Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph) chromosome and bcr/abl gene rearrangement which occurs in pluripotent hematopoietic progenitor cells expressing the c-kit receptor tyrosine kinase (KIT). To elucidate the biological properties of KIT in CML leukemogenesis, we performed analysis of alterations of the c-kit gene and functional analysis of altered KIT proteins. Gene alterations in the c-kit juxtamembrane domain of 80 CML cases were analyzed by reverse transcriptase and polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP). One case had an abnormality at codon 564 (AAT --> AAG, Asn --> Lys), and six cases had the same base abnormality at codon 541 (ATG --> CTG, Met --> Leu) in the juxtamembrane domain. Because the change from Met to Leu at codon 541 was a conservative one which was also observed in the normal population and normal tissues of CML patients, it probably represents a polymorphic variation. Although samples of hair roots and leukemic cells from the chronic phase of one CML patient showed no abnormality, an abnormality at codon 541 (ATG --> CTG, Met --> Leu) was found only at blastic crisis (BC) of this case. In the case with the abnormality at codon 564, the mutation was detected only in a sample of leukemic cells collected at BC. To examine the biological consequence and biological significance of these abnormalities, murine KIT(L540) and KIT(K563) expression vectors were introduced into interleukin-3 (IL-3)-dependent murine Ba/F3 cells to study their state of tyrosine phosphorylation and their growth rate. Ba/F3 cells expressing KIT(WT), KIT(L540) and KIT(K563) showed dose-dependent tyrosine phosphorylation after treatment with increasing concentrations of recombinant mouse stem cell factor (rmSCF). The cells expressing KIT(L540) and KIT(K563) were found to have greater tyrosine phosphorylation than cells expressing KIT(WT) at 0.1 and 1.0 ng/ml of rmSCF. The Ba/F3 cells expressing KIT(K563) proliferated in response to 0.1 and 1.0 ng/ml of rmSCF as well as IL-3. The Ba/F3 cells expressing KIT(L540)showed a relatively higher proliferative response to 0.1 ng/ml of rmSCF than the response of cells expressing KIT(WT). These mutations and in vitro functional analyses raise the possibility that the KIT abnormalities influence the white blood cell counts (P < 0.05) and survival (P < 0.04) of CML patients.
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PMID:Abnormality of c-kit oncoprotein in certain patients with chronic myelogenous leukemia--potential clinical significance. 1630 17

Hemoglobin (Hb) Korle-Bu (beta73; Asp-Asn) is the most frequent of the rare beta-chain variants in the population of West Africa whereas Hb E (beta26; Glu-Lys) is common among the Southeast Asian population. We report a hitherto undescribed condition in which these two beta-chain variants co-segregate. The proband was a 19-year-old Thai pregnant woman in her second trimester of pregnancy who visited our thalassemia screening unit. Cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC) analysis of Hb detected one abnormal Hb in addition to the Hb E. Analysis of DNA sequences revealed a GAT-AAT mutation at codon 73 in trans to a GAG-AAG mutation at codon 26 of the beta-globin gene. Polymerase chain reaction (PCR) analysis of the alpha-globin gene cluster of the patient detected a 3.7-kb deletional alpha-thalassemia 2. Family study identified that her mother had the same genotype and her father was a simple Hb E carrier. The hematological data of these unusual cases of hemoglobinopathy are presented and compared with a simple heterozygote for Hb Korle-Bu found in another unrelated Thai family. beta-Globin gene haplotype linked to the Thai beta(Korle-Bu) and a simple DNA assay based on allele-specific PCR for rapid diagnosis of Hb Korle-Bu are also described.
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PMID:Compound heterozygosity for Hb Korle-Bu (beta(73); Asp-Asn) and Hb E (beta(26); Glu-Lys) with a 3.7-kb deletional alpha-thalassemia in Thai patients. 1218 10

We used multiplex PCR follwed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber's congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of vitamin A in the visual cycle and mutations identified in the gene could have implications for vitamin A-based therapeutic intervention. We were able to identify a homozygous mutation (AAT --> AAG) in exon 9 in an arRP patient and a heterozygous missense transversion (AAT --> AAG) also in exon 9 of an LCA patient. We also identified a polymorphism in exon 10 (GAG --> GAA) in an arRP as well as an LCA patient. Mutation screening would be greatly facilitated by multiplex PCR which could cut down costs, labour and time involved. The nucleotide changes observed in this study could be de novo. Though a larger study has been undertaken, from the preliminary results it appears that in India the RPE65 gene seems to be less involved in causation of LCA.
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PMID:RPE65 gene: multiplex PCR and mutation screening in patients from India with retinal degenerative diseases. 1235 75

