-14,629,321)hmz, arr 9p21.3p13.2 (24,769,722-36,732,597)hmz and arr 9q21.11q34.3 (71,013,799-141,011,581)hmz. Polymorphic DNA marker analysis showed paternal isodisomy 9. Individuals with mosaicism for sSMC(9) and supernumerary r(9) may be associated with paternal UPD 9. Copyright © 2017. Published by Elsevier B.V.

  4. Industrial Computed Tomography using Proximal Algorithm

    KAUST Repository

    Zang, Guangming

    2016-04-14

    In this thesis, we present ProxiSART, a flexible proximal framework for robust 3D cone beam tomographic reconstruction based on the Simultaneous Algebraic Reconstruction Technique (SART). We derive the proximal operator for the SART algorithm and use it for minimizing the data term in a proximal algorithm. We show the flexibility of the framework by plugging in different powerful regularizers, and show its robustness in achieving better reconstruction results in the presence of noise and using fewer projections. We compare our framework to state-of-the-art methods and existing popular software tomography reconstruction packages, on both synthetic and real datasets, and show superior reconstruction quality, especially from noisy data and a small number of projections.

  5. Correlation between social proximity and mobility similarity.

    Science.gov (United States)

    Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao

    2017-09-20

    Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

  6. Infiltrating/sealing proximal caries lesions

    DEFF Research Database (Denmark)

    Martignon, S; Ekstrand, K R; Gomez, J

    2012-01-01

    This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...... proximal lesions identified radiographically around the enamel-dentin junction to the outer third of the dentin, were included. Lesions were randomly allocated for treatment to test-A (Infiltration: ICON-pre-product; DMG), test-B (Sealing: Prime-Bond-NT; Dentsply), or control-C (Placebo). Primary outcome...

  7. Chromosome Aberrations by Heavy Ions

    Science.gov (United States)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  8. Knowledge networks in the Dutch aviation industry: The proximity paradox

    NARCIS (Netherlands)

    Broekel, T.; Boschma, R.A.

    2012-01-01

    The importance of geographical proximity for interaction and knowledge sharing has been discussed extensively in recent years. There is increasing consensus that geographical proximity is just one out of many types of proximities that might be relevant. We argue that proximity may be a crucial

  9. Chromosome imaging by atomic force microscopy: influencing ...

    Indian Academy of Sciences (India)

    investigated factors influencing chromosome ultrastructures or species-specific ultrastructural characteristics. We studied the effects of several factors on AFM imag- ing of chromosomal ultrastructures. We found that process- ing time had little effect on chromosomal ultrastructures, but that trypsin digestion had a large effect.

  10. Morphology and structure of polytene chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Zhimulev, I.F. [Institute of Cytology and Genetics, Novosibirsk (Russian Federation)

    1996-12-31

    The morphology and structure of polytene chromosomes is the subject of this detailed volume of Advances in Genetics. Polytene chromosomes are the only interphase chromosomes that appear throughout as individual structures, and therefore offer the kind of detail of the molecular biology that geneticists need. 2869 refs., 123 figs., 27 tabs.

  11. Chromosome number and cytomorphological characterization of a ...

    African Journals Online (AJOL)

    Chromosome counts from natural populations of Abrus pulchellus in Nigeria were carried out. Tetraploid (2n = 44) chromosome number was constant in all the samples investigated. The 44 chromosomes fall into three cytomorphological categories: eight metacentric and eight submetacentric pairs, and six acrocentric pairs.

  12. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

    A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented...... and discussed, and the previously reported cases of familially transmitted G-group ring chromosomes are reviewed....

  13. High resolution analysis of interphase chromosome domains

    NARCIS (Netherlands)

    Visser, A. E.; Jaunin, F.; Fakan, S.; Aten, J. A.

