Gene Function & Disease最新文献_第5页

An intronic nucleotide variant of the RET proto-oncogene causes Hirschsprung disease by interfering with RNA splicing RET原癌基因的内含子核苷酸变异通过干扰RNA剪接导致巨结肠疾病

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200012)1:5/6<184::AID-GNFD184>3.0.CO;2-6

Paola Griseri, Michele Mishto, Manuela Priolo, Barbara Pesce, Ben C. J. Hamel, Giovanni Romeo, Roberto Ravazzolo, Isabella Ceccherini

{"title":"An intronic nucleotide variant of the RET proto-oncogene causes Hirschsprung disease by interfering with RNA splicing","authors":"Paola Griseri, Michele Mishto, Manuela Priolo, Barbara Pesce, Ben C. J. Hamel, Giovanni Romeo, Roberto Ravazzolo, Isabella Ceccherini","doi":"10.1002/1438-826X(200012)1:5/6<184::AID-GNFD184>3.0.CO;2-6","DOIUrl":"10.1002/1438-826X(200012)1:5/6<184::AID-GNFD184>3.0.CO;2-6","url":null,"abstract":"The RET proto-oncogene is expressed during embryogenesis in neural-crest derived cells and is involved in different human neurocristopathies such as Multiple Endocrine Neoplasia type 2 (MEN2) syndromes and Hirschsprung disease (HSCR or congenital megacolon). While MEN2 are inherited cancer syndromes due to constitutive activation of the Ret receptor, HSCR pathogenesis is caused by loss of function of the RET product. We have analyzed the RET proto-oncogene in a family showing a peculiar recurrence of neurocristopathies: a mother with ganglioneuroblastoma and a daughter with long segment aganglionosis. In the HSCR patient no mutation in the RET gene was detected, except for a C>T substitution in intron 12. Functional evidences that such an intronic mutation introduces a novel splice donor site which is recognized and actively used during RNA splicing are provided. Moreover, a polymorphic RET variant, found overrepresented in sporadic medullary carcinomas, was detected in the mother. The association of HSCR with ganglioneuroblastoma in close relatives could be more than coincidental and further investigation into genes driving neural crest differentiation will help to explain the occurrence of different neurocristopathies within the same pedigree.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 5-6","pages":"184-188"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200012)1:5/6<184::AID-GNFD184>3.0.CO;2-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86063516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Putative regulatory domains in the human and mouse CVADR genes 人类和小鼠CVADR基因的推定调控域

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200009)1:2<82::AID-GNFD82>3.0.CO;2-Y

Björn Andersson, Richard P. Tomko, Kimberly Edwards, Momina Mirza, Hamid Darban, Delal Öncü, Erik Sonnhammer, Kerstin Sollerbrant, Lennart Philipson

{"title":"Putative regulatory domains in the human and mouse CVADR genes","authors":"Björn Andersson, Richard P. Tomko, Kimberly Edwards, Momina Mirza, Hamid Darban, Delal Öncü, Erik Sonnhammer, Kerstin Sollerbrant, Lennart Philipson","doi":"10.1002/1438-826X(200009)1:2<82::AID-GNFD82>3.0.CO;2-Y","DOIUrl":"10.1002/1438-826X(200009)1:2<82::AID-GNFD82>3.0.CO;2-Y","url":null,"abstract":"The gene for the cellular receptor of coxsackievirus group B and adenoviruses (CVADR) has recently been isolated. The complete cDNA of the human and mouse genes has been published and demonstrated to code for a 46 kDa membrane protein that bears similarity to immunoglobulins. In this study, we present the sequence of the entire human CVADR gene and a 5 kb sequence from the 5′-end of the mouse CVADR gene. A comparison of the human and mouse sequences revealed four conserved sequence elements that may be involved in the regulation of gene expression. In addition, three different splice forms of the mouse CVADR gene were identified by RT-PCR of RNA derived from adult mouse organs. Interestingly, one of the forms was unique to mouse heart. Putative alternative exons corresponding to the two dominant alternately spliced mouse forms were identified in the human genomic HCVADR sequence and shown to most likely be functional. However, a splice acceptor site was not found in an HCVADR exon that is homologous to the mouse heart-specific splice form. Therefore, the presence of this alternative C-terminus in humans is in question. The data thus provide an insight into the structure and regulation of the CVADR genes in humans and mice.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 2","pages":"82-86"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200009)1:2<82::AID-GNFD82>3.0.CO;2-Y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84229036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Promoter 1 of LMO2, a master gene for hematopoiesis, is regulated by the erythroid specific transcription factor GATA1 LMO2启动子1是造血主控基因，受红系特异性转录因子GATA1调控

