Genetic background affects relative nonsense mRNA accumulation in wild-type and upf mutant yeast strains

AbstractThe mouse is the most commonly used model species in biomedical research. Just as human physical and mental health are influenced by the commensal gut bacteria, mouse models of disease are influenced by the fecal microbiome (FM). The source of mice represents one of the strongest influences on the FM and can influence the phenotype of disease models. The FM influences behavior in mice leading to the hypothesis that mice of the same genetic background from different vendors, will have different behavioral phenotypes. To test this hypothesis, colonies of CD-1 mice, rederived via embryo transfer into surrogate dams from four different suppliers, were subjected to phenotyping assays assessing behavior and physiological parameters. Significant differences in behavior, growth rate, metabolism, and hematological parameters were observed. Collectively, these findings show the profound influence of supplier-origin FMs on host behavior and physiology in healthy, genetically similar, wild-type mice maintained in identical environments.

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Yeasts as Complementary Model Systems for the Study of the Pathological Repercussions of Enhanced Synphilin-1 Glycation and Oxidation

International Journal of Molecular Sciences ◽

10.3390/ijms22041677 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1677

Author(s):

David Seynnaeve ◽

Daniel P. Mulvihill ◽

Joris Winderickx ◽

Vanessa Franssens

Keyword(s):

Lewy Bodies ◽

Inhibitory Effect ◽

Model Systems ◽

Wild Type ◽

Glyoxalase System ◽

Inclusion Formation ◽

Growth Defects ◽

Yeast Strains ◽

Autophagic Degradation ◽

Detrimental Impact

Synphilin-1 has previously been identified as an interaction partner of α-Synuclein (αSyn), a primary constituent of neurodegenerative disease-linked Lewy bodies. In this study, the repercussions of a disrupted glyoxalase system and aldose reductase function on Synphilin-1 inclusion formation characteristics and cell growth were investigated. To this end, either fluorescent dsRed-tagged or non-tagged human SNCAIP, which encodes the Synphilin-1 protein, was expressed in Saccharomyces cerevisiae and Schizosaccharomyces pombe yeast strains devoid of enzymes Glo1, Glo2, and Gre3. Presented data shows that lack of Glo2 and Gre3 activity in S. cerevisiae increases the formation of large Synphilin-1 inclusions. This correlates with enhanced oxidative stress levels and an inhibitory effect on exponential growth, which is most likely caused by deregulation of autophagic degradation capacity, due to excessive Synphilin-1 aggresome build-up. These findings illustrate the detrimental impact of increased oxidation and glycation on Synphilin-1 inclusion formation. Similarly, polar-localised inclusions were observed in wild-type S. pombe cells and strains deleted for either glo1+ or glo2+. Contrary to S. cerevisiae, however, no growth defects were observed upon expression of SNCAIP. Altogether, our findings show the relevance of yeasts, especially S. cerevisiae, as complementary models to unravel mechanisms contributing to Synphilin-1 pathology in the context of neurodegenerative diseases.

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Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

10.32920/ryerson.14662620 ◽

2021 ◽

Author(s):

Haider Z. Naqvi

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Genetic Background ◽

Germ Line ◽

Strong Indication ◽

Wild Type ◽

C Elegans ◽

Novel Gene ◽

Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

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THE EFFECTS OF HETEROZYGOSITY CHANGES ON VIABILITY IN DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/70.4.595 ◽

1972 ◽

Vol 70 (4) ◽

pp. 595-610

Author(s):

Ray Moree

Keyword(s):

Drosophila Melanogaster ◽

Genetic Background ◽

Laboratory Strain ◽

Theoretical Expectation ◽

Wild Type ◽

Small Deviations ◽

The Third ◽

The Difference

ABSTRACT The viability effects of chromosomes from an old and from a new laboratory strain of D. melanogaster were studied in eight factorial combinations and at two heterozygosity levels. The combinations were so constructed that heterozygosity level could be varied in the third chromosomes of the carriers of a homozygous lethal marker, in the third chromosomes of their wild-type segregants, and in the genetic backgrounds of both. Excluding the effect of the marker and the exceptional outcomes of two of the combinations, and taking into account both large and small deviations from theoretical expectation, the following summary is given as the simplest consistent explanation of the results: 1) If total heterozygosities of two segregant types tend toward equality their viabilities tend toward equality also, whether background heterozygosity is high or low; if background heterozygosities is higher the tendency toward equality is slightly greater. 2) If total heterozygosity of two segregant types are unequal the less heterozygous type has the lower viability; the difference is more pronounced when background heterozygosity is low, less when it is high. 3) Differences between segregant viabilities are correlated with differences between the total heterozygosities of the two segregants; genetic background is effective to the extent, and only to the extent, that it contributes to the magnitude of this difference. This in turn appears to underlie, at least partly, the expression of a pronounced interchromosomal epistasis. Thus in this study viability is seen to depend upon both the quantity and distribution of heterozygosity, not only among the chromosomes of an individual but among the individuals of a given combination as well.

