Unusual inheritance of the AxinFu mutation in mice is associated with widespread rearrangements in the proximal region of chromosome 17

AxinFu is a mutation in mice that causes fused tails and other developmental abnormalities as a result of insertion of an intracisternal-A particle (IAP), a murine retrotransposon, into intron 6. In a small percentage of offspring we found that the mutant allele reverts to wild-type through loss of the insertion with concomitant disappearance of the mutant phenotype. Investigation of a series of microsatellite loci in the proximal region of chromosome 17 revealed novel alleles which arise simultaneously with disappearance of IAP from AxinFu. These novel microsatellite variants are distinct from the parental alleles and those so far discovered are organized into two haplotypes. Both haplotypes demonstrate stable Mendelian inheritance. Results show that these rearrangements, which are involved in the production of the new haplotypes, exceed millions of base pairs.

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Genetic and molecular analysis of the proximal region of the mouse t-complex using new molecular probes and partial t-haplotypes.

Genetics ◽

10.1093/genetics/126.4.1103 ◽

1990 ◽

Vol 126 (4) ◽

pp. 1103-1114 ◽

Cited By ~ 1

Author(s):

C A Howard ◽

G R Gummere ◽

M F Lyon ◽

D Bennett ◽

K Artzt

Keyword(s):

Wild Mouse ◽

Molecular Probes ◽

Proximal Region ◽

Chromosome 17 ◽

Lethal Gene ◽

Strong Linkage Disequilibrium ◽

Wild Type ◽

T Complex ◽

Naturally Occurring ◽

Normal Transmission

Abstract The t-complex is located on the proximal third of chromosome 17 in the house mouse. Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development. Partial t-haplotypes derived through rare recombination between t-haplotypes and wild-type homologs have been critical in the analysis of these properties. Utilizing two new DNA probes. Au3 and Au9, and several previously described probes, we have analyzed the genetic structure of several partial t-haplotypes that have arisen in our laboratory, as well as several wild-type chromosomes deleted for loci in this region. With this approach we have been able to further our understanding of the structural and dynamic characteristics of the proximal region of the t-complex. Specifically, we have localized the D17Tul locus as most proximal known in t-haplotypes, achieved a better structural analysis of the partial t-haplotype t6, and defined the structure and lethal gene content of partial t-haplotypes derived from the lethal tw73 haplotype.

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The hooded mutant of Lathyrus odoratus (Fabaceae) is associated with a cycloidea gene mutation

Botany ◽

10.1139/cjb-2017-0097 ◽

2018 ◽

Vol 96 (1) ◽

pp. 47-55 ◽

Cited By ~ 3

Author(s):

Christine Woollacott ◽

Quentin C.B. Cronk

Keyword(s):

Gene Mutation ◽

Mutant Allele ◽

Gene Sequence ◽

Mendelian Inheritance ◽

Genomic Sequencing ◽

Wild Type ◽

Petal Identity ◽

Lathyrus Odoratus ◽

Lines Of Evidence ◽

Sweet Pea

The hooded (hdd) floral mutant of Lathyrus odoratus L. (sweet pea) has a concave standard petal compared with the flat standard petal of the wild type. This trait was used by Bateson, Punnett, and Saunders in early studies of Mendelian inheritance (c.1905). Here we provide four lines of evidence that this phenotype results from a mutation in the CYCLOIDEA2 (CYC2) gene. (i) CYC2 is expressed in the standard petals of wild-type L. odoratus, whereas the same methods fail to detect expression in hdd plants. (ii) Genomic sequencing reveals that the CYC2 gene sequence of hdd plants is truncated at the TCP box and likely nonfunctional. (iii) In a population of 118 plants, the hdd phenotype cosegregated with the mutant allele of CYC2 without exception. (iv) CYC2 is known to act as a dorsal petal identity gene. Consistent with this, the standard petal in hdd flowers has the epidermal and pigment characteristics of wing petals, indicating that the hdd mutation results in a shift in dorsiventral petal-type identity. We conclude that the mutation in CYC2 is responsible for the hdd phenotype, and is therefore the L. odoratus equivalent of the lobed standard (lst1) mutant in Pisum.

