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Lawrence C. Layman - One of the best experts on this subject based on the ideXlab platform.

  • Comparative Deletion Mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability
    Molecular Cytogenetics, 2016
    Co-Authors: Jonathan D. J. Labonne, Yiping Shen, Il-keun Kong, Michael P. Diamond, Lawrence C. Layman
    Abstract:

    Background While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microDeletions in the short arm have been documented. More than half of the 1p microDeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microDeletions have not been clearly defined. Results We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microDeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal Deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA . Comparative Deletion Mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes ( DAB1 , HOOK1 , NFIA , DOCK7 , DNAJC6 , and PDE4B ) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microDeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. Conclusion We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microDeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.

  • comparative Deletion Mapping at 1p31 3 p32 2 implies nfia responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability
    Molecular Cytogenetics, 2016
    Co-Authors: Jonathan D. J. Labonne, Yiping Shen, Il-keun Kong, Michael P. Diamond, Lawrence C. Layman
    Abstract:

    While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microDeletions in the short arm have been documented. More than half of the 1p microDeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microDeletions have not been clearly defined. We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microDeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal Deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative Deletion Mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microDeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microDeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.

Jonathan D. J. Labonne - One of the best experts on this subject based on the ideXlab platform.

  • Comparative Deletion Mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability
    Molecular Cytogenetics, 2016
    Co-Authors: Jonathan D. J. Labonne, Yiping Shen, Il-keun Kong, Michael P. Diamond, Lawrence C. Layman
    Abstract:

    Background While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microDeletions in the short arm have been documented. More than half of the 1p microDeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microDeletions have not been clearly defined. Results We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microDeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal Deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA . Comparative Deletion Mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes ( DAB1 , HOOK1 , NFIA , DOCK7 , DNAJC6 , and PDE4B ) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microDeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. Conclusion We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microDeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.

  • comparative Deletion Mapping at 1p31 3 p32 2 implies nfia responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability
    Molecular Cytogenetics, 2016
    Co-Authors: Jonathan D. J. Labonne, Yiping Shen, Il-keun Kong, Michael P. Diamond, Lawrence C. Layman
    Abstract:

    While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microDeletions in the short arm have been documented. More than half of the 1p microDeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microDeletions have not been clearly defined. We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microDeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal Deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative Deletion Mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microDeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microDeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.

Yusuke Nakamura - One of the best experts on this subject based on the ideXlab platform.

  • detailed Deletion Mapping of chromosome arm 3p in breast cancers a 2 cm region on 3p14 3 21 1 and a 5 cm region on 3p24 3 25 1 commonly deleted in tumors
    Genes Chromosomes and Cancer, 1997
    Co-Authors: Satoshi Matsumoto, Fujio Kasumi, Goi Sakamoto, Masahiko Onda, Yusuke Nakamura
    Abstract:

    Loss of heterozygosity (LOH) on 3p is frequent in human renal cell carcinomas, lung cancers, and breast cancers. To define the region(s) on 3p that harbor presumptive tumor suppressor gene(s) for breast cancer, we examined 196 primary breast tumors for their patterns of LOH at 22 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 101 (52%) of these tumors. Detailed Deletion Mapping identified two distinct commonly deleted regions; one was localized to a 2-cM interval flanked by D3S1547 and D3S1295 at 3p14.3-21.1, and the other to a 5-cM interval flanked by D3S1286 and D3S1585 at 3p24.3-25.1. The FHIT gene lies in the vicinity of the proximal commonly deleted region. Attempts to correlate LOH on 3p to clinicopathological parameters detected an association with the absence of the progesterone receptor (P = 0.0096). The results suggest that inactivation of unidentified tumor suppressor genes on 3p plays a role in the mechanism whereby hormone dependency is lost in the course of breast carcinogenesis. Genes Chromosomes Cancer 20:268–274, 1997. © 1997 Wiley-Liss, Inc.

