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

NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively

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Tamimi, R.M.; Montgomery-Dyer, K.; Tapscott, S.J. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States)] [and others

1997-03-01

NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD. NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. 16 refs., 2 figs.

Sperm FISH analysis of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat complex chromosome rearrangement.

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Ferfouri, F; Boitrelle, F; Clement, P; Molina Gomes, D; Selva, J; Vialard, F

2014-06-01

Complex chromosome rearrangements (CCR) with two independent chromosome rearrangements are rare. Although CCRs lead to high unbalanced gamete rates, data on meiotic segregation in this context are scarce. A male patient was referred to our clinic as part of a family screening programme prompted by the observation of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat karyotype in his brother. Karyotyping identified the same CCR. Sperm FISH (with locus-specific probes for the segments involved in the translocations and nine chromosomes not involved in both rearrangements) was used to investigate the rearrangements meiotic segregation products and establish whether or not an inter-chromosomal effect was present. Sperm nuclear DNA fragmentation was also evaluated. For rob(13;14) and der(Y), the proportions of unbalanced products were, respectively, 26.4% and 60.6%. Overall, 70.3% of the meiotic segregation products were unbalanced. No evidence of an inter-chromosomal effect was found, and the sperm nuclear DNA fragmentation rate was similar to our laboratory's normal cut-off value. In view of previously published sperm FISH analyses of Robertsonian translocations (and even though the mechanism is still unknown), we hypothesise that cosegregation of der(Y) and rob(13;14) could modify rob(13;14) meiotic segregation. © 2013 Blackwell Verlag GmbH.

Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

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Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

2008-01-01

Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

Chromosome 15q24 microdeletion syndrome

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Magoulas Pilar L

2012-01-01

Full Text Available Abstract Chromosome 15q24 microdeletion syndrome is a recently described rare microdeletion syndrome that has been reported in 19 individuals. It is characterized by growth retardation, intellectual disability, and distinct facial features including long face with high anterior hairline, hypertelorism, epicanthal folds, downslanting palpebral fissures, sparse and broad medial eyebrows, broad and/or depressed nasal bridge, small mouth, long smooth philtrum, and full lower lip. Other common findings include skeletal and digital abnormalities, genital abnormalities in males, hypotonia, behavior problems, recurrent infections, and eye problems. Other less frequent findings include hearing loss, growth hormone deficiency, hernias, and obesity. Congenital malformations, while rare, can be severe and include structural brain anomalies, cardiovascular malformations, congenital diaphragmatic hernia, intestinal atresia, imperforate anus, and myelomeningocele. Karyotypes are typically normal, and the deletions were detected in these individuals by array comparative genomic hybridization (aCGH. The deletions range in size from 1.7-6.1 Mb and usually result from nonallelic homologous recombination (NAHR between paralogous low-copy repeats (LCRs. The majority of 15q24 deletions have breakpoints that localize to one of five LCR clusters labeled LCR15q24A, -B, -C, -D, and -E. The smallest region of overlap (SRO spans a 1.2 Mb region between LCR15q24B to LCR15q24C. There are several candidate genes within the SRO, including CYP11A1, SEMA7A, CPLX3, ARID3B, STRA6, SIN3A and CSK, that may predispose to many of the clinical features observed in individuals with 15q24 deletion syndrome. The deletion occurred as a de novo event in all of the individuals when parents were available for testing. Parental aCGH and/or FISH studies are recommended to provide accurate genetic counseling and guidance regarding prognosis, recurrence risk, and reproductive options. Management

Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands

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Jorgensen, T H; Børglum, A D; Mors, O

2002-01-01

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe...... Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring...

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

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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.

Constitutional chromosomal events at 22q11 and 15q26 in a child with a pilocytic astrocytoma of the spinal cord.

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Mascelli, Samantha; Severino, Mariasavina; Raso, Alessandro; Nozza, Paolo; Tassano, Elisa; Morana, Giovanni; De Marco, Patrizia; Merello, Elisa; Milanaccio, Claudia; Pavanello, Marco; Rossi, Andrea; Cama, Armando; Garrè, Maria Luisa; Capra, Valeria

2014-01-01

We report on a 9-years-old patient with mild intellectual disability, facial dimorphisms, bilateral semicircular canal dysplasia, periventricular nodular heterotopias, bilateral hippocampal malrotation and abnormal cerebellar foliation, who developed mild motor impairment and gait disorder due to a pilocytic astrocytoma of the spinal cord. Array-CGH analysis revealed two paternal inherited chromosomal events: a 484.3 Kb duplication on chromosome 15q26.3 and a 247 Kb deletion on 22q11.23. Further, a second de novo 1.5 Mb deletion on 22q11.21 occurred. Chromosome 22 at q11.2 and chromosome 15 at q24q26 are considered unstable regions subjected to copy number variations, i.e. structural alterations of genome, mediated by low copy repeat sequences or segmental duplications. The link between some structural CNVs, which compromise fundamental processes controlling DNA stability, and genomic disorders suggest a plausible scenario for cancer predisposition. Evaluation of the genes at the breakpoints cannot account simultaneously for the phenotype and tumour development in this patient. The two paternal inherited CNVs arguably are not pathogenic and do not contribute to the clinical manifestations. Similarly, although the de novo large deletion at 22q11.21 overlaps with the Di George (DGS) critical region and results in haploinsufficiency of genes compromising critical processes for DNA stability, this case lacks several hallmarks of DGS.

Physical and transcription map of a 25 Mb region on human chromosome 7 (region q21-q22)

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Scherer, S. [Univ. of Toronto (Canada)]|[Hosptial for Sick Children, Toronto (Canada); Little, S.; Vandenberg, A. [Hospital for Sick Children, Toronto (Canada)] [and others

1994-09-01

We are interested in the q21-q22 region of chromosome 7 because of its implication in a number of diseases. This region of about 25 Mb appears to be involved in ectrodactyly/ectodermal dysplasia/cleft plate (EEC) and split hand/split foot deformity (SHFD1), as well as myelodysplastic syndrome and acute non-lymphocyte leukemia. In order to identify the genes responsible for these and other diseases, we have constructed a physical map of this region. The proximal and distal boundaries of the region were operationally defined by the microsatellite markers D7S660 and D7S692, which are about 35 cM apart. This region between these two markers could be divided into 13 intervals on the basis of chromosome breakpoints contained in somatic cell hybrids. The map positions for 43 additional microsatellite markers and 25 cloned genes were determined with respect to these intervals. A physical map based on contigs of over 250 YACs has also been assembled. While the contigs encompass all of the known genetic markers mapped to the region and almost cover the entire 25-Mb region, there are 3 gaps on the map. One of these gaps spans a set of DNA markers for which no corresponding YAC clones could be identified. To connect the two adjacent contigs we have initiated cosmid walking with a chromosome 7-specific library (Lawrence Livermore Laboratory). A tiling path of 60 contiguous YAC clones has been assembled and used for direct cDNA selection. Over 300 cDNA clones have been isolated and characterized. They are being grouped into transcription units by Northern blot analysis and screening of full-length cDNA libraries. Further, exon amplification and direct cDNA library screening with evolutionarily conserved sequences are being performed for a 1-Mb region spanning the SHFD1 locus to ensure detection of all transcribed sequences.

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

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Qiong Pan

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

Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.

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Coignet, L J; Lima, C S; Min, T; Streubel, B; Swansbury, J; Telford, N; Swanton, S; Bowen, A; Nagai, M; Catovsky, D; Fonatsch, C; Dyer, M J

1999-07-01

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.

Residual myocardial ischaemia in first non-Q versus Q wave infarction: maximal exercise testing and ambulatory ST-segment monitoring

DEFF Research Database (Denmark)

Mickley, H; Pless, P; Nielsen, J R

1993-01-01

the infarction. The prevalence of exercise-induced ischaemic manifestations in the infarct types was similar: chest pain 14% vs 16% and ST-segment depression 54% vs 54%. The ischaemic threshold did not differ either (heart rate at 1 mm of ST-segment depression 120 +/- 27 vs 119 +/- 25 beats.min-1). During early...... in non-Q wave infarction (51%) as compared to Q wave infarction (31%) (P depression on ambulatory recording and exercise testing significantly predicted the development of future angina pectoris, whereas patients at increased risk for subsequent......In a prospective study of 123 consecutive survivors of a first myocardial infarction (43 non-Q wave, 80 Q wave), we determined the total residual ischaemic burden by use of pre-discharge maximal exercise testing and post-discharge 36 h ambulatory ST-segment monitoring initiated 11 +/- 5 days after...

A case of de novo duplication of 15q24-q26.3

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Hye Ran Kim

2011-06-01

Full Text Available Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial malformations. Additional abnormalities typically include an unusually short neck, malformations of the fingers and toes, scoliosis and skeletal malformations, genital abnormalities, particularly in affected males, and, in some cases, cardiac defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. Most reported cases of duplication of the long arm of chromosome 15 frequently have more than one segmental imbalance resulting from unbalanced translocations involving chromosome 15 and deletions in another chromosome, as well as other structural chromosomal abnormalities. We report a female newborn with a de novo duplication, 15q24- q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down-slanting palpebral fissures, a large, prominent nose, and micrognathia, arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and hydroureter. Chromosomal analysis showed a 46,XX,inv(9(p12q13,dup(15(q24q26.3. Array comparative genomic hybridization analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the only reported patient with a de novo 15q24-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component in Korea.

Apparently balanced t(1;7)(q21.3;q34) in an infant with Coffin-Siris syndrome.

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McPherson, E W; Laneri, G; Clemens, M M; Kochmar, S J; Surti, U

1997-09-05

Coffin-Siris syndrome is a multiple anomaly/mental retardation syndrome characterized by "coarse" facial appearance, hypoplastic or absent nails on the fifth digits, generalized hirsutism with sparse scalp hair, hypotonia, and developmental delay. Due to several reports of affected sibs with or without a mildly affected parent, both autosomal recessive and autosomal dominant inheritance have been suggested. All previous patients with well-documented Coffin-Siris syndrome are chromosomally normal, and the gene has not been mapped. We report on an infant with typical findings of Coffin-Siris syndrome who also has a de novo apparently balanced translocation of chromosomes 1 and 7, karyotype 46,XY,t(1;7)(q21.3;q34). The parental chromosomes are normal and none of the relatives have signs of Coffin-Siris syndrome. The breakpoints 1q21.3 and 7q34 are suggested as possible locations for a Coffin-Siris gene.

Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families.

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Logue, Mark W; Bauver, Sarah R; Knowles, James A; Gameroff, Marc J; Weissman, Myrna M; Crowe, Raymond R; Fyer, Abby J; Hamilton, Steven P

2012-04-01

Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy-clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543-553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. Copyright © 2012 Wiley Periodicals, Inc.

Comparative genomic hybridization analysis detects frequent over-representation of DNA sequences at 3q, 7p, 8q and 18q in head and neck carcinomas

DEFF Research Database (Denmark)

Bergamo, N A; Rogatto, S R; Poli-Frederico, R C

2000-01-01

Comparative genomic hybridization (CGH) was used to identify chromosomal imbalances in 19 samples of squamous cell carcinoma of the head and neck (HNSCC). The chromosome arms most often over-represented were 3q (48%), 8q (42%), and 7p (32%); in many cases, these changes were observed at high copy...... and 2q material were detected in patients exhibiting a clinical history of recurrence and/or metastasis followed by terminal disease. This association suggests that gain of 1q and 2q may be a new marker of head and neck tumors with a refractory clinical response....

High-resolution physical map for chromosome 16q12.1-q13, the Blau syndrome locus

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Bonavita Gina

2002-08-01

Full Text Available Abstract Background The Blau syndrome (MIM 186580, an autosomal dominant granulomatous disease, was previously mapped to chromosome 16p12-q21. However, inconsistent physical maps of the region and consequently an unknown order of microsatellite markers, hampered us from further refining the genetic locus for the Blau syndrome. To address this problem, we constructed our own high-resolution physical map for the Blau susceptibility region. Results We generated a high-resolution physical map that provides more than 90% coverage of a refined Blau susceptibility region. The map consists of four contigs of sequence tagged site-based bacterial artificial chromosomes with a total of 124 bacterial artificial chromosomes, and spans approximately 7.5 Mbp; however, three gaps still exist in this map with sizes of 425, 530 and 375 kbp, respectively, estimated from radiation hybrid mapping. Conclusions Our high-resolution map will assist genetic studies of loci in the interval from D16S3080, near D16S409, and D16S408 (16q12.1 to 16q13.

Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia.

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Mulle, Jennifer Gladys; Pulver, Ann E; McGrath, John A; Wolyniec, Paula S; Dodd, Anne F; Cutler, David J; Sebat, Jonathan; Malhotra, Dheeraj; Nestadt, Gerald; Conrad, Donald F; Hurles, Matthew; Barnes, Chris P; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F; Gejman, Pablo V; Sanders, Alan R; Duan, Jubao; Mitchell, Adele A; Peter, Inga; Sklar, Pamela; O'Dushlaine, Colm T; Grozeva, Detelina; O'Donovan, Michael C; Owen, Michael J; Hultman, Christina M; Kähler, Anna K; Sullivan, Patrick F; Kirov, George; Warren, Stephen T

2014-03-01

Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with autism spectrum disorders. The reciprocal deletion of this region causes Williams-Beuren syndrome. We assayed an Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for genome-wide CNV. An excess of large rare and de novo CNVs were observed, including a 1.4 Mb duplication on chromosome 7q11.23 identified in two unrelated patients. To test whether this 7q11.23 duplication is also associated with SZ, we obtained data for 14,387 SZ cases and 28,139 controls from seven additional studies with high-resolution genome-wide CNV detection. We performed a meta-analysis, correcting for study population of origin, to assess whether the duplication is associated with SZ. We found duplications at 7q11.23 in 11 of 14,387 SZ cases with only 1 in 28,139 control subjects (unadjusted odds ratio 21.52, 95% confidence interval: 3.13-922.6, p value 5.5 × 10(-5); adjusted odds ratio 10.8, 95% confidence interval: 1.46-79.62, p value .007). Of three SZ duplication carriers with detailed retrospective data, all showed social anxiety and language delay premorbid to SZ onset, consistent with both human studies and animal models of the 7q11.23 duplication. We have identified a new CNV associated with SZ. Reciprocal duplication of the Williams-Beuren syndrome deletion at chromosome 7q11.23 confers an approximately tenfold increase in risk for SZ. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14.

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Zech, J C; Morlé, L; Vincent, P; Alloisio, N; Bozon, M; Gonnet, C; Milazzo, S; Grange, J D; Trepsat, C; Godet, J; Plauchu, H

1999-05-01

It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. Fourty members of one same family agreed to be examined. Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. Ophthalmological aspects of Wagner's disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner's disease lies in a 20 cM interval on chromosome 5q13-q14.

Familial isolated clubfoot is associated with recurrent chromosome 17q23.1q23.2 microduplications containing TBX4.

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

2010-07-09

Clubfoot is a common musculoskeletal birth defect for which few causative genes have been identified. To identify the genes responsible for isolated clubfoot, we screened for genomic copy-number variants with the Affymetrix Genome-wide Human SNP Array 6.0. A recurrent chromosome 17q23.1q23.2 microduplication was identified in 3 of 66 probands with familial isolated clubfoot. The chromosome 17q23.1q23.2 microduplication segregated with autosomal-dominant clubfoot in all three families but with reduced penetrance. Mild short stature was common and one female had developmental hip dysplasia. Subtle skeletal abnormalities consisted of broad and shortened metatarsals and calcanei, small distal tibial epiphyses, and thickened ischia. Several skeletal features were opposite to those described in the reciprocal chromosome 17q23.1q23.2 microdeletion syndrome associated with developmental delay and cardiac and limb abnormalities. Of note, during our study, we also identified a microdeletion at the locus in a sibling pair with isolated clubfoot. The chromosome 17q23.1q23.2 region contains the T-box transcription factor TBX4, a likely target of the bicoid-related transcription factor PITX1 previously implicated in clubfoot etiology. Our result suggests that this chromosome 17q23.1q23.2 microduplication is a relatively common cause of familial isolated clubfoot and provides strong evidence linking clubfoot etiology to abnormal early limb development. Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

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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.

Mutation screening and association analysis of six candidate genes for autism on chromosome 7q

DEFF Research Database (Denmark)

Bonora, E.; Lamb, J.A.; Barnby, G.

2005-01-01

in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect......Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants...

Deletion 21q22.3 and duplication 7q35q36.3 in a Colombian girl: a case report

OpenAIRE

Ruiz-Botero, Felipe; Pachajoa, Harry

2016-01-01

Background Genetic disorders are a major cause in the etiology of cases with intellectual disability; however, analysis by a conventional technique such as cytogenetic karyotyping only allows the detection of chromosomal alterations in approximately 9.5?% of cases. The inclusion of new technologies such as high resolution microarray analysis has allowed the study of alterations in chromosomal segments that are less than 5?Mb in length; this has led to an increase in the diagnosis of these pat...

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.

Syntenic homology of human unique DNA sequences within chromossome regions 5q31, 10q22, 13q32-33 and 19q13.1 in the great apes

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Rhea U. Vallente-Samonte

2000-09-01

Full Text Available Homologies between chromosome banding patterns and DNA sequences in the great apes and humans suggest an apparent common origin for these two lineages. The availability of DNA probes for specific regions of human chromosomes (5q31, 10q22, 13q32-33 and 19q13.1 led us to cross-hybridize these to chimpanzee (Pan troglodytes, PTR, gorilla (Gorilla gorilla, GGO and orangutan (Pongo pygmaeus, PPY chromosomes in a search for equivalent regions in the great apes. Positive hybridization signals to the chromosome 5q31-specific DNA probe were observed at HSA 5q31, PTR 4q31, GGO 4q31 and PPY 4q31, while fluorescent signals using the chromosome 10q22-specific DNA probe were noted at HSA 10q22, PTR 8q22, GGO 8q22 and PPY 7q22. The chromosome arms showing hybridization signals to the Quint-EssentialTM 13-specific DNA probe were identified as HSA 13q32-33, PTR 14q32-33, GGO 14q32-33 and PPY 14q32-33, while those presenting hybridization signals to the chromosome 19q13.1-specific DNA probe were identified as HSA 19q13.1, PTR 20q13, GGO 20q13 and PPY 20q13. All four probes presumably hybridized to homologous chromosomal locations in the apes, which suggests a homology of certain unique DNA sequences among hominoid species.Homologias entre os padrões de bandamento de cromossomos e seqüências de DNA em grandes macacos e humanos sugerem uma aparente origem comum para estas duas linhagens. A disponibilidade de sondas de DNA para regiões específicas de cromossomos humanos (5q31, 10q22, 13q32-33 e 19q13.1 nos levou a realizar hibridação cruzada com cromossomos de chimpanzé (Pan troglodytes, PTR, gorila (Gorilla gorilla, GGO e orangotango (Pongo pygmaeus, PPY em um pesquisa de regiões equivalentes em grandes macacos. Sinais positivos de hibridação para a sonda de DNA específica para o cromossomo 5q31 foram observados em HSA 5q31, PTR 4q31, GGO 4q31 e PPY 4q31, enquanto que sinais fluorescentes usando a sonda de DNA específica para o cromossomo 10q22 foram

6q16.3q23.3 duplication associated with Prader-Willi-like syndrome.

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Desch, Laurent; Marle, Nathalie; Mosca-Boidron, Anne-Laure; Faivre, Laurence; Eliade, Marie; Payet, Muriel; Ragon, Clemence; Thevenon, Julien; Aral, Bernard; Ragot, Sylviane; Ardalan, Azarnouche; Dhouibi, Nabila; Bensignor, Candace; Thauvin-Robinet, Christel; El Chehadeh, Salima; Callier, Patrick

2015-01-01

Prader-Willi syndrome (PWS) is characterized by hypotonia, delayed neuropsychomotor development, overeating, obesity and mental deficiency. This phenotype is encountered in other conditions, defining Prader-Willi-like syndrome (PWLS). We report a 14-year-old boy with a complex small supernumerary marker chromosome (sSMC) associated with PWLS. The propositus presents clinical features commonly found in patients with PWLS, including growth hormone deficit. Banding karyotype analysis and fluorescence in situ hybridization (FISH) revealed a marker derived from chromosome 6 and a neocentromere as suspected, but array-CGH enabled us to characterize this marker as a der(10)t(6;10)(6qter → 6q23.3::10p11.1 → 10p11.21)dn. As far as we know, this is the first diagnosed case of PWLS associated with a complex sSMC, involving a 30.9 Mb gain in the 6q16.3q23.3 region and a 3.5 Mb gain in the 10p11.21p11.1 region. Several genes have been mapped to the 6q region including the TCBA1 gene, which is associated with developmental delay and recurrent infections, the ENPP1 gene, associated with insulin resistance and susceptibility to obesity and the BMIQ3 gene, associated with body mass index (BMI). No OMIM gene was found in the smallest 10p11.21p11.1 region. We suggest that the duplicated chromosome segment 6q16.3q23.3 may be responsible for the phenotype of our case and may also be a candidate locus of PWLS.

Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy

DEFF Research Database (Denmark)

Kristensen, Lone Krøldrup; Kjaergaard, S; Kirchhoff, Marianne

2012-01-01

with muscular hypertrophy and mildly retarded psychomotor development. Array-CGH identified a small duplication of 7q36.3 including the Sonic Hedgehog (SHH) gene in both the aborted foetus and the live born male sib. Neither of the parents carried the 7q36.3 duplication. The consequences of overexpression...

Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype.

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Barbi, G; Kennerknecht, I; Wöhr, G; Avramopoulos, D; Karadima, G; Petersen, M B

2000-03-13

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively. Copyright 2000 Wiley-Liss, Inc.

Interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q

International Nuclear Information System (INIS)

Le Beau, M.M.; Epstein, N.D.; O'Brien, S.J.; Nienhuis, A.W.; Yang, Y.C.; Clark, S.C.; Rowley, J.D.

1987-01-01

The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, the authors localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33[del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent from the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF, CSF-1, and FMS. The findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q- chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q)

Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis

International Nuclear Information System (INIS)

Klinger, K.W.; Winqvist, R.; Riccio, A.

1987-01-01

The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. The authors frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer

Anterior pituitary failure (panhypopituitarism) with balanced chromosome translocation 46,XY,t(11;22)(q24;q13).

Science.gov (United States)

Yang, C Y; Chou, C W; Chen, S Y; Cheng, H M

2001-04-01

Hypopituitarism is the clinical syndrome that results from failure of the anterior pituitary gland to produce its hormones. Hypopituitarism can result from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease. The etiologies of primary hypopituitarism are miscellaneous. The dominant clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports have associated hypopituitarism with anti-pituitary-antibodies, hereditary syndrome and chromosome defects, but hypopituitarism has rarely been associated with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case of anterior pituitary failure with balanced chromosome translocation. A 19-year-old Chinese teenager presented with failure of pubertal development and sexual infantilism. On examination, the patient had the classic appearance of hypogonadism. Endocrine studies and three combined pituitary function tests revealed panhypopituitarism. A chromosomal study revealed 46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest films showed delayed fusion of bilateral humeral head epiphyses and bilateral acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient received 19 months replacement therapy, including steroids (prednisolone 5 mg each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250 mg every two weeks. His height increased 4 cm with secondary sexual characteristics developed, and muscle power increased.

Blepharophimosis and mental retardation (BMR) phenotypes caused by chromosomal rearrangements: description in a boy with partial trisomy 10q and monosomy 4q and review of the literature.

Science.gov (United States)

Bartholdi, Deborah; Toelle, Sandra P; Steiner, Bernhard; Boltshauser, Eugen; Schinzel, Albert; Riegel, Mariluce

2008-01-01

Blepharophimosis is a rare congenital anomaly of the palpebral fissure which is often associated with mental retardation and additional malformations. We report on a boy with blepharophimosis, ptosis and severe mental retardation carrying an unbalanced 4;10 translocation with terminal duplication of 10q [dup(10)(q25.1-->qter)] and monosomy of a small terminal segment of chromosome 4q [del(4)(34.3-->qter)]. Detailed clinical examination and review of the literature showed that the phenotype of the patient was mainly determined by the dup(10q). This paper reviews the chromosomal aberrations associated with BMR (blepharophimosis mental retardation) phenotypes. Searching different databases and reviewing the literature revealed 14 microscopically visible aberrations (among them UPD(14)pat) and two submicroscopic rearrangements causing blepharophimosis and mental retardation (BMR) syndrome. Some of these rearrangements-like the terminal dup(10q) identified in our patient or interstitial del(2q)-are associated with clearly defined phenotypes and can be well distinguished from each other on basis of clinical examination. This paper should assist clinicians and cytogeneticists when evaluating patients with BMR syndrome.

Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

Science.gov (United States)

Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

2005-02-15

The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

A Rare Interstitial Duplication of 8q22.1–8q24.3 Associated with Syndromic Bilateral Cleft Lip/Palate

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Regina Ferreira Rezek

2014-01-01

Full Text Available We present a rare case of 8q interstitial duplication derived from maternal balanced translocations in a patient with bilateral cleft lip and palate in syndromic form associated with other congenital malformations. G-banding cytogenetic analysis revealed a chromosomal abnormality in the form of the karyotype 46,XX der(22t(8;22(q22.1;p11.1mat. Chromosome microarray analysis evidenced a 49 Mb duplicated segment of chromosome 8q with no pathogenic imbalances on chromosome 22. Two siblings also carry the balanced translocation. We have compared this case with other “pure” trisomies of 8q patients reported in the literature and with genome wide association studies recently published. This work highlights the involvement of chromosome 8q in orofacial clefts.

The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations

DEFF Research Database (Denmark)

Paulsson, Kajsa; Haferlach, Claudia; Fonatsch, Christa

2010-01-01

Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns...... of additional aberrations. We here present an SNP array study of 14 idic(X)-positive myeloid malignancies, collected through an international collaborative effort. The breakpoints clustered in two regions of segmental duplications and were not in a gene, making dosage effects from the concurrent gain of Xpter......-q13 and loss of Xq13-qter, rather than a fusion gene, the most likely pathogenetic outcome. Methylation analysis revealed involvement of the inactive X chromosomes in five cases and of the active in two. The ABCB7 gene, mutated in X-linked sideroblastic anemia and spinocerebellar ataxia...

Dispersals of the Siberian Y-chromosome haplogroup Q in Eurasia.

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Huang, Yun-Zhi; Pamjav, Horolma; Flegontov, Pavel; Stenzl, Vlastimil; Wen, Shao-Qing; Tong, Xin-Zhu; Wang, Chuan-Chao; Wang, Ling-Xiang; Wei, Lan-Hai; Gao, Jing-Yi; Jin, Li; Li, Hui

2018-02-01

The human Y-chromosome has proven to be a powerful tool for tracing the paternal history of human populations and genealogical ancestors. The human Y-chromosome haplogroup Q is the most frequent haplogroup in the Americas. Previous studies have traced the origin of haplogroup Q to the region around Central Asia and Southern Siberia. Although the diversity of haplogroup Q in the Americas has been studied in detail, investigations on the diffusion of haplogroup Q in Eurasia and Africa are still limited. In this study, we collected 39 samples from China and Russia, investigated 432 samples from previous studies of haplogroup Q, and analyzed the single nucleotide polymorphism (SNP) subclades Q1a1a1-M120, Q1a2a1-L54, Q1a1b-M25, Q1a2-M346, Q1a2a1a2-L804, Q1a2b2-F1161, Q1b1a-M378, and Q1b1a1-L245. Through NETWORK and BATWING analyses, we found that the subclades of haplogroup Q continued to disperse from Central Asia and Southern Siberia during the past 10,000 years. Apart from its migration through the Beringia to the Americas, haplogroup Q also moved from Asia to the south and to the west during the Neolithic period, and subsequently to the whole of Eurasia and part of Africa.

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

Science.gov (United States)

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

2015-01-01

Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion. © 2015 S. Karger AG, Basel.

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

Science.gov (United States)

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

2001-01-01

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

Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders

International Nuclear Information System (INIS)

Pettenati, M.J.; Le Beau, M.M.; Lemons, R.S.; Shima, E.A.; Kawasaki, E.S.; Larson, R.A.; Sherr, C.J.; Diaz, M.O.; Rowley, J.D.

1987-01-01

The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, the authors localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5) (q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33.1. Thus, a small segment of chromosome 5 contains GM-CSF (the gene encoding the granulocyte-macrophage CSF), CSF-1, and FMS, which encodes the CSF-1 receptor, in that order from the centromere; this cluster of genes may be involved in the altered hematopoiesis associated with a deletion of 5q

Chromosome 15q overgrowth syndrome: Prenatal diagnosis, molecular cytogenetic characterization, and perinatal findings in a fetus with dup(15(q26.2q26.3

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Chih-Ping Chen

2011-09-01

Conclusion: The present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2→q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.

Candidate region for Coffin-Siris syndrome at 7q32-->34.

Science.gov (United States)

McGhee, E M; Klump, C J; Bitts, S M; Cotter, P D; Lammer, E J

2000-07-31

Coffin-Siris syndrome is characterized by intrauterine growth retardation, mental deficiency, coarse face, hypoplastic fifth fingers and nails, hirsutism, and initial difficulties with feeding. The etiology of this syndrome is unknown. We report on an 11-year-old girl with Coffin-Siris syndrome and a de novo, apparently balanced reciprocal translocation between chromosomes 7 and 22 [t(7;22)(q32;q11.2)]. The 7q breakpoint in our patient is very similar to the breakpoint reported in a previous case [McPherson et al., 1997: Am J Med Genet 71:430-433] with a balanced t(1;7)(q21.3;q34). Together, these patients provide evidence that the region 7q32-->34 is a candidate region for the gene responsible for Coffin-Siris syndrome.

Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men.

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Nick Orr

2011-09-01

Full Text Available Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS have recently identified common single nucleotide polymorphisms (SNPs that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35 (odds ratio (OR  = 1.30, p = 7.98×10⁻⁴, rs10941679 (5p12 (OR = 1.26, p = 0.007, rs9383938 (6q25.1 (OR = 1.39, p = 0.004, rs2981579 (FGFR2 (OR = 1.18, p = 0.03, and rs3803662 (TOX3 (OR = 1.48, p = 4.04×10⁻⁶. Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs--rs13387042 (2q35, rs3803662 (TOX3, and rs6504950 (COX11--showed significant differences in ORs (p<0.05 between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development.

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.

Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome

Energy Technology Data Exchange (ETDEWEB)

Gelernter, J.; Rao, P.A.; Pauls, D.L. [Yale Univ. School of Medicine, West Haven, CT (United States)] [and others

1995-03-20

A novel serotonin receptor designated 5HT7 (genetic locus HTR7) was cloned in 1993. This receptor has interesting properties related to ligand affinity and CNS distribution that render HTR7 a very interesting candidate gene for neuropsychiatric disorders. We mapped this gene, first by physical methods and then by genetic linkage. First, we made a tentative assignment to chromosome 10, based on hybridization of an HTR7 probe to a Southern blot of DNA from somatic cell hybrids. We then identified a genetic polymorphism at the HTR7 locus. We identified one extended pedigree where the polymorphism segregated. Using the LEPED computer program for pairwise linkage analysis, we confirmed the assignment of the gene to chromosome 10, specifically 10q21-q24, based on a lod score of 5.37 at 0% recombination between HTR7 and D10S20 (a chromosome 10 reference marker). Finally, we excluded genetic linkage between this locus and Tourette syndrome under a reasonable set of assumptions. 15 refs., 1 fig., 1 tab.

An Interstitial Deletion at 7q33-36.1 in a Patient with Intellectual Disability, Significant Language Delay, and Severe Microcephaly

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Trupti Kale

2016-01-01

Full Text Available Interstitial deletions of the distal 7q region are considered a rare entity. In this report, we describe a seven-year-old male with a heterozygous interstitial deletion at 7q33-36.1 with characteristic dysmorphic facial features, intellectual disability, severe microcephaly, and significant language delay. The primary focus of our report is to compare our case with the few others in the literature describing interstitial deletions at the long arm of chromosome 7. Based on the various breakpoints in prior studies, a number of phenotypic variations have been identified that are unique to each of the reports. However, there are also a number of similarities among these cases as well. We hope to provide a concise review of the literature and genes involved within our deletion sequence in the hope that it will contribute to creating a phenotypic profile for this patient population.

