86 results on '"Fransson, I."'
Search Results
2. Varicose Vein Recurrence and Patient Satisfaction 10–14 Years Following Combined Superficial and Perforator Vein Surgery: A Prospective Case Study
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Nelzén, O. and Fransson, I.
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- 2013
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3. Auf der Spur von unerlaubten Stoffen in Nahrungsergänzungsmitteln und Sportlerlebensmitteln
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Fransson, I., primary, Schrieck, R., additional, Lorenz, C., additional, and Weidner, M., additional
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- 2021
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- View/download PDF
4. True Long-term Healing and Recurrence of Venous Leg Ulcers Following SEPS Combined with Superficial Venous Surgery: A Prospective Study
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Nelzén, O. and Fransson, I.
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- 2007
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5. A novel gene containing LIM domains (LIMD1) is located within the common eliminated region 1 (C3CER1) in 3p21.3
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Kiss, H., Kedra, D., Yang, Y., Kost-Alimova, M., Kiss, C., O'Brien, K.P., Fransson, I., Klein, G., Imreh, S., and Dumanski, J.P.
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- 1999
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6. Early results from a randomized trial of saphenous surgery with or without subfascial endoscopic perforator surgery in patients with a venous ulcer*
- Author
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Nelzén, O. and Fransson, I.
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- 2011
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7. Etablierung einer UPLC‐Q‐ToF‐MS Methode zum Nachweis unerlaubter / verbotener Stoffe in speziellen Erzeugnissen für Sportler (Booster)
- Author
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Fransson, I., primary, Schrieck, R., additional, and Weidner, M., additional
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- 2020
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8. Familial non-syndromic cleft lip and palate—analysis of the IRF6 gene and clinical phenotypes
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Pegelow, M., Peyrard-Janvid, M., Zucchelli, M., Fransson, I., Larson, O., Kere, J., Larsson, C., and Karsten, A.
- Published
- 2008
9. Association and Mutation Analyses of the IRF6 Gene in Families With Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate
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Pegelow, M., Koillinen, H., Magnusson, M., Fransson, I., Unneberg, P., Kere, J., Karsten, A., Peyrard-Janvid, M., Pegelow, M., Koillinen, H., Magnusson, M., Fransson, I., Unneberg, P., Kere, J., Karsten, A., and Peyrard-Janvid, M.
- Abstract
Objectives: (1) To detect interferon regulatory factor 6 gene (IRF6) mutations in newly recruited Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) families. (2) To test for association, in nonsyndromic cleft lip and/or cleft palate (NSCL/P) and in VWS/PPS families, the single nucleotide polymorphism (SNP) rs642961, from the IRF6 enhancer AP-2 alpha region, alone or as haplotype with rs2235371, a coding SNP (Val274Ile). Design: IRF6 mutation screening was performed by direct sequencing and genotyping of rs642961 and rs2235371 by TaqMan technology. Patients: Seventy-one Swedish NSCL/P families, 24 Finnish cleft palate (CP) families, and 24 VWS/PPS families (seven newly recruited) were studied. Results: Allelic and genotypic frequencies in each phenotype were compared to those of the controls, and no significant difference could be observed. IRF6 gene mutation was detected in six of the seven new VWS/PPS families. Association analysis of the entire VWS/PPS sample set revealed the A allele from rs642961 to be a risk allele. Significant association was detected in the Swedish CP subset of our NSCL/P collection where the G-C haplotype for rs642961-rs2235371 were at risk (P = .013). Conclusions: Our results do not support the previously reported association between the A allele of rs642961 and the NSCL phenotype. However, in the VWS/PPS families, the A allele was a risk allele and was, in a large majority (>80%), transmitted on the same chromosome as the IRF6 mutation., AuthorCount:8
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- 2014
- Full Text
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10. Association and Mutation Analyses of the IRF6 Gene in Families with Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate
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Pegelow, M., primary, Koillinen, H., additional, Magnusson, M., additional, Fransson, I., additional, Unneberg, P., additional, Kere, J., additional, Karsten, A., additional, and Peyrard-Janvid, M., additional
- Published
- 2014
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- View/download PDF
11. Early results from a randomized trial of saphenous surgery with or without subfascial endoscopic perforator surgery in patients with a venous ulcer
- Author
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Nelzén, Olle, Fransson, I, Nelzén, Olle, and Fransson, I
- Abstract
BACKGROUND: The aim was to clarify the role of incompetent perforators (IPs) in venous leg ulcers. This short-term report focused on safety, patient satisfaction and the fate of IPs after subfascial endoscopic perforator surgery (SEPS), or saphenous surgery alone. METHODS: Patients aged 30-78 years with an open or recently healed venous ulcer, and with an incompetent saphenous vein and IPs, were allocated randomly to saphenous surgery alone, or in combination with SEPS. A control duplex scan was performed 6-9 months after surgery, and clinical follow-up was scheduled after 1 week, 3 and 12 months. A standard questionnaire was completed at each clinical visit. RESULTS: Seventy-five patients were enrolled; 37 had SEPS and 38 had saphenous surgery alone. SEPS prolonged the operation by a median of 15 min (P = 0.003). Duplex imaging revealed significantly more remaining IPs in the no-SEPS group (P < 0.001). Compared with the preoperative scan, significantly more legs were free from IPs in the SEPS group compared with the no-SEPS group (21 of 36 versus 7 of 37 respectively; P < 0.001). There were no other major outcome differences between the groups. CONCLUSION: There was no short-term clinical benefit from adding SEPS to saphenous surgery in patients with varicose ulcers and IPs, although SEPS reduced the number of perforators remaining after 1 year.
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- 2011
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12. Strong conservation of the human NF2 locus based on sequence comparison infive species.
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Hansson, CM, Ali, H, Bruder, CE, Fransson, I, Kluge, S, Andersson, B, Roe, BA, Menzel, U, Dumanski, JP, Hansson, CM, Ali, H, Bruder, CE, Fransson, I, Kluge, S, Andersson, B, Roe, BA, Menzel, U, and Dumanski, JP
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- 2003
13. Submicroscopic genomic alterations in Silver-Russell syndrome and Silver-Russell-like patients
- Author
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Bruce, S., primary, Hannula-Jouppi, K., additional, Puoskari, M., additional, Fransson, I., additional, Simola, K. O. J., additional, Lipsanen-Nyman, M., additional, and Kere, J., additional
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- 2009
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14. High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH
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Bruder, CEG, Hirvela, C, Tapia-Paez, I, Fransson, I, Segraves, R, Hamilton, G, Zhang, XX, Evans, DG, Wallace, AJ, Baser, ME, Zucman-Rossi, J, Hergersberg, M, Boltshauser, E, Papi, L, Rouleau, GA, Poptodorov, G, Jordanova, A, Rask-Andersen, H, Kluwe, L, Mautner, V, Sainio, M, Hung, G, Mathiesen, T, Moller, C, Pulst, SM, Harder, Henrik, Heiberg, A, Honda, M, Miimura, M, Sahlen, S, Blennow, E, Albertson, DG, Pinkel, D, Dumanski, JP, Bruder, CEG, Hirvela, C, Tapia-Paez, I, Fransson, I, Segraves, R, Hamilton, G, Zhang, XX, Evans, DG, Wallace, AJ, Baser, ME, Zucman-Rossi, J, Hergersberg, M, Boltshauser, E, Papi, L, Rouleau, GA, Poptodorov, G, Jordanova, A, Rask-Andersen, H, Kluwe, L, Mautner, V, Sainio, M, Hung, G, Mathiesen, T, Moller, C, Pulst, SM, Harder, Henrik, Heiberg, A, Honda, M, Miimura, M, Sahlen, S, Blennow, E, Albertson, DG, Pinkel, D, and Dumanski, JP
- Abstract
Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CON methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.
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- 2001
15. True Long-term Healing and Recurrence of Venous Leg Ulcers Following SEPS Combined with Superficial Venous Surgery: A Prospective Study
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Nelzén, O., primary and Fransson, I., additional
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- 2007
- Full Text
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16. Characterization of the human synaptogyrin gene family.