  • detailed Deletion Mapping of chromosome 17q in ovarian and breast cancers 2 cm region on 17q21 3 often and commonly deleted in tumors
    Cancer Research, 1993
    Co-Authors: Hiroko Saito, Fujio Kasumi, Satoru Sagae, Ryuichi Kudo, Junko Saito, Susumu Saito, Johji Inazawa, K. Noda, Yusuke Nakamura
    Abstract:

    Abstract Using 11 restriction fragment length polymorphism markers, we examined loss of heterozygosity on the long arm of chromosome 17, where one or more genes responsible for hereditary breast and ovarian cancers may be present, in sporadic forms of 94 ovarian and 246 breast cancers. Loss of heterozygosity was observed in 33 of 84 (39.3%) ovarian and in 88 of 214 (41.1%) breast cancers that were informative with at least one marker. Detailed Deletion Mapping of chromosome 17q in these cancers identified two distinct, commonly deleted regions. One was located between 17q12 and 17q21.3 and the other between 17q25.1 and 17q25.3. In breast cancers, the proximal commonly deleted region was between two loci defined by markers CI17-701 and CI17-730 at 17q21.3, which are 2.4 cM apart. This segment overlaps the region that includes the putative gene for hereditary breast and ovarian carcinomas. The results suggest that at least two tumor suppressor genes associated with sporadic ovarian and breast cancers are present on chromosome 17q and that one of them may be the same gene that is responsible for the hereditary form.

  • Deletion Mapping of the short arm of chromosome 8 in non small cell lung carcinoma
    Genes Chromosomes and Cancer, 1993
    Co-Authors: Hiroyuki Ohata, Yoshiyuki Fujiwara, Kazuya Higashino, Ken Nakagawa, Reiko Futagami, Eiju Tsuchiya, Yusuke Nakamura
    Abstract:

    Frequent losses of heterozygosity observed at several chromosomal loci in primary lung cancers have indicated the existence of several tumor suppressor genes associated with this type of cancer. We have examined loss of heterozygosity on chromosomal arm 8p in 49 cases of non-small cell lung carcinoma, using 14 restriction fragment length polymorphism markers. Of 42 cases informative with at least one marker, 21 showed allelic loss, including 15 of 32 adenocarcinomas and 5 of 9 squamous cell carcinomas. The frequency of allelic loss on 8p was similar at all clinical stages. Deletion Mapping defined a single common region of Deletion in these tumors within an 8 cM interval at 8p21.3–p22 flanked by the loci defined by cMSR-32 and cC18–245. © 1993 Wiley-Liss, Inc.

  • Deletion Mapping of chromosomes 14q and 1p in human neuroblastoma
    Oncogene, 1992
    Co-Authors: Hisashi Takayama, Yusuke Nakamura, Takashi Suzuki, Hideo Mugishima, Takahito Fujisawa, Masahiko Ookuni, Manfred Schwab, Manuela Gehring, Takashi Sugimura, Masaaki Terada
    Abstract:

    : It has been suggested that loss of heterozygosity (LOH) on the short arm of chromosome 1 is a critical event for the development of neuroblastoma, and we have previously shown frequent LOH on chromosome 14 in neuroblastoma. To pursue these observations, especially to define further the regions which are commonly deleted in the tumor, we examined for allelic losses in 27 cases of neuroblastomas by using a number of polymorphic DNA markers for chromosomes 14q and 1p. LOH was observed in 10 out of the 25 informative cases (40%) on chromosome 14q and in eight out of the 21 informative cases (38%) on 1p. The commonly deleted regions were distal to the D14S13 locus (14q32-qter) on chromosome 14 and distal to the D1S112 locus (1p36.1-pter) on chromosome 1. These results strongly suggest that tumor-suppressor genes important in the pathogenesis of human neuroblastoma are located on the distal part of both chromosomes 14q and 1p.

Margaret A Knowles - One of the best experts on this subject based on the ideXlab platform.