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

Energy Technology Data Exchange (ETDEWEB)

Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. (Harvard Medical School, Boston, MA (United States)); Altherr, M.R. (Los Alamos National Lab., NM (United States))

1994-04-01

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

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

Science.gov (United States)

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

2014-01-01

Large pericentric inversions in chromosome 10 are rare chromosomal aberrations with only few cases of familial inheritance. Such chromosomal rearrangements may lead to production of unbalanced gametes. As a result of a recombination event in the inversion loop, 2 recombinants with duplicated and deficient chromosome segments, including the regions distal to the inversion, may be produced. We report on 2 relatives in a family with opposite terminal chromosomal rearrangements of chromosome 10, i.e. rec(10)dup(10p)inv(10) and rec(10)dup(10q)inv(10), due to familial pericentric inversion inv(10)(p15.1q26.12). Based on array-CGH results, we characterized the exact genomic regions involved and compared the clinical features of both patients with previous reports on similar pericentric inversions and regional differences within 10p and 10q. The fact that both products of recombination are viable indicates a potentially high recurrence risk of unbalanced offspring. This report of unbalanced rearrangements in chromosome 10 in 2 generations confirms the importance of screening for terminal imbalances in patients with idiopathic intellectual disability by molecular cytogenetic techniques such as FISH, MLPA or microarrays. It also underlines the necessity for FISH to define structural characteristics of such cryptic intrachromosomal rearrangements and the underlying cytogenetic mechanisms. © 2014 S. Karger AG, Basel.

Assignment of FUT8 to chicken chromosome band 5q1.4 and to human chromosome 14q23.2-->q24.1 by in situ hybridization. Conserved and compared synteny between human and chicken

NARCIS (Netherlands)

Coullin, Ph.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Heilig, R.; Mollicone, R.; Oriol, R.; Candelier, J.J.

2002-01-01

The human FUT8 gene is implicated in crucial developmental stages and is overexpressed in some tumors and other malignant diseases. Based on three different experiments we have assigned the FUT8 gene to chromosome bands 14q23.2 --> q24.1 and not 14q24.3 as previously shown (Yamaguchi et al.,

Microdeletion 15q26.2qter and Microduplication 18q23 in a Patient with Prader-Willi-Like Syndrome: Clinical Findings.

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Dello Russo, Patrizia; Demori, Eliana; Sechi, Annalisa; Passon, Nadia; Romagno, Daniela; Gnan, Chiara; Zoratti, Raffaele; Damante, Giuseppe

2016-01-01

The small interstitial deletion in the long arm of chromosome 15 causing Prader-Willi/Angelman syndrome is well known, whereas cases that report terminal deletions in 15q in association with the Prader-Willi-like phenotype are very rare. By using GTG-banding analysis, metaphase FISH, MLPA analysis, and genome-wide array CGH, we detected an unbalanced translocation involving a microdeletion of the distal part of 15q and a microduplication of the distal part of 18q. The unbalanced translocation was found in a boy that was referred with clinical suspicion of Prader-Willi syndrome. In the 15q-deleted region, 23 genes have been identified, and 13 of them are included in the OMIM database. Among these, the deleted IGFR1, MEF2A, CHSY1, and TM2D3 genes could contribute to the patient's phenotype. Seven genes are included in the duplicated chromosome segment 18q, but only one (CTDP1) is present in the OMIM database. We suggest that the deleted chromosome segment 15q26.2qter may be responsible for the phenotype of our case and may also be a candidate locus of Prader-Willi-like syndrome. © 2016 S. Karger AG, Basel.

A chromosome 10 variant with a 12 Mb inversion [inv(10)(q11.22q21.1)] identical by descent and frequent in the Swedish population.

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Entesarian, Miriam; Carlsson, Birgit; Mansouri, Mahmoud Reza; Stattin, Eva-Lena; Holmberg, Eva; Golovleva, Irina; Stefansson, Hreinn; Klar, Joakim; Dahl, Niklas

2009-03-01

We identified a paracentric inversion of chromosome 10 [inv(10)(q11.22q21.1)] in 0.20% of Swedish individuals (15/7,439) referred for cytogenetic analysis. A retrospective analysis of 8,896 karyotypes from amniocenteses in Sweden revealed a carrier frequency of 0.079% (7/8,896) for the inversion. Cloning and detailed analysis of the inversion breakpoint regions show enrichment for interspersed repeat elements and AT-stretches. The centromeric breakpoint coincides with that of a predicted inversion from HapMap data, which suggests that this region is involved in several chromosome 10 variants. No known gene or predicted transcript are disrupted by the inversion which spans approximately 12 Mb. Carriers from four non-related Swedish families have identical inversion breakpoints and haplotype analysis confirmed that the rearrangement is identical by descent. Diagnosis was retrieved in 6 out of the 15 carriers referred for cytogenetic analysis. No consistent phenotype was found to be associated with the inversion. Our study demonstrates that the inv(10)(q11.22q21.1) is a rare and inherited chromosome variant with a broad geographical distribution in Sweden. 2009 Wiley-Liss, Inc.

A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors

International Nuclear Information System (INIS)

Sastre-Garau, X.; Couturier, J.; Favre, M.; Orth, G.

1995-01-01

The SW756 cell line, derived from an invasive cancer of the uterine cervix, harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been located in chromosome band 12q13. By in situ hybridization experiments with tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now localize the integrated viral sequences in 12q14-q15. Interestingly, we have previously localized integrated HPV16 sequences in the same chromosomal region in SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region 12q14-q15 could thus correspond to a preferential site for the integration of HPV DNA in genital tumors. (authors). 29 refs., 2 figs

Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

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Velculescu Victor E

2008-04-01

Full Text Available Abstract Background Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Familial Adenomatous Polyposis (FAP. In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer. Methods Statistical analysis was performed using multipoint parametric and nonparametric linkage. Results Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL = 2.1. Conclusion The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.

Failure to thrive as primary feature in two patients with subtle chromosomal aneuploidy: Interstitial deletion 2q33

Energy Technology Data Exchange (ETDEWEB)

Grace, K.; Mulla, W.; Stump, T. [Children`s Hospital of Philadelpha, PA (United States)] [and others

1994-09-01

It is well known that patients with chromosomal aneuploidy present with multiple congenital anomalies and dysmorphia, and that they may have associated failure to thrive. However, rarely is failure to thrive the predominant presenting feature. We report two such patients. Patient 1 had a marked history of failure to thrive, (weight 50% for 5 1/2 months at 20 months, length 50% for 15 months at 20 months). Patient 2 was noted to be growth retarded at 2 months upon presenting to the hospital with respiratory symptoms (weight 50% for a newborn, length 50% for 36 weeks gestation). There was relative head sparing in both patients. Chromosome analysis in patient 1, prompted by a negative work-up for the failure to thrive, and emerging evidence of developmental delay, revealed a 46,XY,del(2)(q32.2q33) karyotype. Chromosome analysis in patient 2, done as part of a complete workup for the failure to thrive, revealed a 46,XX,del(2)(q33.2q33.2 or q33.2q33.3) karyotype. On careful examination, subtle dysmorphic features were seen. In both patients these included a long flat philtrum, thin upper lip and high arched palate. Patient 1 also had a small posterior cleft of the palate. These patients have the smallest interstitial deletions of chromosome 2 so far reported. Their deletions overlap within 2q33 although they are not identical. Review of the literature reveals 15 patients with interstitial deletions which include 2q33. Marked growth retardation is reported in 14 of these cases. Cleft palate/abnormal uvula were frequently associated. These cases illustrate the need to include high resolution chromosomal studies as part of a complete work-up for unexplained failure to thrive.

Dental developmental abnormalities in a patient with subtelomeric 7q36 deletion syndrome may confirm a novel role for the SHH gene ?

OpenAIRE

Linhares, Nat?lia D.; Svartman, Marta; Salgado, Mauro Ivan; Rodrigues, Tatiane C.; da Costa, Silvia S.; Rosenberg, Carla; Valadares, Eug?nia R.

2013-01-01

Studies in mice demonstrated that the Shh gene is crucial for normal development of both incisors and molars, causing a severe retardation in tooth growth, which leads to abnormal placement of the tooth in the jaw and disrupted tooth morphogenesis. In humans the SHH gene is located on chromosome 7q36. Defects in its protein or signaling pathway may cause holoprosencephaly spectrum, a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres and tha...

The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the δT-cell receptor with TCL3, a conserved and activated locus at 10q24

International Nuclear Information System (INIS)

Zutter, M.; Hockett, R.D.; Roberts, C.W.M.; McGuire, E.A.; Bloomstone, J.; Korsmeyer, S.J.; Morton, C.C.; Deaven, L.L.; Crist, W.M.; Carroll, A.J.

1990-01-01

The authors cloned the t(10;14) recurrent translocation from CD3-negative T-cell acute lymphoblastic leukemia cells. The breakpoint at 14q11 involved an intermediate rearrangement of the δ T-cell receptor locus, suggesting that the translocation arose at the time of antigen receptor assemblage. Translocation introduced chromosome segment 10q24 as proven by hybridization of a breakpoint-derived probe to flow-sorted chromosomes and metaphase chromosomes. Two t(10;14) breakpoints were clustered within a 600-base-pair region of 10q24 but no heptamer-spacer-nonamer motifs resembling T-cell receptor/immunoglobulin rearrangement signals were noted at the breakpoint. A locus distinct from terminal deoxynucleotidyltransferase was found at 10q24. Evolutionarily conserved regions surrounding the 10q24 breakpoint were examined for transcriptional activity. A region telomeric to the 10q24 breakpoint, expected to translocate to the der(14) chromosome, recognized an abundant 2.9-kilobase RNA in a t(10;14) T-cell leukemia. This locus was not active in a variety of other normal and neoplastic T cells, arguing that it was deregulated by he introduction of the T-cell receptor. This locus is a candidate for a putative protooncogene, TCL3, involved in T-cell neoplasia

6q deletion detected by fluorescence in situ hybridization using bacterial artificial chromosome in chronic lymphocytic leukemia.

Science.gov (United States)

Dalsass, Alessia; Mestichelli, Francesca; Ruggieri, Miriana; Gaspari, Paola; Pezzoni, Valerio; Vagnoni, Davide; Angelini, Mario; Angelini, Stefano; Bigazzi, Catia; Falcioni, Sadia; Troiani, Emanuela; Alesiani, Francesco; Catarini, Massimo; Attolico, Immacolata; Scortechini, Ilaria; Discepoli, Giancarlo; Galieni, Piero

2013-07-01

Deletions of the long arm of chromosome 6 are known to occur at relatively low frequency (3-6%) in chronic lymphocytic leukemia (CLL), and they are more frequently observed in 6q21. Few data have been reported regarding other bands on 6q involved by cytogenetic alterations in CLL. The cytogenetic study was performed in nuclei and metaphases obtained after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin-2. Four bacterial artificial chromosome (BAC) clones mapping regions in bands 6q16, 6q23, 6q25, 6q27 were used as probes for fluorescence in situ hybridization in 107 CLL cases in order to analyze the occurrence and localization of 6q aberrations. We identified 11 cases (10.2%) with 6q deletion of 107 patients studied with CLL. The trends of survival curves and the treatment-free intervals (TFI) of patients with deletion suggest a better outcome than the other cytogenetic risk groups. We observed two subgroups with 6q deletion as the sole anomaly: two cases with 6q16 deletion, and three cases with 6q25.2-27 deletion. There were differences of age, stage, and TFI between both subgroups. By using BAC probes, we observed that 6q deletion has a higher frequency in CLL and is linked with a good prognosis. In addition, it was observed that the deletion in 6q16 appears to be the most frequent and, if present as the only abnormality, it could be associated with a most widespread disease. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22)(q32.1;q11.2) chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.

Science.gov (United States)

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

2012-01-01

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

Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22(q32.1;q11.2 chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.

Directory of Open Access Journals (Sweden)

Jun Zhu

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

A Case of 17q21.31 Microduplication and 7q31.33 Microdeletion, Associated with Developmental Delay, Microcephaly, and Mild Dysmorphic Features

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Adrian Mc Cormack

2014-01-01

Full Text Available Concurrent cryptic microdeletion and microduplication syndromes have recently started to reveal themselves with the advent of microarray technology. Analysis has shown that low-copy repeats (LCRs have allowed chromosome regions throughout the genome to become hotspots for nonallelic homologous recombination to take place. Here, we report a case of a 7.5-year-old girl who manifests microcephaly, developmental delay, and mild dysmorphic features. Microarray analysis identified a microduplication in chromosome 17q21.31, which encompasses the CRHR1, MAPT, and KANSL1 genes, as well as a microdeletion in chromosome 7q31.33 that is localised within the GRM8 gene. To our knowledge this is one of only a few cases of 17q21.31 microduplication. The clinical phenotype of patients with this microduplication is milder than of those carrying the reciprocal microdeletions, and suggests that the lower incidence of the former compared to the latter may be due to underascertainment.

Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

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O'Riordan, Aisling M; McGrath, Niamh; Sharif, Farhana; Murphy, Nuala P; Franklin, Orla; Lynch, Sally Ann; O'Grady, Michael J

2017-01-01

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

Prenatal Diagnosis of 4p and 4q Subtelomeric Microdeletion in De Novo Ring Chromosome 4

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Halit Akbas

2013-01-01

Full Text Available Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0 referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH. However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb and 4q35.2 (2.449 Mb. In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

Prenatal diagnosis of 4p and 4q subtelomeric microdeletion in de novo ring chromosome 4.

Science.gov (United States)

Akbas, Halit; Cine, Naci; Erdemoglu, Mahmut; Atay, Ahmet Engin; Simsek, Selda; Turkyilmaz, Aysegul; Fidanboy, Mehmet

2013-01-01

Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15(p11.2;q22.1

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Dalvi Rupa

2016-01-01

Full Text Available BACKGROUND: Balanced non-robertsonian translocation (RT, involving acrocentric chromosomes, is a rare event and only a few cases are reported. Most of the RTs are balanced involving acrocentric chromosomes with the breakpoints (q10;q10. MATERIALS AND METHODS: Chromosome analysis was performed as per standard procedure – Giemsa-trypsin banding with 500 band resolution was analyzed for chromosome identification. RESULTS: In the present study, we report a rare balanced non-RTs involving chromosomes 13 and 15 with cytogenetic finding of 46, XX, t(13;15(p11.2;q22.1. CONCLUSION: To the best of our knowledge, this is the first such report of an unusual non-RT of t(13:15 with (p11.2;q22.1 break points.

Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

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Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

2017-10-05

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

18q- and 18q+ mosaicism in a mentally retarded boy

NARCIS (Netherlands)

Ausems, M. G.; Bhola, S. L.; Post-Blok, C. A.; Hennekam, R. C.; de France, H. F.

1994-01-01

A mentally retarded boy was found to have an unusual chromosomal mosaicism [46,XY, del(18) (q22)/46,XY,iso psu dic(18)(q23)]. The clinical manifestations are compatible with the 18q- syndrome. The chromosome alteration was defined by high resolution banding and fluorescence in situ hybridization

Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene

DEFF Research Database (Denmark)

Avila, Magali; Kirchhoff, Eva Maria; Marle, Nathalie

2013-01-01

We report on three males with de novo overlapping 7.5, 9.8, and 10 Mb duplication of chromosome 20q11.2. Together with another patient previously published in the literature with overlapping 20q11 microduplication, we show that such patients display common clinical features including metopic ridg...

EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome.

Science.gov (United States)

Li, Chuan; Chen, Rongyu; Fan, Xin; Luo, Jingsi; Qian, Jiale; Wang, Jin; Xie, Bobo; Shen, Yiping; Chen, Shaoke

2015-04-11

Waardenburg syndrome type I (WS1), an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1. We reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature (83.5 cm (-5.8SD)). His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 (IGF-1) was 52.7 ng/ml, lower than the normal range (55 ~ 452 ng/ml) and the peak growth hormone level was 7.57 ng/ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone (rhGH) replacement therapy, showing a 9.2 cm/year growth rate and an improvement of 1 standard deviation (SD) of height after one year treatment. CMA test of patient's DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 (hg19; chr2:221,234,146-225,697,363). PAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.

Molecular Mechanisms and Diagnosis of Chromosome 22q11.2 Rearrangements

Science.gov (United States)

Emanuel, Beverly S.

2008-01-01

Several recurrent, constitutional genomic disorders are present on chromosome 22q. These include the translocations and deletions associated with DiGeorge and velocardiofacial syndrome and the translocations that give rise to the recurrent t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement breakpoints on 22q cluster…

Clinical, Molecular, and Prognostic Significance of WHO Type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and Various Other 3q Abnormalities in Acute Myeloid Leukemia

NARCIS (Netherlands)

Lugthart, Sanne; Groschel, Stefan; Beverloo, H. Berna; Kayser, Sabine; Valk, Peter J. M.; van Zelderen-Bhola, Shama Lydia; Ossenkoppele, Gert Jan; Vellenga, Edo; van den Berg-de Ruiter, Eva; Schanz, Urs; Verhoef, Gregor; Vandenberghe, Peter; Ferrant, Augustin; Kohne, Claus-Henning; Pfreundschuh, Michael; Horst, Heinz A.; Koller, Elisabeth; von Lilienfeld-Toal, Marie; Bentz, Martin; Ganser, Arnold; Schlegelberger, Brigitte; Jotterand, Martine; Krauter, Jurgen; Pabst, Thomas; Theobald, Matthias; Schlenk, Richard F.; Delwel, Ruud; Dohner, Konstanze; Lowenberg, Bob; Doehner, Hartmut

2010-01-01

Purpose Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) inv(3)/t(3; 3)] is recognized as a distinctive entity in the WHO classification. Risk assignment and clinical and genetic characterization of AML with chromosome 3q abnormalities other than inv(3)/t(3; 3) remain largely

Partial monosomy 8q and partial trisomy 9q due to the maternal translocation t(8;9(q24.3;q34.1)

DEFF Research Database (Denmark)

Tos, T; Alp, M Y; Eker, H K

2014-01-01

Partial trisomy 9q34-qter and partial monosomy 8q24.3-qter are very rare chromosomal abnormalities. Characteristic features of partial trisomy 9q34-qter are hypotonia, developmental delay, mild intellectual disability, dolichocephaly, distinct facial phenotype, long and thin fingers, and cardiac...

Mandatory chromosomal segment balance in aneuploid tumor cells

International Nuclear Information System (INIS)

Kost-Alimova, Maria; Stanbridge, Eric; Klein, George; Imreh, Stefan; Darai-Ramqvist, Eva; Yau, Wing Lung; Sandlund, Agneta; Fedorova, Ludmila; Yang, Ying; Kholodnyuk, Irina; Cheng, Yue; Li Lung, Maria

2007-01-01

Euploid chromosome balance is vitally important for normal development, but is profoundly changed in many tumors. Is each tumor dependent on its own structurally and numerically changed chromosome complement that has evolved during its development and progression? We have previously shown that normal chromosome 3 transfer into the KH39 renal cell carcinoma line and into the Hone1 nasopharyngeal carcinoma line inhibited their tumorigenicity. The aim of the present study was to distinguish between a qualitative and a quantitative model of this suppression. According to the former, a damaged or deleted tumor suppressor gene would be restored by the transfer of a normal chromosome. If so, suppression would be released only when the corresponding sequences of the exogenous normal chromosome are lost or inactivated. According to the alternative quantitative model, the tumor cell would not tolerate an increased dosage of the relevant gene or segment. If so, either a normal cell derived, or, a tumor derived endogenous segment could be lost. Fluorescence in Situ Hybridization based methods, as well as analysis of polymorphic microsatellite markers were used to follow chromosome 3 constitution changes in monochromosomal hybrids. In both tumor lines with introduced supernumerary chromosomes 3, the copy number of 3p21 or the entire 3p tended to fall back to the original level during both in vitro and in vivo growth. An exogenous, normal cell derived, or an endogenous, tumor derived, chromosome segment was lost with similar probability. Identification of the lost versus retained segments showed that the intolerance for increased copy number was particularly strong for 3p14-p21, and weaker for other 3p regions. Gains in copy number were, on the other hand, well tolerated in the long arm and particularly the 3q26-q27 region. The inability of the cell to tolerate an experimentally imposed gain in 3p14-p21 in contrast to the well tolerated gain in 3q26-q27 is consistent with the

Extra skeletal Soft Tissue Ewing?s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

OpenAIRE

Nagaraj, Prashanth; H, Srinivas C; Rao, Raghavendra; Manohar, Sandesh

2013-01-01

Introduction: Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population .lt is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21 ;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have ...

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

Science.gov (United States)

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

2016-01-01

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

Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review.

Science.gov (United States)

Hemmat, Morteza; Hemmat, Omid; Anguiano, Arturo; Boyar, Fatih Z; El Naggar, Mohammed; Wang, Jia-Chi; Wang, Borris T; Sahoo, Trilochan; Owen, Renius; Haddadin, Mary

2013-05-02

Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.

Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 or r(8(::p12→q13.1:: associated with phenotypic abnormalities

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Chih-Ping Chen

2016-12-01

Conclusion: Mosaic sSMC(8 derived from r(8(::p12→q13.1:: can present phenotypic abnormalities. Chromosome 8q12 duplication syndrome should be included in differential diagnosis when an sSMC(8 contains 8q12.2 and CHD7.

Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements

NARCIS (Netherlands)

Demaerel, Wolfram; Hestand, Matthew S.; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A.; McDonald-Mcginn, Donna M.; Zackai, Elaine; Emanuel, Beverly S.; Morrow, Bernice E.; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R.; Antshel, Kevin M.; Arango, Celso; Armando, Marco; Bassett, Anne S.; Bearden, Carrie E.; Boot, Erik; Bravo-Sanchez, Marta; Breetvelt, Elemi; Busa, Tiffany; Butcher, Nancy J.; Campbell, Linda E.; Carmel, Miri; Chow, Eva W C; Crowley, T. Blaine; Cubells, Joseph; Cutler, David; Demaerel, Wolfram; Digilio, Maria Cristina; Duijff, Sasja; Eliez, Stephan; Emanuel, Beverly S.; Epstein, Michael P.; Evers, Rens; Fernandez Garcia-Moya, Luis; Fiksinski, Ania; Fraguas, David; Fremont, Wanda; Fritsch, Rosemarie; Garcia-Minaur, Sixto; Golden, Aaron; Gothelf, Doron; Guo, Tingwei; Gur, Ruben C.; Gur, Raquel E.; Heine-Suner, Damian; Hestand, Matthew; Hooper, Stephen R.; Kates, Wendy R.; Kushan, Leila; Laorden-Nieto, Alejandra; Maeder, Johanna; Marino, Bruno; Marshall, Christian R.; McCabe, Kathryn; McDonald-Mcginn, Donna M.; Michaelovosky, Elena; Morrow, Bernice E.; Moss, Edward; Mulle, Jennifer; Murphy, Declan; Murphy, Kieran C.; Murphy, Clodagh M.; Niarchou, Maria; Ornstein, Claudia; Owen, Michael J; Philip, Nicole; Repetto, Gabriela M.; Schneider, Maude; Shashi, Vandana; Simon, Tony J.; Swillen, Ann; Tassone, Flora; Unolt, Marta; Van Amelsvoort, Therese; van den Bree, Marianne B M; Van Duin, Esther; Vergaelen, Elfi; Vermeesch, Joris R.; Vicari, Stefano; Vingerhoets, Claudia; Vorstman, Jacob; Warren, Steve; Weinberger, Ronnie; Weisman, Omri; Weizman, Abraham; Zackai, Elaine; Zhang, Zhengdong; Zwick, Michael

2017-01-01

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have

Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

Science.gov (United States)

Cascella, Marco; Muzio, Maria Rosaria

2015-01-01

Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome

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Tomaiuolo Anna

2011-04-01

Full Text Available Abstract Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis. Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms. Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.

Cryptorchidism due to chromosome 5q inversion duplication.

Science.gov (United States)

Dutta, M K; Gundgurthi, A; Garg, M K; Pakhetr, R

2013-12-01

We present a 15 year old boy who was born out of a non consanguineous marriage, and presented with bilateral cryptorchidism, mental retardation, facial dysmorphism, hypergonadotrophic hypogonadism with failure of anatomical and biochemical localisation of testes. Karyotype analysis showed 46 XY with inverted duplication on chromosome 5q22-31.

The first peopling of South America: new evidence from Y-chromosome haplogroup Q.

Science.gov (United States)

Battaglia, Vincenza; Grugni, Viola; Perego, Ugo Alessandro; Angerhofer, Norman; Gomez-Palmieri, J Edgar; Woodward, Scott Ray; Achilli, Alessandro; Myres, Natalie; Torroni, Antonio; Semino, Ornella

2013-01-01

Recent progress in the phylogenetic resolution of the Y-chromosome phylogeny permits the male demographic dynamics and migratory events that occurred in Central and Southern America after the initial human spread into the Americas to be investigated at the regional level. To delve further into this issue, we examined more than 400 Native American Y chromosomes (collected in the region ranging from Mexico to South America) belonging to haplogroup Q - virtually the only branch of the Y phylogeny observed in modern-day Amerindians of Central and South America - together with 27 from Mongolia and Kamchatka. Two main founding lineages, Q1a3a1a-M3 and Q1a3a1-L54(xM3), were detected along with novel sub-clades of younger age and more restricted geographic distributions. The first was also observed in Far East Asia while no Q1a3a1-L54(xM3) Y chromosome was found in Asia except the southern Siberian-specific sub-clade Q1a3a1c-L330. Our data not only confirm a southern Siberian origin of ancestral populations that gave rise to Paleo-Indians and the differentiation of both Native American Q founding lineages in Beringia, but support their concomitant arrival in Mesoamerica, where Mexico acted as recipient for the first wave of migration, followed by a rapid southward migration, along the Pacific coast, into the Andean region. Although Q1a3a1a-M3 and Q1a3a1-L54(xM3) display overlapping general distributions, they show different patterns of evolution in the Mexican plateau and the Andean area, which can be explained by local differentiations due to demographic events triggered by the introduction of agriculture and associated with the flourishing of the Great Empires.

Phenotype and 244k array-CGH characterization of chromosome 13q deletions: an update of the phenotypic map of 13q21.1-qter

DEFF Research Database (Denmark)

Kirchhoff, Maria; Bisgaard, Anne-Marie; Stoeva, Radka

2009-01-01

Partial deletions of the long arm of chromosome 13 lead to variable phenotypes dependant on the size and position of the deleted region. In order to update the phenotypic map of chromosome 13q21.1-qter deletions, we applied 244k Agilent oligonucleotide-based array-CGH to determine the exact break......-genotype correlation on chromosome 13. In contrast to previous reports of carriers of 13q32 band deletions as the most seriously affected patients, we present two such individuals with long-term survival, 28 and 2.5 years....

The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations

DEFF Research Database (Denmark)

Paulsson, Kajsa; Haferlach, Claudia; Fonatsch, Christa

2010-01-01

Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns......, respectively. In total, TET2 mutations were seen in 4/11 (36%) analyzed cases, thus constituting a common secondary event in idic(X)-positive malignancies....

A Pst I polymorphism in the human laminin B2 chain gene on 1q25-q31

Energy Technology Data Exchange (ETDEWEB)

Kallunki, T; Pikkarainen, T; Tryggvason, K; Savolainen, E R [Univ. of Oulu (Finland)

1989-06-12

pHL-210 is a 2.7 kb cDNA insert in pBR322 that codes for the central position of the 7.5 kb mRNA. A Pst I polymorphism was identified with pHL-210. The allele frequency was studied in 40 chromosomes of unrelated Finnish individuals. The probe was localized to chromosome 1q25-q31 by somatic cell and in situ hybridization. Co-dominant inheritance was shown in three families.

Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

Science.gov (United States)

Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

2014-01-01

Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

International Nuclear Information System (INIS)

Ostlund, Cecilia; Guan, Tinglu; Figlewicz, Denise A.; Hays, Arthur P.; Worman, Howard J.; Gerace, Larry; Schirmer, Eric C.

2009-01-01

Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients with FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately re-activated it could affect muscle differentiation and contribute to disease pathology.

Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

Energy Technology Data Exchange (ETDEWEB)

Ostlund, Cecilia [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Guan, Tinglu [Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Figlewicz, Denise A. [Department of Neurology, University of Michigan, Ann Arbor, MI 48109 (United States); Hays, Arthur P. [Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Worman, Howard J. [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Gerace, Larry [Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Schirmer, Eric C., E-mail: e.schirmer@ed.ac.uk [Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037 (United States); Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR (United Kingdom)

2009-11-13

Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients with FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately re-activated it could affect muscle differentiation and contribute to disease pathology.

Increasing of the ST segment in the derivations with Q wave in the early effort test after acute myocardial infarction

International Nuclear Information System (INIS)

Sanfins, V.M.; Machado, I.; Sousa, F.; Quelhas, I.; Fernandes, J.; Reis, F.; Lourenco, A.; Goncalo, L.; Correia, L.; Amorim, I.; Pereira, A.; Almeida, J. de

1997-01-01

Full text: : The objective of this work is to evaluate the raising of the ST segment in the Q wave derivations in the precocious effort test (ET) after acute myocardial infarction (AMI) in patients with AMI of the anterior wall, submitted to thrombolysis. It is a prospective study involving 36 patients (P) with AMI of the anterior wall, consecutively interned in the Coronary Unit and submitted to thrombolysis, between June 1995 to June 1996. All the patients realized ET, according Bruce protocol and isotopic study with Thallium 201, with reinjection until 24 h, both without anti-ischemic therapy. The additional raising of ST greater or equal to 1mm, in two or more consecutive Q wave derivations was considered as positivity criterion in the ET. The quantification of the ischemia and/or viability in Thallium-201 was made through analysis of the tomographic images and the bull's eye, using the habitual criterion of positivity. The obtained results were compared and the sensibility, the specificity, the acuity and the positive and negative predictive values of the ST segment raising were evaluated, in the identification of the ischemia and/or viability detected in the isotopic study. The average age was of 53,4 years old (36-73), 29 (80,5%) were male. From the 21 (58,3%) of the patients who had ischemia and/or viability in Thallium-201, 18 (86%) presented alterations in the ST segment in ET. 24 (66,7%) of the patients who presented alterations in the ST segment in ET, 18 (75%) had also ischemia and/or viability in Thallium-201. Relatively to Thallium-201, the sensibility, specificity, acuity and positive and negative predictive values of the ST segment raising in the Q wave derivations in ET were, respectively of 86%, 60%, 75%, 75% and 75%. The ST segment raising in the Q wave derivations were positively correlated with the existence of ischemia and/or viability in the infarction area. However, it is necessary to continue the study and increase the sample size to

A first case of primary amenorrhea with i(X(qter---q10::---qter, rob(13;14(q10;q10, inv(9(p13q33 karyotype

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Seema Korgaonkar

2011-01-01

Full Text Available Primary amenorrhea (PA refers to the absence of menarche by the age of 16-18 years although secondary sexual characters are developed. PA occurs in 1-3% of women in the reproductive age group. Various factors such as anatomical, genetic and hormonal factors reported to influence PA. We report triple chromosomal abnormalities of rob(13;14(q10;q10,inv(9(p13q33, i(Xq(qter---q10::---qter in a case of PA and short stature. Though proband has multiple chromosome aberrations, genotypic effect of only i(Xq is evident as proband has PA and short stature. The rob(13;14 and inv(9, which are paternally derived may have role in later reproductive age. Therefore, chromosomal analysis is essential in such cases for the accurate diagnosis and management of the disease.

Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

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Courtney M. Anderson

2015-02-01

Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects.

Science.gov (United States)

Lv, Wei; Wang, Shuyu

2014-11-01

Chromosomal abnormalities and the 22q11 microdeletion are implicated in congenital heart defects (CHDs). This study was designed to detect these abnormalities in fetuses and determine the effect of genetic factors on CHD etiology. Between January 2010 and December 2011, 113 fetuses with CHD treated at the Beijing Obstetrics and Gynecology Hospital were investigated, using chromosome karyotyping of either amniotic fluid cell or umbilical cord blood cell samples. Fetuses with a normal result were then investigated for the 22q11 microdeletion by fluorescence in situ hybridization. Of the 113 patients, 12 (10.6%) exhibited chromosomal abnormalities, while 6 (5.3%) of the remaining 101 cases presented with a 22q11 microdeletion. The incidence of chromosomal abnormalities was significantly higher in the group of fetuses presenting with extracardiac malformations in addition to CHD (Pheart defects should also be considered for 22q11 microdeletion detection to evaluate fetal prognosis, particularly prior to surgery.