In the aim to assess whether the tri-repeat shortage reported in vertebrates affects specific motifs, such as those causing neuromuscular diseases in man, we detected approximate di-, tri- and tetra-repeats (STR) longer than 25 bases in human chromosomes 21 and 22, and in some model organisms (M. musculus, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae). We found that overall STR are more represented in mouse and in man than in the other organisms. However, tri-repeats are less represented than di- and tetra- in man and mouse, but show intermediate values between di- and tetra- in the other organisms. In man, ACG shows the lowest both frequency and coverage, ATC the highest coverage and AAT the highest frequency. In general, coverage and frequency of tri-repeats are linearly related, except for ACC, ATC, AAG, AGG motifs in man and AAG, AGG in mouse, which exhibit unexpectedly long repeats. Often their copy numbers exceed that found responsible for the dynamic mutations, set at around 40. The shortage in frequency and coverage of tri- vs. di- and tetra-repeats observed in man and mouse can be ascribed to a subset of the remaining tri-repeat motifs, but among them those recognized as dynamically mutable (AAG, AGC and CCG) are not the least represented. Possible constraints in tri-repeat expansion seem to be structural and conserved along the evolutionary scale: a motif-specific relaxation of the relevant controls may be responsible for the occasional expansions found in mouse and man.
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PMID:Frequency and coverage of trinucleotide repeats in eukaryotes. 1460 99

To accelerate the molecular analysis of genetics,evolution and behavior, etc. in the honey bee (Apis), the frequency and density of simple sequence repeats (SSRs) have been analyzed from the bee EST (expressed sequence tag) database comprising 15 869 sequences amounting to 7.9 Mb. Results showed that the frequency of SSRs was 1/0.52 kb in bee ESTs, and hexanucleotide repeats (45.0%) motifs appeared to be the most abundant type in bee,the dinucleotide, mononucleotide, trinucleotide, tetranucleotide and pentanucleotide repeats are 17.9%, 14.1%, 11.6%, 9.2% and 2.2%, respectively. Meanwhile, the A-rich repeats are predominant in each type of SSRs, such as A, AT, AG, AC, AAT, AAG, AAC, AAAT, AAAG, AAAAG, AAAAT, AATAT, AAAAAG and AAAAAT repeats, whereas G-rich repeats are rare in the coding regions. The further analysis suggests that, apart from minor deviations, there is no significant difference in the distribution and density of microsatellites in the redundant and non-redundant set of bee ESTs. Furthermore, the availability of microsatellite markers can be expected to enhance the power and resolution of genome analysis in bee.
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PMID:Analysis of microsatellites derived from bee Ests. 1555 43

This paper is the first to report the long-range organization of all possible classes of trinucleotide motifs in a higher plant genome. Fluorescent in situ hybridization (FISH), employing the synthetic oligonucleotides (AAC)5, (AAG)5, (AAT)5, (AGG)5, (CAC)5, (CAT)5, (CAG)5, (ACT)5, (ACG)5 and (GCC)5, was used to characterize the nonrandom and motif-dependent distribution of tandem arrays of trinucleotide repeats in the metaphase chromosomes and interphase nuclei of barley (Hordeum vulgare L.). This provided detailed information on the sequence content of barley chromatin and allowed the saturation of the physical map of all barley chromosomes. The following conclusions were also drawn: (1) Except for (AAT)5 and (GCC)5, the studied repetitive motifs have a characteristic pattern of distribution in terms of their in situ FISH signals. Some permit the accurate identification of individual chromosomes. (2) (CAG)5, (CAT)5 and (ACT)5 are not found in all barley chromosomes. (3) With the exception of (ACT)5, the remaining trinucleotide repeats occur predominantly in the heterochromatin and are largely absent from the euchromatic regions. Moreover, (CAC)5, (ACG)5 and (CAG)5 are exclusively concentrated in the centromeres. The employment of simple synthetic probes for the identification of chromosomes and genomic characterization, and their importance in studies on genome organization, function and evolution, are discussed.
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PMID:The nonrandom distribution of long clusters of all possible classes of trinucleotide repeats in barley chromosomes. 1787 12

Tomato bacterial wilt (BW) incited by Ralstonia solanacearum is a constraint on tomato production in tropical, subtropical and humid regions of the world. In this paper, we present the results of a research aimed at the identification of PCR-based markers amplified fragment length polymorphism (AFLP) linked to the genes that confer resistance to tomato BW. To this purpose, bulked segregant analysis was applied to an F(2) population segregating for the BW resistant gene and derived from the pair-cross between a BW resistant cultivar T51A and the susceptible cultivar T9230. Genetic analysis indicated that tomato BW was conferred by two incomplete dominant genes. A CTAB method for total DNA extraction, developed by Murray and Thompson with some modifications was used to isolation the infected tomato leaves. Thirteen differential fragments were detected using 256 primer combinations, and two AFLP markers were linked to the BW resistance. Subsequently, the AFLP markers were converted to co-dominant SCAR markers, named TSCAR(AAT/CGA) and TSCAR(AAG/CAT). Linkage analysis showed that the two markers are on the contralateral side of TRSR-1. Genetic distance between TSCAR(AAT/CGA) and TRS-1 was estimated to 4.6 cM, while 8.4 cM between TSCAR(AAG/CAT) and TRS-1.
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PMID:Identification of two AFLP markers linked to bacterial wilt resistance in tomato and conversion to SCAR markers. 1815