  • high resolution Deletion Mapping of 15q13 2 q21 1 in transitional cell carcinoma of the bladder
    Cancer Research, 2003
    Co-Authors: Rachael Natrajan, Jari Louhelainen, Sarah Williams, Jonathan P Laye, Margaret A Knowles
    Abstract:

    Deletions found in several types of human tumor, including carcinomas of the colorectum, breast, and lung, suggest the presence of a potential tumor suppressor gene(s) on chromosome 15. Common regions of Deletion in these tumors are at 15q15 and 15q21. Here, we have analyzed loss of heterozygosity (LOH) on chromosome 15 to ascertain its potential involvement in the development and progression of transitional cell carcinoma (TCC) of the bladder. A panel of 26 polymorphic markers, spanning 15q12–15q22, were used to map regions of LOH in 51 TCCs. LOH was found for at least one marker in the region 15q14–15q15.3 in 20 of 51 (39%) tumors. Deletion Mapping defined two minimum regions of Deletion: a distal region between the markers D15S514 and D15S537 at 15q15.1–15q15.3 (estimated as 3 Mb) and a more proximal region between the markers D15S971 and D15S1042 at 15q14 (estimated as 1.1 Mb). Analysis of a panel of 33 bladder tumor cell lines revealed regions of contiguous homozygosity for markers in 15q15, indicating likely LOH. Fluorescence in situ hybridization analysis demonstrated that mitotic recombination is the predicted mechanism of LOH in two of these. These regions of LOH on 15q may contain tumor suppressor genes the loss or inactivation of which is associated with TCC development. The DNA repair gene RAD51 at 15q15.1 represents a candidate 15q tumor suppressor gene. Expression analysis of rad51 protein in tumor cell lines revealed variable levels of expression but no significant loss of expression in cell lines with likely 15q LOH.

  • Fluorescence in situ hybridization Deletion Mapping at 4p16.3 in bladder cancer cell lines refines the localisation of the critical interval to 30 kb.
    Genes Chromosomes and Cancer, 1996
    Co-Authors: Sandra M. Bell, Richard M. Myers, Margaret A Knowles
    Abstract:

    : An allelotype analysis of transitional cell carcinoma of the bladder identified loss of heterozygosity (LOH) on chromosome arm 4p in 22% of tumours. In a more detailed LOH study of 178 bladder carcinomas, a 750 kb common region of Deletion was identified between the markers D4S43 and D4S127 just telomeric to the Huntington disease locus. To refine this region of Deletion at 4p16.3, we have carried out detailed fluorescence in situ hybridisation (FISH) analysis of 12 bladder cancer cell lines by using a chromosome 4 centromeric probe combined with a series of cosmid probes from contigs spanning the 750 kb region of Deletion. A common 30 kb region of Deletion was identified at 4p16.3 in over one-third of the bladder cancer cell lines analysed. The present study has refined the localisation of the critical region of Deletion from 750 kb to approximately 30 kb, providing a precise starting point for positional cloning of the gene(s) involved in bladder cancer from within a very gene-rich region on chromosome band 4p16.3. This study demonstrates that FISH can be used for fine Deletion Mapping of potential tumour suppressor gene regions. The utilisation of FISH analysis to map chromosomal Deletions should facilitate positional cloning of other genes as bacterial artificial chromosome (BAC) and yeast artificial chromosome (YAC) contigs of the human genome are established.

  • Deletion Mapping of chromosome II in carcinoma of the bladder
    Genes Chromosomes and Cancer, 1995
    Co-Authors: Margaret E. Shaw, Margaret A Knowles
    Abstract:

    Deletions of the short arm of chromosome II have been identified by both cytogenetic and molecular criteria in bladder and other types of solid tumor, indicating the presence of one or more suppressor loci in this region. To localize the II p Deletion target(s) more precisely and to screen for loss of heterozygosity (LOH) on the long arm of the chromosome, I00 bladder tumors were analyzed for LOH on chromosome II using restriction fragment length polymorphism (RFLPs) and microsatellite markers mapped to both II p and II q. Thirty-four tumors were found to have LOH at I or more loci. Of these, I7 had LOH restricted to II p, I3 had LOH of both II p and II q, and 4 had LOH of II q only. Eight tumors showed LOH at all informative loci indicating probable loss of an entire copy of chromosome II. A common region of Deletion was defined on II p between DIIS922(IIpI5.5) and DlIS569 (IIpI5.I-I5.2). This region does not include the HRAS or WTI loci (at IIpI5.5and IIp13, respectively). Seventeen tumors had LOH on II q, 4 of which had LOH on II q only. The common region of Deletion on II q was between FGF3 and DI IS490 (IIq I3-q23.2). Two tumors showed LOH on both II p and II q with a clear region of retention of heterozygosity between, indicatinn the existence of two Deletion targets on chromosome II. © 1995 Wiley-Liss, Inc.