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SUPPRESSORS OF snf 2 MUTATIONS RESTORE INVERTASE DEREPRESSION AND CAUSE TEMPERATURE-SENSITIVE LETHALITY IN YEAST

Genetics ◽

10.1093/genetics/112.4.741 ◽

1986 ◽

Vol 112 (4) ◽

pp. 741-753

Author(s):

Lenore Neigeborn ◽

Kenneth Rubin ◽

Marian Carlson

Keyword(s):

Genetic Background ◽

Glucose Deprivation ◽

Temperature Sensitive ◽

Wild Type ◽

Suppressor Mutations ◽

Invertase Gene ◽

Selection For ◽

Galactose Utilization ◽

Yeast Genes ◽

Recessive Defect

ABSTRACT Mutations in the SNF2 gene of Saccharomyces cerevisiae prevent derepression of the SUC2 (invertase) gene, and other glucose-repressible genes, in response to glucose deprivation. We have isolated 25 partial phenotypic revertants of a snf2 mutant that are able to derepress secreted invertase. These revertants all carried suppressor mutations at a single locus, designated SSN20 (suppressor of snf2). Alleles with dominant, partially dominant and recessive suppressor phenotypes were recovered, but all were only partial suppressors of snf2, reversing the defect in invertase synthesis but not other defects. All alleles also caused recessive, temperature-sensitive lethality and a recessive defect in galactose utilization, regardless of the SNF2 genotype. No significant effect on SUC2 expression was detected in a wild-type (SNF2) genetic background. The ssn20 mutations also suppressed the defects in invertase derepression caused by snf5 and snf6 mutations, and selection for invertase-producing revertants of snf5 mutants yielded only additional ssn20 alleles. These findings suggest that the roles of the SNF2, SNF5 and SNF6 genes in regulation of SUC2 are functionally related and that SSN20 plays a role in expression of a variety of yeast genes.

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Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP

Genes & Development ◽

10.1101/gad.14.3.272 ◽

2000 ◽

Vol 14 (3) ◽

pp. 272-277 ◽

Cited By ~ 2

Author(s):

Andrew L. Kung ◽

Vivienne I. Rebel ◽

Roderick T. Bronson ◽

Lian-Ee Ch'ng ◽

Colin A. Sieff ◽

...

Keyword(s):

Experimental Evidence ◽

Loss Of Heterozygosity ◽

Tumor Suppression ◽

Genetic Background ◽

Hematologic Malignancies ◽

Hematopoietic Differentiation ◽

Wild Type ◽

Gene Dose ◽

Full Complement ◽

Dose Dependent

Mice with monoallelic inactivation of the CBP gene develop highly penetrant, multilineage defects in hematopoietic differentiation and, with advancing age, an increased incidence of hematologic malignancies. The latter are characterized, at least in some cases, by loss of heterozygosity (LOH) at the CBP locus. No such pathology was observed in wild-type or p300 heterozygous null mice of the same age and genetic background. Thus, a full complement of CBP, but not p300, is required for normal hematopoietic differentiation. These results also provide the first experimental evidence for the hypothesis that CBP has tumor-suppressing activity.

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Isolation of telomere DNA from Neurospora crassa

Molecular and Cellular Biology ◽

10.1128/mcb.7.9.3168-3177.1987 ◽

1987 ◽

Vol 7 (9) ◽

pp. 3168-3177

Author(s):

M G Schechtman

Keyword(s):

Linkage Group ◽

Neurospora Crassa ◽

Genetic Background ◽

Type Strain ◽

Wild Type Strain ◽

The Other ◽

Wild Type ◽

Oak Ridge ◽

Entire Chromosome ◽

Different Genetic Background

The most distal known gene on Neurospora crassa linkage group VR, his-6, was cloned. A genomic walk resulted in isolation of the telomere at VR. It was obtained from a library in which the endmost nucleotides of the chromosome had not been removed by nuclease treatment before being cloned, and mapping indicates that the entire chromosome end has probably been cloned. Sequences homologous to the terminal 2.5 kilobases of DNA from VR from these Oak Ridge N. crassa strains are found at other sites in the genome. To characterize these sites, I crossed an Oak Ridge-derived his-6 strain with a wild-type strain of different genetic background (Mauriceville) and characterized the hybridization patterns seen in the progeny. It appears that the sequences homologous to the VR terminus are found at genetically different sites in the two parental strains, and no hybridization to the VR telomere from Mauriceville was detected. The other genomic copies identified in the Oak Ridge parent were not telomeres. I suggest that any repeating sequence blocks found immediately adjacent to the VR terminus in Oak Ridge strains must be small and that the repeating element identified in that background may be an N. crassa transposable element integrated near the the chromosome end at VR.