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200009)1:2<87::AID-GNFD87>3.0.CO;2-4

Maik Martin Pruess, Matthias Drechsler, Brigitte Royer-Pokora

{"title":"Promoter 1 of LMO2, a master gene for hematopoiesis, is regulated by the erythroid specific transcription factor GATA1","authors":"Maik Martin Pruess, Matthias Drechsler, Brigitte Royer-Pokora","doi":"10.1002/1438-826X(200009)1:2<87::AID-GNFD87>3.0.CO;2-4","DOIUrl":"10.1002/1438-826X(200009)1:2<87::AID-GNFD87>3.0.CO;2-4","url":null,"abstract":"The T cell oncogene LMO2 was first identified at the site of the translocation t(11;14)(p13;q11) in T-acute lymphocytic leukemia (T-ALL) and encodes a cysteine-rich protein with LIM-motifs. It was later shown to have an essential role in yolk sac and adult erythropoiesis. LMO2 encodes two alternative transcripts differing in the length of the 5’ untranslated region, but encoding the same protein. Transcription start site mapping revealed the 5′-end of the longer transcript, LMO2a and promoter 1. Sequencing identified two putative GATA1 sites and an overlapping SP1 site close to the transcription start site, suggesting that promoter 1 (P1) is an erythroid specific promoter. Using EMSA analysis with an oligonucleotide from promoter 1 we now show that GATA1 and SP1 bind to these sites. DNaseI hypersensitive site (DHS) mapping upstream of the transcription start site revealed four erythroid specific sites, corresponding to putative GATA1 motifs and one non-lineage specific site. Reporter gene experiments with P1 and a mutant, where both GATA sites were inactivated, showed that GATA1 plays a functional role in the erythroid specific transcriptional control of LMO2 from P1. These studies confirm that promoter 1 of the LMO2 gene is an erythroid specific promoter.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 2","pages":"87-94"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200009)1:2<87::AID-GNFD87>3.0.CO;2-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78006270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Skeletal myopathy in mice over-expressing the human myotonic dystrophy protein kinase (DMPK) gene 过度表达人肌强直性营养不良蛋白激酶(DMPK)基因的小鼠骨骼肌病

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200010)1:3/4<134::AID-GNFD134>3.0.CO;2-W

Monica A. Narang, James D. Waring, Luc A. Sabourin, Evica Rajcan-Separovic, David Parry, Frank Jirik, Robert G. Korneluk

{"title":"Skeletal myopathy in mice over-expressing the human myotonic dystrophy protein kinase (DMPK) gene","authors":"Monica A. Narang, James D. Waring, Luc A. Sabourin, Evica Rajcan-Separovic, David Parry, Frank Jirik, Robert G. Korneluk","doi":"10.1002/1438-826X(200010)1:3/4<134::AID-GNFD134>3.0.CO;2-W","DOIUrl":"10.1002/1438-826X(200010)1:3/4<134::AID-GNFD134>3.0.CO;2-W","url":null,"abstract":"Myotonic dystrophy (DM) is caused by the expansion of a trinucleotide repeat located in the 3’-untranslated region of a serine-threonine kinase (DMPK), such that repeat size corresponds with severity of disease and age of onset. The mechanism by which this mutation causes DM remains unclear. Recent reports indicate that over-expression of DMPK in murine C2C12 myoblasts inhibits myogenesis, reminiscent of the marked immaturity observed in DM patient muscle. Accordingly, we generated transgenic mice over-expressing the human DMPK gene with expression enhancing matrix attachment region (MAR) sequences. These mice show substantial over-expression of human DMPK transcript and protein in brain, skeletal muscle, tongue, and eye - tissues typically affected in DM. Cryostat sections of skeletal muscle from these transgenic animals revealed diagnostic hallmarks of DM including increased centronucleation, type 1 fiber atrophy and ringed fibers. Additionally, primary myoblasts established from these mice showed reduced fusion potential indicating a delay or defect in myoblast differentiation. These results suggest that over-expression of the human DMPK gene in these mice confers a skeletal muscle pathology similar to that seen in DM patients. ","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 3-4","pages":"134-144"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200010)1:3/4<134::AID-GNFD134>3.0.CO;2-W","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77803900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Determination of the chromosomal location and genomic structure of the Hedgehog-Interacting Protein gene, and analysis of its role in Holoprosencephaly 刺猬相互作用蛋白基因的染色体定位和基因组结构的确定及其在前脑畸形中的作用分析