- Author
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Kedra, D, Pan, H Q, Seroussi, E, Fransson, I, Guilbaud, C, Collins, J E, Dunham, I, Blennow, E, Roe, B A, Piehl, F, Dumanski, J P, Kedra, D, Pan, H Q, Seroussi, E, Fransson, I, Guilbaud, C, Collins, J E, Dunham, I, Blennow, E, Roe, B A, Piehl, F, and Dumanski, J P
- Abstract
Genomic sequencing was combined with searches of databases for identification of active genes on human chromosome 22. A cosmid from 22q13, located in the telomeric vicinity of the PDGFB (platelet-derived growth factor B-chain) gene, was fully sequenced. Using an expressed sequence tag-based approach we characterized human (SYNGR1) and mouse (Syngr1) orthologs of the previously cloned rat synaptogyrin gene (RATSYNGR1). The human SYNGR1 gene reveals three (SYNGR1a, SYNGR1b, SYNGR1c) alternative transcript forms of 4.5, 1.3 and 0.9 kb, respectively. The transcription of SYNGR1 starts from two different promoters, and leads to predicted proteins with different N- and C-terminal ends. The most abundant SYNGR1 a transcript, the 4.5-kb form, which corresponds to RATSYNGR1, is highly expressed in neurons of the central nervous system and at much lower levels in other tissues, as determined by in situ hybridization histochemistry. The levels of SYNGR1b and SYNGR1c transcripts are low and limited to heart, skeletal muscle, ovary and fetal liver. We also characterized two additional members of this novel synaptogyrin gene family in human (SYNGR2 and SYNGR3), and one in mouse (Syngr2). The human SYNGR2 gene transcript of 1.6 kb is expressed at high levels in all tissues, except brain. The 2.2-kb SYNGR3 transcript was detected in brain and placenta only. The human SYNGR2 and SYNGR3 genes were mapped by fluorescence in situ hybridization to 17qtel and 16ptel, respectively. The human SYNGR2 gene has a processed pseudogene localized in 15q11. All predicted synaptogyrin proteins contain four strongly conserved transmembrane domains, which is consistent with the M-shaped topology. The C-terminal polypeptide ends are variable in length, display a low degree of sequence similarity between family members, and are therefore likely to convey the functional specificity of each protein.
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- 1998
17. Characterization of the mouse beta-prime adaptin gene; cDNA sequence, genomic structure, and chromosomal localization.
- Author
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Guilbaud, C, Peyrard, M, Fransson, I, Clifton, S W, Roe, B A, Carter, N P, Dumanski, J P, Guilbaud, C, Peyrard, M, Fransson, I, Clifton, S W, Roe, B A, Carter, N P, and Dumanski, J P
- Abstract
Adaptins are important subunits of heterotetrameric complexes called adaptors, which participate in the clathrin-coated, vesicle-mediated endocytosis and intracellular receptor transport. The gene family of adaptins is divided into three classes, alpha, beta, and gamma, with further subdivision into beta- and beta-prime components. Two beta-prime adaptins, the rat AP105a and the human BAM22, have previously been characterized. The BAM22 gene is located on human Chromosome (Chr) 22q12 and can be considered a candidate meningioma tumor suppressor gene. We report here the characterization of the mouse ortholog of the BAM22 gene, and we suggest the name adtb1 for the mouse gene. Like the BAM22 gene, the adtb1 transcript is highly and ubiquitously expressed. We provide 3885-bp cDNA sequence, which entirely covers the open reading frame of the adtb1, capable of encoding a protein of 943 amino acids. The adtb1 protein is highly conserved (>96% identity) when compared with AP105a and BAM22 proteins. We also report the genomic organization of adtb1, which is similar to the BAM22 gene. The adtb1 gene has been assigned to mouse Chr 11, band 11A2, which confirms the synteny between human Chr 22q12 and mouse Chr 11.
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- 1997
18. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.
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Simon, M P, Pedeutour, F, Sirvent, N, Grosgeorge, J, Minoletti, F, Coindre, J M, Terrier-Lacombe, M J, Mandahl, N, Craver, R D, Blin, N, Sozzi, G, Turc-Carel, C, O'Brien, K P, Kedra, D, Fransson, I, Guilbaud, C, Dumanski, J P, Simon, M P, Pedeutour, F, Sirvent, N, Grosgeorge, J, Minoletti, F, Coindre, J M, Terrier-Lacombe, M J, Mandahl, N, Craver, R D, Blin, N, Sozzi, G, Turc-Carel, C, O'Brien, K P, Kedra, D, Fransson, I, Guilbaud, C, and Dumanski, J P
- Abstract
Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate malignancy, presents specific features such as reciprocal translocations t(17;22)(q22;q13) and supernumerary ring chromosomes derived from the t(17;22). In this report, the breakpoints from translocations and rings in DP and its juvenile form, giant cell fibroblastoma (GCF), were characterised on the genomic and RNA level. These rearrangements fuse the platelet-derived growth factor B-chain (PDGFB, c-sis proto-oncogene) and the collagen type I alpha 1 (COL1A1) genes. PDGFB has transforming activity and is a potent mitogen for a number of cell types, but its role in oncogenic processes is not fully understood. COL1A1 is a major constituent of the connective tissue matrix. Neither PDGFB nor COL1A1 have so far been implicated in any tumour translocations. These gene fusions delete exon 1 of PDGFB, and release this growth factor from its normal regulation.
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- 1997
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19. Perception of information, expectations, and experiences among women and their partners attending a second-trimester routine ultrasound scan
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Eurenius, K, Axelsson, O, Gallstedt-Fransson, I, Sjoden ., P.O., Eurenius, K, Axelsson, O, Gallstedt-Fransson, I, and Sjoden ., P.O.
- Published
- 1997
20. The germinal center kinase gene and a novel CDC25-like gene are located inthe vicinity of the PYGM gene on 11q13.
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Kedra, D, Seroussi, E, Fransson, I, Trifunovic, J, Clark, M, Lagercrantz, J, Blennow, E, Mehlin, H, Dumanski, J, Kedra, D, Seroussi, E, Fransson, I, Trifunovic, J, Clark, M, Lagercrantz, J, Blennow, E, Mehlin, H, and Dumanski, J