    2000-01-01

    Chromosome territories need to be well defined at high resolution before functional aspects of chromosome organization in interphase can be explored. To visualize chromosomes by electron microscopy (EM), the DNA of Chinese hamster fibroblasts was labeled in vivo with thymidine analogue BrdU. Labeled

  14. A DNA Crosslinker Collects Mitotic Chromosomes.

    Science.gov (United States)

    Sun, Mingxuan; Heald, Rebecca

    2017-09-11

    Incorporating each set of daughter chromosomes into a single nucleus at the end of mitosis is essential for genome stability. In a recent Cell paper, Samwer et al. (2017) show that by non-covalently crosslinking DNA, BAF promotes chromosome coalescence, preventing nuclear membranes from enwrapping individual chromosomes to form micronuclei. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A Plain English Map of the Human Chromosomes.

    Science.gov (United States)

    Offner, Susan

    1992-01-01

    Presents a chromosome map for 19 known chromosomes in human genetics. Describes the characteristics attributed to the genetic codes for each of the chromosomes and discusses the teaching applications of the chromosome map. (MDH)

  16. The recombinational anatomy of a mouse chromosome.

    Directory of Open Access Journals (Sweden)

    Kenneth Paigen

    2008-07-01

    Full Text Available Among mammals, genetic recombination occurs at highly delimited sites known as recombination hotspots. They are typically 1-2 kb long and vary as much as a 1,000-fold or more in recombination activity. Although much is known about the molecular details of the recombination process itself, the factors determining the location and relative activity of hotspots are poorly understood. To further our understanding, we have collected and mapped the locations of 5,472 crossover events along mouse Chromosome 1 arising in 6,028 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. Crossovers were mapped to a minimum resolution of 225 kb, and those in the telomere-proximal 24.7 Mb were further mapped to resolve individual hotspots. Recombination rates were evolutionarily conserved on a regional scale, but not at the local level. There was a clear negative-exponential relationship between the relative activity and abundance of hotspot activity classes, such that a small number of the most active hotspots account for the majority of recombination. Females had 1.2x higher overall recombination than males did, although the sex ratio showed considerable regional variation. Locally, entirely sex-specific hotspots were rare. The initiation of recombination at the most active hotspot was regulated independently on the two parental chromatids, and analysis of reciprocal crosses indicated that parental imprinting has subtle effects on recombination rates. It appears that the regulation of mammalian recombination is a complex, dynamic process involving multiple factors reflecting species, sex, individual variation within species, and the properties of individual hotspots.

  17. Sim3C: simulation of Hi-C and Meta3C proximity ligation sequencing technologies.

    Science.gov (United States)

    DeMaere, Matthew Z; Darling, Aaron E

    2017-11-15

    Chromosome conformation capture (3C) and Hi-C DNA sequencing methods have rapidly advanced our understanding of the spatial organization of genomes and metagenomes. Many variants of these protocols have been developed, each with their own strengths. Currently there is no systematic means for simulating sequence data from this family of sequencing protocols, potentially hindering the advancement of algorithms to exploit this new datatype. We describe a computational simulator that, given simple parameters and reference genome sequences, will simulate Hi-C sequencing on those sequences. The simulator models the basic spatial structure in genomes that is commonly observed in Hi-C and 3C datasets, including the distance-decay relationship in proximity ligation, differences in the frequency of interaction within and across chromosomes, and the structure imposed by cells. A means to model the 3D structure of randomly generated topologically associating domains (TADs) is provided. The simulator considers several sources of error common to 3C and Hi-C library preparation and sequencing methods, including spurious proximity ligation events and sequencing error. We have introduced the first comprehensive simulator for 3C and Hi-C sequencing protocols. We expect the simulator to have use in testing of Hi-C data analysis algorithms, as well as more general value for experimental design, where questions such as the required depth of sequencing, enzyme choice, and other decisions can be made in advance in order to ensure adequate statistical power with respect to experimental hypothesis testing.