The Escherichia coli COG1738 Member YhhQ Is Involved in 7-Cyanodeazaguanine (preQ0 Transport

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Rémi Zallot

2017-02-01

Full Text Available Queuosine (Q is a complex modification of the wobble base in tRNAs with GUN anticodons. The full Q biosynthesis pathway has been elucidated in Escherichia coli. FolE, QueD, QueE and QueC are involved in the conversion of guanosine triphosphate (GTP to 7-cyano-7-deazaguanine (preQ0, an intermediate of increasing interest for its central role in tRNA and DNA modification and secondary metabolism. QueF then reduces preQ0 to 7-aminomethyl-7-deazaguanine (preQ1. PreQ1 is inserted into tRNAs by tRNA guanine(34 transglycosylase (TGT. The inserted base preQ1 is finally matured to Q by two additional steps involving QueA and QueG or QueH. Most Eubacteria harbor the full set of Q synthesis genes and are predicted to synthesize Q de novo. However, some bacteria only encode enzymes involved in the second half of the pathway downstream of preQ0 synthesis, including the signature enzyme TGT. Different patterns of distribution of the queF, tgt, queA and queG or queH genes are observed, suggesting preQ0, preQ1 or even the queuine base being salvaged in specific organisms. Such salvage pathways require the existence of specific 7-deazapurine transporters that have yet to be identified. The COG1738 family was identified as a candidate for a missing preQ0/preQ1 transporter in prokaryotes, by comparative genomics analyses. The existence of Q precursor salvage was confirmed for the first time in bacteria, in vivo, through an indirect assay. The involvement of the COG1738 in salvage of a Q precursor was experimentally validated in Escherichia coli, where it was shown that the COG1738 family member YhhQ is essential for preQ0 transport.

Translocation t(11;14 (q13;q32 and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study

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Ivyna Bong Pau Ni

2012-09-01

Full Text Available More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR-based translocation detection assay to detect BCL1/JH t(11;14 (q13;q32 in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14 (q13;q32 translocation (n=15 of 105. We found no significant correlation between this translocation with age (P=0.420, gender (P=0.317, ethnicity (P=0.066 or new/relapsed status of multiple myeloma (P=0.412 at 95% confidence interval level by x2 test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14(q13;q32 translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14 (q13;q32 translocation.

A novel 5p15.33-14.1 deletion and 4q34.24-35.2 duplication in a ...

Indian Academy of Sciences (India)

Both are normal in phenotype and intelligence. His mother ... Bacterial artificial chromosome (BAC) clone RP11-159A22. (4q35.1) was ... However, we can not exclude the impacts ... researchers of State Key Laboratory of Medical Genetics.

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.

Nonmosaic tetrasomy 15q25.2 → qter identified with SNP microarray in a patient with characteristic facial appearance and review of the literature.

Science.gov (United States)

Xu, Huihui; Xiao, Bing; Ji, Xing; Hu, Qin; Chen, Yingwei; Qiu, Wenjuan

2014-07-01

Tetrasomy for the distal chromosome 15q is rare, and only 22 patients (including 6 cases without detailed information) have been described to date in the literature. Here we report on another patient with nonmosaic tetrasomy 15q25.2-qter resulted from an inverted duplication of distal chromosome 15. This patient presents with features of development delay, arachnodactyly, joint contractures and typical facial dysmorphism including frontal bossing, short palpebral fissures, long philtrum, low-set ears, high-arched palate and retrognathia. Unlike most of the related patients, abdominal ultrasound test and brain MRI showed normal. Karyotyping analysis revealed a supernumerary marker chromosome presented in all metaphase cells examined. Parental karyotyping analysis was normal, indicating a de novo chromosome aberration of the patient. SNP microarray analysis found a two copy gain of 17.7 Mb from the distal long arm of chromosome 15 (15q25.2-qter). Further FISH analysis using SureFISH 15q26.3 IGF1R probe proved an inverted duplication of distal long arm of chromosome 15. The segmental duplications which lie in the hotspots of 15q24-26 might increase the susceptibility of chromosome rearrangement. Compared with the George-Abraham' study [2012], ADAMTSL3 might be more related to the cardiac disorders in tetrasomy 15q patients. Considering all patients reported in the literature, different mosaic degrees and segmental sizes don't correlate to the severity of phenotypes. A clear delineation on tetrasomy for distal chromosome 15q could still be investigated. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pericentric inversion of chromosome 18 in parents leading to a phenotypically normal child with segmental uniparental disomy 18.

Science.gov (United States)

Kariminejad, Ariana; Kariminejad, Roxana; Moshtagh, Azadeh; Zanganeh, Maryam; Kariminejad, Mohammad Hassan; Neuenschwander, Stefan; Okoniewski, Michal; Wey, Eva; Schinzel, Albert; Baumer, Alessandra

2011-05-01

In this study, we report a familial inversion of chromosome 18, inv(18)(p11.31q21.33), in both members of a consanguineous couple. Their first child had inherited one balanced pericentric inversion along with a recombinant chromosome 18 resulting in dup(18q)/del(18p), and had mild dysmorphic features in the absence of mental and developmental retardation. The second child had received two recombinant chromosomes 18, from the mother a derivative chromosome 18 with dup(18p)/del(18q) and from the father a derivative chromosome 18 with dup(18q)/del(18p). The aberration was prenatally detected; however, as the two opposite aneuploidies were thought to compensate each other, the family decided to carry on with the pregnancy, knowing that uniparental disomy for the segments outside the inversion could have an adverse influence on the development of the child. Uniparental disomy was confirmed by SNP arrays. The child, who has been followed up until the age of 20 months, is healthy and normal. It seems to be the first reported case with two opposite recombinant chromosomes that compensate each other and lead to segmental uniparental disomy for two segments on the chromosome, one maternal and the other paternal.

Structure of the human gene encoding the associated microfibrillar protein (MFAP1) and localization to chromosome 15q15-q21

Energy Technology Data Exchange (ETDEWEB)

Yeh, H.; Chow, M.; Abrams, W.R. [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

1994-09-15

Microfibrils with a diameter of 10-12 nm, found either in assocation with elastin or independently, are an important component of the extracellular matrix of many tissues. To extend understanding of the proteins composing these microfibrils, the cDNA and gene encoding the human associated microfibril protein (MRAP1) have been cloned and characterized. The coding portion is contained in 9 exons, and the sequence is very homologous to the previously described chick cDNA, but does not appear to share homology or domain motifs with any other known protein. Interestingly, the gene has been localized to chromosome 15q15-q21 by somatic hybrid cell and chromosome in situ analyses. This is the same chromosomal region to which the fibrillin gene, FBN1, known to be defective in the Marfan syndrome, has been mapped. MFAP1 is a candidate gene for heritable diseases affecting microfibrils. 38 refs., 6 figs.

Chromosome 22q11 in a Xhosa schizophrenia population | Koen ...

African Journals Online (AJOL)

Chromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African ...

Genetics Home Reference: distal 18q deletion syndrome

Science.gov (United States)

... 18q deletion syndrome chromosome 18q monosomy chromosome 18q- syndrome De Grouchy syndrome del(18q) syndrome monosomy 18q Related Information How ... MS, Tienari PJ, Wirtavuori KO, Valanne LK. 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on ... RL, Hale DE, Rose SR, Leach RJ, Cody JD. The spectrum ...

Williams Syndrome and 15q Duplication: Coincidence versus Association.

Science.gov (United States)

Khokhar, Aditi; Agarwal, Swashti; Perez-Colon, Sheila

2017-01-01

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN -specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

Trisomy 1q42-qter associated with monosomy 6q27-qter: a case report.

Science.gov (United States)

Tartaglia, Edoardo; Mastrantonio, Pasquale; Costa, Davide; Giugliano, Brunella; Porcellini, Antonio; Costagliola, Ciro

2011-01-01

Partial trisomy 1q42-qter is a rare chromosomal aberration. Most cases arise from de novo unbalanced translocations or from unbalanced inheritance of parental balanced rearrangements. Descriptive case report. A 4-year-old boy had shown an increased neck translucency at the fetal ultrasound examination performed at the 11th week of gestation. Amniocentesis, performed at the 18th week of gestation, did not demonstrate any genetic abnormality. A second fetal ultrasound examination, carried out at the 35th week of gestation, showed congenital clubfeet and hydrocephalus. At birth, clinical examination revealed congenital bilateral ventriculomegaly, bilateral congenital equinovarus clubfeet, low-set ears, plagiocephaly, micrognathia, hypertelorism, prominent forehead, broad nasal bridge, hypertonic syndrome, and inguinal hernia. Ophthalmologic consultation showed the presence of optic pit in his left eye. Genetic counseling was performed. Chromosome analysis demonstrated a partial trisomy 1q42.2-qter associated with a partial monosomy 6q27-qter. Moreover, deletions of the distal region on the long arm of chromosome 6 are frequently associated with both ocular abnormalities and several solid tumor types. Moderate mental and psychomotor retardation has occurred. This case emphasizes the importance of scheduling a screening test for eye diseases and tumor in these patients.

Simultaneous occurrence of t(9;22)(q34;q11.2) and t(16;16)(p13;q22) in a patient with chronic myeloid leukemia in blastic phase.

Science.gov (United States)

Zámecníkova, Adriana; Al Bahar, Soad; Ramesh, Pandita

2008-06-01

Coexistence of two specific chromosomal translocations in the same clone is an infrequent phenomenon and has only rarely been reported in hematological malignancies. We report a combination of t(16;16)(p13;q22), the Philadelphia translocation t(9;22)(q34;q11.2), and deletion of the long arm of chromosome 7 in a patient with chronic myeloid leukemia in blast phase. Monotherapy treatment with imatinib mesylate resulted in the disappearance of the Ph-positive clone, but with persistence of t(16;16) and del(7) in all of the metaphases examined. The case illustrates that, although imatinib mesylate can be an effective treatment in eradication of the BCR-ABL fusion gene cells, the occurrence of additional specific abnormalities in Philadelphia-positive leukemias may pose a significant therapeutic challenge. (c) 2008 Elsevier Inc.

Loss of 11q and 16q in Wilms tumors is associated with anaplasia, tumor recurrence, and poor prognosis.

Science.gov (United States)

Wittmann, Stefanie; Zirn, Birgit; Alkassar, Muhannad; Ambros, Peter; Graf, Norbert; Gessler, Manfred

2007-02-01

Allele loss of chromosome arms 11q and 16q in Wilms tumors has been associated with different clinical parameters in prior studies. To substantiate these findings in a large collection of tumors treated according to the GPOH/SIOP protocol and to narrow down critical regions, we performed loss of heterozygosity (LOH) analyses of chromosome arms 11q and 16q on 225 Wilms tumors. On chromosome arm 11q an overall rate of allele loss of 19.6% (44 of 225 tumors) was found using eleven markers that were almost evenly distributed along the long arm. Chromosome arm 16q was analyzed with six markers selected from gene-rich regions that identified an LOH rate of 18.4% (41/223). Evaluation of LOH with respect to clinical data revealed significant associations of LOH 11q with histology: LOH 11q was 3-4 times more frequent in mixed type and diffuse anaplastic tumors. In contrast, epithelial as well as stromal type tumors never exhibited allele loss on 11q. Furthermore, a significant correlation with tumor recurrence and death was detected, but only for tumors that lost the entire long arm of chromosome 11. Similarly, LOH 16q was correlated with higher risks of later relapse, especially in tumors with complete loss of the long arm. Hence, analyses of LOH on 11q and 16q appear to be helpful to identify tumors with a higher risk of relapse and adverse outcome, which need adjusted therapeutic approaches. Copyright 2006 Wiley-Liss, Inc.

A cross-sectional analysis of the development of response inhibition in children with Chromosome 22q11.2 Deletion Syndrome

Directory of Open Access Journals (Sweden)

Heather M Shapiro

2013-08-01

Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is a neurogenetic disorder that is associated with cognitive impairments and significantly elevated risk for developing schizophrenia. While impairments in response inhibition are central to executive dysfunction in schizophrenia, the nature and development of such impairments in children with 22q11.2DS, a group at high risk for the disorder, are not clear. Here we used a classic Go/No-Go paradigm to quantify proactive (anticipatory stopping and reactive (actual stopping response inhibition in 47 children with 22q11.2DS and 36 typically developing (TD children, all ages 7-14. A cross-sectional design was used to examine age-related associations with response inhibition. When compared with TD individuals, children with 22q11.2DS demonstrated typical proactive response inhibition at all ages. By contrast, reactive response inhibition was impaired in children with 22q11.2DS relative to TD children. While older age predicted better reactive response inhibition in TD children, there was no age-related association with reactive response inhibition in children with 22q11.2DS. Closer examination of individual performance data revealed a wide range of performance abilities in older children with 22q11.2DS; some typical and others highly impaired. The results of this cross-sectional analysis suggest an impaired developmental trajectory of reactive response inhibition in some children with 22q11.2DS that might be related to atypical development of neuroanatomical systems underlying this cognitive process. As part of a larger study, this investigation might help identify risk factors for conversion to schizophrenia and lead to early diagnosis and preventive intervention.

Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9;14)(p21-22;q11) in an acute lymphoblastic leukemia of B-cell type.

Science.gov (United States)

Duro, D; Bernard, O; Della Valle, V; Leblanc, T; Berger, R; Larsen, C J

1996-02-15

We have reported previously a preliminary study of a t(9;14)(p21-22; q11) in B-cell acute lymphoblastic leukemia. This translocation had rearranged the TCRA/D locus on chromosome band 14q11 and the locus encoding the tumor suppressor gene P16INK4/MTS1 (P16) on band 9p21 (D. Duro et al., Oncogene, 11: 21-29, 1995). In the present report, the breakpoints were precisely localized on each chromosome partner. On the 14q- derivative, the sequence derived from chromosome 9 was interrupted at 1.0 kb upstream of the first exon of P16, close to a consensus recombination heptamer, CACTGTG. In addition, the chromosome 14 breakpoint was localized at the end of the TCRD2 (delta 2) segment, and 22 residues with unknown origin were present at the translocation junction. On the 9p+ derivative, chromosome 9 sequences were in continuity with those displaced onto chromosome 14, and the 14q11 breakpoint was located within TCRJA29 segment. These features are consistent with aberrant activity of the TCR gene recombinase complex. Although all three coding exons of P16 were displaced onto the chromosome 14q-derivative, no P16 transcript was detected in the leukemic cells. Because the region spanning the P16 exon 1 was not inactivated by methylation and because the other P16 allele was deleted, the implication is that the chromosome breakpoint was likely to disrupt regulatory elements involved in the normal expression of the gene. As a whole, then, our results show that translocations affecting band 9p21 can participate to the inactivation of P16, thus justifying a systematic survey of translocations of the 9p21 band in acute lymphoblastic leukemia.

Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

LENUS (Irish Health Repository)

Kelly, Kevin

2008-12-01

Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

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

Energy Technology Data Exchange (ETDEWEB)

Murray, J.D.; Bulman, D.E.; Ebers, G.C. [University Hospital, London (Canada)]|[INSERM, Paris (France)] [and others

1994-09-01

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

DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3.

Science.gov (United States)

Khan, Shahid Yar; Riazuddin, Saima; Shahzad, Mohsin; Ahmed, Nazir; Zafar, Ahmad Usman; Rehman, Atteeq Ur; Morell, Robert J; Griffith, Andrew J; Ahmed, Zubair M; Riazuddin, Sheikh; Friedman, Thomas B

2010-01-01

Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at theta=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23-q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602.

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

OpenAIRE

Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Shen, Joseph; Li, Chumei; Roeder, Elizabeth; Cox, Sarah; Karaviti, Lefkothea; Pearson, Margret; Kang, Sung-Hae L; Sahoo, Trilochan; Lalani, Seema R; Stankiewicz, Pawel; Sutton, V Reid; Cheung, Sau Wai

2009-01-01

Deletions in chromosome 17q12 encompassing the HNF1β gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with a...

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12.

Science.gov (United States)

Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Shen, Joseph; Li, Chumei; Roeder, Elizabeth; Cox, Sarah; Karaviti, Lefkothea; Pearson, Margret; Kang, Sung-Hae L; Sahoo, Trilochan; Lalani, Seema R; Stankiewicz, Pawel; Sutton, V Reid; Cheung, Sau Wai

2010-03-01

Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.

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.

Array based characterization of a terminal deletion involving chromosome subband 15q26.2: an emerging syndrome associated with growth retardation, cardiac defects and developmental delay

Directory of Open Access Journals (Sweden)

Björkhem Gudrun

2008-01-01

Full Text Available Abstract Background Subtelomeric regions are gene rich and deletions in these chromosomal segments have been demonstrated to account for approximately 2.5% of patients displaying mental retardation with or without association of dysmorphic features. However, cases that report de novo terminal deletions on chromosome arm 15q are rare. Methods In this study we present the first example of a detailed molecular genetic mapping of a de novo deletion in involving 15q26.2-qter, caused by the formation of a dicentric chromosome 15, using metaphase FISH and tiling resolution (32 k genome-wide array-based comparative genomic hybridization (CGH. Results After an initial characterization of the dicentric chromosome by metaphase FISH, array CGH analysis mapped the terminal deletion to encompass a 6.48 megabase (Mb region, ranging from 93.86–100.34 Mb on chromosome 15. Conclusion In conclusion, we present an additional case to the growing family of reported cases with 15q26-deletion, thoroughly characterized at the molecular cytogenetic level. In the deleted regions, four candidate genes responsible for the phenotype of the patient could be delineated: IGFR1, MEF2A, CHSY1, and TM2D3. Further characterization of additional patients harboring similar 15q-aberrations might hopefully in the future lead to the description of a clear cut clinically recognizable syndrome.

Two girls with a de novo Xq rearrangement of paternal origin: t(X;9(q24;q12 or rea(Xdup q

Directory of Open Access Journals (Sweden)

Ana I. Vásquez-Velásquez

2016-04-01

Full Text Available Objective: We report on two rare Xq rearrangements, namely a t(X;9(q24;q12 found in a mildly-affected girl (Patient 1 and a rea(Xdup q concomitant with a rob(14;21mat in a Down syndrome girl (Patient 2. Case report: Both rearrangements were characterized by banding techniques [Giemsa (G, constitutive heterochromatin (C, and bromodeoxyuridine (BrdU pulse], fluorescence in situ hybridization (FISH assays, human androgen receptor (HUMAR assays, and microarray analyses. Patient 1 had a t(X;9(q24;q12dn. Patient 2 had a de novo rea(X(qter→q23 or q24::p11.2→qter concomitant with an unbalanced rob(14;21mat. X-Inactivation studies in metaphases and DNA revealed a fully skewed inactivation: the normal homolog was silenced in Patient 1 and the rea(X in Patient 2. Both rearranged X chromosomes were of paternal descent. Microarray analyses revealed no imbalances in Patient 1 whereas loss of Xp (∼52 Mb and duplication of Xq (∼44 Mb and 21q were confirmed in Patient 2. Conclusion: Our observations further document the cytogenetic heterogeneity and predominant paternal origin of certain de novo X-chromosome rearrangements.

Open-flavor charm and bottom s q q ¯ Q ¯ and q q q ¯ Q ¯ tetraquark states

Science.gov (United States)

Chen, Wei; Chen, Hua-Xing; Liu, Xiang; Steele, T. G.; Zhu, Shi-Lin

2017-06-01

We provide comprehensive investigations for the mass spectrum of exotic open-flavor charmed/bottom s q q ¯ c ¯ , q q q ¯ c ¯ , s q q ¯ b ¯ , q q q ¯ b ¯ tetraquark states with various spin-parity assignments JP=0+,1+,2+ and 0- , 1- in the framework of QCD sum rules. In the diquark configuration, we construct the diquark-antidiquark interpolating tetraquark currents using the color-antisymmetric scalar and axial-vector diquark fields. The stable mass sum rules are established in reasonable parameter working ranges, which are used to give reliable mass predictions for these tetraquark states. We obtain the mass spectra for the open-flavor charmed/bottom s q q ¯c ¯, q q q ¯c ¯, s q q ¯b ¯, q q q ¯b ¯ tetraquark states with various spin-parity quantum numbers. In addition, we suggest searching for exotic doubly-charged tetraquarks, such as [s d ][u ¯ c ¯ ]→Ds(*)-π- in future experiments at facilities such as BESIII, BelleII, PANDA, LHCb, and CMS, etc.

Baseline Q waves as a prognostic modulator in patients with ST-segment elevation: insights from the PLATO trial.

Science.gov (United States)

Siha, Hany; Das, Debraj; Fu, Yuling; Zheng, Yinggan; Westerhout, Cynthia M; Storey, Robert F; James, Stefan; Wallentin, Lars; Armstrong, Paul W

2012-07-10

Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality. Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29-2.45, p waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10-2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09-2.28, p = 0.02). The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. Clinical Trials.gov registration no. NCT00391872.

AML with t(7;12)(q36;p13) is associated with infancy and trisomy 19. Data from NOPHO-AML and review of the literature

DEFF Research Database (Denmark)

Espersen, Anne Dorte Lerche; Noren-Nyström, Ulrika; Abrahamsson, Jonas

2018-01-01

The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children ...). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation...

Bizarre parosteal osteochondromatous proliferation: a new cytogenetic subgroup characterized by inversion of chromosome 7.

Science.gov (United States)

Broehm, Cory J; M'Lady, Gary; Bocklage, Thèrése; Wenceslao, Stella; Chafey, David

2013-11-01

Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare, benign osteocartilaginous lesion characterized by a mixture of immature bone, bland spindle cells, and irregular, hypercellular cartilage undergoing calcification. A t(1;17)(q32;q21) has been reported as a unique recurring translocation identified in seven cases. Inversion of chromosome 7, inv(7)(q22q32), has also recently been described in one case of BPOP. We report an additional case of inv(7) in a BPOP occurring on the distal radius in a 36-year-old woman who presented with a slow-growing mass on the right wrist. Metaphase karyotype analysis of fresh tissue from tumor taken at resection revealed an inv(7)(q22q32). A review of the literature identified two additional cases of inv(7) (q21.1q31.3 and q22.1q31.3), both paired with inv(6)(p25q15), bringing the total number of cases of inv(7) in BPOP to four. These data suggest inv(7) may be another characteristic cytogenetic abnormality associated with and possibly contributing to the development of BPOP. Copyright © 2013 Elsevier Inc. All rights reserved.

Gain of chromosomal region 20q and loss of 18 discriminates between Lynch syndrome and familial colorectal cancer

DEFF Research Database (Denmark)

Therkildsen, Christina; Jönsson, Göran; Dominguez-Valentin, Mev

2013-01-01

Lynch syndrome and familial colorectal cancer type X, FCCTX, represent the two predominant colorectal cancer syndromes. Whereas Lynch syndrome is clinically and genetically well defined, the genetic cause of FCCTX is unknown and genomic differences between Lynch syndrome and FCCTX tumours...... are largely unknown. We applied array-based comparative genomic hybridisation to 23 colorectal cancers from FCCTX with comparison to 23 Lynch syndrome tumours and to 45 sporadic colorectal cancers. FCCTX tumours showed genomic complexity with frequent gains on chromosomes 20q, 19 and 17 and losses of 18, 8p...... and 15. Gain of genetic material in two separate regions encompassing, 20q12-13.12 and 20q13.2-13.32, was identified in 65% of the FCCTX tumours. Gain of material on chromosome 20q and loss on chromosome 18 significantly discriminated colorectal cancers associated with FCCTX from Lynch syndrome, which...

Tetrasomy 15q11-q13 identified by fluorescence in situ hybridization in a patient with autistic disorder Identificação de tetrassomia 15q11-q13 por hibridação in situ fluorescente em uma paciente com distúrbio autístico

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Ana Elizabete Silva

2002-06-01

Full Text Available We report a female child with tetrasomy of the 15q11-q13 chromosomal region, and autistic disorder associated with mental retardation, developmental problems and behavioral disorders. Combining classical and molecular cytogenetic approaches by fluorescence in situ hybridization technique, the karyotype was demonstrated as 47,XX,+mar.ish der(15(D15Z1++,D15S11++,GABRB3++,PML-. Duplication of the 15q proximal segment represents the most consistent chromosomal abnormality reported in association with autism. The contribution of the GABA receptor subunit genes, and other genes mapped to this region, to the clinical symptoms of the disease is discussed.Relatamos uma criança do sexo feminino com tetrassomia da região cromossômica 15q11-q13 e distúrbio autístico associado com retardo mental, problemas de desenvolvimento e distúrbios comportamentais. A combinação de metodologias da citogenética clássica e molecular pela técnica de hibridação in situ fluorescente, demonstrou o cariótipo como 47,XX,+mar.ish der(15 (D15Z1++,D15S11++,GABRB3++,PML. Duplicação do segmento 15q proximal representa a mais consistente anomalia cromossômica relatada em associação com autismo. A contribuição dos genes das subunidades do recepetor GABA, assim como outros genes mapeados nessa região, para os sintomas clínicos da doença é discutida.

Chronic myeloid leukemia with variation of translocation at (Ph) [ins (22;9) (q11;q21q34)]: a case report.

Science.gov (United States)

Wang, Zhiqiong; Zen, Wen; Meng, Fankai; Xin, Xing; Luo, Li; Sun, Hanying; Zhou, Jianfeng; Huang, Lifang

2015-01-01

Chronic myeloid leukemia (CML) is most frequently observed in middle-aged individuals. In most patients, normal marrow cells are replaced by cells with an abnormal G-group chromosome, the Philadelphia (Ph) chromosome. The Ph chromosome that is characterized by the translocation (9;22) (q34;q11) is noted in 90-95% of patients diagnosed with CML. Studies have also shown that CML can be associated with various other cytogenetic abnormalities, with 5-10% of these cases showing complex translocation involving another chromosome in addition to the Ph chromosome. Here, we report the case of a Ph(+) CML patient with an inserted karyotype who presented clinically in the chronic phase but with atypical features. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review.

Science.gov (United States)

Lennon, P A; Cooper, M L; Peiffer, D A; Gunderson, K L; Patel, A; Peters, Sarika; Cheung, S W; Bacino, C A

2007-04-15

We report on a young male with moderate mental retardation, dysmorphic features, and language delay who is deleted for 7q31.1-7q31.31. His full karyotype is 46,XY,der(7)del(7)(q31.1q31.31)ins(10;7)(q24.3;q31.1q31.31)mat. This child had language impairment, including developmental verbal dyspraxia, but did not meet criteria for autism according to standardized ADOS testing. Our patient's deletion, which is the smallest reported deletion including FOXP2, adds to the body of evidence that supports the role of FOXP2 in speech and language impairment, but not in autism. A reported association between autism and deletions of WNT2, a gene also deleted in our patient, is likewise not supported by our case. Previously, fine mapping with microsatellites markers within in a large three-generation family, in which half the members had severe specific language impairment, aided the localization of the SPCH1 locus to 7q31 within markers D7S2459 (107.1 Mb) and D7S643 (120.5 Mb). Additionally, chromosome rearrangement of 7q31 and mutational analyses have supported the growing evidence that FOXP2, a gene within the SPCH1 region, is involved with speech and language development. It is unclear however whether the AUTS1 (autistic spectrum 1) locus, highly linked to 7q31, overlaps with the SPCH1 and FOXP2. Copyright 2007 Wiley-Liss, Inc.

Highly significant linkage to chromosome 3q13.31 for rhinitis and related allergic diseases

DEFF Research Database (Denmark)

Andersen, Charlotte Brasch; Haagerup, Annette; Børglum, Anders D.

2006-01-01

or all are still inconclusive. Following genome-wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus. OBJECTIVE: To identify candidate loci in the Danish population, two additional independent sets of sib-pair families were fine-scale mapped......BACKGROUND: Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra-individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many...... in candidate regions showing maximum likelihood scores (MLS) > or =1.5 in the genome-wide scans. RESULTS: Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib-pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage...

Duplicación 5q34q35.3 que involucra el gen NSD1: región delimitada por microarreglos de hibridación genómica comparativa. A propósito de un caso

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AR Vázquez del Campo

2016-09-01

Full Text Available La duplicación de la región 5q34q35.3 se ha asociado a un fenotipo inverso de síndrome de Sotos, por contener el gen NSD1 en doble dosis. Se presenta a una paciente con retraso global del desarrollo, peso y talla bajos y dismorfias. Cuenta con antecedente de corrección quirúrgica por defectos de septación auriculoventricular (CIA y CIV, así como remodelación por antecedente de cráneo en trébol. El cariotipo con bandas G mostró un resultado 46,XX,add(5(q35, y para confirmar el origen del material adicional se utilizó sonda de FISH WCP para el cromosoma 5 [46,XX,add(5(q35.ish dup(5(q35(wcp5+]. Para definir puntos de ruptura y realizar correlación genotipo fenotipo se realizó microarreglo CytoScan HD de Affymetrix, que confirmó la duplicación intersticial de novo de 14Mb 46,XX,add(5(q35. arr[hg19] 5q34q35.3(163,110,984-177,227,216x3,177,259,401- 179,330,764x3,179,346,465 180,719,789x3dn, que contiene 80 genes (USCS genome browser, NCBI36/hg19. La descripción de este caso es importante para complementar la delineación del fenotipo, mediante la correlación con la región de la duplicación a nivel de nucleótidos. Cabe resaltar que la paciente demuestra la importancia y la utilidad de las nuevas técnicas de citogenética molecular, con las cuales es posible el análisis detallado de los genes localizados en la región 5q involucrada, así como su correlación con las manifestaciones clínicas.

Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

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Trask, B.J.; Friedman, C. [Univ. of Washington, Seattle, WA (United States); Giorgi, D. [CNRS, Montpelier (France)] [and others

1994-09-01

We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

Patients Carrying 9q31.1-q32 Deletion Share Common Features with Cornelia de Lange Syndrome

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Ruixue Cao

2015-01-01

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

QTL Mapping of Grain Quality Traits Using Introgression Lines Carrying Oryza rufipogon Chromosome Segments in Japonica Rice.

Science.gov (United States)

Yun, Yeo-Tae; Chung, Chong-Tae; Lee, Young-Ju; Na, Han-Jung; Lee, Jae-Chul; Lee, Sun-Gye; Lee, Kwang-Won; Yoon, Young-Hwan; Kang, Ju-Won; Lee, Hyun-Sook; Lee, Jong-Yeol; Ahn, Sang-Nag

2016-12-01

Improved eating quality is a major breeding target in japonica rice due to market demand. Consequently, quantitative trait loci (QTL) for glossiness of cooked rice and amylose content associated with eating quality have received much research focus because of their importance in rice quality. In this study, QTL associated with 12 grain quality traits were identified using 96 introgression lines (IL) of rice developed from an interspecific cross between the Korean elite O. sativa japonica cultivar 'Hwaseong' and O. rufipogon over 7 years. QTL analyses indicated that QTL qDTH6 for heading date, detected on chromosome 6 is associated with variance in grain traits. Most QTLs detected in this study clustered near the qDTH6 locus on chromosome 6, suggesting the effect of qDTH6. O. rufipogon alleles negatively affected grain quality traits except for a few QTLs, including qGCR9 for glossiness of cooked rice on chromosome 9. To characterize the effect of the O. rufipogon locus harboring qGCR9, four lines with a single but different O. rufipogon segment near qGCR9 were compared to Hwaseong. Three lines (O. rufipopgon ILs) having O. rufipogon segment between RM242 and RM245 in common showed higher glossiness of cooked rice than Hwaseong and the other line (Hwaseong IL), indicating that qGCR9 is located in the 3.4-Mb region between RM242 and RM245. Higher glossiness of cooked rice conferred by the O. rufipogon allele might be associated with protein content considering that three lines had lower protein content than Hwaseong (P < 0.1). These three O. rufipogon ILs showed higher yield than Hwaseong and Hwaseong IL due to increase in spikelets per panicle and grain weight indicating the linkage of qGCR9 and yield component QTLs. The qGCR9 locus is of particular interest because of its independence from other undesirable grain quality traits in O. rufipogon. SSR markers linked to qGCR9 can be used to develop high-quality japonica lines and offer a starting point for map

Molecular genetic characterization of a prenatally detected de novo interstitial deletion of chromosome 2q (2q31.1-q32.1 encompassing HOXD13, ZNF385B and ZNF804A associated with syndactyly and increased first-trimester nuchal translucency

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Chih-Ping Chen

2017-06-01

Conclusion: Fetuses with an interstitial deletion of 2q31.1-q32.1 may be associated with increased first-trimester NT. Haploinsufficiency of HOXD13 is associated with syndactyly. Genomic microarray is useful in detecting subtle chromosomal abnormalities in fetuses with increased NT and normal karyotype.

Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25.

Science.gov (United States)

Burkardt, Deepika D'Cunha; Rosenfeld, Jill A; Helgeson, Maria L; Angle, Brad; Banks, Valerie; Smith, Wendy E; Gripp, Karen W; Moline, Jessica; Moran, Rocio T; Niyazov, Dmitriy M; Stevens, Cathy A; Zackai, Elaine; Lebel, Robert Roger; Ashley, Douglas G; Kramer, Nancy; Lachman, Ralph S; Graham, John M

2011-06-01

Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865-172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome. Copyright © 2011 Wiley-Liss, Inc.