- Published
- 1997
21. Prevalence and aetiology of leg ulcers in defined population of industrial workers.
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Nelzen, O, Bergqvist, David, Fransson, I, Lindhagen, A, Nelzen, O, Bergqvist, David, Fransson, I, and Lindhagen, A
- Published
- 1996
22. The DNA sequence of human chromosome 22
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Dunham, I., primary, Hunt, A. R., additional, Collins, J. E., additional, Bruskiewich, R., additional, Beare, D. M., additional, Clamp, M., additional, Smink, L. J., additional, Ainscough, R., additional, Almeida, J. P., additional, Babbage, A., additional, Bagguley, C., additional, Bailey, J., additional, Barlow, K., additional, Bates, K. N., additional, Beasley, O., additional, Bird, C. P., additional, Blakey, S., additional, Bridgeman, A. M., additional, Buck, D., additional, Burgess, J., additional, Burrill, W. D., additional, Burton, J., additional, Carder, C., additional, Carter, N. P., additional, Chen, Y., additional, Clark, G., additional, Clegg, S. M., additional, Cobley, V., additional, Cole, C. G., additional, Collier, R. E., additional, Connor, R. E., additional, Conroy, D., additional, Corby, N., additional, Coville, G. J., additional, Cox, A. V., additional, Davis, J., additional, Dawson, E., additional, Dhami, P. D., additional, Dockree, C., additional, Dodsworth, S. J., additional, Durbin, R. M., additional, Ellington, A., additional, Evans, K. L., additional, Fey, J. M., additional, Fleming, K., additional, French, L., additional, Garner, A. A., additional, Gilbert, J. G. R., additional, Goward, M. E., additional, Grafham, D., additional, Griffiths, M. N., additional, Hall, C., additional, Hall, R., additional, Hall-Tamlyn, G., additional, Heathcott, R. W., additional, Ho, S., additional, Holmes, S., additional, Hunt, S. E., additional, Jones, M. C., additional, Kershaw, J., additional, Kimberley, A., additional, King, A., additional, Laird, G. K., additional, Langford, C. F., additional, Leversha, M. A., additional, Lloyd, C., additional, Lloyd, D. M., additional, Martyn, I. D., additional, Mashreghi-Mohammadi, M., additional, Matthews, L., additional, McCann, O. T., additional, McClay, J., additional, McLaren, S., additional, McMurray, A. A., additional, Milne, S. A., additional, Mortimore, B. J., additional, Odell, C. N., additional, Pavitt, R., additional, Pearce, A. V., additional, Pearson, D., additional, Phillimore, B. J., additional, Phillips, S. H., additional, Plumb, R. W., additional, Ramsay, H., additional, Ramsey, Y., additional, Rogers, L., additional, Ross, M. T., additional, Scott, C. E., additional, Sehra, H. K., additional, Skuce, C. D., additional, Smalley, S., additional, Smith, M. L., additional, Soderlund, C., additional, Spragon, L., additional, Steward, C. A., additional, Sulston, J. E., additional, Swann, R. M., additional, Vaudin, M., additional, Wall, M., additional, Wallis, J. M., additional, Whiteley, M. N., additional, Willey, D., additional, Williams, L., additional, Williams, S., additional, Williamson, H., additional, Wilmer, T. E., additional, Wilming, L., additional, Wright, C. L., additional, Hubbard, T., additional, Bentley, D. R., additional, Beck, S., additional, Rogers, J., additional, Shimizu, N., additional, Minoshima, S., additional, Kawasaki, K., additional, Sasaki, T., additional, Asakawa, S., additional, Kudoh, J., additional, Shintani, A., additional, Shibuya, K., additional, Yoshizaki, Y., additional, Aoki, N., additional, Mitsuyama, S., additional, Roe, B. A., additional, Chen, F., additional, Chu, L., additional, Crabtree, J., additional, Deschamps, S., additional, Do, A., additional, Do, T., additional, Dorman, A., additional, Fang, F., additional, Fu, Y., additional, Hu, P., additional, Hua, A., additional, Kenton, S., additional, Lai, H., additional, Lao, H. I., additional, Lewis, J., additional, Lewis, S., additional, Lin, S.-P., additional, Loh, P., additional, Malaj, E., additional, Nguyen, T., additional, Pan, H., additional, Phan, S., additional, Qi, S., additional, Qian, Y., additional, Ray, L., additional, Ren, Q., additional, Shaull, S., additional, Sloan, D., additional, Song, L., additional, Wang, Q., additional, Wang, Y., additional, Wang, Z., additional, White, J., additional, Willingham, D., additional, Wu, H., additional, Yao, Z., additional, Zhan, M., additional, Zhang, G., additional, Chissoe, S., additional, Murray, J., additional, Miller, N., additional, Minx, P., additional, Fulton, R., additional, Johnson, D., additional, Bemis, G., additional, Bentley, D., additional, Bradshaw, H., additional, Bourne, S., additional, Cordes, M., additional, Du, Z., additional, Fulton, L., additional, Goela, D., additional, Graves, T., additional, Hawkins, J., additional, Hinds, K., additional, Kemp, K., additional, Latreille, P., additional, Layman, D., additional, Ozersky, P., additional, Rohlfing, T., additional, Scheet, P., additional, Walker, C., additional, Wamsley, A., additional, Wohldmann, P., additional, Pepin, K., additional, Nelson, J., additional, Korf, I., additional, Bedell, J. A., additional, Hillier, L., additional, Mardis, E., additional, Waterston, R., additional, Wilson, R., additional, Emanuel, B. S., additional, Shaikh, T., additional, Kurahashi, H., additional, Saitta, S., additional, Budarf, M. L., additional, McDermid, H. E., additional, Johnson, A., additional, Wong, A. C. C., additional, Morrow, B. E., additional, Edelmann, L., additional, Kim, U. J., additional, Shizuya, H., additional, Simon, M. I., additional, Dumanski, J. P., additional, Peyrard, M., additional, Kedra, D., additional, Seroussi, E., additional, Fransson, I., additional, Tapia, I., additional, Bruder, C. E., additional, and O'Brien, K. P., additional
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- 1999
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23. Perception of information, expectations and experiences among women and their partners attending a second-trimester routine ultrasound scan
- Author
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Eurenius, K., primary, Axelsson, O., additional, Gällstedt-Fransson, I., additional, and Sjöden, P.-O., additional
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- 1997
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24. Coating Thickness Prediction and Robot Trajectory Generation of Thermal Sprayed Coatings
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Nylén, P., additional, Fransson, I., additional, Wretland, A., additional, and Mårtensson, N., additional
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- 1996
- Full Text
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25. Prevalence and Aetiology of Leg Ulcers in a Defined Population of Industrial Workers
- Author
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Nelzén, O., primary, Bergqvist, D., additional, Fransson, I., additional, and Lindhagen, A., additional
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- 1996
- Full Text
- View/download PDF
26. Association and Mutation Analyses of the IRF6Gene in Families with Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate
- Author
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Pegelow, M., Koillinen, H., Magnusson, M., Fransson, I., Unneberg, P., Kere, J., Karsten, A., and Peyrard-Janvid, M.
- Abstract
Objectives (1) To detect interferon regulatory factor 6 gene (IRF6) mutations in newly recruited Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) families. (2) To test for association, in nonsyndromic cleft lip and/or cleft palate (NSCL/P) and in VWS/PPS families, the single nucleotide polymorphism (SNP) rs642961, from the IRF6enhancer AP-2a region, alone or as haplotype with rs2235371, a coding SNP (Val274Ile).Design IRF6mutation screening was performed by direct sequencing and genotyping of rs642961 and rs2235371 by TaqMan technology.Patients Seventy-one Swedish NSCL/P families, 24 Finnish cleft palate (CP) families, and 24 VWS/PPS families (seven newly recruited) were studied.Results Allelic and genotypic frequencies in each phenotype were compared to those of the controls, and no significant difference could be observed. IRF6gene mutation was detected in six of the seven new VWS/PPS families. Association analysis of the entire VWS/PPS sample set revealed the A allele from rs642961 to be a risk allele. Significant association was detected in the Swedish CP subset of our NSCL/P collection where the G-C haplotype for rs642961-rs2235371 were at risk (P= .013).Conclusions Our results do not support the previously reported association between the A allele of rs642961 and the NSCL phenotype. However, in the VWS/PPS families, the A allele was a risk allele and was, in a large majority (>80%), transmitted on the same chromosome as the IRF6mutation.
- Published
- 2014
- Full Text
- View/download PDF
27. Ornithine decar☐ylase activity in dorsal root ganglia of regenerating frog sciatic nerve
- Author
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Löwkvist B, Fransson I, Anders Edström, and Martin Kanje
- Subjects
medicine.medical_specialty ,Eflornithine ,genetic structures ,Nerve Crush ,Ornithine Decarboxylase ,Vinblastine ,Axonal Transport ,Ornithine decarboxylase ,Rana ,Lesion ,chemistry.chemical_compound ,Ganglia, Spinal ,Internal medicine ,medicine ,Animals ,Ligation ,Molecular Biology ,General Neuroscience ,Rana esculenta ,Anatomy ,Ornithine Decarboxylase Inhibitors ,Ornithine ,Sciatic Nerve ,Nerve Regeneration ,Endocrinology ,nervous system ,chemistry ,Axoplasmic transport ,GRENOUILLE ,Neurology (clinical) ,Sciatic nerve ,medicine.symptom ,Developmental Biology ,medicine.drug - Abstract
Ornithine decar☐ylase (ODC) activity was studied in dorsal root ganglia (DRG) of regenerating frog sciatic nerve. There was a significant increase in activity two days after a crush lesion of the nerve 2.5 cm distal to the DRG. The increase reached a maximum after 7 days, then declined but remained above control levels for at least 9 days. An endoneural injection of vinblastine, a potent inhibitor of retrograde and orthograde axonal transport, between the DRG and the crush inhibited the increase in ODC. In contrast, injections of vinblastine into undamaged nerves failed to affect ODC. The increase in ODC and also the regenerative properties of the nerve could be prevented by daily i.p. injections of α-difluoromethyl ornithine. We suggest that a signal is formed at the site of injury in the sciatic nerve. This signal is conveyed to the DRG by retrograde axonal transport where it initiates the events leading to an increase in ODC. This increase appears to be necessary for the regeneration of sensory fibers in the frog sciatic nerve.
