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At least 1,801 records · Page 100Linked to original sources
PubMed1999

Identification of the mutation in the alkaptonuria mouse model. Mutations in brief no. 216. Online.

Alkaptonuria (aku), an inborn error of metabolism caused by the loss of homogentisate 1,2-dioxygenase (HGD), has been described in a mouse model created by ethylnitrosourea mutagenesis but the mutation in these mice has not previously been identified. We used RT-PCR to amplify the Hgd cDNA from Hgd(aku)/Hgd(aku) mice. Two products shorter than the wild-type product were amplified. Restriction mapping and DNA sequencing were then used to identify the Hgd(aku) mouse mutation, found to be a single base change in a splice donor consensus sequence, causing exon skipping and frame-shifted products. This base change allowed us to create a non-radioactive genotyping assay for this allele.

Alkaptonuria↗
PubMed2000

Molecular genetic analysis of 40 patients with glycogen storage disease type Ia: 100% mutation detection rate and 5 novel mutations.

Molecular genetic analysis of 40 patients with glycogen storage disease type Ia (GSD Ia) revealed mutations on all 80 alleles and verified the diagnosis in all patients. At least 7 patients were diagnosed with GSD Ia solely on the basis of clinical findings prior to our analysis. Five mutations, Q20R, W50X, G81R, W156L, and G188D have not been reported so far. This study underscores that molecular genetic analysis is a reliable and convenient alternative to the enzyme assay in a fresh liver biopsy specimen to diagnose GSD Ia.

Adult↗
PubMed1989

Mutations, epimutations, and the developmental programming of the maize Suppressor-mutator transposable element.

Information about the structure, function and regulation of the maize Suppressor-mutator (Spm) transposable element has emerged from the genetic and molecular characterization of both deletion mutations and an unconventional type of reversible genetic change (epimutation). The element is subject to an epigenetic mechanism that can either stably inactivate it or specify one of a variety of heritable programs of differential element expression in development. The essay explores the relationship between the Spm element's epigenetic developmental programming mechanism and the determinative events central to plant development and differentiation.

Base Sequence↗
PubMed1984

Spontaneous mutation frequencies in Salmonella: enhancement of G/C to A/T transitions and depression of deletion and frameshift mutation frequencies afforded by anoxic incubation.

Incubation of Salmonella typhimurium under anoxic conditions (0.1% oxygen or less) results in a substantial decrease in small (3-and 6-basepair) deletions in an A/T-rich region of the hisG gene in the hisG428 ochre mutant and also decreases the frequency of minus frameshift mutations in G/C-rich sequences in the his-D3052 and hisC3076 mutants. In contrast, the frequency of G/C-----A/T transition mutations increases substantially during anoxic growth of hisG46. Growth of revertants of strains carrying accessory deletions in the uvrB region of the Salmonella chromosome is drastically impaired on glucose minimal medium when oxygen partial pressures are below 0.1% oxygen.

Aerobiosis↗
PubMed1994

Development of RNA-SSCP protocols for the identification and screening of CFTR mutations: identification of two new mutations.

A strategy is described that allows a rapid and accurate identification and screening of cystic fibrosis gene mutations. It consists of setting up and developing RNA single strand conformation polymorphism (rSSCP) protocols, a technique based on the large repertoire of secondary structure of single-stranded RNA. By incorporating the T7 phage promoter sequence into PCR primers, it is possible to carry out rSSCP and compare it to standard single-strand conformation polymorphism (SSCP). Several parallel tests indicate that rSSCP detects a higher fraction of single base changes, and is less time consuming than SSCP since it requires only one fairly short electrophoretic run. Using this technique we were able to identify two new splicing mutations in introns 5 (711 + 5G-->A) and 10 (1717-8G-->A) of the CFTR gene.

Cystic Fibrosis↗
PubMed1995

A suppressor mutation which suppresses adenylyl cyclase mutations in Neurospora crassa.