Metastic Progression of Breast Cancer by Allelic Loss on Chromosome 18q21

National Research Council Canada - National Science Library

Thiagalingam, Sam

2006-01-01

Genetic and epigenetic inactivation of SMAD4 are rare occurrences in breast tumors despite it is localized to chromosome 18q and serves as a frequent target for inactivation in advanced gastrointestinal cancers...

A Novel 2.3 Mb Microduplication of 9q34.3 Inserted into 19q13.4 in a Patient with Learning Disabilities

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Shalinder Singh

2012-01-01

Full Text Available Insertional translocations in which a duplicated region of one chromosome is inserted into another chromosome are very rare. We report a 16.5-year-old girl with a terminal duplication at 9q34.3 of paternal origin inserted into 19q13.4. Chromosomal analysis revealed the karyotype 46,XX,der(19ins(19;9(q13.4;q34.3q34.3pat. Cytogenetic microarray analysis (CMA identified a ~2.3Mb duplication of 9q, which was confirmed by Fluorescence in situ hybridisation (FISH. The duplication at 9q34.3 is the smallest among the cases reported so far. The proband exhibits similar clinical features to those previously reported cases with larger duplication events.

AMS Measurement of 36Cl with a Q3D Magnetic Spectrometer at CIAE

International Nuclear Information System (INIS)

Li Chaoli; He Ming; Wu Shaoyong; Li Zhenyu; Liu Jiancheng; Dong Kejun; Jiang Shan; Zhang Wei; He Xianwen

2012-01-01

The ratio of 36 Cl/Cl can determine the exposure age of surface rocks and monitor the secular equilibrium of 36 Cl of sedimentary and igneous rock in groundwater. Due to the uncertainty effects of different chemical separation processes for removing 36 S, there is a high degree of uncertainty in 36 Cl accelerator mass spectrometry (AMS) measurements if the ratio of 36 Cl/Cl is lower than 10 -14 . A 36 Cl AMS higher sensitivity measurement has been set up by using a ΔE-Q3D method at the China Institute of Atomic Energy (CIAE). The performances of ΔE-Q3D method for 36 Cl-AMS measurement had been systemically studied. The experimental results show that the ΔE-Q3D method has a higher isobar suppression factor. Taking advantage of direct removing 36 S, the sample preparation can be simplified and the uncertainty effects of different chemical separation processes can be reduced in 36 Cl AMS measurements.

Localization of Usher syndrome type II to chromosome 1q.

Science.gov (United States)

Kimberling, W J; Weston, M D; Möller, C; Davenport, S L; Shugart, Y Y; Priluck, I A; Martini, A; Milani, M; Smith, R J

1990-06-01

Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.

Chromosome 12q24.31-q24.33 deletion causes multiple dysmorphic features and developmental delay: First mosaic patient and overview of the phenotype related to 12q24qter defects

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Sakati Nadia

2011-04-01

Full Text Available Abstract Background Genomic imbalances of the 12q telomere are rare; only a few patients having 12q24.31-q24.33 deletions were reported. Interestingly none of these were mosaic. Although some attempts have been made to establish phenotype/genotype interaction for the deletions in this region, no clear relationship has been established to date. Results We have clinically screened more than 100 patients with dysmorphic features, mental retardation and normal karyotype using high density oligo array-CGH (aCGH and identified a ~9.2 Mb hemizygous interstitial deletion at the 12q telomere (Chromosome 12: 46,XY,del(12(q24.31q24.33 in a severely developmentally retarded patient having dysmorphic features such as low set ears, microcephaly, undescended testicles, bent elbow, kyphoscoliosis, and micropenis. Parents were found to be not carriers. MLPA experiments confirmed the aCGH result. Interphase FISH revealed mosaicism in cultured peripheral blood lymphocytes. Conclusions Since conventional G-Banding technique missed the abnormality; this work re-confirms that any child with unexplained developmental delay and systemic involvement should be studied by aCGH techniques. The FISH technique, however, would still be useful to further delineate the research work and identify such rare mosaicism. Among the 52 deleted genes, P2RX2, ULK1, FZD10, RAN, NCOR2 STX2, TESC, FBXW8, and TBX3 are noteworthy since they may have a role in observed phenotype.

Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

Science.gov (United States)

Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

1995-01-01

Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

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.

Twelve single nucleotide polymorphisms on chromosome 19q13.2-13.3

DEFF Research Database (Denmark)

Yin, Jiaoyang; Vogel, Ulla; Gerdes, Lars Ulrik

2003-01-01

The genetic susceptibility to basal cell carcinoma (BCC) among Danish psoriatic patients was investigated in association studies with 12 single nucleotide polymorphisms on chromosome 19q13.2-3. The results show a significant association between BCC and the A-allele of a polymorphism in ERCCI exon4...

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...

Unbiased ascertainment of a patient with a 47,XY, +pseudic (15)t(15;15)(q13;q13) karyotype by amniocentesis

Energy Technology Data Exchange (ETDEWEB)

Spector, E.; Prochazka, G.; Hamilton, S. [Univ. of Colorado School of Medicine, Denver (United States)] [and others

1994-09-01

A 47,XY,+mar male karyotype was found in all metaphases on an amniocentesis from a 36-year-old woman (G1,P0). The marker was G group size. Chromosome studies on the parents were normal. C-banding, NOR staining and FISH demonstrated that the marker was dicentric, bisatellited, derived from No. 15 and contained 2 copies of the chromosomal region flanked by the Prader-Willi/Angelman A and B probes. The final karyotype was: 47,XY,+pseudic(15)t(15;15)(q13;q13), making the fetus tetrasomic for the genes in the duplicated region. DNA marker studies for No. 15 (performed in the laboratory of Dr. David Ledbetter) revealed that the fetus had inherited on No. 15 from each parent and that the marker was derived from both maternal No. 15 chromosomes. The parents chose to continue the pregnancy. The baby was born at 38 weeks gestation, was mildly edematous and had Apgar scores of 4, 7, and 8 at 1, 5, and 10 min, respectively. The marker was confirmed to be present in placenta and the baby`s blood. Examination at 6 weeks showed appropriate growth and development. Data from published cases predict that this baby will be mentally retarded and may have seizures because he is tetrasomic for 15pter-q13, but will not have Prader-Willi or Angelman syndromes since he has biparental inheritance of his normal No. 15s. However, the published cases may represent a biased sample as most were identified in mentally retarded individuals, not by prenatal diagnosis. This infant`s development will continue to be followed closely.

Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome

Energy Technology Data Exchange (ETDEWEB)

Asou, Hiroya; Matsui, Hirotaka; Ozaki, Yuko; Nagamachi, Akiko; Nakamura, Megumi; Aki, Daisuke [Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan); Inaba, Toshiya, E-mail: tinaba@hiroshima-u.ac.jp [Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan)

2009-05-29

Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common nonrandom chromosomal abnormality found frequently in myeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q.

Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan

Science.gov (United States)

Ansar, Muhammad; Ramzan, Mohammad; Pham, Thanh L.; Yan, Kai; Jamal, Syed Muhammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

2010-01-01

For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod score 3.6). The genetic region for DFNB38 spans 10.1 cM according to the Marshfield genetic map and is bounded by markers D6S980 and D6S1719. This genetic region corresponds to 3.4 MB on the sequence-based physical map. PMID:12890929

Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.

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Mowat, D R; Croaker, G D; Cass, D T; Kerr, B A; Chaitow, J; Adès, L C; Chia, N L; Wilson, M J

1998-01-01

We have identified six children with a distinctive facial phenotype in association with mental retardation (MR), microcephaly, and short stature, four of whom presented with Hirschsprung (HSCR) disease in the neonatal period. HSCR was diagnosed in a further child at the age of 3 years after investigation for severe chronic constipation and another child, identified as sharing the same facial phenotype, had chronic constipation, but did not have HSCR. One of our patients has an interstitial deletion of chromosome 2, del(2)(q21q23). These children strongly resemble the patient reported by Lurie et al with HSCR and dysmorphic features associated with del(2)(q22q23). All patients have been isolated cases, suggesting a contiguous gene syndrome or a dominant single gene disorder involving a locus for HSCR located at 2q22-q23. Review of published reports suggests that there is significant phenotypic and genetic heterogeneity within the group of patients with HSCR, MR, and microcephaly. In particular, our patients appear to have a separate disorder from Goldberg-Shprintzen syndrome, for which autosomal recessive inheritance has been proposed because of sib recurrence and consanguinity in some families. Images PMID:9719364

An Evaluation of Research Replication with Q Method and Its Utility in Market Segmentation.

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Adams, R. C.

Precipitated by questions of using Q methodology in television market segmentation and of the replicability of such research, this paper reports on both a reexamination of 1968 research by Joseph M. Foley and an attempt to replicate Foley's study. By undertaking a reanalysis of the Foley data, the question of replication in Q method is addressed.…

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

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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.

A histone map of human chromosome 20q13.12.

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Pelin Akan

Full Text Available We present a systematic search for regulatory elements in a 3.5 Mb region on human chromosome 20q13.12, a region associated with a number of medical conditions such as type II diabetes and obesity.We profiled six histone modifications alongside RNA polymerase II (PolII and CTCF in two cell lines, HeLa S3 and NTERA-2 clone D1 (NT2/D1, by chromatin immunoprecipitation using an in-house spotted DNA array, constructed with 1.8 kb overlapping plasmid clones. In both cells, more than 90% of transcription start sites (TSSs of expressed genes showed enrichments with PolII, di-methylated lysine 4 of histone H3 (H3K4me2, tri-methylated lysine 4 of histone H3 (H3K4me3 or acetylated H3 (H3Ac, whereas mono-methylated lysine 4 of histone H3 (H3K4me1 signals did not correlate with expression. No TSSs were enriched with tri-methylated lysine 27 of histone H3 (H3K27me3 in HeLa S3, while eight TSSs (4 expressed showed enrichments in NT2/D1. We have also located several CTCF binding sites that are potential insulator elements.In summary, we annotated a number of putative regulatory elements in 20q13.12 and went on to verify experimentally a subset of them using dual luciferase reporter assays. Correlating this data to sequence variation can aid identification of disease causing variants.

Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

LENUS (Irish Health Repository)

Buckley, Patrick G

2011-03-01

Loss of chromosome 1p\\/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p\\/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p\\/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p\\/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p\\/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p\\/19q-deleted tumor phenotype inthese samples.

Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

International Nuclear Information System (INIS)

Diniz, P.R.B.; Brum, D.G.; Santos, A. C.; Murta-Junior, L.O.; Araujo, D.B. de

2010-01-01

The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously. (author)

Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

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Diniz, P.R.B.; Brum, D.G. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Neurociencias e Ciencias do Comportamento; Santos, A. C. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Clinica Medica; Murta-Junior, L.O.; Araujo, D.B. de, E-mail: murta@usp.b [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras. Dept. de Fisica e Matematica

2010-01-15

The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously. (author)

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

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Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

2016-01-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams–Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation. PMID:27617154

Trisomy 2q11.2-->q21.1 resulting from an unbalanced insertion in two generations.

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Glass, I A; Stormer, P; Oei, P T; Hacking, E; Cotter, P D

1998-01-01

In this communication, we describe two cases of proximal 2q trisomy (2q11.2--> q21.1) resulting from an interchromosomal insertion. The chromosomal origin of the insertion was confirmed by fluorescence in situ hybridisation. An unbalanced karyotype, 46,XX,der(8) ,ins(8;2) (p21.3; q21.1q11.2), was found in the proband and her mother, who both have mild mental retardation, short stature, dysmorphic features, insulin dependent diabetes mellitus, and a psychotic illness. This family is a rare example of direct transmission of a partial autosomal trisomy. Images PMID:9598728

Factor VII deficiency and developmental abnormalities in a patient with partial monosomy of 13q and trisomy of 16p: case report and review of the literature

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Meck Jeanne M

2006-01-01

Full Text Available Abstract Background Unbalanced chromosomal translocations may present with a variety of clinical and laboratory findings and provide insight into the functions of genes on the involved chromosomal segments. Case Presentation A 9 year-old boy presented to our clinic with Factor VII deficiency, microcephaly, a seizure disorder, multiple midline abnormalities (agenesis of the corpus callosum, imperforate anus, bilateral optic nerve hypoplasia, developmental delay, hypopigmented macules, short 5th fingers, and sleep apnea due to enlarged tonsils. Cytogenetic and fluorescence in situ hybridization analyses revealed an unbalanced translocation involving the segment distal to 16p13 replacing the segment distal to 13q33 [46, XY, der(13t(13;16(q33;p13.3]. Specific BAC-probes were used to confirm the extent of the 13q deletion. Conclusion This unique unbalanced chromosomal translocation may provide insights into genes important in midline development and underscores the previously-reported phenotype of Factor VII deficiency in 13q deletions.

[Acute myeloid leukemia with monosomy 7 and inv(3)(q21q26.2) complicated with central diabetes insipidus].

Science.gov (United States)

Nanno, Satoru; Hagihara, Kiyoyuki; Sakabe, Manami; Okamura, Hiroshi; Inaba, Akiko; Nagata, Yuki; Nishimoto, Mitsutaka; Koh, Hideo; Nakao, Yoshitaka; Nakane, Takahiko; Nakamae, Hirohisa; Shimono, Taro; Hino, Masayuki

2013-04-01

A 20-year-old female presented with thirst, polyposia, and polyuria and was referred to our hospital because of leukocytosis and anemia. Bone marrow aspiration revealed 66.8% myeloperoxidase-positive blasts and trilineage myelodysplasia. The karyotype was 45, XX, inv(3)(q21q26.2), -7[19]. Therefore, a diagnosis of AML with inv(3)(q21q26.2) complicated by -7 was made. Moreover, hyposthenuria and a low anti-diuretic hormone (ADH) level were observed. Although cerebrospinal fluid analysis was normal, magnetic resonance imaging (MRI) revealed the absence of hyperintensity in the neurohypophysis in T1-weighted images. Therefore, she was also diagnosed with diabetes insipidus. After she was administered a desmopressin nasal spray, the volume of urine produced decreased. Following treatment with second induction therapy containing high-dose cytarabine for AML, she achieved complete remission in the bone marrow. Moreover, when the abnormality on MRI and the volume of urine were normalized, she discontinued desmopressin. Although diabetes insipidus is a rare complication of AML, the majority of AML patients who have diabetes insipidus have the abnormal karyotypes with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7. Further study is required to clarify the pathogenesis and develop a strategy for the treatment of this category of AML.

Usher syndrome type III (USH3) linked to chromosome 3q in an Italian family.

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Gasparini, P; De Fazio, A; Croce, A I; Stanziale, P; Zelante, L

1998-08-01

We report an Italian family affected by Usher type III syndrome. Linkage study, performed using markers corresponding to the Usher loci already mapped, clearly showed linkage with markers on chromosome 3q24-25. Our data further support the presence of an Usher III locus on chromosome 3, as recently reported in a Finnish population.

Usher syndrome type III (USH3) linked to chromosome 3q in an Italian family.

OpenAIRE

Gasparini, P; De Fazio, A; Croce, A I; Stanziale, P; Zelante, L

1998-01-01

We report an Italian family affected by Usher type III syndrome. Linkage study, performed using markers corresponding to the Usher loci already mapped, clearly showed linkage with markers on chromosome 3q24-25. Our data further support the presence of an Usher III locus on chromosome 3, as recently reported in a Finnish population.

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22.

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Mine S Cicek

Full Text Available A substantial proportion of familial colorectal cancer (CRC is not a consequence of known susceptibility loci, such as mismatch repair (MMR genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI-high tumors, or no evidence of linkage to MMR genes. Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR, the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142 and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093. Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively. Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036. These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated.

Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

Directory of Open Access Journals (Sweden)

P.R.B. Diniz

2010-01-01

Full Text Available The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.

Analysis of healthy cohorts for single nucleotide polymorphisms in C1q gene cluster

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MARIA A. RADANOVA

2015-12-01

Full Text Available C1q is the first component of the classical pathway of complement activation. The coding region for C1q is localized on chromosome 1p34.1–36.3. Mutations or single nucleotide polymorphisms (SNPs in C1q gene cluster can cause developing of Systemic lupus erythematosus (SLE because of C1q deficiency or other unknown reason. We selected five SNPs located in 7.121 kbp region on chromosome 1, which were previously associated with SLE and/or low C1q level, but not causing C1q deficiency and analyzed them in terms of allele frequencies and genotype distribution in comparison with Hispanic, Asian, African and other Caucasian cohorts. These SNPs were: rs587585, rs292001, rs172378, rs294179 and rs631090. One hundred eighty five healthy Bulgarian volunteers were genotyped for the selected five C1q SNPs by quantative real-time PCR methods. International HapMap Project has been used for information about genotype distribution and allele frequencies of the five SNPs in, Hispanics, Asians, Africans and others Caucasian cohorts. Bulgarian healthy volunteers and another pooled Caucasian cohort had similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, genotype AA of rs172378 was significantly overrepresented in Bulgarians when compared to other healthy Caucasians from USA and UK (60% vs 31%. Genotype distribution of rs172378 in Bulgarians was similar to Greek-Cyriot Caucasians. For all Caucasians the major allele of rs172378 was A. This is the first study analyzing the allele frequencies and genotype distribution of C1q gene cluster SNPs in Bulgarian healthy population.

Various endocrine disorders in children with t(13;14(q10;q10 Robertsonian translocation

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Byung Ho Choi

2013-09-01

Full Text Available Purpose45,XY,t(13;14(q10;q10 karyotype can suggest infertility associated with more or less severe oligospermia in male adults. In addition, 45,XX,t(13;14(q10;q10 karyotype carries reproductive risks such as miscarriage or infertility in female adults. However, reports on the phenotype of this karyotype in children are very rare. This study was done to observe various phenotypes of this karyotype in children.MethodsBetween January 2007 and December 2012, children diagnosed with 45,XY,t(13;14(q10;q10 or 45,XX,t(13;14(q10;q10 karyotype by chromosome analysis were analyzed retrospectively.ResultsEight children (5 boys and 3 girls were diagnosed with 45,XY,t(13;14(q10;q10 or 45,XX,t(13;14(q10;q10 karyotype. They ranged in age from 5 years and 6 months to 12 years and 4 months. The phenotypes of the study patients consisted of 1 hypogonadotrophic hypogonadism, 1 precocious puberty, 3 early puberty, 2 growth hormone deficiency (GHD (partial and 1 idiopathic short stature. As shown here t(13;14(q10;q10 Robertsonian translocation shows a wide range of phenotypes.ConclusionIt can be said that t(13;14(q10;q10 Robertsonian translocation shows various phenotypes from GHD to precocious puberty in children. Further large-scale studies are necessary.

A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

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Naiel, Abdulbasit [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom); Vetter, Michael [MetaSystems, Altlussheim 68804 (Germany); Plekhanova, Olga [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Fleischman, Elena; Sokova, Olga [N.N. Blokhin Russian Cancer Research Center Russian Academy of Medical Science, Moscow 115478 (Russian Federation); Tsaur, Grigory [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Research Institute of Medical Cell Technologies, Ekaterinburg 620149 (Russian Federation); Harbott, Jochen [Oncogenetic Laboratory, Department of Paediatric Haematology and Oncology, Justus Liebig University, Giessen 35392 (Germany); Tosi, Sabrina, E-mail: sabrina.tosi@brunel.ac.uk [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom)

2013-03-11

The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.

Working Memory Impairments in Chromosome 22q11.2 Deletion Syndrome: The Roles of Anxiety and Stress Physiology

Science.gov (United States)

Sanders, Ashley F.; Hobbs, Diana A.; Stephenson, David D.; Laird, Robert D.; Beaton, Elliott A.

2017-01-01

Stress and anxiety have a negative impact on working memory systems by competing for executive resources and attention. Broad memory deficits, anxiety, and elevated stress have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial…

Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q

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Ryan, S.G.; O' Connell, P. (Univ. of Texas Health Science Center, San Antonio (United States)); Dixon, M.J. (Univ. of Manchester (United Kingdom)); Nigro, M.A. (Wayne State Univ., Detroit, MI (United States)); Kelts, K.A. (Black Hills Neurology, Rapid City, SD (United States)); Markand, O.N. (Indiana Univ., Indianopolis (United States)); Shiang, R.; Wasmuth, J.J. (Univ. of California, Irvine (United States)); Terry, J.C.

1992-12-01

Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. The authors performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. 45 refs., 4 figs., 4 tabs.

Molecular cytogenetic characterization of the first reported case of an inv dup (4p)(p15.1-pter) with a concomitant 4q35.1-qter deletion and normal parents.

Science.gov (United States)

Tassano, E; Alpigiani, M G; Salvati, P; Gimelli, S; Lorini, R; Gimelli, G

2012-12-15

Inverted duplications associated with terminal deletions are complex anomalies described in an increasing of chromosome ends. We report on the cytogenetic characterization of the first de novo inv dup del(4) with partial 4p duplication and 4q deletion in a girl with clinical signs consistent with "recombinant 4 syndrome". This abnormality was suspected by banding, but high-resolution molecular cytogenetic investigations allowed us to define the breakpoints of the rearrangement. The terminal duplicated region extending from 4p15.1 to the telomere was estimated to be 29.27 Mb, while the size of the terminal deletion was 3.114 Mb in the 4q35.1 region. Until now, 10 patients with duplicated 4p14-p15 and deleted 4q35 chromosome 4 have been described. In all cases the abnormal chromosome 4 was derived from a pericentric inversion inherited from one of the parents. In conclusion, we have identified the first case of inv dup del(4) with normal parents suggesting that, often, terminal duplications or terminal deletions mask complex rearrangements. Copyright © 2012 Elsevier B.V. All rights reserved.

A Rare Chromosome 3 Imbalance and Its Clinical Implications

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Karen Sims

2012-01-01

Full Text Available The duplication of chromosome 3q is a rare disorder with varying chromosomal breakpoints and consequently symptoms. Even rarer is the unbalanced outcome from a parental inv(3 resulting in duplicated 3q and a deletion of 3p. Molecular karyotyping should aid in precisely determining the length and breakpoints of the 3q+/3p− so as to better understand a child’s future development and needs. We report a case of an infant male with a 57.5 Mb duplication from 3q23-qter. This patient also has an accompanying 1.7 Mb deletion of 3p26.3. The duplicated segment in this patient encompasses the known critical region of 3q26.3-q27, which is implicated in the previously reported 3q dup syndrome; however, the accompanying 3p26.3 deletion is smaller than the previously reported cases. The clinical phenotype of this patient relates to previously reported cases of 3q+ that may suggest that the accompanying 1.7 Mb heterozygous deletion is not clinically relevant. Taken together, our data has refined the location and extent of the chromosome 3 imbalance, which will aid in better understanding the molecular underpinning of the 3q syndrome.

Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas.

Science.gov (United States)

van Dekken, H; Geelen, E; Dinjens, W N; Wijnhoven, B P; Tilanus, H W; Tanke, H J; Rosenberg, C

1999-02-01

Incidence rates have risen rapidly for esophageal and gastric cardia adenocarcinomas. These cancers, arising at and around the gastroesophageal junction (GEJ), share a poor prognosis. In contrast, there is no consensus with respect to clinical staging resulting in possible adverse effects on treatment and survival. The goal of this study was to provide more insight into the genetic changes underlying esophageal and gastric cardia adenocarcinomas. We have used comparative genomic hybridization for a genetic analysis of 28 adenocarcinomas of the GEJ. Eleven tumors were localized in the distal esophagus and related to Barrett's esophagus, and 10 tumors were situated in the gastric cardia. The remaining seven tumors were located at the junction and could not be classified as either Barrett-related, or gastric cardia. We found alterations in all 28 neoplasms. Gains and losses were distinguished in comparable numbers. Frequent loss (> or = 25% of all tumors) was detected, in decreasing order of frequency, on 4pq (54%), 14q (46%), 18q (43%), 5q (36%), 16q (36%), 9p (29%), 17p (29%), and 21q (29%). Frequent gain (> or = 25% of all tumors) was observed, in decreasing order of frequency, on 20pq (86%), 8q (79%), 7p (61%), 13q (46%), 12q (39%), 15q (39%), 1q (36%), 3q (32%), 5p (32%), 6p (32%), 19q (32%), Xpq (32%), 17q (29%), and 18p (25%). Nearly all patients were male, and loss of chromosome Y was frequently noted (64%). Recurrent high-level amplifications (> 10% of all tumors) were seen at 8q23-24.1, 15q25, 17q12-21, and 19q13.1. Minimal overlapping regions could be determined at multiple locations (candidate genes are in parentheses): minimal regions of overlap for deletions were assigned to 3p14 (FHIT, RCA1), 5q14-21 (APC, MCC), 9p21 (MTS1/CDKN2), 14q31-32.1 (TSHR), 16q23, 18q21 (DCC, P15) and 21q21. Minimal overlapping amplified sites could be seen at 5p14 (MLVI2), 6p12-21.1 (NRASL3), 7p12 (EGFR), 8q23-24.1 (MYC), 12q21.1, 15q25 (IGF1R), 17q12-21 (ERBB2/HER2-neu), 19q

Multistudy fine mapping of chromosome 2q identifies XRCC5 as a chronic obstructive pulmonary disease susceptibility gene

DEFF Research Database (Denmark)

Hersh, Craig P; Pillai, Sreekumar G; Zhu, Guohua

2010-01-01

to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q. METHODS: Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from...... the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families...

Complex distal 10q rearrangement in a girl with mild intellectual disability: follow up of the patient and review of the literature of non-acrocentric satellited chromosomes.

Science.gov (United States)

Sarri, Catherine; Douzgou, Sofia; Gyftodimou, Yolanda; Tümer, Zeynep; Ravn, Kirstine; Pasparaki, Angela; Sarafidou, Theologia; Kontos, Harry; Kokotas, Haris; Karadima, Georgia; Grigoriadou, Maria; Pandelia, Effie; Theodorou, Virginia; Moschonas, Nicholas K; Petersen, Michael B

2011-11-01

We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q. By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change, followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite material. The homology between the repeat sequences at 10q subtelomere region and the sequences on the acrocentric short arms may explain the origin of the rearrangement and it is likely that the submicroscopic microdeletion and microduplication are responsible for the abnormal phenotype in our patient. The patient presented here, with a 15-year follow-up, manifests a distinct phenotype different from the 10q26 pure distal monosomy and trisomy syndromes. Copyright © 2011 Wiley Periodicals, Inc.

A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias.

Science.gov (United States)

Speleman, F; Cauwelier, B; Dastugue, N; Cools, J; Verhasselt, B; Poppe, B; Van Roy, N; Vandesompele, J; Graux, C; Uyttebroeck, A; Boogaerts, M; De Moerloose, B; Benoit, Y; Selleslag, D; Billiet, J; Robert, A; Huguet, F; Vandenberghe, P; De Paepe, A; Marynen, P; Hagemeijer, A

2005-03-01

Chromosomal translocations with breakpoints in T-cell receptor (TCR) genes are recurrent in T-cell malignancies. These translocations involve the TCRalphadelta gene (14q11), the TCRbeta gene (7q34) and to a lesser extent the TCRgamma gene at chromosomal band 7p14 and juxtapose T-cell oncogenes next to TCR regulatory sequences leading to deregulated expression of those oncogenes. Here, we describe a new recurrent chromosomal inversion of chromosome 7, inv(7)(p15q34), in a subset of patients with T-cell acute lymphoblastic leukemia characterized by CD2 negative and CD4 positive, CD8 negative blasts. This rearrangement juxtaposes the distal part of the HOXA gene cluster on 7p15 to the TCRbeta locus on 7q34. Real time quantitative PCR analysis for all HOXA genes revealed high levels of HOXA10 and HOXA11 expression in all inv(7) positive cases. This is the first report of a recurrent chromosome rearrangement targeting the HOXA gene cluster in T-cell malignancies resulting in deregulated HOXA gene expression (particularly HOXA10 and HOXA11) and is in keeping with a previous report suggesting HOXA deregulation in MLL-rearranged T- and B cell lymphoblastic leukemia as the key factor in leukaemic transformation. Finally, our observation also supports the previous suggested role of HOXA10 and HOXA11 in normal thymocyte development.

A genome-wide scan for autoimmune thyroiditis in the Old Order Amish: replication of genetic linkage on chromosome 5q11.2-q14.3.

Science.gov (United States)

Allen, Elsie M; Hsueh, Wen-Chi; Sabra, Mona M; Pollin, Toni I; Ladenson, Paul W; Silver, Kristi D; Mitchell, Braxton D; Shuldiner, Alan R

2003-03-01

Autoimmune thyroiditis (AITD) is a common disorder characterized by circulating antibodies to epitopes of thyroid tissue and hypothyroidism (Hashimoto's thyroiditis or AITD-hypothyroidism), although many subjects with AITD are euthyroid. Current evidence suggests that AITD is familial and polygenic. We studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. We found autoimmune thyroiditis, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. We performed a genome-wide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. We observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (LOD, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428), a region that was previously reported to be linked to AITD-hypothyroidism in a Japanese study. AITD-hypothyroidism showed a more modest linkage peak to the same region (LOD, 1.46; P = 0.005). Possible linkage (nominal P Amish.

Interstitial deletion of 14q24.3-q32.2 in a male patient with plagiocephaly, BPES features, developmental delay, and congenital heart defects

DEFF Research Database (Denmark)

Cingöz, Sultan; Bache, Iben; Bjerglund, Lise

2011-01-01

Distal interstitial deletions of chromosome 14 involving the 14q24-q23.2 region are rare, and only been reported so far in 20 patients. Ten of these patients were analyzed both clinically and genetically. Here we present a de novo interstitial deletion of chromosome 14q24.3-q32.2 in a male patient...... on genotype-phenotype comparisons of the 10 previously published patients and the present case, we suggest that the shortest regions for deletion overlap may include candidate genes for speech impairment, mental retardation, and hypotonia....

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

Science.gov (United States)

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

1998-01-01

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

Vitamin D deficiency, behavioral atypicality, anxiety and depression in children with chromosome 22q11.2 deletion syndrome.

Science.gov (United States)

Kelley, L; Sanders, A F P; Beaton, E A

2016-12-01

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex developmental disorder with serious medical, cognitive and emotional symptoms across the lifespan. This genetic deletion also imparts a lifetime risk for developing schizophrenia that is 25-30 times that of the general population. The origin of this risk is multifactorial and may include dysregulation of the stress response and immunological systems in relation to brain development. Vitamin D is involved in brain development and neuroprotection, gene transcription, immunological regulation and influences neuronal signal transduction. Low levels of vitamin D are associated with schizophrenia, depression and anxiety in the general population. Yet, little is known about how vitamin D levels in children with 22q11.2DS could mediate risk of psychosis in adulthood. Blood plasma levels of vitamin D were measured in children aged 7-16 years with (n=11) and without (n=16) 22q11.2DS in relation to parent reports of children's anxiety and atypicality. Anxiety and atypicality in childhood are risk indicators for the development of schizophrenia in those with 22q11.2DS and the general population. Children with 22q11.2DS had lower vitamin D levels, as well as elevated anxiety and atypicality compared with typical peers. Higher levels of anxiety, depression and internalizing problems but not atypicality were associated with lower levels of vitamin D. Vitamin D insufficiency may relate to higher levels of anxiety and depression, in turn contributing to the elevated risk of psychosis in this population. Further study is required to determine casual linkages between anxiety, stress, mood and vitamin D in children with 22q11.2DS.

Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans.

Science.gov (United States)

Kammerer, Candace M; Schneider, Jennifer L; Cole, Shelley A; Hixson, James E; Samollow, Paul B; O'Connell, Jeffrey R; Perez, Reina; Dyer, Thomas D; Almasy, Laura; Blangero, John; Bauer, Richard L; Mitchell, Braxton D

2003-12-01

We performed a genome scan using BMD data of the forearm and hip on 664 individuals in 29 Mexican-American families. We obtained evidence for QTL on chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q, affecting hip BMD in men. The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families. We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available. We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women. These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. J Bone Miner Res 2003;18:2245-2252

An Interstitial 4q Deletion with a Mosaic Complementary Ring Chromosome in a Child with Dysmorphism, Linear Skin Pigmentation, and Hepatomegaly

Directory of Open Access Journals (Sweden)

J. Carter

2017-01-01

Full Text Available Interstitial deletions of 4q are rarely reported, vary in size, and have limited genotype-phenotype correlations. Here, genome-wide array CGH analysis identified a 21.6 Mb region of copy number loss at 4q12-q21.1 in a patient diagnosed with dysmorphism, linear skin pigmentation, and hepatomegaly. An additional small ring chromosome was detected in 5/30 cells examined via G-banding. Confirmation of the origin of the ring chromosome was obtained by FISH analysis which identified that the ring chromosome contained material from the deleted region of chromosome 4 and was therefore complementary to the 21.6 Mb deletion. Further microarray studies in the proband using a different microarray platform showed no evidence of mosaicism. This case highlights the importance of an integrated approach to cytogenetic analysis and demonstrates the value of G-banding for detecting mosaicism, as current microarray platforms are unable to detect low level mosaics.