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Developing a Genetic System in Deinococcus radiodurans for Analyzing Mutations

Genetics ◽

10.1093/genetics/166.2.661 ◽

2004 ◽

Vol 166 (2) ◽

pp. 661-668

Author(s):

Mandy Kim ◽

Erika Wolff ◽

Tiffany Huang ◽

Lilit Garibyan ◽

Ashlee M Earl ◽

...

Keyword(s):

Dna Sequences ◽

Deinococcus Radiodurans ◽

Genetic System ◽

Base Change ◽

Base Substitution ◽

Wild Type ◽

Base Pairs ◽

E Coli ◽

Radiation Induced ◽

Induced Mutagenesis

Abstract We have applied a genetic system for analyzing mutations in Escherichia coli to Deinococcus radiodurans, an extremeophile with an astonishingly high resistance to UV- and ionizing-radiation-induced mutagenesis. Taking advantage of the conservation of the β-subunit of RNA polymerase among most prokaryotes, we derived again in D. radiodurans the rpoB/Rif r system that we developed in E. coli to monitor base substitutions, defining 33 base change substitutions at 22 different base pairs. We sequenced >250 mutations leading to Rif r in D. radiodurans derived spontaneously in wild-type and uvrD (mismatch-repair-deficient) backgrounds and after treatment with N-methyl-N′-nitro-N-nitrosoguanidine (NTG) and 5-azacytidine (5AZ). The specificities of NTG and 5AZ in D. radiodurans are the same as those found for E. coli and other organisms. There are prominent base substitution hotspots in rpoB in both D. radiodurans and E. coli. In several cases these are at different points in each organism, even though the DNA sequences surrounding the hotspots and their corresponding sites are very similar in both D. radiodurans and E. coli. In one case the hotspots occur at the same site in both organisms.

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Mutator-Suppressible Alleles of rough sheath1 and liguleless3 in Maize Reveal Multiple Mechanisms for Suppression

Genetics ◽

10.1093/genetics/154.1.437 ◽

2000 ◽

Vol 154 (1) ◽

pp. 437-446 ◽

Cited By ~ 1

Author(s):

Lisa Girard ◽

Michael Freeling

Keyword(s):

Untranslated Region ◽

Mutant Allele ◽

Negative Regulation ◽

Wild Type ◽

Knox Gene ◽

Transcript Accumulation ◽

Mu Suppression ◽

Different Types ◽

Rna Blot Analysis

Abstract Insertions of Mutator transposons into maize genes can generate suppressible alleles. Mu suppression is when, in the absence of Mu activity, the phenotype of a mutant allele reverts to that of its progenitor. Here we present the characterization of five dominant Mu-suppressible alleles of the knox (knotted1-like homeobox) genes liguleless3 and rough sheath1, which exhibit neomorphic phenotypes in the leaves. RNA blot analysis suggests that Mu suppression affects only the neomorphic aspect of the allele, not the wild-type aspect. Additionally, Mu suppression appears to be exerting its effects at the level of transcription or transcript accumulation. We show that truncated transcripts are produced by three alleles, implying a mechanism for Mu suppression of 5′ untranslated region insertion alleles distinct from that which has been described previously. Additionally, it is found that Mu suppression can be caused by at least three different types of Mutator elements. Evidence presented here suggests that whether an allele is suppressible or not may depend upon the site of insertion. We cite previous work on the knox gene kn1, and discuss our results in the context of interactions between Mu-encoded products and the inherently negative regulation of neomorphic liguleless3 and rough sheath1 transcription.

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PCR-based genotyping assays to detect germline APC variant associated with hereditary gastrointestinal polyposis in Jack Russell terriers

BMC Veterinary Research ◽

10.1186/s12917-020-02731-7 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Kyoko Yoshizaki ◽

Akihiro Hirata ◽

Hiroyuki Matsushita ◽

Naohito Nishii ◽

Mifumi Kawabe ◽

...

Keyword(s):

Mutant Allele ◽

False Negative ◽

Disease Onset ◽

Pcr Amplification ◽

Buccal Swab ◽

Wild Type ◽

Gastrointestinal Polyposis ◽

Pcr Rflp ◽

Formalin Fixed Paraffin Embedded ◽

Rflp Assay

Abstract Background The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline variant in the APC gene (c.[462_463delinsTT]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC variant were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs. Result First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC variant creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the variant site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the variant was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays. Conclusion In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC variant. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.