  18. Sex chromosome-linked genes in plants.

    Science.gov (United States)

    Matsunaga, Sachihiro

    2006-08-01

    Recent studies of plant sex chromosome-linked genes have revealed many interesting characteristics, although there are limited reports about heteromorphic sex chromosomes in flowering plants. Sex chromosome-linked genes in angiosperms have been characterized mainly in the dioecious plant Silene latifolia. Although all such genes were isolated from transcripts of male flower buds of S. latifolia, most seem to be housekeeping genes except for the petal- and stamen-specific MADS box gene on the Y chromosome (SlAP3Y) and the male reproductive organ-specific gene on the X chromosome (MROS3X). Recent evolutionary studies have revealed at least three evolutionary strata on the X chromosome that are related to stepwise loss of recombination between the sex chromosomes. Moreover, genetic maps showed conservation of gene organization on the X chromosome in the genus Silene and substantial pericentric inversion between the X and Y chromosomes of S. latifolia during evolution. A comparison between paralogs on the sex chromosomes revealed that introns of the Y-linked genes are longer than those of X-linked paralogs. Although analyses of sex chromosome-linked genes suggest that degeneration of the Y chromosome has occurred, the Y chromosome in flowering plants remains the largest in the male genome, unlike that of mammals. Accumulation of repetitive sequences and the entire chloroplast genome on the Y chromosome appear to have contributed to this large size. However, more detailed studies will be required to help explain the basis for the fact that heteromorphic sex chromosomes in angiosperms are large.

  19. Mapping strategies: Chromosome 16 workshop. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    1989-12-31

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

  20. preliminary phytochemical screening, proximate and elemental

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the ...

  1. Proximate, mineral composition, antioxidant activity, and total ...

    African Journals Online (AJOL)

    Four varieties of the red pepper fruits (Capsicum species) were evaluated for chemical composition, antioxidant activity and total phenolic contents using standard analytical technique, ferric-ion reducing antioxidant potential (FRAP) assay and Folin-Colcalteau method respectively. The proximate composition values ...

  2. 9__43 - 50__Tijjani_Proximate

    African Journals Online (AJOL)

    User

    Sena et al., 1998). In Nigeria, the plant is commonly consumed by the Hausa speaking communities as a spice and a sauce (Ibrahim et al., 2012). However, during preparation the leaves and stem are not carefully separated before processing of food. Thus, the present study was aimed at evaluating the proximate, minerals ...

  3. Phytochemistry and proximate composition of ginger ( Zingiber ...

    African Journals Online (AJOL)

    ... a little crude fibre content of 0.92 %. The results indicated that ginger rhizome is an excellent natural remedy for a wide range of ailments. Keywords: Zingiber officinale, spice, rhizome, phytochemistry, proximate analysis, Zingiberaceae, zingerone, methanolic extraction. Journal of Pharmaceutical and Allied Sciences, Vol.

  4. DEPRESSIONARY EFFECT OF PROXIMITY OF RESIDENTIAL ...

    African Journals Online (AJOL)

    Osondu

    2012-10-24

    Oct 24, 2012 ... opinions are analyzed and it revealed that the site has major impacts on the residents perceived quality of life, security and ... Key words: Landfill, Property value, Health and safety, Residential property, Solous. Introduction. The location ... Proximity to landfills and hazardous waste sites can severely affect ...

  5. Renal fibrosis: Primacy of the proximal tubule.

    Science.gov (United States)

    Gewin, Leslie S

    2018-02-06

    Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression. Several proximal tubular responses such as de-differentiation, cell cycle changes, autophagy, and metabolic changes may be adaptive initially, but can lead to maladaptive responses that promote TIF both through autocrine and paracrine effects. This review discusses the current paradigm of TIF progression and the increasingly important role of the proximal tubule in promoting TIF both in tubulointerstitial and glomerular injuries. A better understanding and appreciation of the role of the proximal tubule in TIF has important implications for therapeutic strategies to halt chronic kidney disease progression. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  6. 182 179 Comparative Study on the Proximate

    African Journals Online (AJOL)

    2008-12-02

    Dec 2, 2008 ... Key words: Annona squamosa, Fruits, Proximate, Minerals, nutrient density. INTRODUCTION. Sugar apple (Annona squamosa) also called. “Gwanda masar” in Hausa belong to the family. Annonacae. The most widely grown of all the species are A. muricata, A. cherimola, A reticulata, A. senegalensis and ...