- Published
- 1986
28. Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients 2 from different ethnic groups
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Erdos, M. E., Jiao, H., Toth, B., Erdos, M., Fransson, I., Rakoczi, E., Balogh, I., Magyarics, Z., Derfalvi, B., Csorba, G., Szaflarska, A., Megarbane, A., Akatcherian, C., Dbaibo, G., Hammarstrom, L., Juha Kere, Lefranc, G., and Marodi, L.
29. Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development.
- Author
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Peyrard-Janvid M, Leslie EJ, Kousa YA, Smith TL, Dunnwald M, Magnusson M, Lentz BA, Unneberg P, Fransson I, Koillinen HK, Rautio J, Pegelow M, Karsten A, Basel-Vanagaite L, Gordon W, Andersen B, Svensson T, Murray JC, Cornell RA, Kere J, and Schutte BC
- Subjects
- Abnormalities, Multiple genetics, Alleles, Animals, Cleft Lip genetics, Cleft Palate genetics, Cysts genetics, DNA-Binding Proteins metabolism, Gene Expression Regulation, Developmental, Genotype, Humans, Hybridization, Genetic, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, Lip pathology, Mice, Mice, Knockout, Mutation, Missense, Pedigree, Phenotype, Sequence Analysis, DNA, Transcription Factors metabolism, Zebrafish embryology, Zebrafish genetics, Abnormalities, Multiple pathology, Cleft Lip pathology, Cleft Palate pathology, Cysts pathology, DNA-Binding Proteins genetics, Lip abnormalities, Transcription Factors genetics
- Abstract
Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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30. Submicroscopic genomic alterations in Silver-Russell syndrome and Silver-Russell-like patients.
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Bruce S, Hannula-Jouppi K, Puoskari M, Fransson I, Simola KO, Lipsanen-Nyman M, and Kere J
- Subjects
- Adolescent, Child, Female, Genes, Recessive genetics, Genetic Loci genetics, Genotype, Humans, Infant, Infant, Newborn, Male, Polymorphism, Single Nucleotide genetics, Pregnancy, DNA Copy Number Variations genetics, Genome, Human genetics, Loss of Heterozygosity genetics, Silver-Russell Syndrome genetics, Uniparental Disomy genetics
- Abstract
Background: Silver-Russell syndrome (SRS, OMIM 180860) features fetal and postnatal growth restriction and variable dysmorphisms. Genetic and epigenetic aberrations on chromosomes 7 and 11 are commonly found in SRS. However, a large fraction of SRS cases remain with unknown genetic aetiology., Methods: 22 patients with a diagnosis of SRS (10 with H19 hypomethylation and 12 of unknown molecular aetiology) and their parents were studied with the Affymetrix 250K Sty microarray. Several analytical approaches were used to identify genomic aberrations such as copy number changes (CNCs), loss of heterozygosity (LOH) and uniparental disomy (UPD). Selected CNCs were verified with quantitative real-time PCR., Results: The largest unambiguous CNCs were found in patients with previously molecularly unexplained SRS with relatively mild phenotypes: a heterozygous deletion of chromosome 15q26.3 including the IGF1R gene (2.6 Mb), an atypical distal 22q11.2 deletion (1.1 Mb), and a pseudoautosomal region duplication (2.7 Mb) in a male patient. LOH regions of potential relevance to the SRS phenotype were also identified. Importantly, no duplications or UPD of chromosomes 7 or 11 were identified., Conclusion: Unexpected submicroscopic genomic events with pathogenic potential were found in three patients with molecularly unexplained SRS that was mild. The findings emphasise that SRS is heterogeneous in genetic aetiology beyond the major groups of H19 hypomethylation and maternal UPD7 and that unbiased genome-scale screens may reveal novel genotype-phenotype correlations.
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- 2010
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31. Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups.
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Jiao H, Tóth B, Erdos M, Fransson I, Rákóczi E, Balogh I, Magyarics Z, Dérfalvi B, Csorba G, Szaflarska A, Megarbane A, Akatcherian C, Dbaibo G, Rajnavölgyi E, Hammarström L, Kere J, Lefranc G, and Maródi L
- Subjects
- Adult, Child, Child, Preschool, DNA metabolism, Demography, Female, Humans, Male, Protein Binding, Protein Structure, Tertiary, Restriction Mapping, STAT3 Transcription Factor chemistry, Ethnicity genetics, Job Syndrome genetics, Job Syndrome immunology, Mutation genetics, STAT3 Transcription Factor genetics
- Abstract
We performed clinical, immunological and genetic studies of 12 hyper-IgE syndrome (HIES) patients from 4 Hungarian, 2 Lebanese, one Russian, one Polish, and one Swedish families with autosomal dominant (AD) or sporadic forms of the disease to reveal cross-ethnicity of recurrent and novel mutations in the signal transducer and activator of transcription-3 gene (STAT3). Four patients from 3 Hungarian families, and one Russian, and one Swedish patient carried the heterozygous R382W germline mutation at the DNA-binding site of STAT3. The recurrent V637M mutation affecting the SRC homology 2 (SH2) domain was detected in one Lebanese and one Polish family, and the V463del deletion located in the DNA-binding domain was unveiled in another Lebanese family. A novel H332Y mutation affecting the DNA-binding site of STAT3 in three Hungarian patients from a Gypsy family was also found. The segregation of this mutation with HIES, restriction fragment length polymorphism analysis of STAT3 from patients and controls and the negligible production upon IL-6 stimulation of monocyte chemotactic protein-1 by the patient's blood mononuclear cells suggested that the H332Y mutation was disease-causing. These data suggest, that dominant negative mutations of the DNA-binding and SH2 domains of STAT3 cause AD and sporadic cases of HIES in different ethnic groups with R382W as the predominant mutation found in 5 of the 9 families. Functional and genetic data support that the novel H332Y mutation may result in the loss of function of STAT3 and leads to the HIES phenotype.
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- 2008
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32. Leg ulcer point prevalence can be decreased by broad-scale intervention: a follow-up cross-sectional study of a defined geographical population.
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Forssgren A, Fransson I, and Nelzén O
- Subjects
- Adult, Age Distribution, Aged, Aged, 80 and over, Community Health Services, Cross-Sectional Studies, Diabetes Complications epidemiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prevalence, Reproducibility of Results, Sex Distribution, Sweden epidemiology, Venous Insufficiency complications, Venous Insufficiency epidemiology, Leg Ulcer epidemiology
- Abstract
In 1988 a cross-sectional epidemiological study was performed in Skaraborg County, Sweden, establishing leg ulcer point prevalence. Based on the results of that study a complete change in the care of leg ulcer patients was brought into practice. The objective of this postal cross-sectional follow-up study was to evaluate the success of the new management strategy. Responding healthcare providers were asked to report all patients with an open wound below the knee that did not heal within a 6-week period after onset of ulceration. Validity of results was ensured by examining 203 randomly selected patients. Based on clinical examination, an assessment of the underlying causes of ulceration was made. The study setting was inpatient and outpatient care in hospitals, primary care and community care within Skaraborg, with a population of 254,111. The response rate was 100% from district nurses, hospital wards and outpatient clinics. Reports were collected from healthcare providers, mainly nurses, in all 15 communities. A total of 621 individual patients with active leg ulcers were identified. Age-adjusted sex ratio of ulcer patients was 1:1.1 (M:F). The median age was 79 years. A total of 507 patients (82%) were older than 64 years. District and community nurses provided care for the majority (88.5%) of patients. The study verified a point prevalence of 2.4/1000 population in 2002 compared with 3.1/1000 in 1988, a 23% decrease in leg ulcer prevalence. Venous insufficiency was still the dominating causative factor, although the number of patients with venous leg ulcers was reduced by 46%. Arterial ulcers had decreased by 23%, while patients with ulcers of diabetic and multifactorial causes were increased. In conclusion, it is likely that this reduction in point prevalence reflects the introduction of the change in management strategy undertaken in the area.