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Differential Suppression of priA2::kan Phenotypes in Escherichia coli K-12 by Mutations in priA, lexA, and dnaC

Genetics ◽

10.1093/genetics/143.1.5 ◽

1996 ◽

Vol 143 (1) ◽

pp. 5-13 ◽

Cited By ~ 21

Author(s):

Steven J Sandler ◽

Hardeep S Samra ◽

Alvin J Clark

Keyword(s):

Escherichia Coli ◽

Dna Replication ◽

Mutant Allele ◽

Wild Type ◽

Suppressor Mutations ◽

Dnab Helicase ◽

K 12 ◽

Extragenic Suppressors ◽

Assembly Activity

Abstract First identified as an essential component of the ϕX174 in vitro DNA replication system, PriA has ATPase, helicase, translocase, and primosome-assembly activities. priA1::kan strains of Escherichia coli are sensitive to UV irradiation, deficient in homologous recombination following transduction, and filamentous. priA2::kan strains have eightfold higher levels of uninduced SOS expression than wild type. We show that (1) priA1::kan strains have eightfold higher levels of uninduced SOS expression, (2) priA2::kan strains are UVS and Rec−, (3) lexA3 suppresses the high basal levels of SOS expression of a priA2::kan strain, and (4) plasmid-encoded priA300 (K230R), a mutant allele retaining only the primosome-assembly activity of priA+, restores both UVR and Rec+ phenotypes to a priA2::kan strain. Finally, we have isolated 17 independent UVR Rec+ revertants of priA2::kan strains that carry extragenic suppressors. All 17 map in the C-terminal half of the dnaC gene. DnaC loads the DnaB helicase onto DNA as a prelude for primosome assembly and DNA replication. We conclude that priA's primosome-assembly activity is essential for DNA repair and recombination and that the dnaC suppressor mutations allow these processes to occur in the absence of priA.

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Occurrence of Repeat Induced Point Mutation in Long Segmental Duplications of Neurospora

Genetics ◽

10.1093/genetics/147.1.125 ◽

1997 ◽

Vol 147 (1) ◽

pp. 125-136 ◽

Cited By ~ 2

Author(s):

David D Perkins ◽

Brian S Margolin ◽

Eric U Selker ◽

S D Haedo

Keyword(s):

Point Mutation ◽

Sexual Cycle ◽

Segmental Duplications ◽

Wild Type ◽

Single Chain ◽

Base Pairs ◽

Gene Size ◽

Type Gene ◽

Repeat Induced Point Mutation

Abstract Previous studies of repeat induced point mutation (RIP) have typically involved gene-size duplications resulting from insertion of transforming DNA at ectopic chromosomal positions. To ascertain whether genes in larger duplications are subject to RIP, progeny were examined from crosses heterozygous for long segmental duplications obtained using insertional or quasiterminal translocations. Of 17 distinct mutations from crossing 11 different duplications, 13 mapped within the segment that was duplicated in the parent, one was closely linked, and three were unlinked. Half of the mutations in duplicated segments were at previously unknown loci. The mutations were recessive and were expressed both in haploid and in duplication progeny from Duplication × Normal, suggesting that both copies of the wild-type gene had undergone RIP. Seven transition mutations characteristic of RIP were found in 395 base pairs (bp) examined in one ro-11 allele from these crosses and three were found in ~750 bp of another. A single chain-terminating C to T mutation was found in 800 bp of arg-6. RIP is thus responsible. These results are consistent with the idea that the impaired fertility that is characteristic of segmental duplications is due to inactivation by RIP of genes needed for progression through the sexual cycle.