In plants the marker sequences used to identify chromosomes are mainly repetitive DNA probes. Simple sequence repeats (SSRs) are major components of many plant genomes and could be good markers for chromosome identification. In a previous work, we reported the physical distribution of 4 oligonucleotides, (AG)12, (CAT)5, (AAC)5, and (AAG)5, on Triticum aestivum L. chromosomes. The distinctive distribution pattern found suggested that SSR in situ hybridization is useful as a diagnostic tool in wheat cytogenetics. To check whether that finding is generally applicable, we analyzed the chromosomal distribution of the rest of the 14 possible classes of di- and tri-nucleotide repeats by FISH. A detailed knowledge of the sequence content of hexaploid wheat chromatin was acquired based on the hybridization signals, which also provide a rich set of chromosome markers for chromosome identification. Except for (AT)10 and (GC)10, for which the chromosomal distribution could not be accurately determined, and (AC)8 and (GCC)5, which were found dispersed throughout the chromosomes, the remaining repeats were observed as clusters on specific chromosome sites. (AGG)5, (CAC)5, (ACG)5, (AAT)5, and (CAG)5 exhibited a preferential distribution in the pericentromeric regions of the B genome chromosomes. The richest patterns of intercalary signals on several A and B genome chromosomes were produced by (ACT)5. A karyotype based on the SSR probes providing the best FISH patterns was constructed for T. aestivum 'Chinese Spring'.
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PMID:Increasing the physical markers of wheat chromosomes using SSRs as FISH probes. 1892 32

A pregnant Thai woman with mild hypochromic microcytic anemia caused by alpha- and beta- globin defects is described. The proband was a 26-year-old pregnant woman discovered through our ongoing thalassemia screening program. Initial hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis revealed a homozygosity for an unknown variant at the D window, inconsistent with results of family analyses. Further Hb analysis using automated capillary zone electrophoresis identified that the proband was in fact a compound heterozygote for Hb E [beta26(B8)Glu-->Lys, GAG>AAG] and another beta chain variant. DNA analysis demonstrated that she carried the Hb Korle-Bu mutation [beta73(E17)Asp-->Asn (GAT>AAT)] in trans to the Hb E and an alpha-thalassemia-1 (alpha-thal-1) with the Southeast Asian (- -(SEA)) deletion. Family studies identified that her father and sister were double heterozygotes for Hb Korle-Bu and alpha-thal-1, whereas her mother was a double heterozygote for Hb E/Hb Constant Spring [Hb CS; alpha142, Term-->Gln (TAA>CAA in alpha2)]. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies and methods for characterization are presented.
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PMID:Complex interaction of Hb E [beta26(B8)Glu-->Lys], Hb Korle-Bu [beta73(E17)Asp-->Asn] and a deletional alpha-thalassemia-1 in pregnancy. 1995 98

Abundance of microsatellites with repeated unit lengths of 1-6 base pairs in seven fungi: Aspergillus nidulans, Coprinus cinereus, Cryptococcus neoformans (serotype A), Fusarium graminearum, Magnaporthe grisea, Neurospora crassa and Ustilago maydis were investigated on genomic scale. The results showed that each species has its specific profile for different types and different motifs of SSR loci. Ascomycetes fungi M. grisea, N. crassa and basidiomycete fungus U. maydis adopt much more microsatellites than other fungi examined. Total amount of 15,751, 14,788 and 6,854 SSR loci were observed respectively, average density is 406, 389 and 347 per Mbp sequence; overall length of SSR sequence was 0.82%, 0.95% and 0.79% of genomic sequence respectively. While ascomycetes fungus F. graminearum and A. nidulans contains the least SSRs in the genomic DNA, only 4,679 and 4,837 tracts were observed in 36 Mb and 30 Mb genomic sequence respectively. Microsatellite repeats in protein coding regions are investigated in Aspergillus nidulans, Magnaporthe grisea, and Neurospora crassa also, the results show that the difference of different types and motifs among three fungi is very little than that in whole genomic sequence. For trinucleotide repeats, overrepresent (comparing to the total base pair of protein coding region) of AGC, GGC, AGG, ACG and ACC was observed in coding region, frequencies of AAC and AAG were not difference between coding and non-coding region, AAT, AGT and ATG were underrepresent in coding region excepted for A. nidulans, in which ATG was overrepresentative.
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PMID:Genome-wide analysis of microsatellite sequence in seven filamentous fungi. 2064 Aug 28


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