A spontaneous suppressor mutant, hah, which suppressed the colonial growth of adenylyl cyclase mutants (cr-1) was isolated. The morphology of cr-1 hah was filamentous, but slightly different from that of wild type on solid medium. The hah strain formed many high aerial hyphae, but did not form any conidia. The expression levels of an adenylyl cyclase gene, nac, in both hah and cr-1 hah were much higher than those in wild type or in cr-1. The level of cAMP in cr-1 was very low but returned to close to the wild-type level in the cr-1 hah suppressed strain, whereas that in the strain carrying hah alone was similar to or a little higher than that in wild type. The hah gene was located 13.3 map units from in1 on the right arm of the linkage group V. The hah mutation was recessive and allele specificity of hah for the suppression of cr-1 mutations was weak.

Adenylyl Cyclases↗
PubMed1994

Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3'-flanking region.

Genetic differences in the metabolism of carcinogens may codetermine individual predisposition to cancer. Cytochrome P-4501A1 (CYP1A1) metabolically activates precarcinogens in cigarette smoke, such as benzo(a)pyrene, which is also an inducer of CYP1A1. Two point mutations have been reported, m1 in the 3'-flanking region (6235T to C), and m2 within exon 7 (4889A to G), the latter leading to an isoleucine to valine exchange. In the Japanese population m1 and m2 are correlated with lung cancer, suggesting an increased susceptibility to cigarette smoking related lung cancer. We studied 142 lung cancer and 171 reference patients in an ethnically homogeneous German group for m1 and m2 mutations by restriction fragment length polymorphism and allele-specific polymerase chain reaction, respectively. No statistically significant difference was found in the distribution of m1 alleles between lung cancer and controls; the frequency was 8.5% and 7.3% of the alleles, respectively (odds ratio = 1.17). A trend to an overrepresentation of m1 alleles was observed among 52 squamous cell carcinoma patients (odds ratio = 1.65). In contrast, the frequency of m2 alleles in lung cancer patients was twofold higher (6.7%) than in the reference group (3.2%; odds ratio = 2.16; 95% confidence limits 0.96-5.11, P = 0.033); the odds ratio of m2 alleles in squamous cell carcinoma was 2.51 (95% confidence limits 0.85-7.05, P = 0.05). There was a close genetic linkage of m2 to m1 (10 of 11 reference patients), but a significantly higher number of cancer patients showed no linkage compared to the controls (odds ratio = 8.89, 95% confidence limits 0.83-433, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Creutzfeldt-Jakob disease with codon 129 polymorphism (valine): a comparative study of patients with codon 102 point mutation or without mutations.

We examined 7 patients with Creutzfeldt-Jakob disease (CJD) with a methionine-to-valine change at prion protein (PrP) codon 129 (CJD129 patients). These CJD129 patients did not have either a codon 117 or 198 point mutation. For comparison, we also examined 7 patients with Gerstmann-Sträussler syndrome (GSS) with a proline-to-leucine change at PrP codon 102 (GSS102 patients) and 13 patients without any known mutations at codons 102, 117, 129, 178, or 200 (CJDwild patients). CJD129 patients had a long clinical duration and ataxia at onset, but rarely had any periodic synchronous discharge in their electroencephalogram. Unlike CJDwild patients, all CJD129 patients have typical congophilic PrP plaques in their brain. These clinicopathological findings were similar to those of GSS102. However, the distribution and morphology of PrP deposits revealed by immunohistochemistry were different between CJD129 and GSS102. In GSS102 more numerous and various types of PrP plaques are seen throughout the brain, while in CJD129 patients a unicentric core was the major feature of PrP plaques. The change in codon 129 influences the clinical course and pathological findings in CJD.

Adult↗
PubMed1992

Two non-gypsy rudimentary mutations and their suppression by mutations of suppressor of Hairy-wing in Drosophila.

