Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cDNA clones encoding zinc finger motifs were isolated by screening human placenta and T-cell (Peer) cDNA libraries with zinc finger (ZNF) consensus sequences. Unique cDNA clones were mapped in the human genome by rodent-human somatic cell hybrid analysis and in some cases in situ chromosomal hybridization. ZNF80 mapped to 3p12-3qter, ZNF7 was previously mapped to 8q24 and is here shown by in situ hybridization and use of appropriate hybrids to map telomeric to the MYC locus. ZNF79 mapped to 9q34 centromeric to the ABL gene and between a constitutional chromosomal translocation on the centromeric side and the CML specific ABL translocation on the telomeric side. ZNF77 mapped to 19p while ZNF78L1 (pT3) mapped to 19q. Chromosome 19 carries many ZNF loci and other genes with zinc finger encoding motifs; the pT3 clone additionally detected a locus designated ZNF78L2, which mapped to chromosome region 1p, most likely in the region 1p32 where the MYCL and JUN loci map.
...
PMID:Chromosomal localization of four human zinc finger cDNAs. 847 4

A chronic myelogenous leukemia (CML) patient with a masked Ph chromosome due to the translocation (9;10;22)(q34;q24;q11) is reported. Banding analysis showed a 9q+ chromosome typical of standard t(9;22)(q34;q11), and fluorescence in situ hybridization studies confirmed the involvement of a chromosome 10 in the masked Ph formation and also the presence of 3' ABL-DNA sequences in the der(22). This complex rearrangement could be explained by two consecutive translocations: the first, a standard t(9;22) (q34;q11), the second, a translocation between a chromosome 10 and the der(22) with a breakpoint in sequences derived from chromosome 9 telomeric to the ABL gene. By reverse transcription polymerase chain reaction (RT-PCR), we studied the BCR/ABL transcript junction: a chimeric m-RNA b3-a2, indicating a breakpoint within the major breakpoint cluster region, was found.
...
PMID:Fluorescence in situ hybridization provides evidence for two-step rearrangement in a masked Ph chromosome formation. 863 61

We describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.
...
PMID:Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. 864 22

Chronic myeloid leukaemia (CML) is characterized cytogenetically by a t(9;22)(q34;ql1) reciprocal translocation which gives origin to a hybrid BCR-ABL gene, encoding a p2lO(BCR-ABL) fusion protein with elevated tyrosine kinase activity and transforming abilities. The t(9;22) was suggested to be associated with genomic imprinting of centromeric regions of chromosomes 9 and 22, but the genes directly affected by the translocation, ABL and BCR, were shown not to be imprinted. For most diagnostic and research purposes the BCR-ABL gene can be efficiently identified by reverse-transcription and polymerase chain reaction (RT/PCR) amplification of its fusion transcripts, which can be quantified by competitive PCR and similar assays for assessment of residual disease in the follow-up of therapy. In the great majority of CML patients the BCR-ABL transcripts exhibit a b2a2 and/or a b3a2 junction; in rare cases, the only detectable BCR-ABL transcripts have unusual junctions, such as b2a3, b3a3, e1a2 or e6a2. There is a recent suggestion that the BCR-ABL gene may not be always 'functional', since extremely low levels of BCR-ABL transcripts can be found in leucocytes from normal individuals and, conversely, it appears that no BCR-ABL transcription can be detected in a proportion of Ph-positive haematopoietic progenitors from some CML patients. The role, if any, of the reciprocal ABL-BCR hybrid gene in CML is unknown. Although its mRNA message is in frame, no ABL-BCR fusion protein has yet been identified in CML patients. The blast crisis of CML has been variably associated with abnormalities of proto-oncogenes, such as RAS and MYC, or of tumour suppressor genes, in particular RB, p53 and p16, or with the generation of chimeric transcription factors, as in the AML1-EVI1 gene fusion. It is likely, therefore, that multiple and alternative molecular defects, as opposed to a single universal mechanism, underlie the acute transformation of the disease.
...
PMID:The molecular biology of chronic myeloid leukaemia. 865 67

The LH2 gene encodes a putative transcription factor containing two N-terminal LIM and one C-terminal HOX domains. The LH2 locus was mapped to 9q33-34.1, centromeric to the ABL gene. In a recent report, it was suggested that high levels of LH2 expression are consistently observed in chronic myeloid leukemia (CML) patients, whereas no transcription is detected in normal individuals. This led to the hypothesis that aberrant expression of LH2 may represent an additional mechanism for malignant cell proliferation in CML. We have studied the expression of LH2 in leucocytes from patients with CML or with other chronic myeloproliferative disorders (CMD), and from normal individuals, using an optimised reverse-transcription and polymerase chain reaction (PCR) technique. Twenty-seven out of 29 cDNA samples from normal individuals (93%), 49 out of 51 samples from CML patients (96%) and 20 out of 20 from Philadelphia chromosome-negative CMD showed evidence of LH2 expression. Similarly, LH2 transcription was also detected in leucocytes from CML patients in complete cytogenetic remission after treatment with interferon-alpha. Furthermore, all 36 EBV-induced lymphoblastoid cell lines established from six chronic phase CML patients showed unequivocal LH2 expression, regardless of the BCR-ABL status of the line (9 BCR-ABL positive, 27 BCR-ABL negative). We conclude that LH2 expression is not confined to CML cells, and that the t(9;22)(q34;qll) does not promote 'de novo' transcriptional activation of this gene.
...
PMID:Expression of the LH2 gene in chronic myeloid leukaemia cells. 868 90