  7. Phytochemical Screening, Proximate and Mineral Composition of ...

    African Journals Online (AJOL)

    Leaves of sweet potato (Ipomoea batatas) grown in Tepi area was studied for their class of phytochemicals, mineral and proximate composition using standard analytical methods. The phytochemical screening revealed the presence of alkaloids, flavonoid, terpenoids, saponins, quinones, phenol, tannins, amino acid and ...

  8. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Citrus sinensis was screened for its phytochemical composition and was evaluated for the proximate and elemental analysis. The phytochemical analysis indicated the presence of reducing sugar, saponins, cardiac glycosides, tannins and flavonoids. The elemental analysis indicated the presence of the following mineral ...

  9. Phytochemical Screening and Proximate Analysis of Newbouldia ...

    African Journals Online (AJOL)

    The study was conducted to assess the phytochemical and proximate composition of Newboudia laevis leaves and Allium sativum bulb extracts. The leaves and bulbs extracts were analyzed for their chemical composition and antinutritional factors (ANFs) which include moisture, crude protein, crude fat, crude fiber, total ash ...

  10. Disability occurrence and proximity to death

    NARCIS (Netherlands)

    Klijs, Bart; Mackenbach, Johan P.; Kunst, Anton E.

    2010-01-01

    Purpose. This paper aims to assess whether disability occurrence is related more strongly to proximity to death than to age. Method. Self reported disability and vital status were available from six annual waves and a subsequent 12-year mortality follow-up of the Dutch GLOBE longitudinal study.

  11. [Four family members with proximal myotonic myopathy

    NARCIS (Netherlands)

    Tieleman, A.A.; Velden, M.P. van der; Visser, M.C.; Wokke, J.H.J.; Scheffer, H.; Engelen, B.G.M. van

    2004-01-01

    A 41-year-old woman had a 15-year history of pain in her thighs and arms, which also became weaker, and a decrease in visual acuity. Her 35-year-old brother, their 38-year-old sister and their 64-year-old mother also had myalgia, myotonia and proximal muscle weakness, and the women also had

  12. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    ... was about 0.01 in concentration. Proximate analysis also shows that it has a high nutritional value such as carbohydrate, fibre, Ash, fat and protein. These results recommended the consumption of these peels of desired physiochemical properties as sources of food fibres or low-calorie bulk ingredients in food applications ...

  13. Proximate composition and consumer acceptability of African ...

    African Journals Online (AJOL)

    The aim of the study was to assess the organoleptic differences of Clarias gariepinus smoked with two different energy sources, Anogeissus leiocarpus and Tamarindus indica with the help of a hedonic scale and to determine possible proximate composition difference between the smoked products. Smoking of the fishes ...

  14. Controllable proximity effect in superconducting hybrid devices

    NARCIS (Netherlands)

    Bakurskiy, S.V.

    2015-01-01

    This thesis is devoted to the study of controllable proximity effects in superconductors, both in terms of fundamental aspects and applications. As a part of this thesis theoretical description was suggested for a number of structures with superconducting electrodes and multiple interlayers. These

  15. Proximate, chemical compositions and sulphur concentrations on ...

    African Journals Online (AJOL)

    0, 10, 20, 50, 100, 150, 200, 250 and 300 ppm) on the nutritional value and the proximate composition of six selected mango cultivars (Tommy Atkins, Peach, Saber, Sunshine, Keitt and Vhavenda) grown in South Africa. The study shows that ...

  16. Proximate composition, bread characteristics and sensory ...

    African Journals Online (AJOL)

    This study was carried out to investigate proximate composition, bread characteristics and sensory evaluation of cocoyam-wheat composite breads at different levels of cocoyam flour substitution for human consumption.A whole wheat bread (WWB) and cocoyam-composite breads (CCB1,CCB 2 and CCB 3) were prepared ...

  17. Evaluation of the Proximate, Chemical and Phytochemical ...

    African Journals Online (AJOL)

    The increased interest in the utilization of the leaves of Moringa oleifera necessitated this study which evaluated the proximate, chemical and phytochemical composition, especially the presence of anti- physiological and toxic factors in the leaves. The results of the phytochemical analyses were: alkaloid 1.24 ± 0.141%; ...