Possible Heavy Tetraquarks qQ(-q-Q), qq(-Q-Q) and qQ(-Q-Q)%可能的qQ(-q-Q),qq(-Q-Q)和qQ(-Q-Q)重四夸克态

Institute of Scientific and Technical Information of China (English)

崔莹; 陈晓林; 邓卫真; 朱世琳

2007-01-01

Assuming X(3872) is a qc-q-c tetraquark and using its mass as input, we perform a schematic study of the masses of possible heavy tetraquarks using the color-magnetic interaction with the flavor symmetry breaking corrections.%假设X(3872)是一个qc(-q-c)四夸克态,并用它的质量作为输入,用具有味对称性破坏的色磁相互作用系统研究了可能的重四夸克态的质量谱.

Refinement of genotype-phenotype correlation in 18 patients carrying a 1q24q25 deletion

DEFF Research Database (Denmark)

Chatron, Nicolas; Haddad, Véronique; Andrieux, Joris

2015-01-01

of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1...

Radiative stabilization of double-Rydberg states formed in slow Xeq+-Xe (15 ≤ q ≤ 35) collisions

International Nuclear Information System (INIS)

Anderson, H.; Cederquist, H.; Astner, G.; Hvelplund, P.; Pedersen, J.O.P.

1990-01-01

Electron capture processes, in which the projectile charge (q) is lowered by one unit, have been recorded by means of high-resolution energy-gain spectroscopy for 4q keV Xe q+ -Xe (15 ≤ q ≤ 35) collisions. The ratios, R, between the cross sections for the transfer ionisation and single-electron capture were extracted from the measured spectra. The quantity R increases slowly for charges up to q = 25 and decreases rapidly for higher q. Relying on the extended classical over-barrier model we relate R to the branching ratio for autoionisation, F, through R = k.F, and estimate the variation in k as a function of q. On the basis of the extended classical over-barrier model we ascribe the decrease in R at high q to an increase in radiative stabilization of double-Rydberg states formed in slow Xe q+ -Xe, q > 25, collisions. (orig.)

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

DEFF Research Database (Denmark)

Becker, Kerstin; Di Donato, Nataliya; Holder-Espinasse, Muriel

2012-01-01

with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.......3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14...

qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots

OpenAIRE

Turner, Stephen

2014-01-01

Summary: Genome-wide association studies (GWAS) have identified thousands of human trait-associated single nucleotide polymorphisms. Here, I describe a freely available R package for visualizing GWAS results using Q-Q and manhattan plots. The qqman package enables the flexible creation of manhattan plots, both genome-wide and for single chromosomes, with optional highlighting of SNPs of interest. Availability: qqman is released under the GNU General Public License, and is freely available on ...

The Development of Cognitive Control in Children with Chromosome 22q11.2 Deletion Syndrome

Directory of Open Access Journals (Sweden)

Heather M Shapiro

2014-06-01

Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children (TD were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also conducted in order to examine genotype of catechol-O-methyltransferase (COMT, a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ. When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures.

Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32-q27.2.

Science.gov (United States)

Dworschak, G C; Crétolle, C; Hilger, A; Engels, H; Korsch, E; Reutter, H; Ludwig, M

2017-05-01

Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

Energy Technology Data Exchange (ETDEWEB)

D`Angelo, J.A.; Pillers, D.M.; Jett, P.L. [Oregon Health Sciences Univ. Portland, OR (United States)] [and others

1994-09-01

Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

Replication the association of 2q32.2-q32.3 and 14q32.11 with hepatocellular carcinoma.

Science.gov (United States)

Chen, Wei; Wang, Mingquan; Zhang, Zhen; Tang, Huayang; Zuo, Xianbo; Meng, Xiangling; Xiong, Maoming; Zhou, Fusheng; Liang, Bo; Dai, Fen; Fang, Jun; Gao, Jinping; Zhu, Jun; Zhu, Yong; Wan, Hong; Wang, Miaofeng; Chan, Shixin; Sun, Liangdan

2015-04-25

Hepatocellular carcinoma (HCC) is a malignant tumor. The morbidity and mortality of HCC tend to ascend and become a serious threat to the population health. Genetic studies of HCC have identified several susceptibility loci of HCC. In this study, we aim to replicate the association of these loci in our samples from Chinese population and further investigate the genetic interaction. We selected 16 SNPs within 1p36.22, 2q32.2-q32.3, 3p21.33, 8p12, 14q32.11 and 21q21.3 and genotyped in 507 HCC patients and 3014 controls by using Sequenom MassARRAY system. Association analyses were performed by using PLINK 1.07. We observed that the STAT4 (2q32.2-q32.3) at rs7574865 (P=1.17×10(-3), OR=0.79) and EFCAB11 (14q32.11) at rs8013403 (P=1.54×10(-3), OR=0.80) were significantly associated with HCC in this study. In 3p21.33, genetic variant rs6795737 within GLB1 was also observed with suggestive evidence (P=9.98×10(-3), OR=0.84). In the interaction analysis, the pair of associated SNPs (rs7574865 within STAT4, rs8013403 within EFCAB11) generated evidence for interaction (P=4.10×10(-3)). In summary, our work first reported the association of 14q32.11 (EFCAB11) with HCC in Chinese Han population and revealed the genetic interaction between STAT4 (2q32.2-q32.3) and EFCAB11 (14q32.11) in HCC. Copyright © 2015 Elsevier B.V. All rights reserved.

Severe intellectual disability, omphalocele, hypospadia and high blood pressure associated to a deletion at 2q22.1q22.3: case report

Directory of Open Access Journals (Sweden)

Mulatinho Milene

2012-06-01

Full Text Available Abstract Background Recently, array-comparative genomic hybridization (aCGH platforms have significantly improved the resolution of chromosomal analysis allowing the identification of genomic copy number gains and losses smaller than 5 Mb. Here we report on a young man with unexplained severe mental retardation, autism spectrum disorder, congenital malformations comprising hypospadia and omphalocele, and episodes of high blood pressure. An ~ 6 Mb interstitial deletion that includes the causative genes is identified by oligonucleotide-based aCGH. Results Our index case exhibited a de novo chromosomal abnormality at 2q22 [del(2(q22.1q22.3dn] which was not visible at the 550 haploid band level. The deleted region includes eight genes: HNMT, SPOPL, NXPH2, LOC64702, LRP1B, KYNU, ARHGAP15 and GTDC1. Discussion aCGH revealed an ~ 6 Mb deletion in 2q22.1 to 2q22.3 in an as-yet unique clinical case associated with intellectual disability, congenital malformations and autism spectrum disorder. Interestingly, the deletion is co-localized with a fragile site (FRA2K, which could be involved in the formation of this chromosomal aberration. Further studies are needed to determine if deletions of 2q22.1 to 2q22.3 define a new microdeletion syndrome.

The del(2)(q32.2q33) deletion syndrome defined by clinical and molecular characterization of four patients.

NARCIS (Netherlands)

Buggenhout, G.J.C.M. van; Ravenswaaij-Arts, C.M.A. van; Maas, N.; Thoelen, R.; Vogels, A.; Smeets, D.F.C.M.; Salden, I.; Matthijs, G.; Fryns, J.P.; Vermeesch, J.

2005-01-01

We report four patients with an interstitial deletion of chromosome 2q32-->2q33. They presented similar clinical findings including pre- and postnatal growth retardation, distinct facial dysmorphism, thin and sparse hair and fair built, micrognathia, cleft or high palate, relative macroglossia,

Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

International Nuclear Information System (INIS)

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

2003-01-01

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. 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. 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. 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

Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13(q26.2;p11.2: Further Delineation of 3q Duplication Syndrome

Directory of Open Access Journals (Sweden)

M. Abreu-González

2013-01-01

Full Text Available Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13(q26.2;p11.2. As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.

HELICOBACTER PYLORI AND t(11;18(q21;q21 TRANSLOCATION IN GASTRIC MALT LYMPHOMA

Directory of Open Access Journals (Sweden)

Karine Sampaio LIMA

2014-04-01

Full Text Available Context Gastric mucosa-associated lymphoid tissue (MALT lymphoma is clearly associated with Helicobacter pylori gastritis and can be cured with anti- H pylori therapy alone. The presence of t(11;18(q21;q21 translocation is thought to predict a lower response rate to anti- H pylori treatment. Objectives To study the presence of t(11;18(q21;q21 genetic translocation and its clinical impact in low-grade gastric MALT lymphoma Brazilian patients. Methods A consecutive series of eight patients with gastric MALT lymphoma were submitted to gastroscopy, endoscopic ultrasound, histopathological examination, H pylori search and RT-PCR-based methodology. All patients received anti-H pylori treatment. Eradicated patients were followed-up every 3-6 months for 2 years. Results Eight patients were studied. All patients had tumor involvement restricted to the mucosa or submucosa and seven patients had low-grade gastric MALT lymphoma. All infected patients achieved H pylori eradication. Histological tumor regression was observed in 5/7 (71% of the low-grade gastric MALT lymphoma patients. The presence of t(11;18(q21;q21 translocation was found in 4 (57% of these patients; among them only two had histological tumor regression following H pylori eradication. Conclusions RT-PCR is a feasible and efficient method to detect t(11;18(q21;q21 translocation, being carried out in routine molecular biology laboratories. The early detection of such translocation can be very helpful for better targeting the therapy to be applied to gastric MALT lymphoma patients.

A gene prenature ovarian failure associated with eyelid malformation maps to chromosomes 3q22-q23

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-05-01

Premature ovarian failure and XX gonadal dysgenesis leading to female infertility have been reported in association with an autosomal dominantly inherited malformation of the eyelids: blepharophimosis-ptosis-epicanthus inversus syndrome (BPES; MIM 110100). This association distinguishes BPES type I from BPES type II, in which affected females are fertile and the transmission occurs through both sexes. Recently, a gene responsible for BPES type II has been mapped to chromosome 3q22-q23, and the critical region for the gene location has been reduced to the interval between loci D3S1615 and D3S1316. Hitherto, however, no information regarding the localization of the gene for BPES type I, in which female ovarian failure is associated with eyelid malformation, has been available. We have studied two independent families affected with BPES type I, including a total of 12 affected individuals (6 infertile women) and 6 healthy relatives. The diagnostic criteria for the ophthalmological anomaly included (1) reduced horizontal diameter of palpebral fissures, (2) drooping of the upper eyelids, and (3) an abnormal skinfold running from the lower lids. Telecanthus and a flat nasal bridge were present in most cases. In both families the disease was transmitted only by the male, and no affected woman of childbearing age was fertile. 12 refs., 2 figs., 1 tab.

Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands

DEFF Research Database (Denmark)

Jorgensen, Tove H; Børglum, A.D; Mors, O

2002-01-01

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe...... was found at a segment of at least 1.1 cM including markers D22S1161 and D22S922 (P=0.0081 in the test for association). Our results also support the a priori evidence of a susceptibility gene to schizophrenia at a segment of at least 0.45 cM including markers D22S279 and D22S276 (P=0.0075). Patients were...... tested for the presence of a missense mutation in the WKL1 gene encoding a putative cation channel close to segment D22S1161-D22S922, which has been associated with schizophrenia. We did not find this mutation in schizophrenic or bipolar patients or the controls from the Faroe Islands. © 2002 Wiley...

Experimental cross sections for two-electron capture into nitrogen autoionising states in Nsup(q+) (q=6,7) on He and H2 collisions at 10.5q keV

International Nuclear Information System (INIS)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Marrakchi, A.I.

1985-01-01

Singly differential cross sections for two-electron capture into autoionising states (nl,n'l') with n=2,3,4 and n'>=n in Nsup(q+) (q=6,7) on He and H 2 collisions have been measured at 10,5q ke V collision energy and an observation angle thetasub(lab)=11.6 0 . Total cross sections are estimated assuming isotropic angular distributions. (orig.)

Use of a human chromosome 11 radiation hybrid panel to map markers at 11q13

International Nuclear Information System (INIS)

Withers, D.; Richard, C. III; Meeker, T.C.; Maurer, S.; Evans, G.; Myers, R.M.; Cox, D.R.

1990-01-01

A human/hamster hybrid cell line containing human chromosome 11 was X-irradiated and 102-independent derivative lines were recovered. These 'radiation hybrids' contain random fragments of human chromosome 11. This radiation hybrid panel was used to score the retention of markers at band 11q13. Statistical analysis of marker co-retention patterns in the radiation hybrid panel permits a preliminary ordering and mapping of the markers used. The best order for six scored markers is: proximal - CD5 - CD20 - PGA - HST - BCL1 - SEA - distal. Additional markers are currently being scored. The six 11q13 markers above are spread over approximately 10-12 mB of DNA. The mapping data has implications for the identification of the bcl-1 gene. bcl-1 is the site of chromosome breakage in translocations associated with B lymphocytic malignancy. bcl-1 markers map at least 4 Mb away from any of four genes previously hypothesized to be activated by such translocations, thereby making them unlikely candidates for activation

7Q10 flows for SRS streams

International Nuclear Information System (INIS)

Chen, K.F.

1996-01-01

The Environmental Transport Group of the Environmental Technology Section was requested to predict the seven-day ten-year low flow (7Q10 flow) for the SRS streams based on historical stream flow records. Most of the historical flow records for the SRS streams include reactor coolant water discharged from the reactors and process water released from the process facilities. The most straight forward way to estimate the stream daily natural flow is to subtract the measured upstream reactor and/or facility daily effluents from the measured downstream daily flow. Unfortunately, this method does not always work, as indicated by the fact that sometimes the measured downstream volumetric flow rates are lower than the reactor effluent volumetric flow rates. For those cases that cannot be analyzed with the simple subtracting method, an alternative method was used to estimate the stream natural flows by statistically separating reactor coolant and process water flow data. The correlation between the calculated 7Q10 flows and the watershed areas for Four Mile Branch and Pen Branch agrees with that calculated by the USGS for Upper Three Runs and Lower Three Runs Creeks. The agreement between these two independent calculations lends confidence to the 7Q10 flow calculations presented in this report

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Science.gov (United States)

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

2017-01-01

GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042

DEFF Research Database (Denmark)

Milne, Roger L; Benítez, Javier; Nevanlinna, Heli

2009-01-01

BACKGROUND: A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. METHODS: 2q35...

The human homologue of unc-93 maps to chromosome 6q27 - characterisation and analysis in sporadic epithelial ovarian cancer

DEFF Research Database (Denmark)

Liu, Ying; Dodds, Phillippa; Emilion, Gracy

2002-01-01

In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To id...

No significant effect of monosomy for distal 21q22. 3 on the Down syndrom phenotype in mirror' duplications of chromosome 21

Energy Technology Data Exchange (ETDEWEB)

Pangalos, C.; Prieur, M.; Rethore, M.O.; Lejeune, J. (Institut de Progenese, Paris (France)); Theophile, D.; Sinet, P.M.; Chettouh, Z.; Delabar, J.M. (Hopital Necker Enfants Malades, Paris (France)); Marks, A. (Univ. of Toronto, Ontario (Canada)); Stamboulieh-Abazis, D. (Diagnostic Genetic Center, Athens (Greece)); Verellen, C. (Centre de Genetique Humaine, Brussels (Belgium))

1992-12-01

Three Down syndrome patients for whom karyotypic analysis showed a mirror' (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region - namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B - by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation. 54 refs., 5 figs., 3 tabs.

Deletion 22q13.3 syndrome

Directory of Open Access Journals (Sweden)

Phelan Mary C

2008-05-01

Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements

Skew cyclic codes over F_q+uF_q+vF_q+uvF_q

Directory of Open Access Journals (Sweden)

Ting Yao

2015-09-01

Full Text Available In this paper, we study skew cyclic codes over the ring $R=F_q+uF_q+vF_q+uvF_q$, where $u^{2}=u,v^{2}=v,uv=vu$, $q=p^{m}$ and $p$ is an odd prime. We investigate the structural properties of skew cyclic codes over $R$ through a decomposition theorem. Furthermore, we give a formula for the number of skew cyclic codes of length $n$ over $R.$

Association study of candidate genes for susceptibility to schizophrenia and bipolar disorder on chromosome 22Q13

DEFF Research Database (Denmark)

Severinsen, Jacob; Binderup, Helle; Mors, Ole

Chromosome 22q is suspected to harbor risk genes for schizophrenia as well as bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. In a recent study of distantly related patients from...... the Faroe Islands we have obtained evidence suggesting two regions on chromosome 22q13 to potentially harbor susceptibility genes for both schizophrenia and bipolar affective disorder. We have selected a number of candidate genes from these two regions for further analysis, including the neuro-gene WKL1...... and unrelated controls, and in a Scottish case-control sample comprising 200 schizophrenics, 200 bipolar patients and 200 controls. None of the investigated SNPs have so far showed strong evidence of association to either bipolar disorder or schizophrenia....

Search for massive resonances decaying into W W , W Z , Z Z , q W , and q Z with dijet final states at √{s }=13 TeV

Science.gov (United States)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caputo, C.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Shopova, M.; Stoykova, S.; Sultanov, G.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhang, S.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Assran, Y.; Elgammal, S.; Mahrous, A.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ö.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Zhukov, V.; Albert, A.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Guthoff, M.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Raspereza, A.; Roland, B.; Savitskyi, M.; Saxena, P.; Shevchenko, R.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Bein, S.; Blobel, V.; Centis Vignali, M.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hinzmann, A.; Hoffmann, M.; Karavdina, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schäfer, D.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Karathanasis, G.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Kousouris, K.; Evangelou, I.; Foudas, C.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Csanad, M.; Filipovic, N.; Pasztor, G.; Veres, G. I.; Bencze, G.; Hajdu, C.; Horvath, D.; Hunyadi, Á.; Sikler, F.; Veszpremi, V.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Komaragiri, J. R.; Bahinipati, S.; Bhowmik, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Dhingra, N.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Kumari, P.; Mehta, A.; Singh, J. B.; Walia, G.; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A.; Chauhan, S.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Bhardwaj, R.; Bhattacharya, R.; Bhattacharya, S.; Bhawandeep, U.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy, D.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Thakur, S.; Behera, P. 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M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Errico, F.; Fiore, L.; Iaselli, G.; Lezki, S.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. 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T.; Ligabue, F.; Lomtadze, T.; Manca, E.; Mandorli, G.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Di Marco, E.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, J.; Lee, S.; Lee, S. W.; Moon, C. S.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Moon, D. H.; Oh, G.; Brochero Cifuentes, J. A.; Goh, J.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Kim, J. S.; Lee, H.; Lee, K.; Nam, K.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Choi, Y.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Reyes-Almanza, R.; Ramirez-Sanchez, G.; Duran-Osuna, M. C.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Rabadan-Trejo, R. I.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Pyskir, A.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Di Francesco, A.; Faccioli, P.; Galinhas, B.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Seixas, J.; Strong, G.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Afanasiev, S.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Palichik, V.; Perelygin, V.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Stepennov, A.; Toms, M.; Vlasov, E.; Zhokin, A.; Aushev, T.; Bylinkin, A.; Chadeeva, M.; Markin, O.; Parygin, P.; Philippov, D.; Polikarpov, S.; Rusinov, V.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Bunichev, V.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Blinov, V.; Skovpen, Y.; Shtol, D.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Dordevic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Barrio Luna, M.; Cerrada, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Moran, D.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Álvarez Fernández, A.; de Trocóniz, J. F.; Missiroli, M.; Cuevas, J.; Erice, C.; Fernandez Menendez, J.; Gonzalez Caballero, I.; González Fernández, J. R.; Palencia Cortezon, E.; Sanchez Cruz, S.; Vischia, P.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Chazin Quero, B.; Curras, E.; Duarte Campderros, J.; Fernandez, M.; Garcia-Ferrero, J.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Martinez Ruiz del Arbol, P.; Matorras, F.; Piedra Gomez, J.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Baillon, P.; Ball, A. H.; Barney, D.; Bianco, M.; Bloch, P.; Bocci, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Dobson, M.; Dorney, B.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Fallavollita, F.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Glege, F.; Gulhan, D.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Karacheban, O.; Kieseler, J.; Kirschenmann, H.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Stakia, A.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Verweij, M.; Zeuner, W. D.; Bertl, W.; Caminada, L.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Bachmair, F.; Bäni, L.; Berger, P.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Klijnsma, T.; Lustermann, W.; Mangano, B.; Marionneau, M.; Meinhard, M. 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R.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Si, W.; Wang, L.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Macneill, I.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mullin, S. D.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bendavid, J.; Bornheim, A.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cerati, G. B.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Martinez, G.; Perry, T.; Prosper, H.; Saha, A.; Santra, A.; Sharma, V.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Royon, C.; Sanders, S.; Schmitz, E.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Das, S.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Delannoy, A. G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Padeken, K.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Joyce, M.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.; CMS Collaboration

2018-04-01

Results are presented from a search in the dijet final state for new massive narrow resonances decaying to pairs of W and Z bosons or to a W /Z boson and a quark. Results are based on data recorded in proton-proton collisions at √{s }=13 TeV with the CMS detector at the CERN LHC. The data correspond to an integrated luminosity of 35.9 fb-1 . The mass range investigated extends upwards from 1.2 TeV. No excess is observed above the estimated standard model background and limits are set at 95% confidence level on cross sections, which are interpreted in terms of various models that predict gravitons, heavy spin-1 bosons, and excited quarks. In a heavy vector triplet model, W' and Z' resonances, with masses below 3.2 and 2.7 TeV, respectively, and spin-1 resonances with degenerate masses below 3.8 TeV are excluded at 95% confidence level. In the case of a singlet W' resonance masses between 3.3 and 3.6 TeV can be excluded additionally. Similarly, excited quark resonances, q*, decaying to q W and q Z with masses less than 5.0 and 4.7 TeV, respectively, are excluded. In a narrow-width bulk graviton model, upper limits are set on cross sections ranging from 0.6 fb for high resonance masses above 3.6 TeV, to 36.0 fb for low resonance masses of 1.3 TeV.

Complex chromosome rearrangement in a child with microcephaly, dysmorphic facial features and mosaicism for a terminal deletion del(18(q21.32-qter investigated by FISH and array-CGH: Case report

Directory of Open Access Journals (Sweden)

Kokotas Haris

2008-11-01

Full Text Available Abstract We report on a 7 years and 4 months old Greek boy with mild microcephaly and dysmorphic facial features. He was a sociable child with maxillary hypoplasia, epicanthal folds, upslanting palpebral fissures with long eyelashes, and hypertelorism. His ears were prominent and dysmorphic, he had a long philtrum and a high arched palate. His weight was 17 kg (25th percentile and his height 120 cm (50th percentile. High resolution chromosome analysis identified in 50% of the cells a normal male karyotype, and in 50% of the cells one chromosome 18 showed a terminal deletion from 18q21.32. Molecular cytogenetic investigation confirmed a del(18(q21.32-qter in the one chromosome 18, but furthermore revealed the presence of a duplication in q21.2 in the other chromosome 18. The case is discussed concerning comparable previously reported cases and the possible mechanisms of formation.

Q-instantons

NARCIS (Netherlands)

Bergshoeff, E. A.; Hartong, J.; Ploegh, A.; Sorokin, D.

We construct the half-supersymmetric instanton solutions that are electric-magnetically dual to the recently discussed half-supersymmetric Q7-branes. We call these instantons "Q-instantons". Whereas the D-instanton is most conveniently described using the RR axion chi and the dilaton phi, the

Disparities in visuo-spatial constructive abilities in Williams syndrome patients with typical deletion on chromosome 7q11.23.

Science.gov (United States)

Muramatsu, Yukako; Tokita, Yoshihito; Mizuno, Seiji; Nakamura, Miho

2017-02-01

Williams syndrome (WS) is known for its uneven cognitive abilities, especially the difficulty in visuo-spatial cognition, though there are some inter-individual phenotypic differences. It has been proposed that the difficulty in visuo-spatial cognition of WS patients can be attributed to a haploinsufficiency of some genes located on the deleted region in 7q11.23, based on an examination of atypical deletions identified in WS patients with atypical cognitive deficits. According to this hypothesis, the inter-individual differences in visuo-spatial cognitive ability arise from variations in deletion. We investigated whether there were inter-individual differences in the visuo-spatial constructive abilities of five unrelated WS patients with the typical deletion on chromosome 7q11.23 that includes the candidate genes contributing visuo-spatial difficulty in WS patients. We used tests with three-dimensional factors such as Benton's three-dimensional block construction test, which are considered to be more sensitive than those with only two-dimensional factors. There were diverse inter-individual differences in the visuo-spatial constructive abilities among the present participants who shared the same typical genomic deletion of WS. One of the participants showed almost equivalent performances to typically developing adults in those tests. In the present study, we found a wide range of cognitive abilities in visuo-spatial construction even among the patients with a common deletion pattern of WS. The findings suggest that attributing differences in the phenotypes entirely to genetic factors such as an atypical deletion may not be always correct. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Multistudy fine mapping of chromosome 2q identifies XRCC5 as a chronic obstructive pulmonary disease susceptibility gene

DEFF Research Database (Denmark)

Hersh, Craig P; Pillai, Sreekumar G; Zhu, Guohua

2010-01-01

RATIONALE: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q. OBJECTIVES: We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead to the ident......RATIONALE: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q. OBJECTIVES: We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead...... the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families...

Search of type 2 diabetes susceptibility gene on chromosome 20q

International Nuclear Information System (INIS)

Takeuchi, F.; Yanai, K.; Inomata, H.; Kuzuya, N.; Kajio, H.; Honjo, S.; Takeda, N.; Kaburagi, Y.; Yasuda, K.; Shirasawa, S.; Sasazuki, T.; Kato, N.

2007-01-01

Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4α (HNF4A) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP, with an estimated odds ratio of 1.73 (95% CI 1.30-2.31) (P 0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

OpenAIRE

Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

2016-01-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and deve...

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression

DEFF Research Database (Denmark)

Wyszynski, Asaf; Hong, Chi-chen; Lam, Kristin

2016-01-01

Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35...... suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5....

Partial trisomy 14q and monosomy 20q due to an unbalanced familial translocation

Energy Technology Data Exchange (ETDEWEB)

Menasse-Palmer, L; Leo, J.; Cannizaro, L. [Albert Einstein College of Medicine, Bronx, NY (United States)] [and others

1994-09-01

Partial trisomy of distal 14q and monosomy of 20q are rare. There have been several reports of a partial distal trisomy 14q with characteristic clinical findings, including hypogonadism and a conotruncal cardiac anomaly. There is no deletion distal 20q syndrome. We have recently examined a newborn with this unique duplication/deletion syndrome. Case report: J.S. was the 2980 gm product of a term uneventful pregnancy delivered to a 24-year-old gravida 2, para 1001 mother. The newborn exam revealed a dysmorphic newborn male with a sloping forehead, bitemporal narrowing, glabellar furrowing and micrognathia. A systolic murmur was audible. The genital abnormalities were micropenis, hypospadias with chordee and bifid scrotum with prominent raphe, and gonads were palpable. A CAT scan of the head revealed grade I IVH. An echocardiogram showed a VSD, ASD and an AP window. A sonogram of the liver showed absence of the gallbladder. Chromosome analysis revealed an abnormal male karyotype containing a derivative 20, subsequently shown to be inherited as a result of malsegregation of a paternal translocation: 46,XY,-20,+der(20)t(14;20)(q32.1;q13.3)pat. The infant fed poorly and required tube feedings and was treated for congestive heart failure with Digoxin, Lasix and oxygen. A decreased cortisol level and cholestasis were noted. The infant died after a cardiopulmonary arrest at one month of age. No post-mortem was obtained. Clinical cytogenetic correlation (conotruncal abnormality and hypogonadism) with partial duplication of distal 14q was positive. This case helps to further delineate duplication 14q and a syndrome due to partial deletion 20q.

Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints

International Nuclear Information System (INIS)

Croce, C.M.; Huebner, K.; Isobe, M.; Fainstain, E.; Lifshitz, B.; Shtivelman, E.; Canaani, E.

1987-01-01

A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the other contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kikobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin λ light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph 1 ). Similarly, in mouse-human hybrids retaining a Ph 1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q + and 22, only BCR2 and BCR4 loci are retained. Thus, the order of loci on chromosome 22 is centromere → BCR2, BCR4, and IGL → BCR1 → BCR3 → SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph 1 chromosome

Experimental cross sections for two-electron capture into nitrogen autoionising states in Nsup(q+) (q=6,7) on He and H/sub 2/ collisions at 10. 5q keV

Energy Technology Data Exchange (ETDEWEB)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Marrakchi, A.I.; Dousson, S.; Hitz, D.

1985-07-01

Singly differential cross sections for two-electron capture into autoionising states (nl,n'l') with n=2,3,4 and n'>=n in Nsup(q+) (q=6,7) on He and H/sub 2/ collisions have been measured at 10,5q ke V collision energy and an observation angle thetasub(lab)=11.6/sup 0/. Total cross sections are estimated assuming isotropic angular distributions. (orig.).

Chromosome r(10(p15.3q26.12 in a newborn child: case report

Directory of Open Access Journals (Sweden)

Jonasson Jon

2009-12-01

Full Text Available Abstract Background Ring chromosome 10 is a rare cytogenetic finding. Of the less than 10 reported cases we have found in the literature, none was characterized using high-resolution microarray analysis. Ring chromosomes are frequently unstable due to sister chromatid exchanges and mitotic failures. When mosaicism is present, the interpretation of genotype-phenotype correlations becomes extremely difficult. Results We report on a newborn girl with growth retardation, microcephaly, congenital heart defects, dysmorphic features and psychomotor retardation. Karyotyping revealed a non-mosaic apparently stable ring chromosome 10 replacing one of the normal homologues in all analyzed metaphases. High-resolution oligonucleotide microarray analysis showed a de novo approximately 12.5 Mb terminal deletion 10q26.12 -> qter and a corresponding 285 kb terminal deletion of 10pter -> p15.3. Conclusion This case demonstrates that an increased nuchal translucency thickness detected by early ultrasonography should preferably lead to not only QF-PCR for the diagnosis of Down syndrome but also karyotyping. In the future, microarray analysis, which needs further evaluation, might become the method of choice. The clinical phenotype of our patient was in agreement with that of patients with a terminal 10q deletion. For the purpose of genotype-phenotype analysis, there seems to be no need for a "ring syndrome" concept.

[A case of mosaic ring chromosome 4 with subtelomeric 4p deletion].

Science.gov (United States)

Kim, Jeong Hyun; Oh, Phil Soo; Na, Hye Yeon; Kim, Sun-Hee; Cho, Hyoun Chan

2009-02-01

Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2

Preparation and in vitro-in vivo evaluation of Witepsol H35 based self-nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q(10).

Science.gov (United States)

Nepal, Pushp R; Han, Hyo-Kyung; Choi, Hoo-Kyun

2010-02-19

Coenzyme Q(10) (CoQ(10)) was formulated into self-nanoemulsifying drug delivery systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature of the drug. Screening of oil phase, surfactants and co-surfactants were performed to select Witepsol H35, Solutol HS15 and Lauroglycol FCC, respectively. Ternary phase diagrams were drawn to identify nanoemulsifying region followed by optimization of SNEDDS formulation. The optimized formulation, CoQ(10), Witepsol H35, Solutol HS15 and Lauroglycol FCC in the weight ratio of 1:0.7:4:2, respectively, emulsified readily at 37 degrees C with mean emulsion droplet size of 32.4 nm. The stability test of the optimized formulation in pH 1.2 and 6.8 buffers confirmed no pH effect on emulsion droplet size. In vitro dissolution (emulsification) test and in vivo animal study of the formulation elucidated the complete emulsification of drug and improved oral bioavailability of poorly soluble CoQ(10). 2009 Elsevier B.V. All rights reserved.