- Published
- 2008
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33. Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe.
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Salmela E, Lappalainen T, Fransson I, Andersen PM, Dahlman-Wright K, Fiebig A, Sistonen P, Savontaus ML, Schreiber S, Kere J, and Lahermo P
- Subjects
- Cohort Studies, Europe, Finland, Gene Frequency, Genetic Markers, Humans, Language, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Population genetics
- Abstract
Background: Genome-wide data provide a powerful tool for inferring patterns of genetic variation and structure of human populations., Principal Findings: In this study, we analysed almost 250,000 SNPs from a total of 945 samples from Eastern and Western Finland, Sweden, Northern Germany and Great Britain complemented with HapMap data. Small but statistically significant differences were observed between the European populations (F(ST) = 0.0040, p<10(-4)), also between Eastern and Western Finland (F(ST) = 0.0032, p<10(-3)). The latter indicated the existence of a relatively strong autosomal substructure within the country, similar to that observed earlier with smaller numbers of markers. The Germans and British were less differentiated than the Swedes, Western Finns and especially the Eastern Finns who also showed other signs of genetic drift. This is likely caused by the later founding of the northern populations, together with subsequent founder and bottleneck effects, and a smaller population size. Furthermore, our data suggest a small eastern contribution among the Finns, consistent with the historical and linguistic background of the population., Significance: Our results warn against a priori assumptions of homogeneity among Finns and other seemingly isolated populations. Thus, in association studies in such populations, additional caution for population structure may be necessary. Our results illustrate that population history is often important for patterns of genetic variation, and that the analysis of hundreds of thousands of SNPs provides high resolution also for population genetics.
- Published
- 2008
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34. A locus on 2p12 containing the co-regulated MRPL19 and C2ORF3 genes is associated to dyslexia.
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Anthoni H, Zucchelli M, Matsson H, Müller-Myhsok B, Fransson I, Schumacher J, Massinen S, Onkamo P, Warnke A, Griesemann H, Hoffmann P, Nopola-Hemmi J, Lyytinen H, Schulte-Körne G, Kere J, Nöthen MM, and Peyrard-Janvid M
- Subjects
- Animals, Chromosome Mapping, Evolution, Molecular, Family, Female, Finland, Germany, Haplotypes, Heterozygote, Humans, Linkage Disequilibrium, Male, Phenotype, Phylogeny, Polymorphism, Single Nucleotide, Transcription, Genetic, Brain metabolism, Chromosomes, Human, Pair 2, Dyslexia genetics, Mitochondrial Proteins genetics, Repressor Proteins genetics, Ribosomal Proteins genetics
- Abstract
DYX3, a locus for dyslexia, resides on chromosome 2p11-p15. We have refined its location on 2p12 to a 157 kb region in two rounds of linkage disequilibrium (LD) mapping in a set of Finnish families. The observed association was replicated in an independent set of 251 German families. Two overlapping risk haplotypes spanning 16 kb were identified in both sample sets separately as well as in a joint analysis. In the German sample set, the odds ratio for the most significantly associated haplotype increased with dyslexia severity from 2.2 to 5.2. The risk haplotypes are located in an intergenic region between FLJ13391 and MRPL19/C2ORF3. As no novel genes could be cloned from this region, we hypothesized that the risk haplotypes might affect long-distance regulatory elements and characterized the three known genes. MRPL19 and C2ORF3 are in strong LD and were highly co-expressed across a panel of tissues from regions of adult human brain. The expression of MRPL19 and C2ORF3, but not FLJ13391, were also correlated with the four dyslexia candidate genes identified so far (DYX1C1, ROBO1, DCDC2 and KIAA0319). Although several non-synonymous changes were identified in MRPL19 and C2ORF3, none of them significantly associated with dyslexia. However, heterozygous carriers of the risk haplotype showed significantly attenuated expression of both MRPL19 and C2ORF3, as compared with non-carriers. Analysis of C2ORF3 orthologues in four non-human primates suggested different evolutionary rates for primates when compared with the out-group. In conclusion, our data support MRPL19 and C2ORF3 as candidate susceptibility genes for DYX3.
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- 2007
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35. Novel and de novo mutations of the IRF6 gene detected in patients with Van der Woude or popliteal pterygium syndrome.
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Peyrard-Janvid M, Pegelow M, Koillinen H, Larsson C, Fransson I, Rautio J, Hukki J, Larson O, Karsten AL, and Kere J
- Subjects
- DNA Mutational Analysis, Female, Genes, Dominant, Genitalia abnormalities, Humans, Leg abnormalities, Male, Mutation, Pedigree, Polymorphism, Genetic, Syndrome, Cleft Lip genetics, Cleft Palate genetics, Interferon Regulatory Factors genetics, Skin Abnormalities genetics
- Abstract
The interferon regulatory factor 6 gene (IRF6) has been identified as the major Van der Woude (VWS) syndrome and popliteal pterygium (PPS) syndrome gene with mutations in the majority of the kindreds. We have studied altogether 17 kindreds from Sweden, Finland, Norway, Thailand and Singapore, and report here 10 mutations, six of them previously unseen. In two kindreds, we could document de novo mutations, both of them changing a codon for a glutamine residue to a stop. No mutation could be detected in the four VWS kindreds from Finland, suggesting a founder effect for a mutation in an atypical noncoding position. Our findings demonstrate that several distinct mutations occur in the Swedish population, and confirm the general notion of a broad spectrum of IRF6 mutations underlying the VWS/PPS phenotypes.
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- 2005
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36. Strong conservation of the human NF2 locus based on sequence comparison in five species.
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Hansson CM, Ali H, Bruder CE, Fransson I, Kluge S, Andersson B, Roe BA, Menzel U, and Dumanski JP
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- Amino Acid Sequence, Animals, Cluster Analysis, Gene Duplication, Gene Library, Humans, Intercellular Signaling Peptides and Proteins, Models, Genetic, Molecular Sequence Data, Phylogeny, Proteins genetics, Sequence Alignment, Sequence Homology, Conserved Sequence genetics, Genes, Neurofibromatosis 2, Mammals genetics, Takifugu genetics
- Abstract
We analyzed 137 kb covering human neurofibromatosis 2 ( NF2) tumor suppressor locus and orthologous loci from baboon, mouse, rat, and pufferfish Takifugu rubripes. A predominant feature of human-rodent conservation is a very similar distribution of conserved islands, regarding length, position, and degree of identity. By use of a threshold of 75% identity over > or =100 bp of gap-free alignment, comparisons of human-mouse sequences resulted in 3.58% for extra-exonic conservation, which can be compared to 4.5% of exonic sequence content within the human locus. We identified a duplication of neurofibromin 2 in pufferfish, which resulted in two putative proteins with 74% and 76% identity to the human protein. One distinct island (called inter 1), conserved between all analyzed species, was located between promoters of the NIPSNAP1 and NF2 genes. Inter 1 might represent a novel regulatory element, important for the function of this locus. The high level of intronic conservation in the NF2 locus suggests that a number of unknown regulatory elements might exist within this gene. These elements could be affected by disease-causing mutations in NF2 patients and NF2-associated tumors. Alternatively, this conservation might be explained by presence of not yet characterized transcriptional unit(s) within this locus.
- Published
- 2003
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37. A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications.
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Buckley PG, Mantripragada KK, Benetkiewicz M, Tapia-Páez I, Diaz De Ståhl T, Rosenquist M, Ali H, Jarbo C, De Bustos C, Hirvelä C, Sinder Wilén B, Fransson I, Thyr C, Johnsson BI, Bruder CE, Menzel U, Hergersberg M, Mandahl N, Blennow E, Wedell A, Beare DM, Collins JE, Dunham I, Albertson D, Pinkel D, Bastian BC, Faruqi AF, Lasken RS, Ichimura K, Collins VP, and Dumanski JP
- Subjects
- Chromosome Mapping methods, Female, Gene Amplification genetics, Gene Deletion, Gene Dosage, Genes, Tumor Suppressor, Humans, Male, Nucleic Acid Hybridization methods, Chromosomes, Human, Pair 22 genetics, Genomics methods, Molecular Diagnostic Techniques methods, Oligonucleotide Array Sequence Analysis methods
- Abstract
We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
- Published
- 2002
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38. Analysis of short stature homeobox-containing gene ( SHOX) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity.