  18. comparative proximate composition and antioxidant vitamins

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The proximate composition and antioxidant vitamins analysis of two varieties of honey (dark amber and light amber) were carried out using standard methods. The values for moisture, ash, crude lipid, crude protein and crude carbohydrate contents of the two honeys, (light amber and dark amber) are 9.39 ...

  19. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    Proximate composition and cholesterol concentrations of Rhynchophorus phoenicis and Oryctes monoceros larvae subjected to different heat treatments. ... 514.63 mg/100g dry weight basis (DWB) for raw and fried samples, respectively, but decreased to 295.20 mg/100 g DWB in the smoke-dried samples. Similarly, the ...

  20. Preliminary Phytochemical Screening, Elemental and Proximate ...

    African Journals Online (AJOL)

    The study aimed at phytochemical screening, elemental and proximate composition of two varieties of Cyperus esculentus (tiger nut) big yellow and small brown nuts using standard methods. The phytochemicals tested for were alkaloid, saponin, tannin, glycoside, flavonoid, steroid and resin. All the aforementioned ...

  1. Protein biomarker validation via proximity ligation assays.

    Science.gov (United States)

    Blokzijl, A; Nong, R; Darmanis, S; Hertz, E; Landegren, U; Kamali-Moghaddam, M

    2014-05-01

    The ability to detect minute amounts of specific proteins or protein modifications in blood as biomarkers for a plethora of human pathological conditions holds great promise for future medicine. Despite a large number of plausible candidate protein biomarkers published annually, the translation to clinical use is impeded by factors such as the required size of the initial studies, and limitations of the technologies used. The proximity ligation assay (PLA) is a versatile molecular tool that has the potential to address some obstacles, both in validation of biomarkers previously discovered using other techniques, and for future routine clinical diagnostic needs. The enhanced specificity of PLA extends the opportunities for large-scale, high-performance analyses of proteins. Besides advantages in the form of minimal sample consumption and an extended dynamic range, the PLA technique allows flexible assay reconfiguration. The technology can be adapted for detecting protein complexes, proximity between proteins in extracellular vesicles or in circulating tumor cells, and to address multiple post-translational modifications in the same protein molecule. We discuss herein requirements for biomarker validation, and how PLA may play an increasing role in this regard. We describe some recent developments of the technology, including proximity extension assays, the use of recombinant affinity reagents suitable for use in proximity assays, and the potential for single cell proteomics. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013.

  2. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Michael Horsfall

    2009). The aim of this study was to analyses the extract of. Citrus sinensis peels for the phytochemical, proximate and elemental composition. MATERIALS AND METHODS. Plant materials Fresh peels of Citrus sinensis were collected from Uselu market in Benin City, Edo. State, Nigeria. It was identified and authenticated by.

  3. Keldysh proximity action for disordered superconductors

    Indian Academy of Sciences (India)

    Abstract. We review a novel approach to the superconductive proximity effect in dis- ordered normal–superconducting (N–S) structures. The method is based on the multi- charge Keldysh action and is suitable for the treatment of interaction and fluctuation effects. As an application of the formalism, we study the subgap ...

  4. Goal-Proximity Decision-Making

    Science.gov (United States)

    Veksler, Vladislav D.; Gray, Wayne D.; Schoelles, Michael J.

    2013-01-01

    Reinforcement learning (RL) models of decision-making cannot account for human decisions in the absence of prior reward or punishment. We propose a mechanism for choosing among available options based on goal-option association strengths, where association strengths between objects represent previously experienced object proximity. The proposed…

  5. Novel insights into mitotic chromosome condensation

    Science.gov (United States)

    Piskadlo, Ewa; Oliveira, Raquel A.