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Molecular Evidence for Hybrid Origin and Phenotypic Variation of Rosa Section Chinenses

Genes ◽

10.3390/genes11090996 ◽

2020 ◽

Vol 11 (9) ◽

pp. 996

Author(s):

Chenyang Yang ◽

Yujie Ma ◽

Bixuan Cheng ◽

Lijun Zhou ◽

Chao Yu ◽

...

Keyword(s):

Genetic Markers ◽

Genetic Background ◽

Morphological Traits ◽

Taxonomic Status ◽

Single Copy ◽

Hybrid Origin ◽

Biological Research ◽

Molecular Evidence ◽

Germplasm Resources ◽

Wild Type

Rosa sect. Chinenses (Rosaceae) is an important parent of modern rose that is widely distributed throughout China and plays an important role in breeding and molecular biological research. R. sect. Chinenses has variable morphological traits and mixed germplasm. However, the taxonomic status and genetic background of sect. Chinenses varieties remain unclear. In this study, we collected germplasm resources from sect. Chinenses varieties with different morphological traits. Simple sequence repeat (SSR) markers, chloroplast markers, and single copy nuclear markers were used to explore the genetic background of these germplasm resources. We described the origin of hybridization of rose germplasm resources by combining different molecular markers. The results showed that the flower and hip traits of different species in R. sect. Chinenses were significantly different. The SSR analysis showed that the two wild type varieties have different genetic backgrounds. The double petal varieties of R. sect. Chinenses could be hybrids of two wild type varieties. A phylogenetic analysis showed that the maternal inheritance of sect. Chinenses varieties had two different origins. To some extent, variation in the morphological traits of double petal species of R. sect. Chinenses reflects the influence of cultivation process. This study emphasizes that different genetic markers vary in their characteristics. Therefore, analyzing different genetic markers in could provide an insight into highly heterozygous species.

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KRAS mutation profile in colorectal cancer patients in Brazil: A cohort of 989 individuals

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15017 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15017-e15017

Author(s):

M. G. Zalis ◽

F. M. Vieira ◽

I. Zalcberg-Renault ◽

M. H. Bonamino ◽

C. G. Ferreira ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Kras Mutation ◽

Genetic Background ◽

Brazilian Population ◽

Wild Type ◽

Asian Populations ◽

Mutation Profile ◽

Significant Difference ◽

Colorectal Cancer Patients

e15017 Background: KRAS mutation is common event in colorectal cancer occurring in around 40% of the patients. It is well- known that patients harboring the KRAS mutation do not derive benefit from cetuximab. However data available KRAS mutation profile is limited to Caucasian and Asian individuals and there is a lack of data in the population from Latin America. Brazilian population has a heterogeneous genetic background and this may have pharmacogenetic implications (Suarez-Kurtz, 2006). Methods: Between July and November 2008, we analyzed 989 consecutive patient samples sent to our laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, exons 1 were amplified by PCR and submitted to automatic sequencing. Codons 12 and 13 were analyzed. Results: The median age was 59 years and 53% of the patients were male and 47% female. The percentage of wild-type and mutated KRAS was 62 and 38%, respectively. Among the 375 mutated cases, 87% were in codon 12 versus 13% in codon 13. Mutation Gly12Asp was the most common being detected in 39% of the mutated cases. Due to the sample size a comparison among patients from different regions of Brazil was possible. However, no significant difference was observed in relation to the type or percentage of patients harboring the KRAS mutation. Interestingly, a significant difference in the percentage of mutated KRAS patients was observed between male and female (41 versus 35%, p= 0.05). Conclusions: The profile of KRAS mutation in the Brazilian population is similar to that reported for Caucasian and Asian populations. This is one of the largest cohorts of KRAS genotyping in colorectal cancer patients ever reported. To the best of our knowledge our data is the first to put forward the issue of a potential difference in the mutation rate according to gender. The observed higher incidence of KRAS-mutation in male than female deserves further investigation. No significant financial relationships to disclose.

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Construction of isomitochondrial and isonuclear strains for recombinational analysis of mitochondrial loci in S. cerevisiae

Genetics Research ◽

10.1017/s0016672300014075 ◽

1980 ◽

Vol 35 (2) ◽

pp. 225-229 ◽

Cited By ~ 18

Author(s):

A. Kruszewska ◽

B. Szcześniak

Keyword(s):

Genetic Background ◽

Nutritional Requirements ◽

Mating Types ◽

Wild Type ◽

Recombinational Analysis ◽

Mitochondrial Loci

SUMMARYIn the mitochondrial and nuclear genetic background of the 777-3A strain (op1, ade1, α) a set of strains with different nutritional requirements and mating types, carrying the op1 mutation versus its wild-type OP1 allele was constructed. This makes possible the use of strains with the same genetic background in recombinational analysis of mitochondrial loci.

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