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Grigelioniene G, Schoumans J, Neumeyer L, Ivarsson A, Eklöf O, Enkvist O, Tordai P, Fosdal I, Myhre AG, Westphal O, Nilsson NO, Elfving M, Ellis I, Anderlid BM, Fransson I, Tapia-Paez I, Nordenskjöld M, Hagenäs L, and Dumanski JP
- Subjects
- Blotting, Southern, Humans, In Situ Hybridization, Fluorescence, Phenotype, Polymerase Chain Reaction, Short Stature Homeobox Protein, Syndrome, Body Height genetics, Genes, Homeobox, Homeodomain Proteins genetics, Osteochondrodysplasias genetics
- Abstract
Dyschondrosteosis (DCO; also called Léri-Weill syndrome) is a skeletal dysplasia characterised by disproportionate short stature because of mesomelic shortening of the limbs. Madelung deformity is a feature of DCO that is distinctive, variable in expressivity and frequently observed. Mutations of the SHOX (short stature homeobox-containing) gene have been previously described as causative in DCO. Isolated Madelung deformity (IMD) without the clinical characteristics of DCO has also been described in sporadic and a few familial cases but the genetic defect underlying IMD is unknown. In this study, we have examined 28 probands with DCO and seven probands with IMD for mutations in the SHOX gene by using polymorphic CA-repeat analysis, fluorescence in situ hybridisation (FISH), Southern blotting, direct sequencing and fibre-FISH analyses. This was combined with auxological examination of the probands and their family members. Evaluation of the auxological data showed a wide intra- and interfamilial phenotype variability in DCO. Out of 28 DCO probands, 22 (79%) were shown to have mutations in the SHOX gene. Sixteen unrelated DCO families had SHOX gene deletions. Four novel DCO-associated mutations were found in different families. In two additional DCO families, the previously described nonsense mutation (Arg195Stop) was detected. We conclude that mutations in the SHOX gene are the major factor in the pathogenesis of DCO. In a female proband with severe IMD and her unaffected sister, we detected an intrachromosomal duplication of the SHOX gene.
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- 2001
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39. High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.
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Bruder CE, Hirvelä C, Tapia-Paez I, Fransson I, Segraves R, Hamilton G, Zhang XX, Evans DG, Wallace AJ, Baser ME, Zucman-Rossi J, Hergersberg M, Boltshauser E, Papi L, Rouleau GA, Poptodorov G, Jordanova A, Rask-Andersen H, Kluwe L, Mautner V, Sainio M, Hung G, Mathiesen T, Möller C, Pulst SM, Harder H, Heiberg A, Honda M, Niimura M, Sahlén S, Blennow E, Albertson DG, Pinkel D, and Dumanski JP
- Subjects
- Adolescent, Child, Chromosomes, Human, Pair 22 genetics, Cloning, Molecular, Contig Mapping, DNA chemistry, Female, Gene Deletion, Humans, In Situ Hybridization, Fluorescence, Male, Membrane Proteins genetics, Middle Aged, Neurofibromatosis 2 pathology, Neurofibromin 2, Nucleic Acid Hybridization methods, Sequence Analysis, DNA, Chromosome Deletion, DNA genetics, Neurofibromatosis 2 genetics
- Abstract
Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.
- Published
- 2001
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40. A 1-Mb PAC contig spanning the common eliminated region 1 (CER1) in microcell hybrid-derived SCID tumors.
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Yang Y, Kiss H, Kost-Alimova M, Kedra D, Fransson I, Seroussi E, Li J, Szeles A, Kholodnyuk I, Imreh MP, Fodor K, Hadlaczky G, Klein G, Dumanski JP, and Imreh S
- Subjects
- Animals, Chromosomes, Human, Pair 3 genetics, Genes, Genetic Markers, Humans, Hybrid Cells, In Situ Hybridization, Fluorescence, Mice, Molecular Sequence Data, Bacteriophage P1 genetics, Contig Mapping methods, Fibrosarcoma genetics, Mice, SCID genetics
- Abstract
We have developed an elimination test to identify chromosomal regions that contain tumor inhibitory genes. Monochromosomal human/mouse microcell hybrids are generated and passaged through SCID mice. Derived tumors are then analyzed for deletions on the transgenomic chromosome. Using this strategy, we have previously identified a 1.6-cM common eliminated region 1 (CER1) on human 3p21. 3. We now report that CER1 contains 14 markers that are deleted in 19 SCID-derived tumors. A 1-Mb PAC contig that spans CER1 was assembled. Five chemokine receptor genes (CCR1, CCR3, CCR2, CCR5, and CCR6) were localized in CER1 in a 225-kb cluster. The lactotransferrin gene (LTF, or lactoferrin, LF), which reportedly has tumor inhibitory activity, also maps to CER1. Our results create a basis for characterization and further functional testing of genes within CER1., (Copyright 1999 Academic Press.)
- Published
- 1999
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41. TOM1 genes map to human chromosome 22q13.1 and mouse chromosome 8C1 and encode proteins similar to the endosomal proteins HGS and STAM.
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Seroussi E, Kedra D, Kost-Alimova M, Sandberg-Nordqvist AC, Fransson I, Jacobs JF, Fu Y, Pan HQ, Roe BA, Imreh S, and Dumanski JP
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA, Complementary, Endosomal Sorting Complexes Required for Transport, Endosomes chemistry, Gene Expression, Humans, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Oncogene Proteins v-myb, Promoter Regions, Genetic, Virus Integration, Adaptor Proteins, Signal Transducing, Chromosome Mapping, Chromosomes, Human, Pair 22, Hepatocyte Growth Factor genetics, Phosphoproteins genetics, Proteins genetics, Retroviridae Proteins, Oncogenic genetics
- Abstract
The avian tom1 (target of myb 1) gene has been previously characterized from v-myb-transformed cells. We report here cloning of the human and mouse tom1 orthologs. Both genes are expressed ubiquitously, with the highest levels in skeletal muscle, brain, and intestines, as assessed by Northern blot and mRNA in situ hybridization. The N-terminal domain of the TOM1 protein shares similarity with HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), which are associated with vesicular trafficking at the endosome. A putative coiled-coil domain was also detected in the central part of the TOM1 protein. This domain structure suggests that TOM1 is another member of a family of genes implicated in the trafficking regulation of growth-factor-receptor complexes that are destined for degradation in the lysosome. We also show that a human paralog of TOM1 (TOM1-like gene 1) exists. Furthermore, we provide a transcription map over a 190-kb contig of the TOM1 region. This map includes its distal neighbors HMOX1 and MCM5 and two proximal novel genes, one of which is a HMG-box-containing gene (HMG2L1), and the other of unknown function. Using a genomic PAC clone, we demonstrate that the mouse Tom1 and Hmox1 genes are part of an as yet undescribed syntenic group between mouse chromosome 8C1 and human chromosome 22q13.1., (Copyright 1999 Academic Press.)
- Published
- 1999
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42. The human LARGE gene from 22q12.3-q13.1 is a new, distinct member of the glycosyltransferase gene family.