    2016-01-01

    The fidelity of mitosis is essential for life, and successful completion of this process relies on drastic changes in chromosome organization at the onset of nuclear division. The mechanisms that govern chromosome compaction at every cell division cycle are still far from full comprehension, yet recent studies provide novel insights into this problem, challenging classical views on mitotic chromosome assembly. Here, we briefly introduce various models for chromosome assembly and known factors involved in the condensation process (e.g. condensin complexes and topoisomerase II). We will then focus on a few selected studies that have recently brought novel insights into the mysterious way chromosomes are condensed during nuclear division. PMID:27508072

  6. Automated clinical system for chromosome analysis

    Science.gov (United States)

    Castleman, K. R.; Friedan, H. J.; Johnson, E. T.; Rennie, P. A.; Wall, R. J. (Inventor)

    1978-01-01

    An automatic chromosome analysis system is provided wherein a suitably prepared slide with chromosome spreads thereon is placed on the stage of an automated microscope. The automated microscope stage is computer operated to move the slide to enable detection of chromosome spreads on the slide. The X and Y location of each chromosome spread that is detected is stored. The computer measures the chromosomes in a spread, classifies them by group or by type and also prepares a digital karyotype image. The computer system can also prepare a patient report summarizing the result of the analysis and listing suspected abnormalities.

  7. Chromosome congression explained by nanoscale electrostatics.

    Science.gov (United States)

    Gagliardi, L John; Shain, Daniel H

    2014-02-24

    Nanoscale electrostatic microtubule disassembly forces between positively charged molecules in kinetochores and negative charges on plus ends of microtubules have been implicated in poleward chromosome motions and may also contribute to antipoleward chromosome movements. We propose that chromosome congression can be understood in terms of antipoleward nanoscale electrostatic microtubule assembly forces between negatively charged microtubule plus ends and like-charged chromosome arms, acting in conjunction with poleward microtubule disassembly forces. Several other aspects of post-attachment prometaphase chromosome motions, as well as metaphase oscillations, are consistently explained within this framework.

  8. The Hypermethylated Regions in Avian Chromosomes.

    Science.gov (United States)

    Schmid, Michael; Steinlein, Claus

    2017-01-01

    Chromosomal locations and amounts of 5-methylcytosine-rich chromosome regions were detected in the karyotypes of 13 bird species by indirect immunofluorescence using a monoclonal anti-5-methylcytosine antibody. These species belong to 7 orders and 10 families of modern (Neognathae) and primitive (Palaeognathae) birds and are characterized by macro- and microchromosomes as well as ZW sex chromosomes. In all 13 species, the hypermethylated chromosome segments are confined to constitutive heterochromatin. The chromosomal locations of hypermethylated DNA regions in the karyotypes are constant and species-specific. There is no general rule with regard to the distribution of these hypermethylated chromosome regions in the genomes of birds. In most instances, hypermethylated segments are located in the centromeric regions of chromosomes, but in the sex chromosomes, these can also be found in telomeric and interstitial postitions. In most of the species studied, the centromeric heterochromatin in many, if not all, of the microchromosomes is hypermethylated. However, in one species, the only detectable hypermethylated heterochromatic regions are located in one pair of macroautosomes and in the Z sex chromosome, but none of the microchromosomes contains visible quantities of 5-methylcytosine. The analysis of 5-methylcytosine-rich chromosome regions can be very helpful for the comparative cytogenetics of closely related species or subspecies. It also reflects the dynamic evolutionary process operating in the highly repetitive DNA of eukaryotic chromosomes. © 2017 S. Karger AG, Basel.

  9. Chromosomes aberations and enviromental factors

    Directory of Open Access Journals (Sweden)

    Marković Srđan Z.

    2017-01-01

    Full Text Available Explanation the topic: Changes in genetic material can lead to aberrant cell in the direction of disorders of cellular regulation, malignant transformation, cell death, or if the adjustment was made at the level of the reproductive cells, to genetic changes in some of the consequent off spring. The topic position in scientific/professional public: Breaking of chromosomes can occur spontaneously or can be induced. Chromatid/chromosome breakings can be induced by different environmental factors: chemicals, biological clastogenic agents, accidentally or intentionally. Conclusions: The authors suggest: - making conditions for strong respect of environmental regulations; - to use higher plants for the early detection of environmental mutagens; - create and orderly update National radionuclide database.