Two spontaneous mutations of rudimentary, the gene encoding the first steps of de novo pyrimidine biosynthesis in Drosophila, are suppressed by mutant alleles of the suppressor of Hairy-wing locus. This interaction differs from typical su(Hw) suppression in that neither rudimentary allele is associated with an insertion of the gypsy retrotransposon. One allele, rsP1, appears to be a point mutation. Adult rsP1 homozygous females accumulate substantially less 7.3 kb rudimentary transcript than do wild-type females. The other allele, rsP2, is an insertion of an mdg3 retrotransposon in the sixth exon of rudimentary and in the opposite transcriptional orientation. This insertion divides the rudimentary locus into two separate, yet functional, transcription units by truncating transcription from the rudimentary promoter and promoting transcription of downstream rudimentary sequences. Phenotypic suppression of both rsP1 and rsP2 by mutant alleles of the suppressor of Hairy-wing locus correlates with enhanced levels of the rsP1 and rsP2 transcripts.

Alleles↗
PubMed1984

Amplification versus mutation as a mechanism for reversion of an HGPRT mutation.

We have used a cloned cDNA for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to analyze the HGPRT gene and mRNA in an HGPRT-deficient mutant of Chinese hamster cells (RJK10) and its HGPRT-positive revertants. By Southern blot analysis, no DNA rearrangements were detected within the genes from any of the cell lines examined. However, four of five spontaneous revertants each contained 10- to 20-fold more copies of the HGPRT gene than did RJK10 or wild-type cells. In contrast, the gene was not amplified in four mutagen-induced revertants. The RJK10 mutation did not alter the size or concentration of HGPRT mRNA and representatives of the revertants contained the mRNA in amounts proportional to the number of genes they carried. Examples of clones with either stable or unstable gene amplification were identified and their HGPRT-positive phenotypes were shown to be dependent on the gene amplification. In a stably amplified revertant, the extra genes were found to be syntenic with the X chromosome marker glucose-6-phosphate dehydrogenase. In an unstable revertant only one of the 10 to 20 copies of the gene could be shown to be X linked. Thus, we found that RJK10 can revert by at least two distinct mechanisms: amplification of the HGPRT gene, which occurred spontaneously, or point mutation, which predominated after exposure to mutagens.

Animals↗
PubMed1997

C-kit mutations and mast cell disorders. A model of activating mutations of growth factor receptors.

Mastocytosis are a group of diseases characterized by abnormal proliferation of mast cells. Various forms are observed in respect to the organ system involving, clinical manifestations, and association with hematological disorders. The c-kit proto-oncogene encodes for a receptor tyrosine kinase, which plays a crucial role in hematopoiesis, especially in mast cell growth and differentiation. Mutations in the tyrosine kinase domain of c-kit have been reported in murine and human malignant cell lines, and more recently in some cases of human mast cell diseases. The biochemical and clinical aspects of these mutations are reviewed with special emphasis on the experiments which demonstrate their role in oncogenesis and mast cell proliferation.

Animals↗
PubMed2000

Advanced glycation endproduct-modified superoxide dismutase-1 (SOD1)-positive inclusions are common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutations and transgenic mice expressing human SOD1 with a G85R mutation.

To clarify the biological significance of the neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions characteristically found in patients with familial amyotrophic lateral sclerosis with superoxide dismutase-1 (SOD1) gene mutations and in transgenic mice expressing human SOD1 with G85R mutation, the detailed protein composition in both types of inclusions was immunohistochemically analyzed using 45 different antibodies. Both types of inclusions had very strong immunoreactivity for SOD1. The SOD1-positive inclusions in both cell types were also immunoreactive for the insoluble advanced glycation endproducts (AGEs) such as Nepsilon-(carboxymethyl)lysine (CML), pyrraline and pentosidine: both inclusions in both conditions were ultrastructurally composed of the granule-coated fibrils that had immunoreactivities to CML and pyrraline. Both types of inclusions were negative for stress-response proteins (SRPs), 4-hydroxy-2-nonenal (HNE), acrolein, nitric oxide synthases (NOSs) and nitrotyrosine as representative markers of oxidative stress. The neurons and astrocytes of the normal individuals and non-transgenic mice showed no significant immunoreactivity for SOD1, AGEs, SRPs, HNE, acrolein, NOSs or nitrotyrosine. Our results suggest that a portion of the SOD1 composing both type of inclusions, probably toxic mutant SOD1, is modified by the AGEs, and that the formation of the AGE-modified SOD1 is one of the mechanisms responsible for the aggregation involving no significant oxidative mechanisms.