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Peyrard M, Seroussi E, Sandberg-Nordqvist AC, Xie YG, Han FY, Fransson I, Collins J, Dunham I, Kost-Alimova M, Imreh S, and Dumanski JP
- Subjects
- Amino Acid Sequence, Animals, Chromosome Mapping, Cloning, Molecular, Gangliosides genetics, Gene Deletion, Gene Expression Regulation, Neoplastic genetics, Glycosyltransferases genetics, Humans, In Situ Hybridization, Fluorescence, Mice, Molecular Sequence Data, Protein Conformation, RNA, Messenger metabolism, Sequence Alignment, Sequence Analysis, DNA, Chromosomes, Human, Pair 22 genetics, Meningeal Neoplasms genetics, Meningioma genetics, N-Acetylglucosaminyltransferases genetics, Neoplasm Proteins genetics
- Abstract
Meningioma, a tumor of the meninges covering the central nervous system, shows frequent loss of material from human chromosome 22. Homozygous and heterozygous deletions in meningiomas defined a candidate region of >1 Mbp in 22q12.3-q13.1 and directed us to gene cloning in this segment. We characterized a new member of the N-acetylglucosaminyltransferase gene family, the LARGE gene. It occupies >664 kilobases and is one of the largest human genes. The predicted 756-aa N-acetylglucosaminyltransferase encoded by LARGE displays features that are absent in other glycosyltransferases. The human like-acetylglucosaminyltransferase polypeptide is much longer and contains putative coiled-coil domains. We characterized the mouse LARGE ortholog, which encodes a protein 97.75% identical with the human counterpart. Both genes reveal ubiquitous expression as assessed by Northern blot analysis and in situ histochemistry. Chromosomal mapping of the mouse gene reveals that mouse chromosome 8C1 corresponds to human 22q12.3-q13.1. Abnormal glycosylation of proteins and glycosphingolipids has been shown as a mechanism behind an increased potential of tumor formation and/or progression. Human tumors overexpress ganglioside GD3 (NeuAcalpha2,8NeuAcalpha2, 3Galbeta1,4Glc-Cer), which in meningiomas correlates with deletions on chromosome 22. It is the first time that a glycosyltransferase gene is involved in tumor-specific genomic rearrangements. An abnormal function of the human like-acetylglucosaminyltransferase protein may be linked to the development/progression of meningioma by altering the composition of gangliosides and/or by effect(s) on other glycosylated molecules in tumor cells.
- Published
- 1999
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43. Characterization of the human synaptogyrin gene family.
- Author
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Kedra D, Pan HQ, Seroussi E, Fransson I, Guilbaud C, Collins JE, Dunham I, Blennow E, Roe BA, Piehl F, and Dumanski JP
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, DNA, Complementary, Female, Humans, Mice, Molecular Sequence Data, Multigene Family, Pseudogenes, Rats, Sequence Homology, Amino Acid, Synaptogyrins, Membrane Proteins genetics, Nerve Tissue Proteins genetics
- Abstract
Genomic sequencing was combined with searches of databases for identification of active genes on human chromosome 22. A cosmid from 22q13, located in the telomeric vicinity of the PDGFB (platelet-derived growth factor B-chain) gene, was fully sequenced. Using an expressed sequence tag-based approach we characterized human (SYNGR1) and mouse (Syngr1) orthologs of the previously cloned rat synaptogyrin gene (RATSYNGR1). The human SYNGR1 gene reveals three (SYNGR1a, SYNGR1b, SYNGR1c) alternative transcript forms of 4.5, 1.3 and 0.9 kb, respectively. The transcription of SYNGR1 starts from two different promoters, and leads to predicted proteins with different N- and C-terminal ends. The most abundant SYNGR1 a transcript, the 4.5-kb form, which corresponds to RATSYNGR1, is highly expressed in neurons of the central nervous system and at much lower levels in other tissues, as determined by in situ hybridization histochemistry. The levels of SYNGR1b and SYNGR1c transcripts are low and limited to heart, skeletal muscle, ovary and fetal liver. We also characterized two additional members of this novel synaptogyrin gene family in human (SYNGR2 and SYNGR3), and one in mouse (Syngr2). The human SYNGR2 gene transcript of 1.6 kb is expressed at high levels in all tissues, except brain. The 2.2-kb SYNGR3 transcript was detected in brain and placenta only. The human SYNGR2 and SYNGR3 genes were mapped by fluorescence in situ hybridization to 17qtel and 16ptel, respectively. The human SYNGR2 gene has a processed pseudogene localized in 15q11. All predicted synaptogyrin proteins contain four strongly conserved transmembrane domains, which is consistent with the M-shaped topology. The C-terminal polypeptide ends are variable in length, display a low degree of sequence similarity between family members, and are therefore likely to convey the functional specificity of each protein.
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- 1998
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44. Cloning, expression pattern, and chromosomal assignment to 16q23 of the human gamma-adaptin gene (ADTG).
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Peyrard M, Parveneh S, Lagercrantz S, Ekman M, Fransson I, Sahlén S, and Dumanski JP
- Subjects
- Adaptor Protein Complex gamma Subunits, Animals, Blotting, Northern, Chromosome Mapping, DNA, Complementary, Humans, In Situ Hybridization, Fluorescence, Mice, Molecular Sequence Data, Sequence Analysis, DNA, Chromosomes, Human, Pair 16, Cloning, Molecular, Membrane Proteins genetics, Membrane Proteins metabolism
- Abstract
Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. We present the cloning and sequencing of the human gamma-adaptin cDNA (HGMW-approved symbol ADTG) consisting of 3723 bp with an open reading frame capable of encoding a protein of 825 amino acids, 98.9% identical to the mouse protein. Northern blot analysis of the mouse and human gamma-adaptin genes revealed a ubiquitous and abundant expression, except in human adult lung. Using a monochromosomal somatic cell hybrid panel and fluorescence in situ hybridization, we mapped this gene to human chromosome 16q23, which is syntenic with mouse chromosome 8, band D. In addition, we localized genes for two other components of the AP-1 adaptor, i.e., the medium (AP47) and small (AP19) subunits, to chromosomes 19 and 7, respectively. Expression analysis of these genes in human tissues revealed ubiquitously expressed transcripts of approximately 2.5 and 1.5 kb, respectively.
- Published
- 1998
- Full Text
- View/download PDF
45. The germinal center kinase gene and a novel CDC25-like gene are located in the vicinity of the PYGM gene on 11q13.
- Author
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Kedra D, Seroussi E, Fransson I, Trifunovic J, Clark M, Lagercrantz J, Blennow E, Mehlin H, and Dumanski J
- Subjects
- Amino Acid Sequence, Carrier Proteins genetics, Cloning, Molecular methods, Exons genetics, Genes genetics, Germinal Center Kinases, Humans, Introns genetics, Molecular Sequence Data, Multiple Endocrine Neoplasia Type 1 genetics, Muscles enzymology, Myotonic Dystrophy, Myotonin-Protein Kinase, Nuclear Proteins genetics, RNA Splicing Factors, RNA, Messenger analysis, Sequence Analysis, DNA, Sequence Homology, Amino Acid, ras-GRF1, Cell Cycle Proteins genetics, Chromosome Mapping, Chromosomes, Human, Pair 11 genetics, DNA-Binding Proteins, Phosphoprotein Phosphatases genetics, Phosphorylases genetics, Protein Serine-Threonine Kinases genetics, Transcription Factors
- Abstract
Multiple endocrine neoplasia type 1 (MEN1) is tightly linked to the muscle-type glycogen phosphorylase (PYGM) gene in 11q13. This region of the human genome contains additional disease-related loci implicated in the development of insulin-dependent diabetes mellitus, familial paraganglioma type 2, spinocerebellar ataxia type 5, Bardet-Biedl syndrome and translocation t(11;17) described in B-cell non-Hodgkin's lymphoma. We approached cloning of candidate disease genes from 11q13 by large-scale genomic sequencing. We obtained > 106 kb of sequence around the PYGM gene and established a transcriptional map that includes: (i) two genes previously localized to 11q13, PYGM and a zinc-finger protein (ZFM1) gene; (ii) the germinal center kinase (GCK, human B-lymphocyte serine/threonine protein kinase) gene; (iii) a novel human CDC25-like (HCDC25L) gene; (iv) a dystrophia myotonica protein kinase-like (DMPKL) gene; and (v) a novel ubiquitously expressed gene of unknown function (germinal center kinase- neighboring gene, GCKNG).
- Published
- 1997
- Full Text
- View/download PDF
46. Characterization of the mouse beta-prime adaptin gene; cDNA sequence, genomic structure, and chromosomal localization.