  10. Dynamics of chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck

    2007-01-01

    Since the 1960’es the conformation and segregation of the chromosome in Escherichia coli has been a subject of interest for many scientists. However, after 40 years of research, we still know incredibly little about how the chromosome is organized inside the cell, how it manages to duplicate...... this incredibly big molecule and separate the two daughter chromosomes and how it makes sure that the daughter cells receives one copy each. The fully extended chromosome is two orders of magnitude larger than the cell in which it is contained. Hence the chromosome is heavily compacted in the cell......, and it is obvious that structured cellular actions are required to unpack it, as required for its replication, and refold the two daughter chromosomes separately without getting them entangled in the process each generation. The intention of the study was initially to find out how the chromosome is organized...

  11. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    Directory of Open Access Journals (Sweden)

    Daniela Mierla

    2012-06-01

    Full Text Available Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, karyotype analysis by G-banding was performed from peripheral blood in 967 women infertility. Results: Chromosomal abnormalities were found to 79 women (8,17%. The percentage of chromosomal abnormalities in the studied population correlates with the data in the literature. Chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions.

  12. Structure and Barr body formation of an Xp + chromosome with two inactivation centers.

    Science.gov (United States)

    Daly, R F; Patau, K; Therman, E; Sarto, G E

    1977-01-01

    A patients with seizures, Von Willebrand disease, and symptoms of Turner syndrome was a chromosomal mosaic. In blood culture (1974), 56% of the cells were 45, X 33% 46, XXp+ and 11% 47,XXp + Xp +; in the skin, no cells with 47 chromosomes were found. Presumably the Xp + chromosome arose through a break in the Q-banded dark region next to the centromere on Xp to which an Xq had been attached. The abnormal X was late-labeling and formed a larger than normal Barr body. Of the chromatin-positive fibroblasts, 18.2% showed bipartite Barr bodies, which agrees with the hypothesis that the X inactivation center lies on the proximal part of the Xq. On the basis of the structure and behavior of the bipartite bodies in the present patient, as compared to those formed by other chromosomes with two presumed inactivation centers, we propose that the dark region next to the centromere of Xp remains active in the inactive X. In cells with 45,X and 46,XY, this region has the same relative size, whereas it is significantly shorter in the active X of three females, including the present patient, with one abnormal X. We propose that this region on the active X reveals different states of activity, as reflected in its length, depending on how many other X chromosomes are in the cell. Images Fig. 1 Fig. 2 Fig. 3 PMID:299980

  13. Environmental pollution, chromosomes, and health

    Science.gov (United States)

    Bell, Peter M.

    In mid-May, 1980, President Carter declared a state of emergency at the Love Canal area, near Niagara Falls, New York. The reason for this was for the U.S. to underwrite the relocation costs ($3-5 million) of some 2500 residents who, according to a report by the EPA (Environmental Protection Agency) may have suffered damaged chromosomes. These injuries were apparently caused by contact with toxic wastes that had been dumped in the area in the years prior to development for housing.That the toxic compounds exist in the Love Canal and Niagara Falls subsurface zones, including public water supplies, appears to be established fact. That the residents of the Love Canal area suffered chromosomal damage may be established fact as well. Whether or not these two findings can be linked to ill health of the residents is another matter. Recently, the EPA report has been described as having ‘close to zero scientific significance,’ and has been ‘discredited’(Science, 208, 123a, 1980). The reasons for this disparity go beyond differences of opinion, beyond possible inadequacies of the EPA study, and even beyond problems that probably will arise from future studies, including those now in the planning stages. The problem is that even if victims have easily recognizable injuries from toxic substances (injury that apparently has not occurred to Love Canal residents), medical science usually cannot show a causal relationship. Even chromosomal damage is, at best, difficult to interpret. In ideal studies of significant populations and control groups, the association of toxic chemical to chromosome damage and to cancer and birth defects is indirect and, up to now, has been shown to have little or no significance to an individual member of the exposed population.