19q12q13.2 duplication syndrome: neuropsychiatric long-term follow-up of a new case and literature update

Directory of Open Access Journals (Sweden)

Nacinovich R

2017-10-01

Full Text Available Renata Nacinovich,1,2 Nicoletta Villa,3 Fiorenza Broggi,1,2 Cristina Tavaniello,1 Monica Bomba,1 Donatella Conconi,2 Serena Redaelli,2 Elena Sala,3 Marialuisa Lavitrano,2 Francesca Neri1,2 1Childhood and Adolescence Neuropsychiatric Unit, San Gerardo Hospital, 2School of Medicine and Surgery, University of Milano Bicocca, 3Medical Genetics Laboratory, Clinical Pathology Department, San Gerardo Hospital, Monza, Italy Abstract: Genetic syndromes are well characterized by the phenotypic point of view, but little is known about their progression and patients’ quality of life. We report a 10-year neuropsychiatric follow-up of a boy with duplication of chromosome 19. Cytogenetic investigation was requested at the age of 5 years for psychomotor and speech delay. The genomic study identified an 8.17 Mb duplication on chromosome 19q12q13.2. We propose that the long-term follow-up of our patient would help to delineate the neuropsychiatric phenotype associated with 19q duplication. This study could be a model for further long-term research in the neuropsychiatric follow-up of patients with 19q duplication syndrome. Keywords: 19q duplication, neuropsychiatric follow-up, array-CGH

Chromosomal localization of the human diazepam binding inhibitor gene

International Nuclear Information System (INIS)

DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.

1988-01-01

The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the γ-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes

Complex chromosomal rearrangement in a girl with psychomotor-retardation and a de novo inversion: inv(2)(p15;q24.2).

Science.gov (United States)

Granot-Hershkovitz, Einat; Raas-Rothschild, Annick; Frumkin, Ayala; Granot, David; Silverstein, Shira; Abeliovich, Dvorah

2011-08-01

Cytogenetic analysis of DNA from a girl with severe psychomotor retardation revealed a de novo pericentric inversion of chromosome 2: 46,XX,inv(2)(p15q24.2). In order to elucidate the possible role of the inversion in the girl's abnormal phenotype, we analyzed the inversion breakpoints. FISH analysis revealed BAC clones spanning the breakpoints at 2p and 2q of the inversion. Southern blot hybridization with DNA probes from the BAC regions was used to refine the localization of the breakpoints, followed by inverse-PCR which enabled us to sequence the inversion breakpoints. We found a complex chromosomal rearrangement, including five breakpoints, four at 2q and one at 2p joined with minor insertions/deletions of a few bases. The breakpoint at 2p was within the NRXN1 gene that has previously been associated with autism, intellectual disabilities, and psychiatric disorders. In 2q, the breakpoints disrupted two genes, TANC1 and RBMS1; the phenotypic effect of these genes is not currently known. Copyright © 2011 Wiley-Liss, Inc.

High rates of de novo 15q11q13 inversions in human spermatozoa

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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.

A Case with 46,XX,dup(X(q21.3q24 karyotype

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Selda Şimşek

2010-03-01

Full Text Available The relationship between phenotype and Xq duplicationsin females remains unclear. Some females are normal;some have short stature; and others have features suchas microcephaly, developmental delay/mental retardation,body asymmetries, and gonadal dysgenesis. Somefeatures in these females resemble those in Turner syndrome.We, herein, presented a 15 years-old girl withshort stature and primary amenorrhea, who was referredto cytogenetic laboratory. Through karyotipe analysis performedby Giemsa banding technique, the patient wasdetermined to have positive Barr body and 46,XX,dup(X(q21.3q24 chromosomal constitution. Case was discussedaccording to information of present literatures.

Chromosomal Changes in relation to Clinical Outcome in Larynx and Pharynx Squamous Cell Carcinoma

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Mario Hermsen

2005-01-01

Full Text Available Invasive head and neck squamous carcinomas are among the cytogenetically most complex tumors. Perhaps for this reason, there is little consensus on the prognostic value of specific chromosomal aberrations. Here we present Results of CGH analysis of 56 clinically well-characterized set of head and neck cancers, consisting of larynx and pharynx only. The aim was to find possible associations with clinical outcome. The major chromosome arms showing gains were (in decreasing order: 3q, 7q, 8q, 5p, 11q13, 17q and 18p, and losses occurred at 3p, 11qter, 4p, 18q, and 5q. The segments most frequently amplified were 3q26-qter, 11q13, 11q22, 3q12–13, 18p11.3, 18q11.2 and 8q24.3. Tumors with stages III and IV, and lymph node positive tumors had a worse clinical outcome. Surprisingly, no specific chromosomal abnormality correlated with disease-free survival. The only aberration that correlated to one of the clinico-pathological parameters was amplification 11q13, that occurred solely in lymph node positive, stage IV tumors. However 11q13 amplification did not correlate with disease-free survival. These Results seem to indicate that genetic alterations at the level of chromosomes have limited prognostic value in patients with invasive larynx and pharynx squamous cell carcinomas.

Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence.

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Lin, Peng; Hartz, Sarah M; Wang, Jen-Chyong; Agrawal, Arpana; Zhang, Tian-Xiao; McKenna, Nicholas; Bucholz, Kathleen; Brooks, Andrew I; Tischfield, Jay A; Edenberg, Howard J; Hesselbrock, Victor M; Kramer, John R; Kuperman, Samuel; Schuckit, Marc A; Goate, Alison M; Bierut, Laura J; Rice, John P

2012-09-01

Excessive alcohol use is the third leading cause of preventable death and is highly correlated with alcohol dependence, a heritable phenotype. Many genetic factors for alcohol dependence have been found, but many remain unknown. In search of additional genetic factors, we examined the association between Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition (DSM-IV) alcohol dependence and all common copy number variations (CNVs) with good reliability in the Study of Addiction: Genetics and Environment (SAGE). All participants in SAGE were interviewed using the Semi-Structured Assessment for the Genetics of Alcoholism, as a part of 3 contributing studies. A total of 2,610 non-Hispanic European American samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNVPartition, PennCNV, and QuantiSNP, and only CNVs identified by all 3 software programs were examined. Association was conducted with the CNV (as a deletion/duplication) as well as with probes in the CNV region. Quantitative polymerase chain reaction (qPCR) was used to validate the CNVs in the laboratory. CNVs in 6q14.1 (p = 1.04 × 10(-6)) and 5q13.2 (p = 3.37 × 10(-4)) were significantly associated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2, there were multiple candidate genes previously associated with various neurological disorders. The region on chromosome 6q14.1 is a gene desert that has been associated with mental retardation and language delay. The CNV in 5q13.2 was validated, whereas only a component of the CNV on 6q14.1 was validated by qPCR. Thus, the CNV on 6q14.1 should be viewed with caution. This is the first study to show an association between DSM-IV alcohol dependence and CNVs. CNVs in regions previously associated with neurological disorders may be associated with alcohol dependence. Copyright © 2012 by the Research Society on Alcoholism.

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors

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Bystroem, C.; Larsson, C.; Blomberg, C.; Nordenskjoeld, M.; Sandelin, K.; Falkmer, U.; Werner, S.; Skogseid, B.; Oeberg, K.

1990-01-01

The gene for multiple endocrine neoplasia type 1 (MEN1), and inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. The authors now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, they could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas

Identification of susceptibility genes for bipolar affective disorder and schizophrenia on chromosome 22q13

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Severinsen, Jacob Eg

2006-01-01

Linkage analyses suggest that chromosome 22q12-13 may harbor one or more shared susceptibility loci for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of distantly related cases and control individuals from the Faeroe Islands our group has previously reported that chromosome 22...... samples (total of 1,751 individuals), and by bioinformatic and expression analyses of a subset of disease associated genes and gene variants. In total 67 single nucleotide polymorphisms (SNPs) located in 18 positional candidate genes, and 4 microsattelite markers were investigated, using a Scottish case...

The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report

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Yonal Ipek

2012-02-01

Full Text Available Abstract Introduction Therapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens. Case presentation We report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a. Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34, deletion 20 (q11.2q13.1 karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situhybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine and our patient died in the 11th month after diagnosis. Conclusions The median survival in therapy-related acute myeloid leukemia is shorter compared to de novoacute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal.

A case of refractory anemia with chromosomal abnormality (5q-) in Nagasaki atomic bomb survivor

International Nuclear Information System (INIS)

Kusano, Miyuki; Ikeda, Shuichi; Tomonaga, Yu; Sadamori, Naoki; Matsunaga, Masako

1978-01-01

Although assumed to be almost free from the effect of A-bomb radiation on the basis of the estimated dose, this case had progressive anemia with a specific manifestation and disclosed a clone with chromosomal abnormality (5q - ). In pure leukemia, a clone of abnormal chromosome is considered exactly that of leukemia. However, the presence of clones with chromosomal abnormality which are found in polycythemia vera or myelofibrosis do not always denote the leukemic changes. There is no established theory as to the significance of the clones with chromosomal abnormality in refractory anemia. Thus the interpretation of chromosomal abnormality in blood diseases is very difficult. Therefore analysis of chromosomes will be made actively in leukemia and related diseases as well as refractory anemia and preleukemia, and those will be compared in detail to search the relation between on occurrence of leukemia and chromosomal abnormality and also that between chromosomal abnormality and exposure to radiation. (Ueda, J.)

Chromosome 15q25 (CHRNA3-CHRNA5 variation impacts indirectly on lung cancer risk.

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Yufei Wang

2011-04-01

Full Text Available Genetic variants at the 15q25 CHRNA5-CHRNA3 locus have been shown to influence lung cancer risk however there is controversy as to whether variants have a direct carcinogenic effect on lung cancer risk or impact indirectly through smoking behavior. We have performed a detailed analysis of the 15q25 risk variants rs12914385 and rs8042374 with smoking behavior and lung cancer risk in 4,343 lung cancer cases and 1,479 controls from the Genetic Lung Cancer Predisposition Study (GELCAPS. A strong association between rs12914385 and rs8042374, and lung cancer risk was shown, odds ratios (OR were 1.44, (95% confidence interval (CI: 1.29-1.62, P = 3.69×10(-10 and 1.35 (95% CI: 1.18-1.55, P = 9.99×10(-6 respectively. Each copy of risk alleles at rs12914385 and rs8042374 was associated with increased cigarette consumption of 1.0 and 0.9 cigarettes per day (CPD (P = 5.18×10(-5 and P = 5.65×10(-3. These genetically determined modest differences in smoking behavior can be shown to be sufficient to account for the 15q25 association with lung cancer risk. To further verify the indirect effect of 15q25 on the risk, we restricted our analysis of lung cancer risk to never-smokers and conducted a meta-analysis of previously published studies of lung cancer risk in never-smokers. Never-smoker studies published in English were ascertained from PubMed stipulating--lung cancer, risk, genome-wide association, candidate genes. Our study and five previously published studies provided data on 2,405 never-smoker lung cancer cases and 7,622 controls. In the pooled analysis no association has been found between the 15q25 variation and lung cancer risk (OR = 1.09, 95% CI: 0.94-1.28. This study affirms the 15q25 association with smoking and is consistent with an indirect link between genotype and lung cancer risk.

Overlapping Numerical Cognition Impairments in Children with Chromosome 22q11.2 Deletion or Turner Syndromes

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Simon, T. J.; Takarae, Y.; DeBoer, T.; McDonald-McGinn, D. M.; Zackai, E. H.; Ross, J. L.

2008-01-01

Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor…

q-bosons and the q-analogue quantized field

International Nuclear Information System (INIS)

Nelson, C.A.

1994-01-01

The q-analogue coherent states |z > q are used to identify physical signatures for the presence of a q-analogue quantized radiation field in the | > q classical limit where |z| is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/|z|) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H N = ℎω(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (ΔN) 2 / → 0 as |z| → ∞. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, φ q , still exhibits normal classical behavior. The standard number-phase uncertainty-relation, ΔN Δφ q = 1/2, and the approximate commutation relation, [N,φ q ] = i, still hold for the single-mode q-analogue quantized field. So, N and φ q are almost canonically conjugate operators in the |z > q classical limit. The |z > q CS's minimize this uncertainty relation for moderate |z| 2

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

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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.

Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma

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Wang Shengyue

2011-07-01

Full Text Available Abstract Background Hepatocellular carcinoma (HCC is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution. Methods A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR. Results A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64% mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%, 11 (21%, 11 (21% and 23 (44% of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts. Conclusions Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus.

Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

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Silke Wemmert

2005-10-01

Full Text Available Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group and 30 patients received radiotherapy alone (RT group. The most common aberrations detected were gains of parts of chromosome 7 and losses of 10% 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months. Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.

Evidence for an asthma risk locus on chromosome Xp: a replication linkage study

DEFF Research Database (Denmark)

Brasch-Andersen, C; Møller, M U; Haagerup, A

2008-01-01

replication sample as used in the present study. The aim of the study was to replicate linkage to candidate regions for asthma in an independent Danish sample. METHODS: We performed a replication study investigating linkage to candidate regions for asthma on chromosomes 1p36.31-p36.21, 5q15-q23.2, 6p24.3-p22...... studies have been carried out the results are still conflicting and call for replication experiments. A Danish genome-wide scan has prior reported evidence for candidate regions for asthma susceptibility genes on chromosomes 1p, 5q, 6p, 12q and Xp. Linkage to chromosome 12q was later confirmed in the same.......3, and Xp22.31-p11.4 using additional markers in an independent set of 136 Danish asthmatic sib pair families. RESULTS: Nonparametric multipoint linkage analyses yielded suggestive evidence for linkage to asthma to chromosome Xp21.2 (MLS 2.92) but failed to replicate linkage to chromosomes 1p36.31-p36.21, 5...

Identification of a Cryptic Insertion ins(11;X)(q23;q28q12) Resulting in a KMT2A-FLNA Fusion in a 13-Month-Old Child with Acute Myelomonocytic Leukemia.

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Lentes, Jana; Thomay, Kathrin; Schneider, Dominik T; Bernbeck, Benedikt; Reinhardt, Dirk; Marschalek, Rolf; Meyer, Claus; Schlegelberger, Brigitte; Göhring, Gudrun

2016-01-01

In pediatric acute myeloid leukemia (AML), chromosomal abnormalities leading to a disruption of the lysine methyltransferase 2A (KMT2A) gene in 11q23 are the most frequent rearrangements. Here, we report on the identification of a novel cryptic insertion, ins(11;X)(q23;q28q12), resulting in a translocation of the KMT2A gene in 11q23, leading to a KMT2A-FLNA fusion in a 13-month-old boy with de novo acute myelomonocytic leukemia, who died 38 days after diagnosis. The patient presented a complex karyotype 48∼49,Y,del(X)(q12),+del(X)(q12),+8,ins(11;X)(q23; q28q12),+19. The identified fusion gene was predicted to be out-of-frame (fusion of portions of KMT2A exon 11 with FLNA exon 11). However, RT-PCR experiments demonstrated that a potentially functional transcript was generated by alternative splicing where KMT2A exon 10 was spliced in-frame to the truncated FLNA exon 11. This case report helps to better understand the rare but potentially severe impact of KMT2A- FLNA fusions in infants with AML to improve prognostic stratification of therapy and clinical management. © 2017 S. Karger AG, Basel.

Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the dic(9;20)(p11-13;q11) show recurrent involvement of genes at 20q11.21.

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An, Qian; Wright, Sarah L; Moorman, Anthony V; Parker, Helen; Griffiths, Mike; Ross, Fiona M; Davies, Teresa; Harrison, Christine J; Strefford, Jon C

2009-08-01

The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia. Although it results in loss of material from 9p and 20q, the molecular targets on both chromosomes have not been fully elucidated. From an initial cohort of 58 with acute lymphoblastic leukemia patients with this translocation, breakpoint mapping with fluorescence in situ hybridization on 26 of them revealed breakpoint heterogeneity of both chromosomes. PAX5 has been proposed to be the target gene on 9p, while for 20q, FISH analysis implicated the involvement of the ASXL1 gene, either by a breakpoint within (n=4) or centromeric (deletion, n=12) of the gene. Molecular copy-number counting, long-distance inverse PCR and direct sequence analysis identified six dic(9;20) breakpoint sequences. In addition to the three previously reported: PAX5-ASXL1, PAX5-C20ORF112 and PAX5-KIF3B; we identified three new ones in this study: sequences 3' of PAX5 disrupting ASXL1, and ZCCHC7 disrupted by sequences 3' of FRG1B and LOC1499503. This study provides insight into the breakpoint complexity underlying dicentric chromosomal formation in acute lymphoblastic leukemia and highlights putative target gene loci.

RECENT ADVANCES IN THE 5Q- SYNDROME

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Andrea Pellagatti

2015-05-01

Full Text Available The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS and patients with this disorder have a deletion of chromosome 5q [del(5q] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q MDS patients. Potential new therapeutic agents for del(5q MDS include the translation enhancer L-leucine.

Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-κB Gene Network

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Jing Fang

2014-09-01

Full Text Available Chromosome 5q deletions (del[5q] are common in high-risk (HR myelodysplastic syndrome (MDS and acute myeloid leukemia (AML; however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q HR MDS/AML and miR-146a−/− hematopoietic stem/progenitor cells (HSPCs results in TRAF6/NF-κB activation. Increased survival and proliferation of HSPCs from miR-146alow HR MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62, expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-κB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-κB signaling, as disrupting the p62-TRAF6 signaling complex results in cell-cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q HR MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-κB to sustain TRAF6/NF-κB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q MDS/AML.

Refinement of the deletion in 8q22.2-q22.3: the minimum deletion size at 8q22.3 related to intellectual disability and epilepsy.

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Kuroda, Yukiko; Ohashi, Ikuko; Saito, Toshiyuki; Nagai, Jun-ichi; Ida, Kazumi; Naruto, Takuya; Iai, Mizue; Kurosawa, Kenji

2014-08-01

Kuechler et al. [2011] reported five patients with interstitial deletions in 8q22.2-q22.3 who had intellectual disability, epilepsy, and dysmorphic features. We report on a new patient with the smallest overlapping de novo deletion in 8q22.3 and refined the phenotype. The proposita was an 8-year-old girl, who developed seizures at 10 months, and her epileptic seizure became severe and difficult to control with antiepileptic drugs. She also exhibited developmental delay and walked alone at 24 months. She was referred to us for evaluation for developmental delay and epilepsy at the age of 8 years. She had intellectual disability (IQ 37 at 7 years) and autistic behavior, and spoke two word sentences at 8 years. She had mild dysmorphic features, including telecanthus and thick vermilion of the lips. Array comparative genomic hybridization detected a 1.36 Mb deletion in 8q22.3 that encompassed RRM2B and NCALD, which encode the small subunit of p53-inducible ribonucleotide reductase and neurocalcin delta in the neuronal calcium sensor family of calcium-binding proteins, respectively. The minimum overlapping region between the present and previously reported patients is considered to be a critical region for the phenotype of the deletion in 8q22.3. We suggest that the deletion in 8q22.3 may represent a clinically recognizable condition, which is characterized by intellectual disability and epilepsy. © 2014 Wiley Periodicals, Inc.

Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

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Konstantina Fragaki

Full Text Available BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %, thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

Q-bank phytoplasma database

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Contaldo, Nicoletta; Bertaccini, Assunta; Nicolaisen, Mogens

2014-01-01

The setting of the Q-Bank database free available on line for quarantine phytoplasma and also for general phytoplasma identification is described. The tool was developed in the frame of the EU-FP7 project Qbol and is linked with a new project Q-collect in order to made widely available the identi......The setting of the Q-Bank database free available on line for quarantine phytoplasma and also for general phytoplasma identification is described. The tool was developed in the frame of the EU-FP7 project Qbol and is linked with a new project Q-collect in order to made widely available...

On the q-exponential of matrix q-Lie algebras

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Ernst Thomas

2017-01-01

Full Text Available In this paper, we define several new concepts in the borderline between linear algebra, Lie groups and q-calculus.We first introduce the ring epimorphism r, the set of all inversions of the basis q, and then the important q-determinant and corresponding q-scalar products from an earlier paper. Then we discuss matrix q-Lie algebras with a modified q-addition, and compute the matrix q-exponential to form the corresponding n × n matrix, a so-called q-Lie group, or manifold, usually with q-determinant 1. The corresponding matrix multiplication is twisted under τ, which makes it possible to draw diagrams similar to Lie group theory for the q-exponential, or the so-called q-morphism. There is no definition of letter multiplication in a general alphabet, but in this article we introduce new q-number systems, the biring of q-integers, and the extended q-rational numbers. Furthermore, we provide examples of matrices in suq(4, and its corresponding q-Lie group. We conclude with an example of system of equations with Ward number coeficients.

The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes

Science.gov (United States)

2017-10-01

chromosome 5q (del(5q)). There are two common deleted regions (CDRs) identified on 5q: a distal locus that is often deleted in 5q- syndrome with good ...chromosome 5q being the most common . Our recently published work demonstrated that loss of mDia1, a protein with its encoding genes located at chromosome 5...is the most common cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). We discovered in 2014 that CD14 was aberrantly

Heavy-Quark Symmetry Implies Stable Heavy Tetraquark Mesons Q_{i}Q_{j}q[over ¯]_{k}q[over ¯]_{l}.

Science.gov (United States)

Eichten, Estia J; Quigg, Chris

2017-11-17

For very heavy quarks Q, relations derived from heavy-quark symmetry predict the existence of novel narrow doubly heavy tetraquark states of the form Q_{i}Q_{j}q[over ¯]_{k}q[over ¯]_{l} (subscripts label flavors), where q designates a light quark. By evaluating finite-mass corrections, we predict that double-beauty states composed of bbu[over ¯]d[over ¯], bbu[over ¯]s[over ¯], and bbd[over ¯]s[over ¯] will be stable against strong decays, whereas the double-charm states ccq[over ¯]_{k}q[over ¯]_{l}, mixed beauty+charm states bcq[over ¯]_{k}q[over ¯]_{l}, and heavier bbq[over ¯]_{k}q[over ¯]_{l} states will dissociate into pairs of heavy-light mesons. Observation of a new double-beauty state through its weak decays would establish the existence of tetraquarks and illuminate the role of heavy color-antitriplet diquarks as hadron constituents.

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

Science.gov (United States)

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

2016-10-01

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

Concurrent deletion of 16q23 and PTEN is an independent prognostic feature in prostate cancer.

Science.gov (United States)

Kluth, Martina; Runte, Frederic; Barow, Philipp; Omari, Jazan; Abdelaziz, Zaid M; Paustian, Lisa; Steurer, Stefan; Christina Tsourlakis, Maria; Fisch, Margit; Graefen, Markus; Tennstedt, Pierre; Huland, Hartwig; Michl, Uwe; Minner, Sarah; Sauter, Guido; Simon, Ronald; Adam, Meike; Schlomm, Thorsten

2015-11-15

The deletion of 16q23-q24 belongs to the most frequent chromosomal changes in prostate cancer, but the clinical consequences of this alteration have not been studied in detail. We performed fluorescence in situ hybridization analysis using a 16q23 probe in more than 7,400 prostate cancers with clinical follow-up data assembled in a tissue microarray format. Chromosome 16q deletion was found in 21% of cancers, and was linked to advanced tumor stage, high Gleason grade, accelerated cell proliferation, the presence of lymph node metastases (p Deletion was more frequent in ERG fusion-positive (27%) as compared to ERG fusion-negative cancers (16%, p deletions including phosphatase and tensin homolog (PTEN) (p deletion of 16q was linked to early biochemical recurrence independently from the ERG status (p deletion of 16q alone. Multivariate modeling revealed that the prognostic value of 16q/PTEN deletion patterns was independent from the established prognostic factors. In summary, the results of our study demonstrate that the deletion of 16q and PTEN cooperatively drives prostate cancer progression, and suggests that deletion analysis of 16q and PTEN could be of important clinical value particularly for preoperative risk assessment of the clinically most challenging group of low- and intermediated grade prostate cancers. © 2015 UICC.

Abnormalities of chromosome No. 1: significance in malignant transformation

Energy Technology Data Exchange (ETDEWEB)

Rowley, J D

1978-01-01

Studies of human hematologic malignancies have provided sufficient data not only for the identification of nonrandom abnormalities of whole chromosomes, but also for determination of the specific chromosome regions involved. In clonal aberrations leading to an excess of chromosome No. 1, or a partial excess of No. 1, trisomy for bands 1q25 to 1q32 was noted in the myeloid cells obtained from every one of 35 patients who had various disorders, such as acute leukemia, polycythemia vera, or myelofibrosis. Similar chromosome changes were a consistent finding in various solid tumors as well. This rearrangement was not the result of a particularly fragile site in that region of the chromosome, since the break points in reciprocal translocations that involve No. 1 occurred almost exclusively in the short arm. The nonrandom chromosome changes found in neoplastic cells can now be correlated with the gene loci on these chromosomes or chromosome segments as an attempt is made to identify specific genes that might be related to malignancy.

Detection of Chromosome X;18 Breakpoints and Translocation of the Xq22.3;18q23 Regions Resulting in Variable Fertility Phenotypes

Directory of Open Access Journals (Sweden)

Attila Szvetko

2012-01-01

Full Text Available We describe a familial pattern of gonosomal-autosomal translocation between the X and 18 chromosomes, balanced and unbalanced forms, in male and female siblings. The proposita was consulted for hypergonadotropic hypogonadism. Karyotype analysis revealed a balanced 46, X, t(X;18(q22.3;q23 genotype. The sister of the proband presented with oligomenorrhea with irregular menses and possesses an unbalanced form of the translocation 46, X, der(X, t(X;18(q22.3;q23. The brother of the proband was investigated and was found to possess the balanced form of the same translocation, resulting in disrupted spermatogenesis. Maternal investigation revealed the progenitor karyotype 46, X, t(X;18(q22.3;q23. Maternal inheritance and various genomic events contributed to the resultant genotypes. Primary infertility was initially diagnosed in all progeny; however, the male individual recently fathered twins. We briefly review the mechanisms associated with X;18 translocations and describe a pattern of inheritance, where breakpoints and translocation of the Xq22.3;18q23 regions have resulted in variable fertility.

De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy.

Science.gov (United States)

Vari, Maria Stella; Traverso, Monica; Bellini, Tommaso; Madia, Francesca; Pinto, Francesca; Minetti, Carlo; Striano, Pasquale; Zara, Federico

2017-08-01

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and may be associated with acquired central nervous system lesions or could be genetic. Various susceptibility genes and environmental factors are believed to be involved in the aetiology of TLE, which is considered to be a heterogeneous, polygenic, and complex disorder. Rare point mutations in LGI1, DEPDC5, and RELN as well as some copy number variations (CNVs) have been reported in families with TLE patients. We perform a genetic analysis by Array-CGH in a patient with dysmorphic features and temporal lobe epilepsy. We report a de novo duplication of the long arm of chromosome 12. We confirm that 12q22-q23.3 is a candidate locus for familial temporal lobe epilepsy with febrile seizures and highlight the role of chromosomal rearrangements in patients with epilepsy and intellectual disability. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Olanzapine induced Q-Tc shortening.

Science.gov (United States)

Shoja Shafti, Saeed; Fallah Jahromi, Parisa

2014-12-01

Prolongation of Q-Tc interval is commonly accepted as a surrogate marker for the ability of a drug to cause torsade de pointes. In the present study, safety of olanzapine versus risperidone was compared among a group of patients with schizophrenia to see the frequency of the electrocardiographic alterations induced by those atypical antipsychotics. Two hundred and sixty-eight female inpatients with schizophrenia entered in one of the two parallel groups to participate in an open study for random assignment to olanzapine (n = 148) or risperidone (n = 120). Standard 12-lead surface electrocardiogram (ECG) was taken from each patient at baseline, before initiation of treatment, and then at the end of management, just before discharge. The parameters that were assessed included heart rate (HR), P-R interval, QRS interval, Q-T interval (corrected = Q-Tc), ventricular activation time (VAT), ST segment, T wave, axis of QRS, and finally, interventricular conduction process. A total of 37.83% of cases in the olanzapine group and 30% in the risperidone group showed some Q-Tc changes; 13.51% and 24.32% of the patients in the olanzapine group showed prolongation and shortening of the Q-Tc, respectively, while changes in the risperidone group were restricted to only prolongation of Q-Tc. Comparison of means showed a significant increment in Q-Tc by risperidone (p = 0.02). Also, comparison of proportions in the olanzapine group showed significantly more cases with shortening of Q-Tc versus its prolongation (p = 0.01). No significant alterations with respect to other variables were evident. Olanzapine and risperidone had comparable potentiality for induction of Q-Tc changes, while production of further miscellaneous alterations in ECG was more observable in the olanzapine group compared with the risperidone group. Also shortening of Q-Tc was specific to olanzapine.

[Recombinant chromosome 4 with partial 4p deletion and 4q duplication inherited from paternal pericentric inversion].

Science.gov (United States)

Mun, Se Jin; Cho, Eun Hae; Chey, Myoung-Jae; Shim, Gyu-Hong; Shin, Bo-Moon; Lee, Rae-Kyung; Ko, Ji-Kyung; Yoo, Soo Jin

2010-02-01

Pericentric inversion of chromosome 4 can give rise to 2 alternate recombinant (rec) chromosomesby duplication or deletion of 4p. The deletion of distal 4p manifests as Wolf-Hirschhorn syndrome (WHS). Here, we report the molecular cytogenetic findings and clinical manifestations observed in an infant with 46,XX,rec(4)dup(4q)inv(4)(p16q31.3)pat. The infant was delivered by Cesarean section at the 33rd week of gestation because pleural effusion and polyhydramnios were detected on ultrasonography. At birth, the infant showed no malformation or dysfunction, except for a preauricular skin tag. Array comparative genomic hybridization analysis of neonatal peripheral blood samples showed a gain of 38 Mb on 4q31.3-qter and a loss of 3 Mb on 4p16.3, and these results were consistent with WHS. At the last follow-up at 8 months of age (corrected age, 6 months), the infant had not achieved complete head control.

q-Virasoro algebra, q-conformal dimensions and free q-superstring

International Nuclear Information System (INIS)

Chaichian, M.

1996-01-01

The commutators of standard Virasoro generators and fields generate various representations of the centreless Virasoro algebra depending on a conformal dimension J of the field in question (J is related to the Bargmann index of SU(1,1) generated by L m , m=0,±1). We introduce the notion of q-conformal dimension for various oscillator realizations of q-deformed Virasoro (super)algebras proposed earlier. We use the field theoretical approach introduced recently in which the q-Virasoro currents L α (z) are expressed as Schwinger-like point-split normally ordered quadratic expressions in elementary fields. We extend this approach and probe the elementary fields A(z) (the q-superstring coordinate, momentum and fermionic field) and their powers by the q-Virasoro generators L α m (i.e. we calculate the commutators [L α m ,A(z)]) and show that to all of them can be assigned just the standard non-deformed conformal dimension. (orig.)

Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

International Nuclear Information System (INIS)

Skirnisdottir, Ingiridur; Mayrhofer, Markus; Rydåker, Maria; Åkerud, Helena; Isaksson, Anders

2012-01-01

Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome

DNA gains at 8q23.2

DEFF Research Database (Denmark)

da Silva Veiga, Luciana Caricati; Bérgamo, Nádia Aparecida; dos Reis, Patrícia Pintor

2003-01-01

Gains or amplifications involving chromosome arm 8q are one of the most recurrent chromosomal alterations in head and neck tumors. To characterize previously reported gains, we performed fluorescence in situ hybridization (FISH) using the sequences BAC RP1179E1 and 8-centromere PMJ 128 as probes....

Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan

OpenAIRE

Ansar, Muhammad; Ramzan, Mohammad; Pham, Thanh L.; Yan, Kai; Jamal, Syed Muhammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

2003-01-01

For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod...

C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

Energy Technology Data Exchange (ETDEWEB)

Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan [Hospital for Sick Children, Diagnostic Imaging, Toronto (Canada); Clarke, Howard [Hospital for Sick Children, Plastic Surgery, Toronto (Canada); Weksberg, Rosanna [Hospital for Sick Children, Clinical and Metabolic Genetics, Toronto (Canada)

2008-07-15

Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

International Nuclear Information System (INIS)

Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan; Clarke, Howard; Weksberg, Rosanna

2008-01-01

Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

High-resolution mapping and characterization of qRgls2, a major quantitative trait locus involved in maize resistance to gray leaf spot.

Science.gov (United States)

Xu, Ling; Zhang, Yan; Shao, Siquan; Chen, Wei; Tan, Jing; Zhu, Mang; Zhong, Tao; Fan, Xingming; Xu, Mingliang

2014-08-31

Gray leaf spot (GLS) caused by Cercospora zeae-maydis (Czm) or Cercospora zeina (Cz) is a devastating maize disease and results in substantial yield reductions worldwide. GLS resistance is a quantitatively inherited trait. The development and cultivation of GLS-resistant maize hybrids are the most cost-effective and efficient ways to control this disease. We previously detected a major GLS resistance QTL, qRgls2, in bin 5.03-04, which spans the whole centromere of chromosome 5 encompassing a physical distance of ~110-Mb. With advanced backcross populations derived from the cross between the resistant Y32 and susceptible Q11 inbred lines, a sequential recombinant-derived progeny testing strategy was adapted to fine map qRgls2. We narrowed the region of qRgls2 from an initial ~110-Mb to an interval of ~1-Mb, flanked by the markers G346 and DD11. qRgls2 showed predominantly additive genetic effects and significantly increased the resistance percentage by 20.6 to 24.6% across multiple generations. A total of 15 genes were predicted in the mapped region according to the 5b.60 annotation of the maize B73 genome v2. Two pieces of the mapped qRgls2 region shared collinearity with two distant segments on maize chromosome 4. qRgls2, a major QTL involved in GLS resistance, was mapped to a ~1-Mb region close to the centromere of chromosome 5. There are 15 predicted genes in the mapped region. It is assumed that qRgls2 could be widely used to improve maize resistance to GLS.