Alterations in dopamine neurotransmission and disturbed norepinephrine activity have been implicated in the pathogenesis of schizophrenia. We considered the dopamine-beta-hydroxylase (DBH) gene located on the long arm of chromosome 9 (9q34.3) as a candidate gene for schizophrenia. DBH catalyzes the synthesis of norepinephrine from dopamine in noradrenergic neurons. In addition to DBH we used in the linkage study DNA markers ABL (centromeric) and D9S114 (telomeric). The aim of this study was to test linkage and association between PCR-based genotyped markers and schizophrenia. A simulation was done to investigate the power of our sample. In 34 Austrian families we could not detect linkage between schizophrenia and schizophrenia spectrum disorders and the three genetic markers. We could not find any significant deviation in allelic or genotypic distribution from expectations. Based on our results we conclude that the DBH gene seems to have no strong contribution in the etiology of schizophrenia.
...
PMID:Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study. 892 53

Allelic loss of chromsome 19q occurs frequently in malignant gliomas, suggesting the presence of a chromosome 19q glioma tumor suppressor gene. Deletion mapping studies have delineated a 3.5 Mb candidate region between D19S219 and HRC. Cloned sequences from the proximal 425 kb of this interval, however, have not shown tumor-specific alterations. To refine the location of the tumor suppressor gene further, we conducted loss of heterozygosity studies on 191 malignant gliomas using nine PCR-based polymorphisms. These included the previously identified and physically mapped markers D19S219, DM, D19S112, HRC and the recently physically mapped polymorphisms at D19S412, STD, D19S596 and GYS. In addition, we isolated a novel microsatellite polymorphism that maps 400 kb telomeric to D19S112. Oligodendroglial tumors showed frequent loss of heterozygosity in all grades, and typically displayed allelic loss at all studied markers. Astrocytomas, however, showed frequent loss primarily in anaplastic astrocytomas and displayed deletion breakpoints within the candidate region. Deletion mapping revealed a minimal region of overlap between D19S412 and STD, a distance of 900 kb. These data suggest that the D19S412-STD interval represents the most likely location for a chromsome 19q glioma tumor suppressor gene involved in astrocytoma, and perhaps oligodendroglioma, tumorigenesis.
...
PMID:Refined deletion mapping of the chromosome 19q glioma tumor suppressor gene to the D19S412-STD interval. 895 92

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi-generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease-causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.
...
PMID:Localization of a gene for otosclerosis to chromosome 15q25-q26. 942 36

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder with multisystemic manifestations caused by heterozygosity for a partial deletion of chromosome band 7q11.23. The breakpoints cluster within regions located approximately 1 cM either side of the elastin (ELN) locus. We have characterized a duplicated region near the common deletion breakpoints, which includes a transcribed gene. The centromeric (C) and telomeric (T) copies are almost identical in the duplicated 3[prime] portions but diverge at their 5[prime]-ends. C-specific 4.3 kb mRNA and T-specific 5.4 kb mRNA are widely expressed in embryonic and adult tissues. The telomeric gene gives rise to several alternatively spliced forms and is deleted in all WBS individuals who have documented ELN deletions. Database searches revealed that this gene encodes BAP-135, a protein phosphorylated by Bruton's tyrosine kinase in B cells, as well as the multifunctional transcription factor TFII-I, hence the gene name GTF2I. The centromeric gene is not deleted in WBS and appears to be a partially truncated expressed pseudogene with no protein product (gene name GTF2IP1). Both loci map to different genomic clone contigs that also contain other deleted and non-deleted loci. A probe from the shared region recognizes a >3 Mb Not I junction fragment that is unique to individuals with the WBS deletion. Therefore, the duplicated region containing GTF2I and GTF2IP1 respectively is located close to the deletion breakpoints and may predispose to unequal meiotic recombination between chromosome 7 homologs and/or to intrachromosomal rearrangements. Hemizygosity for GTF2I may also contribute to the WBS phenotype.
...
PMID:A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. 946 87

We have cloned and characterized Gtf2i, the mouse homolog of human GTF2I (general transcription factor II-I), which encodes BAP-135, a target for Bruton's tyrosine kinase. GTF2I represents the telomeric and functional copy of a duplicated gene flanking the 2-Mb Williams-Beuren syndrome (WBS) common deletion at 7q11.23. GTF2I is deleted in WBS, while a truncated centromeric pseudogene (GTF2IP1) is not deleted. In mouse, there appears to be only a single locus, Gtf2i, which we mapped to mouse chromosome 5 in a region of conserved mouse-human synteny. Gtf2i is 87.7% identical to GTF2I at the nucleotide and 97% at the amino acid level and generates several alternatively spliced transcripts. The gene is widely expressed in adult tissues and equally in all areas of the brain. Gtf2i transcript is detectable in ES cells by RT-PCR and on Northern blots of tissues from 7-dpc embryos. A ubiquitous expression pattern is seen by Northern and tissue in situ hybridization studies of 14-dpc embryos.
...
PMID:A mouse single-copy gene, Gtf2i, the homolog of human GTF2I, that is duplicated in the Williams-Beuren syndrome deletion region. 952 69


<< Previous 1 2 3 4 5 Next >>

---