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PubMed1977

Genetic analysis of mutations affecting ribonuclease II in Escherichia coli.

Exonuclease activity in an Escherichia coli K12 mutant S296 is less than 1% of that in the wild type strain (Nikolaev et al., 1976). Another mutant N464 has thermolabile ribonuclease II (Castles and Singer, 1968; Kuwano et al., 1969). Genetic analysis of these mutants by Hfr conjugation and P1 transduction indicates that the structural gene (rnb) for ribonuclease II is located near the pyrF gene (28 min on the E. coli genetic map of Bachmann, Low and Taylor (1976)), and the most probable gene order is tyrT-trp-pyrF-rnb.

Chromosome Mapping↗
PubMed1977

A genetic analysis of aggressive behavior in two strains of mice.

Examination of BALB/cJ and A/J mouse strains revealed marked differences in their levels of isolation-induced aggression. Using the dangler paradigm, we found that BALB/cJ males were uniformly aggressive, while A/J males showed no tendency to attack. Genetic analysis showed that the expression of aggressive behavior in the F1, F2, and backcross generations was consistent with the transmission of high aggressivity as a single, autosomal recessive trait. Although the data are consistent with a major-locus effect, more complex polygenic modes of inheritance have not been excluded.

Aggression↗
PubMed1977

Behavior-genetic analysis of Phormia regina: conditioning, reliable individual differences, and selection.

Using proboscis extension (unconditioned response) to sucrose (unconditioned stimulus), individual blowflies (Phormia regina) were classically conditioned to saline and to water (conditioned stimuli) with sensitization controls, thus providing unique, independently replicated evidence both of learning in Diptera and of reliably measured individual differences. Directional and stabilizing selection have bred high and low performance lines markedly different from an unselected control line as a step in the analysis of behavior-genetic correlates. This replicates and extends previous selection analysis with improved conditioning technique. Also, some unwarranted claims of learning in Diptera are discussed.

Animals↗
PubMed2004

Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.

The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated alpha subunits of hypoxia-inducible factor (HIF). Although studies of VHL-defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF-dependent and -independent effects of VHL inactivation by studying gene expression patterns in Caenorhabditis elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1-independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17, and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1-independent function of VHL-1 that is connected with extracellular matrix function.

Animals↗
PubMed2025

Genetic analysis of four cases of Poirier Bienvenu neurodevelopmental syndrome associated with CSNK2B variant.

BACKGROUND: CSNK2B deficiency underlies the pathogenesis of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). In this study, we present four cases of pediatric seizures caused by de novo variants in CSNK2B, with the aim to reinforce the clinical and variant data pertaining to early genetic factors associated with epilepsy. METHODS: Trio whole exome sequencing were used to detect variants in the proband and her family members, and bioinformatics annotation was performed for the variant. Sanger sequencing and CSNK2B cDNA sequencing were employed to ascertain the carrier status of additional family members and evaluate the potential impact of variants on splicing. RESULTS: All four cases presented with epilepsy as the initial manifestation, accompanied by global developmental delay, particularly in language and motor developmental delay. Cases 1, 3 and 4 exhibited full-scale tonic-clonic seizures, while case 2 displayed myoclonic and typical absence seizures. Furthermore, case 2 demonstrated delayed growth and development compared to age-matched peers. No abnormality was detected in the head magnetic resonance imaging (MRI). Genetic analysis revealed novel heterozygous variants in the CSNK2B gene in all four cases, including c.175 + 1G > A, c.73-2A > G, c.291 + 1G > A and c.481delA. In case 2, reverse transcription analysis of CSNK2B mRNA revealed the retention of the 3' end sequence of Intron 2 and deletion of the 5' end sequence of Exon 3. In treatment, four case received a combination of one to three types of antiseizure medication and rehabilitation training individually. Case 1 continued to experience seizures to varying degrees, while cases 2-4 demonstrated effective seizure control. Overall motor and intellectual development improved in all four cases, however, there was slow recovery in language function. CONCLUSION: This study elucidates the molecular etiology of epilepsy in four cases with POBINDS and expands the mutational spectrum of pathogenic variants in the CSNK2B, highlighting their impact on splicing. The highly genetic heterogeneous phenotype of POBINDS relies on the detection of pathogenic variants in CSNK2B. Conventional antiseizure medication effectively control seizures, while rehabilitation treatment can significantly improve intelligence and motor function to varying degrees; however, language recovery tends to be relatively slow.