Atrial Fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human adult left atrial appendages.

Directory of Open Access Journals (Sweden)

Shamone R Gore-Panter

Full Text Available Atrial Fibrillation (AF, the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS have identified that the single nucleotide polymorphisms (SNPs most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

Restriction of the Patau syndrome to duplication of 13q22{yields}q.32 and possible role of interphase nuclear structure

Energy Technology Data Exchange (ETDEWEB)

Helali, A.N.; Jafolla, A.K.; Oumsiych, M.B. [Duke Univ. Medical Center, Durham, NC (United States)

1994-09-01

A 10-year-old white male presented with mild microcephaly, slight growth and psychomotor retardation, soft fleshy ears, and normal facial features except for thin lips. No other significant anomalies were reported except for tethered cord discovered at age 8 years. The karyotype was found to be 46,XY,der(18)t(13;18)(q32;p11.32)pat. The mild phenotype appears to be primarily due to the duplication of 13q32{yields}qter. None of the cardinal features of trisomy 13 are found in cases of duplication of bands 13q22 to qter. This case shows that Patau syndrome phenotype does not originate by duplication of 13q32{yields}qter and may thus be restricted to 13q22 to 13q32. The variability in phenotypes points to an alternative explanation to the classical one of additive and interactive gene effects. This model involves effects of changes in chromosome position in the interphase nucleus on gene expression.

Breakpoint mapping and haplotype analysis of translocation t(1;12)(q43;q21.1) in two apparently independent families with vascular phenotypes

DEFF Research Database (Denmark)

Luukkonen, Tiia Maria; Mehrjouy, Mana M; Pöyhönen, Minna

2018-01-01

BACKGROUND: The risk of serious congenital anomaly for de novo balanced translocations is estimated to be at least 6%. We identified two apparently independent families with a balanced t(1;12)(q43;q21.1) as an outcome of a "Systematic Survey of Balanced Chromosomal Rearrangements in Finns." In th...

USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21-q21.1.

Science.gov (United States)

Jaworek, Thomas J; Bhatti, Rashid; Latief, Noreen; Khan, Shaheen N; Riazuddin, Saima; Ahmed, Zubair M

2012-10-01

We ascertained two large Pakistani consanguineous families (PKDF231 and PKDF608) segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa; the defining features of Usher syndrome type 1 (USH1). To date, seven USH1 loci have been reported. Here, we map a novel locus, USH1K, on chromosome 10p11.21-q21.1. In family PKDF231, we performed a genome-wide linkage screen and found a region of homozygosity shared among the affected individuals at chromosome 10p11.21-q21.1. Meiotic recombination events in family PKDF231 define a critical interval of 11.74 cM (20.20 Mb) bounded by markers D10S1780 (63.83 cM) and D10S546 (75.57 cM). Affected individuals of family PKDF608 were also homozygous for chromosome 10p11.21-q21.1-linked STR markers. Of the 85 genes within the linkage interval, PCDH15, GJD4, FZD4, RET and LRRC18 were sequenced in both families, but no potential pathogenic mutation was identified. The USH1K locus overlaps the non-syndromic deafness locus DFNB33 raising the possibility that the two disorders may be caused by allelic mutations.

Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial single-photon emission tomography

Energy Technology Data Exchange (ETDEWEB)

Kim, Yong-ih [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Sawada, Yoshihiro [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Fujiwara, Go [Department of Radiology, Nishiyodo Hospital, Nishiyodo (Japan); Chiba, Hiroshi [Department of Internal Medicine, Mimihara General Hospital, Mimihara (Japan); Nishimura, Tsunehiko [Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Osaka (Japan)

1997-06-10

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64{+-}12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7{+-}12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slices x nine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39{+-}0.39 to 2.54{+-}0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1{+-}4.3, compared to 13.9{+-}4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2{+-}8.1 vs 19.7{+-}7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging. (orig.). With 5 figs., 1 tab.

Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered

International Nuclear Information System (INIS)

Finver, S.N.; Nishikura, K.; Finger, L.R.; Haluska, F.G.; Finan, J.; Nowell, P.C.; Croce, C.M.

1988-01-01

The authors cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8; 14)(q24; q11) translocation, and determined the sequence of the MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments utilizing a MYC first exon probe demonstrated transcriptional deregulation of the MYC gene associated with the T-cell receptor α locus on the 8q + chromosome of SKW-3 cells. Nucleotide sequence analysis of the translocation-associated (8q +) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion. None of the deletions or substitutions localized to putative 5' regulatory regions. The MYC first exon sequence was germ line in both alleles. These results demonstrate that alterations within the putative 5' MYC regulatory regions are not necessarily involved in MYC deregulation in T-cell leukemias, and they show that juxtaposition of the T-cell receptor α locus to a germ-line MYC oncogene results in MYC deregulation

The human thyroglobulin gene: a polymorphic marker localized distal to C-MYC on chromosome 8 band q24

NARCIS (Netherlands)

Baas, F.; Bikker, H.; Geurts van Kessel, A.; Melsert, R.; Pearson, P. L.; de Vijlder, J. J.; van Ommen, G. J.

1985-01-01

The human thyroglobulin (Tg) gene is localized to chromosome 8 and regionally to band q24 as shown independently by both in situ hybridization techniques and Southern blot analysis of human-rodent somatic cell hybrids. Analysis of hybrids derived from a Burkitt lymphoma, with a translocation

Tissue-specific expression of the human laminin alpha5-chain, and mapping of the gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the locus for the ragged (Ra) mutation

DEFF Research Database (Denmark)

Durkin, M E; Loechel, F; Mattei, M G

1997-01-01

, heart, lung, skeletal muscle, kidney, and pancreas. The human laminin alpha5-chain gene (LAMA5) was assigned to chromosome 20q13.2-q13.3 by in situ hybridization, and the mouse gene (Lama5) was mapped by linkage analysis to a syntonic region of distal chromosome 2, close to the locus for the ragged (Ra...

A 45 X male patient with 7q distal deletion and rearrangement with SRY gene translocation: a case report.

Science.gov (United States)

Bilen, S; Okten, A; Karaguzel, G; Ikbal, M; Aslan, Y

2013-01-01

Here we present a male newborn with multiple congenital anomalies who also has an extremely rare form of testicular disorder of sex development (DSD). His karyotype was 45X, without any mosaicism. SRY gene was positive by polymerase chain reaction (PCR), and rearranged on distal part of the 7th chromosome by fluorescence in situ hybridization (FISH) analysis. SRY, normally located on the Y chromosome, is the most important gene that plays a role in the development of male sex. SRY gen may be translocated onto another chromosome, mostly X chromosome in the XX testicular DSD. On the other hand very few cases of 45 X testicular DSD were published to date. Other clinical manifestations of our patient were compatible with distal 7 q deletion syndrome. To the best of our knowledge this is the first case of 45 X testicular DSD with SRY gene rearranged on the 7th autosomal chromosome.

Social cognitive training in adolescents with chromosome 22q11.2 deletion syndrome: feasibility and preliminary effects of the intervention.

Science.gov (United States)

Shashi, V; Harrell, W; Eack, S; Sanders, C; McConkie-Rosell, A; Keshavan, M S; Bonner, M J; Schoch, K; Hooper, S R

2015-10-01

Children with chromosome 22q11.2 deletion syndrome (22q11DS) often have deficits in social cognition and social skills that contribute to poor adaptive functioning. These deficits may be of relevance to the later occurrence of serious psychiatric illnesses such as schizophrenia. Yet, there are no evidence-based interventions to improve social cognitive functioning in children with 22q11DS. Using a customised social cognitive curriculum, we conducted a pilot small-group-based social cognitive training (SCT) programme in 13 adolescents with 22q11DS, relative to a control group of nine age- and gender-matched adolescents with 22q11DS. We found the SCT programme to be feasible, with high rates of compliance and satisfaction on the part of the participants and their families. Our preliminary analyses indicated that the intervention group showed significant improvements in an overall social cognitive composite index. SCT in a small-group format for adolescents with 22q11DS is feasible and results in gains in social cognition. A larger randomised controlled trial would permit assessment of efficacy of this promising novel intervention. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).

Science.gov (United States)

Machida, Junichiro; Félix, Têmis M; Murray, Jeffrey C; Yoshiura, Koh-ichiro; Tanemura, Mitsuyo; Kamamoto, Munefumi; Shimozato, Kazuo; Sonta, Shin-ichi; Ono, Takao

2009-09-01

Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate. We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations. Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17. The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.

q-Sumudu transforms of q-analogues of Bessel functions.

Science.gov (United States)

Uçar, Faruk

2014-01-01

The main purpose of this paper is to evaluate q-Sumudu transforms of a product of q-Bessel functions. Interesting special cases of theorems are also discussed. Further, the results proved in this paper may find certain applications of q-Sumudu transforms to the solutions of the q-integrodifferential equations involving q-Bessel functions. The results may help to extend the q-theory of orthogonal functions.

Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3.

Science.gov (United States)

Peddareddygari, Leema Reddy; Hanna, Philip A; Igo, Robert P; Luo, Yuqun A; Won, Sungho; Hirano, Michio; Grewal, Raji P

2016-01-01

Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy. A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis. All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected. We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.

Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

Science.gov (United States)

Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

2015-01-01

Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Correlation of chromosome patterns in leukemic cells of patients with exposure to chemicals and/or radiation

International Nuclear Information System (INIS)

Rowley, J.D.

1989-10-01

We have identified two new recurring translocations involving chromosome 5; one is a 3;5 translocation and the other involves a rearrangement between chromosomes 5 and 7. The first is t(3;5)(q25.1;q35). We studied five patients with AML and a t(3;5) in their leukemic cells. At diagnosis, four of the patients had a t(3;5) as their sole karyotypic anomaly; the remaining patient had additional structural and numerical abnormalities. Careful cytogenetic analysis indicated that the breakpoints of this rearrangement were 3q25.1 and 5q34, in contrast to the various breakpoints reported in earlier studies (3q21 to 3q25 and 5q31 to 5q35). The karyotypic, morphologic, and clinical characteristics of this group, as well as those of 15 previously reported patients with the t(3;5), were compared to identify any features that might warrant consideration of this anomaly as a specific syndrome. The median age of the group, 37 years, as younger than that of all patients with AML, 49 years. A preceding myelodysplastic syndrome was observed in three patients. We have no information regarding the occupation of most of these patients. Except for acute promyelocytic leukemia, each morphologic subtype occurred in these patients; however, the frequency of erythroleukemia (M6) was much greater than expected. 11 refs., 2 figs., 5 tabs

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect.

Science.gov (United States)

Aleksiūnienė, Beata; Preiksaitiene, Egle; Morkūnienė, Aušra; Ambrozaitytė, Laima; Utkus, Algirdas

2018-01-01

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features. © 2018 S. Karger AG, Basel.

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

Energy Technology Data Exchange (ETDEWEB)

Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M. [Univ. of Iowa, Iowa City, IA (United States)] [and others

1994-09-01

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

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.

Genetic mapping and development of co-segregating markers of RpsQ, which provides resistance to Phytophthora sojae in soybean.

Science.gov (United States)

Li, Yinping; Sun, Suli; Zhong, Chao; Wang, Xiaoming; Wu, Xiaofei; Zhu, Zhendong

2017-06-01

The RpsQ Phytophthora resistance locus was finely mapped to a 118-kb region on soybean chromosome 3. A best candidate gene was predicted and three co-segregating gene markers were developed. Phytophthora root rot (PRR), caused by Phytophthora sojae, is a major threat to sustainable soybean production. The use of genetically resistant cultivars is considered the most effective way to control this disease. The Chinese soybean cultivar Qichadou 1 exhibited a broad spectrum resistance, with a distinct resistance phenotype, following inoculation with 36 Chinese P. sojae isolates. Genetic analyses indicated that the disease resistance in Qichadou 1 is controlled by a single dominant gene. This gene locus was designated as RpsQ and mapped to a 118-kb region between BARCSOYSSR_03_0165 and InDel281 on soybean chromosome 3, and co-segregated with Insert11, Insert144 and SNP276. Within this region, there was only one gene Glyma.03g27200 encoding a protein with a typical serine/threonine protein kinase structure, and the expression pattern analysis showed that this gene induced by P. sojae infection, which was suggested as a best candidate gene of RpsQ. Candidate gene specific marker Insert144 was used to distinguish RpsQ from the other known Rps genes on chromosome 3. Identical polymerase chain reaction amplification products were produced for cultivars Qichadou 1 (RpsQ) and Ludou 4 (Rps9). All other cultivars carrying Rps genes on chromosome 3 produced different PCR products, which all lacked a 144-bp fragment present in Qichadou 1 and Ludou 4. The phenotypes of the analyzed cultivars combined with the physical position of the PRR resistance locus, candidate gene analyses, and the candidate gene marker test revealed RpsQ and Rps9 are likely the same gene, and confer resistance to P. sojae.

HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13

DEFF Research Database (Denmark)

Asad, Samina; Nikamo, Pernilla; Gyllenberg, Alexandra

2012-01-01

We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD≤2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D...

Properties of ΣQ*, ΞQ* and ΩQ* heavy baryons in cold nuclear matter

Science.gov (United States)

Azizi, K.; Er, N.

2018-02-01

The in-medium properties of the heavy spin-3/2 ΣQ*, ΞQ* and ΩQ* baryons with Q being b or c quark are investigated. The shifts in some spectroscopic parameters of these particles due to the saturated cold nuclear matter are calculated. The variations of those parameters with respect to the changes in the density of the cold nuclear medium are studied, as well. It is observed that the parameters of ΣQ* baryons are considerably affected by the nuclear matter compared to the ΞQ* and ΩQ* particles that roughly do not see the medium. The results obtained may be used in analyses of the data to be provided by the in-medium experiments like PANDA.

Molecular cytogenetic and phenotypic characterization of ring chromosome 13 in three unrelated patients

Science.gov (United States)

Abdallah-Bouhjar, Inesse B.; Mougou-Zerelli, Soumaya; Hannachi, Hanene; Gmidène, Abir; Labalme, Audrey; Soyah, Najla; Sanlaville, Damien; Saad, Ali; Elghezal, Hatem

2013-01-01

We report on the cytogenetic and molecular investigations of constitutional de-novo ring chromosome 13s in three unrelated patients for better understanding and delineation of the phenotypic variability characterizing this genomic rearrangement. The patient’s karyotypes were as follows: 46,XY,r(13)(p11q34) dn for patients 1 and 2 and 46,XY,r(13)(p11q14) dn for patient 3, as a result of the deletion in the telomeric regions of chromosome 13. The patients were, therefore, monosomic for the segment 13q34 → 13qter; in addition, for patient 3, the deletion was larger, encompassing the segment 13q14 → 13qter. Fluorescence in situ hybridization confirmed these rearrangement and array CGH technique showed the loss of at least 2.9 Mb on the short arm and 4.7 Mb on the long arm of the chromosome 13 in patient 2. Ring chromosome 13 (r(13)) is associated with several phenotypic features like intellectual disability, marked short stature, brain and heart defects, microcephaly and genital malformations in males, including undescended testes and hypospadias. However, the hearing loss and speech delay that were found in our three patients have rarely been reported with ring chromosome 13. Although little is known about its etiology, there is interesting evidence for a genetic cause for the ring chromosome 13. We thus performed a genotype-phenotype correlation analysis to ascertain the contribution of ring chromosome 13 to the clinical features of our three cases. PMID:27625853

PTPN13, a Fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3

Energy Technology Data Exchange (ETDEWEB)

Inazawa, Johji; Ariyama, Takeshi; Abe, Tatsuo [Kyoto Prefectural Univ. of Medicine (Japan)] [and others

1996-01-15

PTPN13 is a protein tyrosine phosphatase that associates with the C-terminal negative regulatory domain in the Fas (APO-1/CD95) receptor. The PTPN13 protein contains six GLGF repeats that have been found in the rat postsynaptic density protein (PSD-95) and the Drosophila tumor suppressor protein, lethal-(1)-disclarge-1 (dlg-1). The localization of the PTPN13 gene to human chromosome 4q21.3 was determined by both FISH and PCR analysis of somatic cell hybrids. This 4q21.3 chromosomal region contains a gene for autosomal dominant polycystic kidney disease as well as the region frequently deleted in liver and ovarian cancers, suggesting that PTPN13 is a candidate for one of the putative tumor suppressor genes on the long arm of chromosome 4. 21 refs., 1 fig.

Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood

DEFF Research Database (Denmark)

Bisgaard, Hans; Bønnelykke, Klaus; Sleiman, Patrick M A

2009-01-01

RATIONALE: An asthma predisposition locus on chromosome 17q12-q21 has recently been replicated in different ethnic groups. OBJECTIVES: To characterize the asthma and atopy phenotypes in early childhood that associate with the 17q12-21 locus. METHODS: The single nucleotide polymorphism (SNP), rs......7216389, was genotyped in 376 of 411 children from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort born to mothers with asthma together with 305 mothers and 224 fathers. Nineteen additional SNPs in the region were genotyped in the children. Investigator-diagnosed clinical...... of wheeze (hazard ratio 1.64 [1.05-2.59], P value = 0.03), asthma (hazard ratio, 1.88 [1.15-3.07], P = 0.01), and acute severe exacerbations (hazard ratio 2.66 [1.58-4.48], P value = 0.0002). The effect on wheeze and asthma was observed for early onset but not late onset of disease. The increased risk...

Production and characterization of a murine monoclonal IgM antibody to human C1q receptor (C1qR)

International Nuclear Information System (INIS)

Ghebrehiwet, B.

1986-01-01

A hybridoma cell line that produces a monoclonal antibody (MAb) to cell surface C1q receptor (C1qr) has been produced by fusion of the P3 x 63-Ag8.653 mouse myeloma cell line with the spleen cells of a CD-1 mouse that had been hyperimmunized with viable Raji cell suspensions (5 x 10 7 cells/inoculum). This MAb, designated II1/D1, is an IgM antibody with lambda-light chain specificity. Radiolabeled or unlabeled, highly purified II1/D1 was used to determine that: a) this antibody competes for C1q binding sites on C1qR-bearing cells; b) the molecule recognized by this MAb is the C1qR; and c) cells that are known to bind C1q also bind II1/D1 in a specific manner. Western blot analysis of solubilized Raji, or U937 cell membranes, showed that the 125 I-MAb detected a major protein band of approximately 85000 m.w. in its unreduced state, indicating that the C1qR is similar, if not identical, in both types of cells. Analyses of 125 I-II/D1 binding experiments revealed that the antibody bound to Raji cells or u937 cells in a specific manner. Uptake of the antibody was saturable, with equilibrium virtually attained within 35 min. Scatchard analysis of the binding data using the intact MAb suggests that the affinity constant K/sub D/ is 2.9 x 10 -10 M, and at apparent saturation, 24.6 ng of the antibody were bound per 2 x 10 6 cells, giving an estimated 7.8 x 10 3 antibody molecules bound per cell. That the II1/D1 antibody is specifically directed to the C1q was further evidenced by an ELISA in which the ability of C1qR-bearing cells to bind the MAb was abrogated by c-C1q in a specific dose-dependent manner

Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.

Science.gov (United States)

Sankila, E M; Pakarinen, L; Kääriäinen, H; Aittomäki, K; Karjalainen, S; Sistonen, P; de la Chapelle, A

1995-01-01

Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)

The Possible Heavy Tetraquarks $qQ\\bar q \\bar Q$, $qq\\bar Q \\bar Q$ and $qQ\\bar Q \\bar Q$

OpenAIRE

Cui, Ying; Chen, Xiao-Lin; Deng, Wei-Zhen; Zhu, Shi-Lin

2006-01-01

Assuming X(3872) is a $qc \\bar q \\bar c$ tetraquark and using its mass as input, we perform a schematic study of the masses of possible heavy tetraquarks using the color-magnetic interaction with the flavor symmetry breaking corrections.

22q11.2 deletion syndrome

Science.gov (United States)

McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

2016-01-01

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

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.

HiQ - A high-Q diffractometer for PDF measurements

International Nuclear Information System (INIS)

Brunelli, M.; Fischer, H.E.; Gaehler, R.; Chatterji, T.

2011-01-01

The local structure of many important functional materials is often different from the average structure, as revealed by diffraction, due to, e.g. doping, mixed site occupancy, or formation of time-dependent local distortions. To get information on both the average and the local structures one needs to perform a joint Rietveld and PDF (Pair Distribution Function) analysis of the total scattering, for which we need data to Q = 30 - 35 Angstroms with Δd/d ∼ 3*10 -3 . Here, we describe how the hot-source diffractometer D4 can be adapted to achieve this capability, and outline one possible design of a dedicated high-Q diffractometer at the ILL (Laue Langevin Institute), using the vacant inclined hot-neutron beam IH2. (authors)

Association Of Common Variants On Chromosome 8q24 With Gastric Cancer In Venezuelan Patients

OpenAIRE

Labrador; Luis; Torres; Keila; Camargo; Maria; Santiago; Laskhmi; Valderrama; Elvis; Angel Chiurillo; Miguel

2016-01-01

Gastric cancer remains one of the leading causes of death in the world, being Central and South America among the regions showing the highest incidence and mortality rates worldwide. Although several single nucleotide polymorphisms (SNPs) identified in the chromosomal region 8q24 by genome-wide association studies have been related with the risk of different kinds of cancers, their role in the susceptibility of gastric cancer in Latin American populations has not been evaluated yet. Hereby, w...

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.

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.

Discrete q-derivatives and symmetries of q-difference equations

Energy Technology Data Exchange (ETDEWEB)

Levi, D [Dipartimento di Fisica, Universita Roma Tre and INFN-Sezione di Roma Tre, Via della Vasca Navale 84, 00146 Rome (Italy); Negro, J [Departamento de FIsica Teorica, Universidad de Valladolid, E-47011, Valladolid (Spain); Olmo, M A del [Departamento de FIsica Teorica, Universidad de Valladolid, E-47011, Valladolid (Spain)

2004-03-12

In this paper we extend the umbral calculus, developed to deal with difference equations on uniform lattices, to q-difference equations. We show that many properties considered for shift invariant difference operators satisfying the umbral calculus can be implemented to the case of the q-difference operators. This q-umbral calculus can be used to provide solutions to linear q-difference equations and q-differential delay equations. To illustrate the method, we will apply the obtained results to the construction of symmetry solutions for the q-heat equation.

Neuropsychiatry of 18q{sup {minus}} syndrome

Energy Technology Data Exchange (ETDEWEB)

Mahr, R.N.; Moberg, P.J.; Campbell, H.; Reber, M.E. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

1996-04-09

Our understanding of neuropsychiatric abnormalities in patients with deletions of the long arm of chromosome 18 (18q{sup {minus}} syndrome) is based mainly on sporadic case reports. We characterized the neuropsychiatric phenotype in 27 patients across a wide age range (2-47 years) with breakpoints ranging from 18q22.3-18q21.2. Adaptive behavior scores (Vineland Composite) were significantly higher in females than in males (62 {+-} 5 vs. 43 {+-} 3). Intelligence ranged from borderline to severely deficient (IQ, 73-<40), with academic achievement similarly impaired. Performance in specific neuropsychological functions, including attention, novel problem solving, memory, language, visuomotor integration, and fine motor dexterity, was consistently in the moderately-to-severely impaired range. Behavioral problems were common in both sexes, including aggressivity, hyperactivity, and temper tantrums. Contrary to the few previous reports, we found no evidence of psychosis in any patient. In a subset of patients selected on the basis of no prior knowledge of behavioral problems, 1 of 16 patients (61%) had autism, as defined by the Autistic Diagnostic Interview-Revised (ADI-R). Thus, the prevalence of autism in 18q{sup {minus}} syndrome is probably no greater than that in other developmental disabilities with a similar level of cognitive impairment. In contrast to what has been believed since 18q{sup {minus}} was first described 30 years ago, we found no relationship between chromosome deletion size and any measure of cognition or behavior; nor were there any correlations between any of these measures with the presence or absence of abnormalities on MRI or somatosensory-evoked potentials. 38 refs., 3 figs., 2 tabs.

Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

DEFF Research Database (Denmark)

Bisgaard, A-M; Kirchhoff, M; Nielsen, J E

2008-01-01

A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA......) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA....

Clinical and molecular description of a 17q21.33 microduplication in a girl with severe kyphoscoliosis and developmental delay.

Science.gov (United States)

Kemeny, Stéphan; Pebrel-Richard, Céline; Eymard-Pierre, Eléonore; Gay-Bellile, Mathilde; Gouas, Laetitia; Goumy, Carole; Tchirkov, Andreï; Francannet, Christine; Vago, Philippe

2014-10-01

High proportion of disease-associated copy number variant maps to chromosome 17. Genomic studies have provided an insight into its complex genomic structure such as relative abundance of segmental duplication and intercepted repetitive elements. 17q21.31, 17q11.2 and 17q12 loci are well known on this chromosome and are associated with microdeletion and microduplication syndrome. No syndrome associated with 17q21.33 locus have been described. We report clinical, cytogenetic and molecular investigations of a 13 years-old girl admitted for evaluation of microcephaly, scoliosis, skeletal defects and learning difficulties. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis using Agilent 180K Array Comparative Genomic Hybridization. We identified a ∼0.9 Mb de novo microduplication on chromosome 17q21.33. Four genes, COL1A1, SGCA, PPP1R9B and CHAD located within the duplicated region are possible candidates for clinical features present in our patients. Gene expression studies by real-time RT-PCR assay only showed an overexpression of SGCA (P < 0.01), a component of the dystrophin glycoprotein complex. Defect of SGCA was previously shown to lead to severe childhood autosomal recessive muscular dystrophy (LGMD2D) which result in progressive muscle weakness and can also be associated with hyperlordosis or scoliosis. Further cases with similar duplications are expected to be diagnosed. This will contribute to the delineation of this potential new microduplication syndrome and to improve genetic counseling. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Functional differential equations for the q-Fourier transform of q-Gaussians

International Nuclear Information System (INIS)

Umarov, S; Queiros, S M Duarte

2010-01-01

In this paper the question 'is the q-Fourier transform of a q-Gaussian a q'-Gaussian (with some q') up to a constant factor?' is studied for the whole range of q in (- infty, 3). This question is connected with applicability of the q-Fourier transform in the study of limit processes in nonextensive statistical mechanics. Using the functional differential equation approach we prove that the answer is affirmative if and only if 1 ≤ q < 3, excluding two particular cases of q < 1, namely q=1/2 and q=2/3. Complementarily, we discuss some applications of the q-Fourier transform to nonlinear partial differential equations such as the porous medium equation.

Functional differential equations for the q-Fourier transform of q-Gaussians

Energy Technology Data Exchange (ETDEWEB)

Umarov, S [Department of Mathematics, Tufts University, Medford, MA (United States); Queiros, S M Duarte, E-mail: sdqueiro@gmail.co [Unilever R and D Port Sunlight, Quarry Road East, Wirral, CH63 3JW (United Kingdom)

2010-02-05

In this paper the question 'is the q-Fourier transform of a q-Gaussian a q'-Gaussian (with some q') up to a constant factor?' is studied for the whole range of q in (- infty, 3). This question is connected with applicability of the q-Fourier transform in the study of limit processes in nonextensive statistical mechanics. Using the functional differential equation approach we prove that the answer is affirmative if and only if 1 <= q < 3, excluding two particular cases of q < 1, namely q=1/2 and q=2/3. Complementarily, we discuss some applications of the q-Fourier transform to nonlinear partial differential equations such as the porous medium equation.

q-Deformed KP Hierarchy and q-Deformed Constrained KP Hierarchy

OpenAIRE

He, Jingsong; Li, Yinghua; Cheng, Yi

2006-01-01

Using the determinant representation of gauge transformation operator, we have shown that the general form of $au$ function of the $q$-KP hierarchy is a $q$-deformed generalized Wronskian, which includes the $q$-deformed Wronskian as a special case. On the basis of these, we study the $q$-deformed constrained KP ($q$-cKP) hierarchy, i.e. $l$-constraints of $q$-KP hierarchy. Similar to the ordinary constrained KP (cKP) hierarchy, a large class of solutions of $q$-cKP hierarchy can be represent...

Neural correlates of reward processing in adults with 22q11 deletion syndrome

NARCIS (Netherlands)

van Duin, Esther D. A.; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

2016-01-01

Background: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic

[Distribution of abnormal cell clone with deletion of chromosome 20q in marrow cell lineages and apoptosis cells in myelodysplastic syndrome].

Science.gov (United States)

Qin, Ling; Wang, Chun; Qin, You-Wen; Xie, Kuang-Cheng; Yan, Shi-Ke; Gao, Yan-Rong; Wang, Xiao-Rui; Zhao, Chu-Xian

2008-06-01

This study was aimed to investigate the distribution of abnormal clone in marrow cell lineages and apoptosis cells in myelodysplastic syndrome (MDS) with deletion of chromosome 20q. Monoclonal antibodies recognizing myeloid precursors (CD15), erythroid precursors (GPA), T cells (CD3(+)CD56(-)CD16(-)), B cells (CD19), NK cells (CD3(-)CD56(+)CD16(+)) were used to sort bone marrow cells in a MDS patient with del (20q) by fluorescence activated cell sorting (FACS). Annexin V-FITC and PI were used to sort bone marrow Annexin V(+)PI(-) and Annexin V(-)PI(-) cells by FACS. The sorted positive cells were detected by interphase dual-color fluorescence in situ hybridization (D-FISH) using a LSI D20S108 probe (Spectrum Orange) and a Telvysion TM 20p probe (Spectrum Green). FACS and FISH analysis were also performed on the samples from 4 cases with normal karyotype. The results showed that the proportions of MDS clone in the myeloid and erythroid precursors were 70.50% and 93.33% respectively, in the RAEB-1 patient with del (20q) and were obviously higher than that in control group (5.39% and 6.17%). The proportions of abnormal clone in T, B and NK cells were 3.23%, 4.32% and 5.77% respectively and were less than that in control group (5.76%, 4.85%, 6.36%). The percentage of apoptotic cells in the bone marrow nucleated cells was 16.09%. The proportions of MDS clone in Annexin V(+)PI(-) and Annexin V(-)PI(-) cells were 32.48% and 70.11%, respectively. It is concluded that most myeloid and erythroid precursors are originated from the abnormal clone in MDS with del (20q). A little part of apoptotic cells are derived from the abnormal clone.

Bose-Einstein correlation and Q-υKυ(Q) distribution

International Nuclear Information System (INIS)

Dai Qirun; Zhao Shusong

1995-01-01

Bose-Einstein correlation is one of the most useful means to study the source emitting hadrons. Based on the non-perturbative theory of quantum fields, we have proposed a kind of source distribution, i.e., the Q -υ K υ (Q) distribution, which is applied to calculate single inclusion distribution of P // , P perpecular , N, Y and the correlation with each other, i.e., Seagull effect. The results have a better approximation to the corresponding experimental data. The paper emphasizes the calculation of Bose-Einstein correlation for inclusive two particle based on the Q -υ K υ (Q) distribution. The fitted curves agree with experimental data, especially, in the small Q range. The Q -υ K υ (Q) distribution is a more advanced theory as compared with Gauss source and K-P source distribution

Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24.

Science.gov (United States)

Schüle, R; Bonin, M; Dürr, A; Forlani, S; Sperfeld, A D; Klimpe, S; Mueller, J C; Seibel, A; van de Warrenburg, B P; Bauer, P; Schöls, L

2009-06-02

Hereditary spastic paraplegias (HSP) are genetically exceedingly heterogeneous. To date, 37 genetic loci for HSP have been described (SPG1-41), among them 16 loci for autosomal dominant disease. Notwithstanding, further genetic heterogeneity is to be expected in HSP, as various HSP families do not link to any of the known HSP loci. In this study, we aimed to map the disease locus in a German family segregating autosomal dominant complicated HSP. A genome-wide linkage analysis was performed using the GeneChip Mapping 10Kv2.0 Xba Array containing 10,204 SNP markers. Suggestive loci were further analyzed by mapping of microsatellite markers. One locus on chromosome 12q23-24, termed SPG36, was confirmed by high density microsatellite fine mapping with a significant LOD score of 3.2. SPG36 is flanked by markers D12S318 and D12S79. Linkage to SPG36 was excluded in >20 additional autosomal dominant HSP families. Candidate genes were selected and sequenced. No disease-causing mutations were identified in the coding regions of ATXN2, HSPB8, IFT81, Myo1H, UBE3B, and VPS29. SPG36 is complicated by a sensory and motor neuropathy; it is therefore the eighth autosomal dominant subtype of complicated HSP. We report mapping of a new locus for autosomal dominant hereditary spastic paraplegia (HSP) (SPG36) on chromosome 12q23-24 in a German family with autosomal dominant HSP complicated by peripheral neuropathy.