Adult↗
PubMed1996

beta-Glucuronidase P408S, P415L mutations: evidence that both mutations combine to produce an MPS VII allele in certain Mexican patients.

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is an autosomal recessively inherited lysosomal storage disease caused by a deficiency in beta-glucuronidase. We identified and studied a novel allele containing two C-to-T transitions resulting in P408S and P415L alterations, which is present in homozygous state in one Mexican patient and in heterozygous state in another. None of the previous reports describing mutations in the MPS VII gene include Mexican patients. Expression of either of the mutations individually showed only modest effects on the properties of the enzyme. However, expression of the doubly mutant allele resulted in markedly reduced activity and rapid degradation in an early biosynthetic compartment.

Animals↗
PubMed1982

Effects of a recA operator mutation on mutant phenotypes conferred by lexA and recF mutations.

Derepression of recA by an operator mutation (recAo281) produces effects opposite to those obtained from its derepression following DNA damage. Inducible reactivation of lambda vir and S13 phages is decreased and inducible UV mutagenesis of a phi X174 amber mutant is lessened in a recAo281 strain compared to a recAo+ strain. The decreases could not be accounted for by increases in constitutive levels of these processes. Consistent with these results the UV resistance of a recAo281 strain is less than that of a recAo+ strain. This may indicate that too much recA protein immediately after irradiation interferes with derepression of the lexA regulon or functioning of its products. Effects of increasing the recAo+ and recA+ copy number on a Co1E1 plasmid are compared with the effects of recAo281. recAo281 partially suppresses UV sensitivity due to lexA102 and lexA3 in E. coli K-12. This increase in resistance is not correlated with an increase in constitutive or inducible reactivation of UV-irradiated lambda vir or S13. This is consistent with the previous suggestion that the UV resistance stems from a decrease in DNA degradation allowing an increase in DNA repair. lexA3 blocks UV mutagenesis of phi X174 as measured by reversion of amber mutations and this was not suppressed by recAo281. recF143 blocks UV mutagenesis of phi X174. recAo281 suppresses neither this effect nor the decrease in bacterial UV resistance caused by recF143.

Bacteriophage phi X 174↗
PubMed1987

Mutation at the APRT locus in Friend erythroleukaemia cells. 1. Mutation rates and properties of mutants.

Spontaneous mutation at the adenine phosphoribosyl transferase (APRT) locus in clone 707 of the Friend cell line was examined. The frequency of cells resistant to 2,6-diaminopurine (DAP) was found to be 2.6 X 10(-5) with a mutation rate of 1.81 X 10(-6) cell-1 generation-1. APRT activities in 9 DAP-resistant clones were found to vary between 0 and 27% the level observed in wild-type cells. It is suggested that clone 707 cells are heterozygous or functionally hemizygous at the APRT locus.

Adenine Phosphoribosyltransferase↗
PubMed1989

X-ray-induced specific-locus mutations in the ad-3 region of two-component heterokaryons of Neurospora crassa. II. More extensive genetic tests reveal an unexpectedly high frequency of multiple-locus mutations.

More extensive genetic tests have been performed on a series of 832 X-ray-induced specific-locus mutations in the ad-3 region of a 2-component heterokaryon (H-12) of Neurospora crassa, reported earlier (Webber and de Serres 1965). Using new tester strains and techniques for performing large-scale genetic tests (heterokaryon, dikaryon and trikaryon) to characterize ad-3 mutants induced in 2-component heterokaryons, new data have been obtained on this sample of X-ray-induced ad-3 mutants. These new data show that unexpectedly high frequencies of both single-locus (gene/point) mutations and multilocus deletions in the ad-3 region have additional, but separate, sites of recessive lethal (RLCL) damage in the immediately adjacent genetic regions. The frequencies of these X-ray-induced multiple-locus mutants in the ad-3 region are orders of magnitude higher than expected on the basis of target theory and classical models of chromosome structure during interphase. Current models of interphase chromosome structure in higher eukaryotes as revealed by chromosome "painting" offer a possible explanation of the Neurospora data.

Adenine↗

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