Premature chromosome condensation is induced by a point mutation in the hamster RCC1 gene

1990 ◽  
Vol 10 (2) ◽  
pp. 577-584
Author(s):  
S Uchida ◽  
T Sekiguchi ◽  
H Nishitani ◽  
K Miyauchi ◽  
M Ohtsubo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mutant Gene ◽  
Polymerase Chain Reaction Method ◽  
Base Change ◽  
Chromosome Condensation ◽  
Premature Chromosome Condensation ◽  
Base Sequences ◽  
Single Base Change ◽  
Polymerase Chain ◽  
Tsbn2 Cells

At the nonpermissive temperature, premature chromosome condensation (PCC) occurs in tsBN2 cells derived from the BHK cell line, which can be converted to the Ts+ phenotype by the human RCC1 gene. To prove that the RCC1 gene is the mutant gene in tsBN2 cells, which have RCC1 mRNA and protein of the same sizes as those of BHK cells, RCC1 cDNAs were isolated from BHK and tsBN2 cells and sequenced to search for mutations. The hamster (BHK) RCC1 cDNA encodes a protein of 421 amino acids homologous to the human RCC1 protein. In a comparison of the base sequences of BHK and BN2 RCC1 cDNAs, a single base change, cytosine to thymine (serine to phenylalanine), was found in the 256th codon of BN2 RCC1 cDNA. The same transition was verified in the RCC1 genomic DNA by the polymerase chain reaction method. BHK RCC1 cDNA, but not tsBN2 RCC1 cDNA, complemented the tsBN2 mutation, although both have the same amino acid sequence except for one amino acid at the 256th codon. This amino acid change, serine to phenylalanine, was estimated to cause a profound structural change in the RCC1 protein.

scholarly journals Premature chromosome condensation is induced by a point mutation in the hamster RCC1 gene.

1990 ◽  
Vol 10 (2) ◽  
pp. 577-584 ◽  
Author(s):  
S Uchida ◽  
T Sekiguchi ◽  
H Nishitani ◽  
K Miyauchi ◽  
M Ohtsubo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mutant Gene ◽  
Polymerase Chain Reaction Method ◽  
Base Change ◽  
Chromosome Condensation ◽  
Premature Chromosome Condensation ◽  
Base Sequences ◽  
Single Base Change ◽  
Polymerase Chain ◽  
Tsbn2 Cells

At the nonpermissive temperature, premature chromosome condensation (PCC) occurs in tsBN2 cells derived from the BHK cell line, which can be converted to the Ts+ phenotype by the human RCC1 gene. To prove that the RCC1 gene is the mutant gene in tsBN2 cells, which have RCC1 mRNA and protein of the same sizes as those of BHK cells, RCC1 cDNAs were isolated from BHK and tsBN2 cells and sequenced to search for mutations. The hamster (BHK) RCC1 cDNA encodes a protein of 421 amino acids homologous to the human RCC1 protein. In a comparison of the base sequences of BHK and BN2 RCC1 cDNAs, a single base change, cytosine to thymine (serine to phenylalanine), was found in the 256th codon of BN2 RCC1 cDNA. The same transition was verified in the RCC1 genomic DNA by the polymerase chain reaction method. BHK RCC1 cDNA, but not tsBN2 RCC1 cDNA, complemented the tsBN2 mutation, although both have the same amino acid sequence except for one amino acid at the 256th codon. This amino acid change, serine to phenylalanine, was estimated to cause a profound structural change in the RCC1 protein.

scholarly journals A unique sequence of the NZW I-E beta chain and its possible contribution to autoimmunity in the (NZB x NZW)F1 mouse.

1989 ◽  
Vol 170 (3) ◽  
pp. 971-984 ◽  
Author(s):  
J Schiffenbauer ◽  
D M McCarthy ◽  
N R Nygard ◽  
S L Woulfe ◽  
D K Didier ◽  
...  
Keyword(s):  
Amino Acid ◽  
Early Death ◽  
Class Ii ◽  
Base Change ◽  
Unique Sequence ◽  
Chain Reaction ◽  
S Haplotype ◽  
Severe Renal Disease ◽  
Single Base Change ◽  
Polymerase Chain

The (NZB x NZW)F1 mouse strain develops a syndrome of accelerated autoimmunity including severe renal disease and early death. Evidence suggests that class II molecules play a central role in this process. Previous studies have suggested that the NZW strain contributes at least one gene to the development of accelerated autoimmunity that is linked to the H-2 complex, and antibodies to murine class II molecules have been used to ameliorate disease in (NZB x NZW)F1 mice. We therefore wished to sequence the class II molecules from NZW mice to identify any unique sequences that may contribute to disease development. We constructed oligonucleotide primers corresponding to the 5' and 3' regions of the second exon of class II genes from a variety of haplotypes, and used these primers in a polymerase chain reaction to sequence the second exon of the NZW I-A alpha, I-A beta, and I-E beta genes. We report that the second exons of NZW I-A alpha, I-A beta, and I-E alpha are identical to their counterparts of the previously sequenced u haplotype, and that the second exon of NZW I-E beta is identical to its counterpart from u except for a single base change that results in a substitution of arginine for threonine at amino acid 72. This base and amino acid are identical to those found at the same positions in the s haplotype.