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200010)1:3/4<119::AID-GNFD119>3.0.CO;2-K

Liang Huo, Erich Roessler, Amalia Dutra, Pao-Tien Chuang, A. P. McMahon, Maximilian Muenke

{"title":"Determination of the chromosomal location and genomic structure of the Hedgehog-Interacting Protein gene, and analysis of its role in Holoprosencephaly","authors":"Liang Huo, Erich Roessler, Amalia Dutra, Pao-Tien Chuang, A. P. McMahon, Maximilian Muenke","doi":"10.1002/1438-826X(200010)1:3/4<119::AID-GNFD119>3.0.CO;2-K","DOIUrl":"10.1002/1438-826X(200010)1:3/4<119::AID-GNFD119>3.0.CO;2-K","url":null,"abstract":"Hedgehog-Interacting Protein (HIP) is a novel component of the Sonic Hedgehog (SHH) signaling pathway. Recently, defects in this pathway have been shown to cause holoprosencephaly (HPE), which is the most common birth defect of the brain and face in humans. In animal models knockout mice with homozygous null mutations for Shh displayed abnormalities consistent with HPE. Hip has been shown to function as a co-receptor and attenuate Hedgehog signaling by cell-surface binding of the Hedgehog protein and is hypothesized to act as part of a negative regulatory feedback loop. Although Hip is an important factor in the Shh signaling pathway, its potential role in HPE had not been examined in humans. Here, we report the complete gene structure of the human HIP gene and present its mutational analysis in HPE patients. No mutations were found either in the entire coding region or 1 kb upstream of the transcriptional start site (representing the putative promotor) suggesting this gene may not be involved in HPE pathogenesis.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 3-4","pages":"119-127"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200010)1:3/4<119::AID-GNFD119>3.0.CO;2-K","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91061305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Cell-line specific transcription rates of the RET gene and functional domains in its minimal promoter RET基因的细胞系特异性转录率及其最小启动子的功能域

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200010)1:3/4<145::AID-GNFD145>3.0.CO;2-O

Giovanna Patrone, Francesca Puppo, Monica Scaranari, Roberto Cusano, Paola Griseri, Giovanni Romeo, Isabella Ceccherini, Aldamaria Puliti, Roberto Ravazzolo

{"title":"Cell-line specific transcription rates of the RET gene and functional domains in its minimal promoter","authors":"Giovanna Patrone, Francesca Puppo, Monica Scaranari, Roberto Cusano, Paola Griseri, Giovanni Romeo, Isabella Ceccherini, Aldamaria Puliti, Roberto Ravazzolo","doi":"10.1002/1438-826X(200010)1:3/4<145::AID-GNFD145>3.0.CO;2-O","DOIUrl":"10.1002/1438-826X(200010)1:3/4<145::AID-GNFD145>3.0.CO;2-O","url":null,"abstract":"To gain insight into the RET gene transcriptional regulation we analysed its mRNA expression, transcription rate, and promoter activity in different cell lines, showing that RET transcription is highly cell-line specific. By using a panel of promoter deletion constructs in transient transfection assays we identified the −147/+53 fragment as the main functional element. GMSA experiments indicated binding by Sp1 and a CACCC binding protein to multiple sites within the promoter. Upon deletion analysis Sp1 appeared to be the main positive regulator of promoter activity. The −147/+53 sequence did not reproduce the cell-line specific activity of the endogenous gene in vitro, raising the question of how the regulated pattern of RET transcription is achieved at the molecular level. To address this topic, both the search for far-sited tissue-specific enhancers/silencers and the study of chromatin structure within the RET locus should be envisaged. ","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 3-4","pages":"145-153"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200010)1:3/4<145::AID-GNFD145>3.0.CO;2-O","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83564387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Human chromosome 21 sequence: impact for the molecular genetics of Down syndrome 人类21号染色体序列:对唐氏综合症分子遗传学的影响