- Author
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Guilbaud C, Peyrard M, Fransson I, Clifton SW, Roe BA, Carter NP, and Dumanski JP
- Subjects
- Adaptor Protein Complex beta Subunits, Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Cloning, Molecular, Conserved Sequence, DNA, Complementary, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Mice, Inbred Strains, Molecular Sequence Data, Rats, Restriction Mapping, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Tissue Distribution, Adaptor Protein Complex 1, Chromosome Mapping, Membrane Proteins genetics
- Abstract
Adaptins are important subunits of heterotetrameric complexes called adaptors, which participate in the clathrin-coated, vesicle-mediated endocytosis and intracellular receptor transport. The gene family of adaptins is divided into three classes, alpha, beta, and gamma, with further subdivision into beta- and beta-prime components. Two beta-prime adaptins, the rat AP105a and the human BAM22, have previously been characterized. The BAM22 gene is located on human Chromosome (Chr) 22q12 and can be considered a candidate meningioma tumor suppressor gene. We report here the characterization of the mouse ortholog of the BAM22 gene, and we suggest the name adtb1 for the mouse gene. Like the BAM22 gene, the adtb1 transcript is highly and ubiquitously expressed. We provide 3885-bp cDNA sequence, which entirely covers the open reading frame of the adtb1, capable of encoding a protein of 943 amino acids. The adtb1 protein is highly conserved (>96% identity) when compared with AP105a and BAM22 proteins. We also report the genomic organization of adtb1, which is similar to the BAM22 gene. The adtb1 gene has been assigned to mouse Chr 11, band 11A2, which confirms the synteny between human Chr 22q12 and mouse Chr 11.
- Published
- 1997
- Full Text
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47. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.
- Author
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Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C, O'Brien KP, Kedra D, Fransson I, Guilbaud C, and Dumanski JP
- Subjects
- Chromosome Breakage, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 22, Collagen Type I, alpha 1 Chain, DNA, Neoplasm, Gene Library, Humans, Molecular Sequence Data, Proto-Oncogene Mas, Proto-Oncogene Proteins c-sis, Ring Chromosomes, Translocation, Genetic, Cloning, Molecular, Collagen genetics, Dermatofibrosarcoma genetics, Platelet-Derived Growth Factor genetics, Proto-Oncogene Proteins genetics, Skin Neoplasms genetics
- Abstract
Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate malignancy, presents specific features such as reciprocal translocations t(17;22)(q22;q13) and supernumerary ring chromosomes derived from the t(17;22). In this report, the breakpoints from translocations and rings in DP and its juvenile form, giant cell fibroblastoma (GCF), were characterised on the genomic and RNA level. These rearrangements fuse the platelet-derived growth factor B-chain (PDGFB, c-sis proto-oncogene) and the collagen type I alpha 1 (COL1A1) genes. PDGFB has transforming activity and is a potent mitogen for a number of cell types, but its role in oncogenic processes is not fully understood. COL1A1 is a major constituent of the connective tissue matrix. Neither PDGFB nor COL1A1 have so far been implicated in any tumour translocations. These gene fusions delete exon 1 of PDGFB, and release this growth factor from its normal regulation.
- Published
- 1997
- Full Text
- View/download PDF
48. Structure of the promoter and genomic organization of the human beta'-adaptin gene (BAM22) from chromosome 22q12.
- Author
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Peyrard M, Pan HQ, Kedra D, Fransson I, Swahn S, Hartman K, Clifton SW, Roe BA, and Dumanski JP
- Subjects
- Adaptor Protein Complex beta Subunits, Base Composition, Base Sequence, CpG Islands genetics, DNA chemistry, DNA Mutational Analysis, Exons genetics, Genes, Tumor Suppressor genetics, Humans, Introns genetics, Molecular Sequence Data, Point Mutation genetics, Polymorphism, Restriction Fragment Length, Sequence Analysis, DNA, Adaptor Protein Complex 1, Chromosomes, Human, Pair 22 genetics, Genes genetics, Membrane Proteins genetics, Meningeal Neoplasms genetics, Meningioma genetics, Promoter Regions, Genetic genetics
- Abstract
Adaptins are major structural components of heterotetrameric protein complexes called adaptors, which are essential in intracellular receptor transport via clathrin-coated vesicles. beta-adaptins constitute one of three known classes (alpha, beta, gamma) of adaptins, including beta and beta' subtypes. We previously cloned the human beta'-adaptin gene (BAM22) (GDB symbol, ADTB1) from chromosome 22q12 and proposed its involvement in the development of meningiomas. Here we describe the genomic organization of this gene, which consists of 22 exons spanning over approximately 100 kb. We also report results from point mutation screening of 7 randomly chosen exons analyzed in 110 sporadic meningiomas. As part of the genomic characterization of the BAM22 locus, we sequenced 40 kb covering exons 1-4 and 12 kb upstream from the start of gene transcription. Analysis of the sequence suggests that the BAM22 gene has a CG-rich promoter.
- Published
- 1996
- Full Text
- View/download PDF
49. Characterization of a second human clathrin heavy chain polypeptide gene (CLH-22) from chromosome 22q11.
- Author
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Kedra D, Peyrard M, Fransson I, Collins JE, Dunham I, Roe BA, and Dumanski JP
- Subjects
- Alternative Splicing, Amino Acid Sequence, Base Sequence, Blotting, Northern, Chromosomes, Human, Pair 17, Clathrin Heavy Chains, Gene Expression Regulation, Humans, Meningeal Neoplasms genetics, Meningioma genetics, Molecular Sequence Data, Restriction Mapping, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Chromosomes, Human, Pair 22, Clathrin genetics
- Abstract
We report cloning and characterization of the second human clathrin heavy chain polypeptide gene (CLH-22) localized to chromosome 22q11. Hence H. sapiens is the first species for which two clathrin heavy chain genes have been reported. We provide 5470 bp cDNA sequence covering the entire open reading frame of the CLH-22 gene. The predicted polypeptide is composed of 1640 amino acids. Its 6 kb transcript is expressed in all of 16 tested human tissues, suggesting it is a housekeeping gene. Skeletal muscle, testis and heart show significantly higher expression levels. Compared to the previously characterized human clathrin heavy chain gene localized on chromosome 17 (CLH-17), CLH-22 shows different transcript size and expression profile in human tissues. Northern analysis of CLH-22 suggests that several alternatively spliced transcripts exist. A presumably single, 171 bp long alternatively spliced exon has been characterized. Amino acid sequence comparison between CLH-22 and CLH-17 shows an overall identify and similarity of 84.7 and 91.1%, respectively. At the nucleic acid level, identity between open reading frames of both genes is 74.3%. Sequence comparison with previously cloned genes in other species suggests that counterparts of the CLH-17 gene have been cloned in B. taurus and R. norvegicus, whereas presumptive mammalian homologues of the CLH-22 gene are yet to be characterized. Our Northern and Southern blot analyses of meningiomas clearly suggest the CLH-22 gene may be involved in the tumor development and can be considered as a candidate for a tumor suppressor.
- Published
- 1996
- Full Text
- View/download PDF
50. Characterization of a new member of the human beta-adaptin gene family from chromosome 22q12, a candidate meningioma gene.
- Author
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Peyrard M, Fransson I, Xie YG, Han FY, Ruttledge MH, Swahn S, Collins JE, Dunham I, Collins VP, and Dumanski JP
- Subjects
- Adaptor Protein Complex beta Subunits, Alternative Splicing, Base Sequence, Blotting, Northern, Chromosome Mapping, Cloning, Molecular, Gene Deletion, Humans, Molecular Sequence Data, Point Mutation genetics, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Adaptor Protein Complex 1, Chromosomes, Human, Pair 22, Membrane Proteins genetics, Meningeal Neoplasms genetics, Meningioma genetics
- Abstract
A 140 kb homozygous deletion from 22q12 in one meningioma directed us towards the cloning and characterization of a new member of the human beta-adaptin gene family (named BAM22). Adaptins are essential for the formation of clathrin coated vesicles in the course of intracellular transport of receptor-ligand complexes. The BAM22 gene is totally inactivated in the tumor with homozygous deletion. Northern blot analysis of 70 sporadic meningiomas showed specific loss of expression in 8 tumors, suggesting inactivation of BAM22. Based on this, we propose BAM22 as a second chromosome 22 locus important in meningioma development, after the neurofibromatosis type 2 gene.
- Published
- 1994
- Full Text
- View/download PDF
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