  • Homozygous Deletion Mapping at 9p21 in bladder carcinoma defines a critical region within 2cM of IFNA.
    Oncogene, 1994
    Co-Authors: Devlin J, Keen Aj, Margaret A Knowles
    Abstract:

    : We have screened 165 cases of primary transitional cell carcinoma of the bladder for loss of heterozygosity of markers on chromosome 9. High density Deletion Mapping was then carried out on a panel of 16 tumours with partial Deletions of 9p using 15 microsatellite markers. Seven tumours had hemizygous Deletions which included small interstitial losses and large terminal Deletions. Homozygous Deletions of one or more markers were identified in the remaining 9 tumours. By comparing the limits of hemi- and homozygous Deletions in these tumours we have defined a single common region of 2cM flanked by IFNA and D9S171.

  • Deletion Mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms
    Oncogene, 1993
    Co-Authors: Margaret A Knowles, M E Shaw, A J Proctor
    Abstract:

    : We have used a combination of restriction fragment length polymorphism (RFLP) markers and highly informative microsatellite polymorphisms to map a common region of Deletion on chromosome 8p in cancers of the urinary bladder. Analysis of loss of heterozygosity (LOH) using microsatellite polymorphisms was shown to be at least as sensitive as detection of RFLPs by Southern blotting. A total of 110 tumours was analysed for loss of heterozygosity (LOH) on 8p and 8q; 109 patients were informative for at least one marker on each chromosome arm and 29 tumours (26%) showed LOH of chromosome 8 markers, 26 of which (25%) showed LOH on 8p. Sixteen tumours (14%) showed LOH on 8q. Thirteen of these also had LOH on 8p. Of the 29 tumours with LOH, five had LOH at all informative loci, indicating loss of an entire copy of chromosome 8. An association was found between high tumour grade and stage and chromosome 8 LOH. Fifty-three per cent of grade 3 muscle-invasive tumours showed LOH compared with 11% of grade 1 non-invasive tumours (0.01 < P < 0.025 and 0.025 < P < 0.05 for grade and stage respectively). Deletion Mapping of tumours with chromosome 8 LOH suggests the presence of a suppressor gene(s) for urothelial cancer within a region defined by the loci NEFL and PLAT (8p21-q11.2). If there is a common target for Deletions in bladder and those in hepatocellular and colorectal tumours reported previously, this defines a common region of Deletion at 8p21.3.

Il-keun Kong - One of the best experts on this subject based on the ideXlab platform.

  • Comparative Deletion Mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability
    Molecular Cytogenetics, 2016
    Co-Authors: Jonathan D. J. Labonne, Yiping Shen, Il-keun Kong, Michael P. Diamond, Lawrence C. Layman
    Abstract:

    Background While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microDeletions in the short arm have been documented. More than half of the 1p microDeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microDeletions have not been clearly defined. Results We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microDeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal Deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA . Comparative Deletion Mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes ( DAB1 , HOOK1 , NFIA , DOCK7 , DNAJC6 , and PDE4B ) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microDeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. Conclusion We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microDeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.

  • comparative Deletion Mapping at 1p31 3 p32 2 implies nfia responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability
    Molecular Cytogenetics, 2016
    Co-Authors: Jonathan D. J. Labonne, Yiping Shen, Il-keun Kong, Michael P. Diamond, Lawrence C. Layman
    Abstract:

    While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microDeletions in the short arm have been documented. More than half of the 1p microDeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microDeletions have not been clearly defined. We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microDeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal Deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative Deletion Mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microDeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microDeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.