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200012)1:5/6<175::AID-GNFD175>3.0.CO;2-6

Pascal Kahlem, Marie-Laure Yaspo

引用次数: 5

Rapid detection of an Angiotensin Type 2 Receptor Gene variant: no evidence for linkage and association with primary vesicoureteral reflux 快速检测血管紧张素2型受体基因变异:无证据表明与原发性膀胱输尿管反流相关

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200012)1:5/6<202::AID-GNFD202>3.0.CO;2-5

Iris Körner, Britta Fischer, Rolf Beetz, Karin Buiting, Anne-Margret Wingen, Herbert Rübben, Thomas F. Wienker, Bernhard Horsthemke, Gabriele Gillessen-Kaesbach

引用次数: 0

Identification of polymorphisms in the GABAB receptor gene and linkage study of attention-deficit hyperactivity disorder GABAB受体基因多态性鉴定及注意缺陷多动障碍的连锁研究

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200012)1:5/6<194::AID-GNFD194>3.0.CO;2-2

Cathy L. Barr, Yu Feng, Karen Wigg, Wendy Roberts, Molly Malone, Russell Schachar, Rosemary Tannock, Jeffrey R. Gruen, Vita Goei, James L. Kennedy

{"title":"Identification of polymorphisms in the GABAB receptor gene and linkage study of attention-deficit hyperactivity disorder","authors":"Cathy L. Barr, Yu Feng, Karen Wigg, Wendy Roberts, Molly Malone, Russell Schachar, Rosemary Tannock, Jeffrey R. Gruen, Vita Goei, James L. Kennedy","doi":"10.1002/1438-826X(200012)1:5/6<194::AID-GNFD194>3.0.CO;2-2","DOIUrl":"10.1002/1438-826X(200012)1:5/6<194::AID-GNFD194>3.0.CO;2-2","url":null,"abstract":"Individuals with attention-deficit hyperactivity disorder (ADHD) are often diagnosed with comorbid reading disabilities (RD) and twin studies have suggested a genetic relationship. Genetic linkage to several chromosome locations has been reported for RD, including a region located on chromosome 6p, near the human leukocyte antigen (HLA) region. The gene for the gamma-aminobutyric acid (GABA) beta receptor 1 gene (GABABR1), has recently been cloned and localized to the region of 6p with the strongest support for linkage to RD. GABABR1 is an interesting candidate gene for RD based on its location and its proposed role in cognition. The genetic link between RD and ADHD supports the GABABR1 receptor gene as a candidate for ADHD as well. In addition, the role of the GABAB receptor in modulating the release of a number of neurotransmitters, including dopamine and norepinephrine, both postulated to be involved in ADHD, suggests that this receptor may play a role in the ADHD phenotype. Based on this hypothesis, we screened this gene for DNA sequence variants. We identified nine DNA sequence variants in a sample of ADHD probands with and without comorbid RD. Three of the common variants were used for linkage analysis to the ADHD phenotype in a sample of 98 families identified through an ADHD proband. We did not observe significant evidence for linkage in our sample. Our findings do not support a role of this gene in ADHD..","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"1 5-6","pages":"194-201"},"PeriodicalIF":0.0,"publicationDate":"2001-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200012)1:5/6<194::AID-GNFD194>3.0.CO;2-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81315327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Genotypic and phenotypic expressions of protein 4.2 in human erythroid cells 蛋白4.2在人红细胞中的基因型和表型表达

Gene Function & Disease Pub Date : 2001-08-17 DOI: 10.1002/1438-826X(200009)1:2<61::AID-GNFD61>3.0.CO;2-7

Yoshihito Yawata, Akio Kanzaki, Ayumi Yawata

引用次数: 7