scholarly journals The mutagenicity of amino acid analogues inCoprinus lagopus

1974 ◽  
Vol 23 (1) ◽  
pp. 47-61 ◽  
Author(s):  
Philippa J. Talmud ◽  
D. Lewis
Keyword(s):  
Amino Acid ◽  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Base Change ◽  
Response Curves ◽  
Amino Acid Analogues ◽  
Single Base Change ◽  
Protein Incorporation ◽  
Dose Dependent ◽  
Spontaneous Mutation Frequency

SummaryThe amino acid analoguesp-fluorophenylalanine (PFP) and ethionine (ETH) are strongly mutagenic inCoprinus lagopus. The most pronounced effect was found with suppressor mutations of themet-1locus. PFP, at a concentration of 2·4 × 10−4M, increased the mutation frequency 500 fold and ETH, at a concentration of 2·4 × 10−3M, 30 fold over the spontaneous mutation frequency. From the spectrum of suppressors of themet-1locus and the dominant revertants of thead-82locus, induced by analogue treatments, it was concluded that both analogues induce single base-change mutations. The dose response curves follow a sigmoid plot, revealing that within a certain range of analogue concentrations, muta-genesis is strongly dose dependent.Using analogue resistant mutants, it has been shown that PFP mutagenesis is a function of its incorporation into protein. However, ETH mutagenesis is independent of protein incorporation but can be correlated with the degree of ethylation of nucleic acids. The synergistic effect PFP and ETH supports the evidence of the different mutagenic actions of the two analogues.

scholarly journals Familial amyloid polyneuropathy associated with TTRSer50Arg mutation in two Iberian families presenting a novel single base change in the mutant gene

Amyloid ◽  
2007 ◽  
Vol 14 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Miguel Munar-Qués ◽  
Jaime Masjuan ◽  
Teresa Coelho ◽  
Paul Moreira ◽  
Carlos Viader-Farré ◽  
...  
Keyword(s):  
Mutant Gene ◽  
Base Change ◽  
Familial Amyloid Polyneuropathy ◽  
Single Base ◽  
Single Base Change ◽  
Amyloid Polyneuropathy

Paris I Dysfibrinogenemia: A Point Mutation in Intron 8 Results in Insertion of a 15 Amino Acid Sequence in the Fibrinogen γ-Chain

1993 ◽  
Vol 69 (03) ◽  
pp. 217-220 ◽  
Author(s):  
Jonathan B Rosenberg ◽  
Peter J Newman ◽  
Michael W Mosesson ◽  
Marie-Claude Guillin ◽  
David L Amrani
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Point Mutation ◽  
Genomic Dna ◽  
Comparative Sequence Analysis ◽  
Chain Gene ◽  
Molecular Defect ◽  
Nucleotide Position ◽  
Normal Individuals ◽  
Polymerase Chain

SummaryParis I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal γ-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the γ-chain region of the Paris I subject’s genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A→G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I γ-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature γparis I chain mRNA, and encodes a 15 amino acid insert after γ350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I γ-chain mRNA also results after translation into a substitution of S for G at position γ351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the γpariS I chain. We conclude that the insertion of this amino acid sequence leads to a conformationallyaltered, and dysfunctional γ-chain in Paris I fibrinogen.

scholarly journals A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yavor K. Bozhilov ◽  
Damien J. Downes ◽  
Jelena Telenius ◽  
A. Marieke Oudelaar ◽  
Emmanuel N. Olivier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Diseases ◽  
Regulatory Elements ◽  
Base Change ◽  
Dependent Manner ◽  
Globin Genes ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Super Enhancer ◽  
Single Base Change

AbstractMany single nucleotide variants (SNVs) associated with human traits and genetic diseases are thought to alter the activity of existing regulatory elements. Some SNVs may also create entirely new regulatory elements which change gene expression, but the mechanism by which they do so is largely unknown. Here we show that a single base change in an otherwise unremarkable region of the human α-globin cluster creates an entirely new promoter and an associated unidirectional transcript. This SNV downregulates α-globin expression causing α-thalassaemia. Of note, the new promoter lying between the α-globin genes and their associated super-enhancer disrupts their interaction in an orientation-dependent manner. Together these observations show how both the order and orientation of the fundamental elements of the genome determine patterns of gene expression and support the concept that active genes may act to disrupt enhancer-promoter interactions in mammals as in Drosophila. Finally, these findings should prompt others to fully evaluate SNVs lying outside of known regulatory elements as causing changes in gene expression by creating new regulatory elements.

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