X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.

Science.gov (United States)

Lagerström-Fermér, M; Sundvall, M; Johnsen, E; Warne, G L; Forrest, S M; Zajac, J D; Rickards, A; Ravine, D; Landegren, U; Pettersson, U

1997-01-01

We present a linkage analysis and a clinical update on a previously reported family with X-linked recessive panhypopituitarism, now in its fourth generation. Affected members exhibit variable degrees of hypopituitarism and mental retardation. The markers DXS737 and DXS1187 in the q25-q26 region of the X chromosome showed evidence for linkage with a peak LOD score (Zmax) of 4.12 at zero recombination fraction (theta(max) = 0). An apparent extra copy of the marker DXS102, observed in the region of the disease gene in affected males and heterozygous carrier females, suggests that a segment including this marker is duplicated. The gene causing this disorder appears to code for a dosage-sensitive protein central to development of the pituitary. Images Figure 2 PMID:9106538

PHIP – a novel candidate breast cancer susceptibility locus on 6q14.1

OpenAIRE

Jiao, X; Easton, Douglas Frederick

2017-01-01

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast...

Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter.

Science.gov (United States)

Glasser, Lewis; Meloni-Ehrig, Aurelia; Joseph, Plakyil; Mendiola, Jennifer

2006-04-01

We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. Copyright 2006

Comparison of q anti qg and q anti qγ events in e+e- annihilation at PEP

International Nuclear Information System (INIS)

Hofmann, W.

1986-07-01

In comparing the particle flow in the event plane of three-jet (q anti qg) events and of radiative annihilation events (q anti qγ) for similar kinematic configurations, two PEP experiments find a significant decrease in particle density in the angular region opposite to the gluon jet in q anti qg events, relative to the particle density in the region opposite to the photon in q anti qγ events. The effect is predicted both by QCD and by phenomenological string models. 5 refs., 5 figs

q-conformally covariant q-Minkowski space-time and invariant equations

International Nuclear Information System (INIS)

Dobrev, V.K.

1997-09-01

We present explicitly the covariant action of the q-conformal algebra on the q-Minkowski space we proposed earlier. We also present some q-conformally invariant equations, namely a hierarchy of q-Maxwell equations, and also a q-d'Alembert equation, proposed earlier by us, in a form different from the original . (author). 19 refs

Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

Directory of Open Access Journals (Sweden)

Anthony R Isles

2016-05-01

Full Text Available Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS region have been associated with developmental delay (DD, autism spectrum disorder (ASD and schizophrenia (SZ. Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA, but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15 or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of

Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

Science.gov (United States)

Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

2016-01-01

Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array CGH

Science.gov (United States)

Ichimura, Koichi; Mungall, Andrew J; Fiegler, Heike; Pearson, Danita M.; Dunham, Ian; Carter, Nigel P; Collins, V. Peter

2009-01-01

Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1780 clones (778 PACs and 1002 BACs) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs. PMID:16205629

De novo acute leukemia with a sole 5q-: morphological, immunological, and clinical correlations.

Science.gov (United States)

Duchayne, E; Dastugue, N; Kuhlein, E; Huguet, F; Pris, J

1993-11-01

The 5 q deletion is frequently found in myelodysplastic syndromes and acute non lymphoid leukemia, but this anomaly is usually found in secondary diseases and associated with many other chromosomal aberrations. This report describes four cases of "de novo" acute leukemia with a sole 5q- anomaly. They had no cytological, genetic or clinical characteristics of secondary disorders. It is important to note that of the four patients studied, three had proliferation of immature blast cells. One case was classified as a MO AML and two as "undifferentiated" acute leukemia. Furthermore, these four cases of acute leukemia showed a deletion of the same portion of the long arm of chromosome 5: q22q33. On the same part of this chromosome many hematopoietic growth factor genes have been located, like IL3 and GM-CSF which have early undifferentiated hematopoietic stem cells as a their target.

Rheumatoid arthritis in an adult patient with mosaic distal 18q-, 18p- and ring chromosome 18 [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Alanna Chau

2018-02-01

Full Text Available Ring chromosome 18 has a highly variable phenotype, depending on the extent of distal arm deletions. It is most commonly presented as a combination of 18p- and distal 18q- syndrome. IgA deficiency and autoimmune diseases have been previously described in these patients. Seven cases of juvenile rheumatoid arthritis (JRA have been reported. Here we report the first case of late onset rheumatoid arthritis (RA in a 32 year old Dominican woman with hypothyroidism, vitiligo, IgA deficiency, interstitial lung disease (ILD, cystic bronchiectasis, and features consistent with ringed 18, 18p- and distal 18q syndrome.  The multiple autoimmune findings in our patient lends further support to the idea of loci on chromosome 18 playing a role in autoimmune disease expression. Late onset RA and ILD in a patient with chromosome 18 abnormalities are novel findings and are additional conditions to be aware of in this population.

Association of sequence variants on chromosomes 20, 11, and 5 (20q13.33, 11q23.3, and 5p15.33) with glioma susceptibility in a Chinese population.

Science.gov (United States)

Chen, Hongyan; Chen, Yuanyuan; Zhao, Yao; Fan, Weiwei; Zhou, Keke; Liu, Yanhong; Zhou, Liangfu; Mao, Ying; Wei, Qingyi; Xu, Jianfeng; Lu, Daru

2011-04-15

Two genome-wide association studies of glioma in European populations identified 14 genetic variants strongly associated with risk of glioma, but it is unknown whether these variants are associated with glioma risk in Asian populations. The authors genotyped these 14 variants in 976 glioma patients and 1,057 control subjects to evaluate their associations with risk of glioma, particularly high-grade glioma (glioblastoma; n = 312), in a Chinese population (2004-2009). Overall, the authors identified 3 susceptibility loci for glioma risk at 20q13.33 (RTEL1 rs6010620 (P = 2.79 × 10(-6))), 11q23.3 (PHLDB1 rs498872 (P = 3.8 × 10(-6))), and 5p15.33 (TERT rs2736100 (P = 3.69 × 10(-4))) in this study population; these loci were also associated with glioblastoma risk (20q13.33: RTEL1 rs6010620 (P = 3.57 × 10(-7)); 11q23.3: PHLDB1 rs498872 (P = 7.24 × 10(-3)); 5p15.33: TERT rs2736100 and TERT rs2736098 (P = 1.21 × 10(-4) and P = 2.84 × 10(-4), respectively)). This study provides further evidence for 3 glioma susceptibility regions at 20q13.33, 11q23.3, and 5p15.33 in Chinese populations.

Identification of a rare de novo three-way complex t(5;20;8(q31;p11.2;p21 with microdeletions on 5q31.2, 5q31.3, and 8p23.2 in a patient with hearing loss and global developmental delay: case report

Directory of Open Access Journals (Sweden)

Bejjani Bassem A

2009-01-01

Full Text Available Abstract Background Complex chromosome rearrangements (CCRs, which involve more than two breakpoints on two or more chromosomes, are uncommon occurrences. Although most CCRs appear balanced at the level of the light microscope, many demonstrate cryptic, submicroscopic imbalances at the translocation breakpoints. Results We report a female with hearing loss and global developmental delay with a complex three-way unbalanced translocation (5;20;8(q31;p11.2;p21 resulting in microdeletions on 5q31.2, 5q31.3, and 8p23.2 identified by karyotyping, microarray analysis and fluorescence in situ hybridization. Discussion The microdeletion of bands 8p23.2 may be associated with the hearing impairment. Furthermore, the characterization of this patient's chromosomal abnormalities demonstrates the importance of integrated technologies within contemporary cytogenetics laboratories.

Exotic tetraquark states with the qq anti Q anti Q configuration

Energy Technology Data Exchange (ETDEWEB)

Luo, Si-Qiang; Chen, Kan; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics, CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Liu, Yan-Rui [Shandong University, School of Physics and Key Laboratory of Particle Physics and Particle Irradiation (MOE), Jinan (China); Zhu, Shi-Lin [Peking University, School of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Peking University, Center for High Energy Physics, Beijing (China)

2017-10-15

In this work, we study systematically the mass splittings of the qq anti Q anti Q (q = u, d, s and Q = c, b) tetraquark states with the color-magnetic interaction by considering color mixing effects and estimate roughly their masses. We find that the color mixing effect is relatively important for the J{sup P} = 0{sup +} states and possible stable tetraquarks exist in the nn anti Q anti Q (n = u, d) and ns anti Q anti Q systems either with J = 0 or with J = 1. Possible decay patterns of the tetraquarks are briefly discussed. (orig.)

Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

Science.gov (United States)

Wafa, Abdulsamad; As'sad, Manar; Liehr, Thomas; Aljapawe, Abdulmunim; Al Achkar, Walid

2017-04-07

The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20. Moreover, the translocation t(1;19) correlates with known clinical high risk factors, such as elevated white blood cell count, high serum lactate dehydrogenase levels, and central nervous system involvement; early reports indicated that patients with translocation t(1;19) had a poor outcome under standard treatment. We report the case of a 15-year-old Syrian boy with pre-B cell acute lymphoblastic leukemia with abnormal karyotype with a der(19)t(1;19)(q21.1;p13.3) and two yet unreported chromosomal aberrations: an interstitial deletion 6q12 to 6q26 and a der(13)t(1;13)(q21.1;p13). According to the literature, cases who are translocation t(1;19)-positive have a significantly higher incidence of central nervous system relapse than patients with acute lymphoblastic leukemia without the translocation. Of interest, central nervous system involvement was also seen in our patient. To the best of our knowledge, this is the first case of childhood pre-B cell acute lymphoblastic leukemia with an unbalanced translocation t(1;19) with two additional chromosomal aberrations, del(6)(q12q26) and t(1;13)(q21.3;p13), which seem to be recurrent and could influence clinical outcome. Also the present case confirms the impact of the translocation t(1;19) on central nervous system relapse, which should be studied for underlying mechanisms in future.

Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q.

Science.gov (United States)

Pieke-Dahl, S; Möller, C G; Kelley, P M; Astuto, L M; Cremers, C W; Gorin, M B; Kimberling, W J

2000-04-01

Usher syndrome is a group of autosomal recessive disorders that includes retinitis pigmentosa (RP) with hearing loss. Usher syndrome type II is defined as moderate to severe hearing loss with RP. The USH2A gene at 1q41 has been isolated and characterised. In 1993, a large Usher II family affected with a mild form of RP was found to be unlinked to 1q41 markers. Subsequent linkage studies of families in our Usher series identified several type II families unlinked to USH2A and USH3 on 3q25. After a second unlinked family with many affected members and a mild retinal phenotype was discovered, a genome search using these two large families showed another Usher II locus on 5q (two point lod = 3.1 at D5S484). To date, we have identified nine unrelated 5q linked families (maximum combined multipoint lod = 5.86) as well as three Usher II families that show no significant linkage to any known Usher loci. Haplotype analysis of 5q markers indicates that the new locus is flanked by D5S428 and D5S433. Review of ophthalmological data suggests that RP symptoms are milder in 5q linked families; the RP is often not diagnosed until patients near their third decade. Enamel hypoplasia and severe, very early onset RP were observed in two of the three unlinked families; dental anomalies have not been previously described as a feature of Usher type II.

Economic significance of Q for mirror reactors: combinations of Q and M which look promising

International Nuclear Information System (INIS)

Werner, R.W.

1978-01-01

This term Q is the ratio of the fusion powder produced to the power input. It is a driven device. Q is truly the success parameter for mirrors--widely discussed but not succinctly specified as to required value. The problem is that Q can be treated as a subjective parameter--there are many milestone Qs; for scientific demonstration, for breakeven power, etc. Yet for a successful reactor, there is only one Q and that is the Q which produces mirror fusion power at the busbar that is less than the cost of delivered power in mills/kwhr by other means. We call this Q/sub PRACTICAL/ and believe there is a convincing argument that says this Q/sub PRACTICAL/ can be about 5.0 even assuming modest efficiencies for system components. A direct convertor is necessary. If the direct convertor were deleted, a Q/sub PRACTICAL/ of approximately 7.5 would be required. If we wish to soften the value of Q further, then the technical logic for the fusion fission hybrid is very powerful. With the hybrid a Q/sub PRACTICAL/ of 1.5 to 2.0 appears to be a very reasonable value. The key in being able to specify values of Q/sub PRACTICAL/ lies in economically comparing the capital cost of fusion power to the sum of the capital cost and the present value of all the fuel costs for the competitive fuel intensive plants

The Q Continuum: Encounter with the Cloud Mask

Science.gov (United States)

Ackerman, S. A.; Frey, R.; Holz, R.; Philips, C.; Dutcher, S.

2017-12-01

We are developing a common cloud mask for MODIS and VIIRS observations, referred to as the MODIS VIIRS Continuity Mask (MVCM). Our focus is on extending the MODIS-heritage cloud detection approach in order to generate appropriate climate data records for clouds and climate studies. The MVCM is based on heritage from the MODIS cloud mask (MOD35 and MYD35) and employs a series of tests on MODIS reflectances and brightness temperatures. Cloud detection is based on contrasts (i.e., cloud versus background surface) at pixel resolution. The MVCM follows the same approach. These cloud masks use multiple cloud detection tests to indicate the confidence level that the observation is of a clear-sky scene. The outcome of a test ranges from 0 (cloudy) to 1 (clear-sky scene). Because of overlap in the sensitivities of the various spectral tests to the type of cloud, each test is considered in one of several groups. The final cloud mask is determined from the product of the minimum confidence of each group and is referred to as the Q value as defined in Ackerman et al (1998). In MOD35 and MYD35 processing, the Q value is not output, rather predetermined Q values determine the result: If Q ≥ .99 the scene is clear; .95 ≤ Q laws of physics are followed, at least according to normal human notions. Using CALIOP as representing truth, a receiver operating characteristic curve (ROC) will be analyzed to determine the optimum Q for various scenes and seasons, thus providing a continuum of discriminating thresholds.

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.

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.

Characterization of a novel cation transporter ATPase gene (ATP13A4) interrupted by 3q25-q29 inversion in an individual with language delay.

Science.gov (United States)

Kwasnicka-Crawford, Dorota A; Carson, Andrew R; Roberts, Wendy; Summers, Anne M; Rehnström, Karola; Järvelä, Irma; Scherer, Stephen W

2005-08-01

Specific language impairment (SLI) is defined as failure to acquire normal language skills despite adequate intelligence and environmental stimulation. Although SLI disorders are often heritable, the genetic basis is likely to involve a number of risk factors. This study describes a 7-year-old girl carrying an inherited paracentric inversion of the long arm of chromosome 3 [46XX, inv(3)(q25.32-q29)] having clinically defined expressive and receptive language delay. Fluorescence in situ hybridization (FISH) with locus-specific bacterial artificial chromosome clones (BACs) as probes was used to characterize the inverted chromosome 3. The proximal and distal inversion breakpoint was found to reside between markers D3S3692/D3S1553 and D3S3590/D3S2305, respectively. ATP13A4, a novel gene coding for a cation-transporting P-type ATPase, was found to be disrupted by the distal breakpoint. The ATP13A4 gene was shown to comprise a 3591-bp transcript encompassing 30 exons spanning 152 kb of the genomic DNA. This study discusses the characterization of ATP13A4 and its possible involvement in speech-language disorder.

Assignment of the human gene for pregnancy-associated plasma protein A (PAPPA) to 9q33.1 by fluorescence in situ hybridization to mitotic and meiotic chromosomes

DEFF Research Database (Denmark)

Silahtaroglu, A N; Tümer, Z; Kristensen, Torsten

1993-01-01

Low levels of pregnancy-associated plasma protein A (PAPPA) during the first trimester has been suggested as a biochemical indicator of pregnancies with aneuploid fetuses. Furthermore, the complete absence of PAPPA in pregnancies associated with Cornelia de Lange syndrome (CL) has suggested...... a causal connection between PAPPA and the development of CL. We have assigned the locus for PAPPA to chromosome region 9q33.1 on mitotic and meiotic chromosomes by fluorescence in situ hybridization, using a 3.7-kb partial PAPPA cDNA probe...

Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

Science.gov (United States)

Lin, Amy; Ching, Christopher R K; Vajdi, Ariana; Sun, Daqiang; Jonas, Rachel K; Jalbrzikowski, Maria; Kushan-Wells, Leila; Pacheco Hansen, Laura; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M; Bearden, Carrie E

2017-06-28

Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly

The Danish 22q11 research initiative

DEFF Research Database (Denmark)

Schmock, Henriette; Vangkilde, Anders; Larsen, Kit Melissa

2015-01-01

mechanisms may come from studies of subjects with homogenous etiologies. Breakthroughs in psychiatric genetics have shown that several genetic anomalies predispose for neurodevelopmental brain disorders. We have established a Danish research initiative to study the common microdeletion at chromosome 22q11...

q-Bernoulli numbers and q-Bernoulli polynomials revisited

Directory of Open Access Journals (Sweden)

Kim Taekyun

2011-01-01

Full Text Available Abstract This paper performs a further investigation on the q-Bernoulli numbers and q-Bernoulli polynomials given by Acikgöz et al. (Adv Differ Equ, Article ID 951764, 9, 2010, some incorrect properties are revised. It is point out that the generating function for the q-Bernoulli numbers and polynomials is unreasonable. By using the theorem of Kim (Kyushu J Math 48, 73-86, 1994 (see Equation 9, some new generating functions for the q-Bernoulli numbers and polynomials are shown. Mathematics Subject Classification (2000 11B68, 11S40, 11S80

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density

Science.gov (United States)

Alonso, Nerea; Estrada, Karol; Albagha, Omar M E; Herrera, Lizbeth; Reppe, Sjur; Olstad, Ole K; Gautvik, Kaare M; Ryan, Niamh M; Evans, Kathryn L; Nielson, Carrie M; Hsu, Yi-Hsiang; Kiel, Douglas P; Markozannes, George; Ntzani, Evangelia E; Evangelou, Evangelos; Feenstra, Bjarke; Liu, Xueping; Melbye, Mads; Masi, Laura; Brandi, Maria Luisa; Riches, Philip; Daroszewska, Anna; Olmos, José Manuel; Valero, Carmen; Castillo, Jesús; Riancho, José A; Husted, Lise B; Langdahl, Bente L; Brown, Matthew A; Duncan, Emma L; Kaptoge, Stephen; Khaw, Kay-Tee; Usategui-Martín, Ricardo; Del Pino-Montes, Javier; González-Sarmiento, Rogelio; Lewis, Joshua R; Prince, Richard L; D’Amelio, Patrizia; García-Giralt, Natalia; NoguéS, Xavier; Mencej-Bedrac, Simona; Marc, Janja; Wolstein, Orit; Eisman, John A; Oei, Ling; Medina-Gómez, Carolina; Schraut, Katharina E; Navarro, Pau; Wilson, James F; Davies, Gail; Starr, John; Deary, Ian; Tanaka, Toshiko; Ferrucci, Luigi; Gianfrancesco, Fernando; Gennari, Luigi; Lucas, Gavin; Elosua, Roberto; Uitterlinden, André G; Rivadeneira, Fernando; Ralston, Stuart H

2018-01-01

Objectives To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. Methods Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. Results A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10−9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. Conclusion We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism. PMID:29170203

Chromosome 13q deletion and IgH abnormalities may be both masked by near-tetraploidy in a high proportion of multiple myeloma patients: a combined morphology and I-FISH analysis.

Science.gov (United States)

Koren-Michowitz, Maya; Hardan, Izhar; Berghoff, Janina; Yshoev, Galina; Amariglio, Ninette; Rechavi, Gideon; Nagler, Arnon; Trakhtenbrot, Luba

2007-10-08

Ploidy status and chromosomal aberrations involving chromosome 13q and the immunoglobulin heavy chain locus (IgH) are important prognostic features in multiple myeloma (MM). However, conventional cytogenetic studies are often not reveling and determination of plasma cells (PC) ploidy status in MM is technically difficult. We have used a combined cell morphology and interphase FISH (I-FISH) analysis in 184 consecutive BM samples from 136 MM patients for the diagnosis of chromosome 13q deletion [del (13q)] and IgH abnormalities. We have found a high prevalence (37%) of near-tetraploid (NT) PC in the BM samples studied. NT status of PC was verified with DNA index (DI) measurements. del (13q) was found in 69% and a total absence of one IgH copy (loss of IgH) in 20% of NT samples. We have shown that the presence of del (13q) and loss of IgH can be masked in NT cases: in 12 NT samples originally identified as normal for del (13q) the abnormality was obscured in the majority of plasma cells due to the presence of NT. Similarly, loss of IgH was masked in four samples with a large population of NT cells. Moreover, in one case the appearance of a 100% tetraploidy during disease progression masked the presence of del (13q), originally present, and could therefore falsely appear as disappearance of this prognostic marker. In conclusion, we have shown that a combination of three abnormalities, i.e., del (13q), loss of IgH and NT, all of potential prognostic significance, can be overlooked unless NT is specifically searched for and ruled out. Therefore, we suggest that a search for NT should be added to the routine BM assessment in MM patients.

A rec(4) dup 4p inherited from a maternal inv(4)(p15q35): case report and review.

Science.gov (United States)

Garcia-Heras, Jaime; Martin, Judith

2002-05-01

A rec(4) dup 4p inherited from a maternal inv(4)(p15q35) was detected in a four-year-old girl with malformations, developmental delay, and behavioral problems that resemble those for trisomy 4p. A review of eight other liveborns with rec(4) dup 4p shows that about 40% of them also have manifestations in common with trisomy 4p, but the rest have a variable spectrum of malformations. Overall, the rec(4) dup 4p phenotype is not specific, and a diagnosis would not have been feasible without cytogenetic studies. This lack of a clinically recognizable phenotype could reflect the effects of the variable sizes of deletions of 4q, molecular differences in the break points, or the known variable expression of trisomy 4p. The fact that 79% of the recombinants in the offspring of inv(4)(p13-p15q35) carriers are rec(4) dup 4p suggests that meiotic recombination favors its generation or that rec(4) dup 4q are more lethal in utero. Copyright 2002 Wiley-Liss, Inc.

Exotic open-flavor $bc\\bar{q}\\bar{q}$, $bc\\bar{s}\\bar{s}$ and $qc\\bar{q}\\bar{b}$, $sc\\bar{s}\\bar{b}$ tetraquark states

OpenAIRE

Chen, Wei; Steele, T. G.; Zhu, Shi-Lin

2013-01-01

We study the exotic $bc\\bar{q}\\bar{q}$, $bc\\bar{s}\\bar{s}$ and $qc\\bar{q}\\bar{b}$, $sc\\bar{s}\\bar{b}$ systems by constructing the corresponding tetraquark currents with $J^P=0^+$ and $1^+$. After investigating the two-point correlation functions and the spectral densities, we perform QCD sum rule analysis and extract the masses of these open-flavor tetraquark states. Our results indicate that the masses of both the scalar and axial vector tetraquark states are about $7.1-7.2$ GeV for the $bc\\...

Constitutional chromothripsis involving the critical region of 9q21.13 microdeletion syndrome.

Science.gov (United States)

Genesio, Rita; Fontana, Paolo; Mormile, Angela; Casertano, Alberto; Falco, Mariateresa; Conti, Anna; Franzese, Adriana; Mozzillo, Enza; Nitsch, Lucio; Melis, Daniela

2015-01-01

The chromothripsis is a biological phenomenon, first observed in tumors and then rapidly described in congenital disorders. The principle of the chromothripsis process is the occurrence of a local shattering to pieces and rebuilding of chromosomes in a random order. Congenital chromothripsis rearrangements often involve reciprocal rearrangements on multiple chromosomes and have been described as cause of contiguous gene syndromes. We hypothesize that chromothripsis could be responsible for known 9q21.13 microdeletion syndrome, causing a composite phenotype with additional features. The case reported is a 16- years-old female with a complex genomic rearrangement of chromosome 9 including the critical region of 9q21.13 microdeletion syndrome. The patient presents with platelet disorder and thyroid dysfunction in addition to the classical neurobehavioral phenotype of the syndrome. The presence of multiple rearrangements on the same chromosome 9 and the rebuilding of chromosome in a random order suggested that the rearrangement could origin from an event of chromthripsis. To our knowledge this is the first report of congenital chromothripsis involving chromosome 9. Furthermore this is the only case of 9q21.13 microdeletion syndrome due to chromothripsis.

Fine mapping and identification of a novel locus qGL12.2 control grain length in wild rice (Oryza rufipogon Griff.).

Science.gov (United States)

Qi, Lan; Ding, Yingbin; Zheng, Xiaoming; Xu, Rui; Zhang, Lizhen; Wang, Yanyan; Wang, Xiaoning; Zhang, Lifang; Cheng, Yunlian; Qiao, Weihua; Yang, Qingwen

2018-04-19

A wild rice QTL qGL12.2 for grain length was fine mapped to an 82-kb interval in chromosome 12 containing six candidate genes and none was reported previously. Grain length is an important trait for yield and commercial value in rice. Wild rice seeds have a very slender shape and have many desirable genes that have been lost in cultivated rice during domestication. In this study, we identified a quantitative trait locus, qGL12.2, which controls grain length in wild rice. First, a wild rice chromosome segment substitution line, CSSL41, was selected that has longer glume and grains than does the Oryza sativa indica cultivar, 9311. Next, an F 2 population was constructed from a cross between CSSL41 and 9311. Using the next-generation sequencing combined with bulked-segregant analysis and F 3 recombinants analysis, qGL12.2 was finally fine mapped to an 82-kb interval in chromosome 12. Six candidate genes were found, and no reported grain length genes were found in this interval. Using scanning electron microscopy, we found that CSSL41 cells are significantly longer than those of 9311, but there is no difference in cell widths. These data suggest that qGL12.2 is a novel gene that controls grain cell length in wild rice. Our study provides a new genetic resource for rice breeding and a starting point for functional characterization of the wild rice GL gene.

Triply heavy tetraquark states with the $QQ\\bar{Q}\\bar{q}$ configuration

OpenAIRE

Chen, Kan; Liu, Xiang; Wu, Jing; Liu, Yan-Rui; Zhu, Shi-Lin

2016-01-01

In the framework of the color-magnetic interaction, we systematically investigate the mass splittings of the $QQ\\bar{Q}\\bar{q}$ tetraquark states and estimated their rough masses in this work. These systems include the explicitly exotic states $cc\\bar{b}\\bar{q}$ and $bb\\bar{c}\\bar{q}$ and the hidden exotic states $cc\\bar{c}\\bar{q}$, $cb\\bar{b}\\bar{q}$, $bc\\bar{c}\\bar{q}$, and $bb\\bar{b}\\bar{q}$. If a state around the estimated mass region could be observed, its nature as a genuine tetraquark ...

DK phocomelia phenotype (von Voss-Cherstvoy syndrome) caused by somatic mosaicism for del(13q).

Science.gov (United States)

Bamforth, J S; Lin, C C

1997-12-31

DK phocomelia (von Voss-Cherstvoy syndrome) is a rare condition characterized by radial ray defects, occipital encephalocoele, and urogenital abnormalities. Lubinsky et al. [1994: Am J Med Genet 52:272-278] pointed out similarities between this and the del(13q) syndrome. To date, all reported cases of DK phocomelia have been apparently normal chromosomally. We report on a case of DK phocomelia in which the proposita had normal lymphocyte chromosomes, but was mosaic in fibroblasts for del(13)(q12). Fibroblast chromosomes studies on other cases of DK phocomelia have not been reported: this raises the possibility that some cases of DK phocomelia may be somatic mosaics for del(13)(q12).

Recurrent duplications of 17q12 associated with variable phenotypes

DEFF Research Database (Denmark)

Mitchell, Elyse; Douglas, Andrew; Kjaegaard, Susanne

2015-01-01

The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information......, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing...... to phenotypic variability....

Alternative Splicing of CHEK2 and Codeletion with NF2 Promote Chromosomal Instability in Meningioma

Directory of Open Access Journals (Sweden)

Hong Wei Yang

2012-01-01

Full Text Available Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.

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

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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.

7q21-rs6964587 and breast cancer risk

DEFF Research Database (Denmark)

Milne, Roger L; Lorenzo-Bermejo, Justo; Burwinkel, Barbara

2011-01-01

Using the Breast Cancer Association Consortium, the authors previously reported that the single nucleotide polymorphism 7q21-rs6964587 (AKAP9-M463I) is associated with breast cancer risk. The authors have now assessed this association more comprehensively using 16 independent case-control studies....

Q-phonons, Q-invariants, and company

International Nuclear Information System (INIS)

Brentano, P. von; Gade, A.; Pietralla, N.; Werner, V.

2002-01-01

The paper discusses the concept of Q-phonons and its connection to the concept of Q-invariants and the shape parameters of nuclei. It will also discuss some useful relations between Q-invariants and observables. These relations allow one to determine crucial nuclear observables such as the square of the quadrupole moment of the first 2+ state from lifetime data of the gamma- and ground band which may have applications, in future measurements with rare isotopes beams. These concepts are discussed for the Barium, Xenon and Cerium nuclei with mass numbers around A = 130, because some of these concepts were either introduced or at least heavily used in the discussion of the nuclear structure of these nuclei

Chemistry and Molecular Dynamics Simulations of Heme b-HemQ and Coproheme-HemQ.

Science.gov (United States)

Hofbauer, Stefan; Dalla Sega, Marco; Scheiblbrandner, Stefan; Jandova, Zuzana; Schaffner, Irene; Mlynek, Georg; Djinović-Carugo, Kristina; Battistuzzi, Gianantonio; Furtmüller, Paul G; Oostenbrink, Chris; Obinger, Christian

2016-09-27

Recently, a novel pathway for heme b biosynthesis in Gram-positive bacteria has been proposed. The final poorly understood step is catalyzed by an enzyme called HemQ and includes two decarboxylation reactions leading from coproheme to heme b. Coproheme has been suggested to act as both substrate and redox active cofactor in this reaction. In the study presented here, we focus on HemQs from Listeria monocytogenes (LmHemQ) and Staphylococcus aureus (SaHemQ) recombinantly produced as apoproteins in Escherichia coli. We demonstrate the rapid and two-phase uptake of coproheme by both apo forms and the significant differences in thermal stability of the apo forms, coproheme-HemQ and heme b-HemQ. Reduction of ferric high-spin coproheme-HemQ to the ferrous form is shown to be enthalpically favored but entropically disfavored with standard reduction potentials of -205 ± 3 mV for LmHemQ and -207 ± 3 mV for SaHemQ versus the standard hydrogen electrode at pH 7.0. Redox thermodynamics suggests the presence of a pronounced H-bonding network and restricted solvent mobility in the heme cavity. Binding of cyanide to the sixth coproheme position is monophasic but relatively slow (∼1 × 10(4) M(-1) s(-1)). On the basis of the available structures of apo-HemQ and modeling of both loaded forms, molecular dynamics simulation allowed analysis of the interaction of coproheme and heme b with the protein as well as the role of the flexibility at the proximal heme cavity and the substrate access channel for coproheme binding and heme b release. Obtained data are discussed with respect to the proposed function of HemQ in monoderm bacteria.

q-Space Upsampling Using x-q Space Regularization.

Science.gov (United States)

Chen, Geng; Dong, Bin; Zhang, Yong; Shen, Dinggang; Yap, Pew-Thian

2017-09-01

Acquisition time in diffusion MRI increases with the number of diffusion-weighted images that need to be acquired. Particularly in clinical settings, scan time is limited and only a sparse coverage of the vast q -space is possible. In this paper, we show how non-local self-similar information in the x - q space of diffusion MRI data can be harnessed for q -space upsampling. More specifically, we establish the relationships between signal measurements in x - q space using a patch matching mechanism that caters to unstructured data. We then encode these relationships in a graph and use it to regularize an inverse problem associated with recovering a high q -space resolution dataset from its low-resolution counterpart. Experimental results indicate that the high-resolution datasets reconstructed using the proposed method exhibit greater quality, both quantitatively and qualitatively, than those obtained using conventional methods, such as interpolation using spherical radial basis functions (SRBFs).

Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.