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Molecular Characterization of the CytochromebGene andIn VitroAtovaquone Susceptibility of Plasmodium falciparum Isolates from Kenya

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03956-14 ◽

2015 ◽

Vol 59 (3) ◽

pp. 1818-1821 ◽

Cited By ~ 6

Author(s):

Luicer A. Ingasia ◽

Hoseah M. Akala ◽

Mabel O. Imbuga ◽

Benjamin H. Opot ◽

Fredrick L. Eyase ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Genetic Polymorphism ◽

Molecular Characterization ◽

Mutant Allele ◽

Inhibitory Concentration ◽

Wild Type Allele ◽

Wild Type ◽

Western Kenya ◽

Content Type

ABSTRACTThe prevalence of a genetic polymorphism(s) at codon 268 in the cytochromebgene, which is associated with failure of atovaquone-proguanil treatment, was analyzed in 227Plasmodium falciparumparasites from western Kenya. The prevalence of the wild-type allele was 63%, and that of the Y268S (denoting a Y-to-S change at position 268) mutant allele was 2%. There were no pure Y268C or Y268N mutant alleles, only mixtures of a mutant allele(s) with the wild type. There was a correlation between parasite 50% inhibitory concentration (IC50) and parasite genetic polymorphism; mutant alleles had higher IC50s than the wild type.

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Regulatory elements controlling pituitary-specific expression of the human prolactin gene

Molecular and Cellular Biology ◽

10.1128/mcb.10.9.4690-4700.1990 ◽

1990 ◽

Vol 10 (9) ◽

pp. 4690-4700

Author(s):

B Peers ◽

M L Voz ◽

P Monget ◽

M Mathy-Hartert ◽

M Berwaer ◽

...

Keyword(s):

Regulatory Elements ◽

Distal Region ◽

Dnase I ◽

Proximal Region ◽

Base Pairs ◽

Specific Expression ◽

Positive Region ◽

Dnase I Footprinting ◽

Human Prolactin ◽

Flanking Sequences

We have performed transfection and DNase I footprinting experiments to investigate pituitary-specific expression of the human prolactin (hPRL) gene. When fused to the chloramphenicol acetyltransferase (CAT) reporter gene, 5,000 base pairs of the 5'-flanking sequences of the hPRL gene were able to drive high cat gene expression in prolactin-expressing GH3B6 cells specifically. Deletion analysis indicated that this pituitary-specific expression was controlled by three main positive regulatory regions. The first was located just upstream from the TATA box between coordinates -40 and -250 (proximal region). We have previously shown that three motifs of this region bind the pituitary-specific Pit-1 factor. The second positive region was located in the vicinity of coordinates -1300 to -1750 (distal region). DNase I footprinting assays revealed that eight DNA motifs of this distal region bound protein Pit-1 and that two other motifs were recognized by ubiquitous factors, one of which seems to belong to the AP-1 (jun) family. The third positive region was located further upstream, between -3500 and -5000 (superdistal region). This region appears to enhance transcription only in the presence of the distal region.

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The incompatibility product of IncFII R plasmid NR1 controls gene expression in the plasmid replication region

Journal of Bacteriology ◽

10.1128/jb.152.2.829-839.1982 ◽

1982 ◽

Vol 152 (2) ◽

pp. 829-839

Author(s):

A M Easton ◽

R H Rownd

Keyword(s):

Gene Expression ◽

Target Site ◽

Plasmid Replication ◽

Lacz Gene ◽

Origin Of Replication ◽

Wild Type ◽

Base Pairs ◽

Replication Region ◽

Lambda Phages ◽

Beta Galactosidase

The incompatibility properties of IncFII R plasmid NR1 were compared with those of two of its copy number mutants, pRR12 and pRR21. pRR12 produced an altered incompatibility product and also had an altered incompatibility target site. The target site appeared to be located within the incompatibility gene, which is located more than 1,200 base pairs from the plasmid origin of replication. The incompatibility properties of pRR21 were indistinguishable from those of NR1. Lambda phages have been constructed which contain the incompatibility region of NR1 or of one of its copy mutants fused to the lacZ gene. In lysogens constructed with these phages, beta-galactosidase was produced under the control of a promoter located within the plasmid incompatibility region. Lysogens containing prophages with the incompatibility regions from pRR12 and pRR21 produced higher levels of beta-galactosidase than did lysogens containing prophages with the incompatibility region from the wild-type NR1. The introduction into these inc-lac lysogens of pBR322 plasmids carrying the incompatibility regions of the wild-type or mutant plasmids resulted in decreased levels of beta-galactosidase production. For a given lysogen, the decrease was greater when the pBR322 derivative expressed a stronger incompatibility toward the plasmid from which the fragment in the prophage was derived. This suggested that the incompatibility product acts on its target to repress gene expression in the plasmid replication region.

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