  14. Chromosome microarrays in human reproduction.

    Science.gov (United States)

    Rajcan-Separovic, Evica

    2012-01-01

    Chromosome microarray (CMA) testing allows automatic and easy identification of large chromosomal abnormalities detectable by conventional cytogenetics as well as the detection of submicroscopic chromosomal imbalances. A PubMed search was performed in order to review the current use of CMA testing in the field of human reproduction. Articles discussing the use of CMA in the preimplantation setting, ongoing pregnancies, miscarriages and patients with reproductive disorders were considered. A high rate of concordance between conventional methods of detecting chromosomal abnormalities [e.g. fluorescence in situ hybridization (FISH), karyotyping] and CMA was reported in the prenatal setting with CMA providing more comprehensive and detailed results as it investigates the whole genome at higher resolution. In preimplantation genetic screening, CMA is replacing FISH and the selection of embryos based on CMA has already resulted in live births. For ongoing pregnancies and miscarriages, CMA eliminates tissue culture failures and artifacts and allows a quick turnaround time. The detection of submicroscopic imbalances [or copy number variants (CNVs)] is beneficial when the imbalance has a clear clinical consequence but is challenging for previously undescribed imbalances, particularly for ongoing pregnancies. Recurrent CNVs have been documented in patients with reproductive disorders; however, the application of CMA in this field is still limited. CMA enhances reproductive medicine as it facilitates better understanding of the genetic aspects of human development and reproduction and more informed patient management. Further clinical validation of CMA in the prenatal setting, creation of practice guidelines and catalogs of newly discovered submicroscopic imbalances with clinical outcomes are areas that will require attention in the future.

  15. Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium

    Science.gov (United States)

    The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...

  16. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  17. De Novo Chromosome Structure Prediction

    Science.gov (United States)

    di Pierro, Michele; Cheng, Ryan R.; Lieberman-Aiden, Erez; Wolynes, Peter G.; Onuchic, Jose'n.

    Chromatin consists of DNA and hundreds of proteins that interact with the genetic material. In vivo, chromatin folds into nonrandom structures. The physical mechanism leading to these characteristic conformations, however, remains poorly understood. We recently introduced MiChroM, a model that generates chromosome conformations by using the idea that chromatin can be subdivided into types based on its biochemical interactions. Here we extend and complete our previous finding by showing that structural chromatin types can be inferred from ChIP-Seq data. Chromatin types, which are distinct from DNA sequence, are partially epigenetically controlled and change during cell differentiation, thus constituting a link between epigenetics, chromosomal organization, and cell development. We show that, for GM12878 lymphoblastoid cells we are able to predict accurate chromosome structures with the only input of genomic data. The degree of accuracy achieved by our prediction supports the viability of the proposed physical mechanism of chromatin folding and makes the computational model a powerful tool for future investigations.

  18. Mechanisms of Chromosome Congression during Mitosis

    Directory of Open Access Journals (Sweden)

    Helder Maiato

    2017-02-01

    Full Text Available Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle

  19. Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

    Directory of Open Access Journals (Sweden)

    Sebastian Pita

    2013-05-01

    Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

  20. Fine-structure analysis and gentic organization at the base of the x chromosome in Drosophila melanogaster. [X-ray-induced chromosome breakage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lifschytz, E.

    1978-03-01

    Genetic organization at the base of the X chromosome was studied through the analysis of x-ray-induced deficiencies. Deficiencies were recovered so as to have a preselected right end anchored in the centric heterochromatin to the right of the su(f) locus. Free ends of deficiencies occurred at any of 22 intervals in Section 20 and in the proximal portion of Section 19 of Bridges' (1938) polytene chromosome map. The distribution of 130 such free ends of deficiencies induced in normal, In(1)sc/sup 8/, and In(1)w/sup m4/ chromosomes suggests that on the single section level, genes are flanked by hot or cold sites for x-ray-induced breaks, and that occurrence of the hot spots is dependent on their interaction with the fixed-end sites in the centric heterochromatin. In the light of these results, it is argued that long heterochromatic sequences separate the relatively few genes in Section 20, and thus endow it with several characteristics typical of heterochromatic regions. Section 20 is considered to be a transition region between the mostly heterochromatic and mostly euchromatic regions of the X chromosome; the differences between them are suggested as being merely quantitative.