Humans↗
PubMed1979

Genetic analysis of alcohol dehydrogenase isozymes in pearl millet (Pennisetum typhoides).

Pearl millet (Pennisetum typhoides) produces three ADH isozymes, sets I, II, and III, with set III being expressed only in anaerobically treated seeds of seedlings. Variant strains have been identified which produce ADH isozymes with altered electrophoretic mobilities for sets I and II but not for set III activity. Based on genetic analysis of these variants and on dissociation-reassociation experiments, we propose that the three ADH isozymes are dimers of subunits coded by two structural genes, Adh1 and Adh2, with set I being a homodimer specified by Adh1, set III a homodimer specified by Adh2, and set II a heterodimer formed between the products of Adh1 and Adh2.

Alcohol Oxidoreductases↗
PubMed1976

Genetic analysis of aspartate aminotransferase isozymes from hybrids between Drosophila melanogaster and Drosophila simulans and mutagen-induced isozyme variants.

The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster for which naturally occurring electrophoretic variants were not found. There is an electrophoretic difference between D. melanogaster and D. simulans. Since the F1 hybrid offspring of these species are sterile, a genetic analysis of the ordinary type cannot be done on differences between the two species. A method was devised to make "partial hybrids" in which one chromosome arm is homozygous for melanogaster genes in an otherwise hybrid background. By using this method, Got1 was localized to 2R and Got2 to 2L. Once a gene can be assigned to a chromosome, it may be followed in crossing schemes and mutations from mutagen treatments may be looked for. At the locus of Got1 a mutation with low activity was recovered and designated Got1lo. It was located at a genetic map position of 75 on 2R. A Got2 mutant with a greater migration to the anode was recovered and designated Got2J. It was located at a genetic map position of 3.0, and in the salivary chromosome was between 22B1 and 22B4 inclusive.

Animals↗
PubMed1979

[Yeast resistance to polyene antibiotics. I. Production of Saccharomyces cerevisiae mutants resistant to nystatin and their genetic analysis].

239 nistatin-resistant mutants were selected after UV-irradiation of yeasts. Phenotypical analysis has revealed two main groups of the mutants: 1) resistant to nistatin and resistant or sensitive (in different combinations) to haptaens; 2) resistant to nistatin and having an increased resistance to haptens. It is found that the sensitivity dominates over the resistance and hyper-resistance. Genetic analysis of the mutant collection has shown that the resistance to nistatin is determined by 5 nuclear genes (hysr). Hyper-resistance is controlled by mutations in other genes, which are not connected with stable phenotype. Genes of hyper-resistance can be considered as minus-modificators of pleiothrophic cross-resistance, characteristic of hysr genes. Plus-modificator genes of polyenic resistance are described. The gene hysr1 is linked with its chromosome.

Crosses, Genetic↗
PubMed1976

Biogenesis of mitochondria. XLII. Genetic analysis of the control of cellular mitochondrial DNA levels in Saccharomyces cerevisiae.

The proportion of total cell DNA which is mitochondrial DNA was measured in haploid, diploid and tetraploid strains of S. cerevisiae grown under a standard set of conditions. For all strains tested the mitochondrial DNA level was in the range 16%-25% of total cell DNA. Repeated measurements of the cellular level of mitochondrial DNA in two haploid strains showed that these strains have measurably different cellular mitochondrial DNA levels (17% and 24% of total DNA, respectively) under our conditions. These two grande strains were used to investigate the role of the mitochondrial and nuclear genomes in the regulation of the mitochondrial DNA level. We have shown by genetic analysis that the difference between these two strains is determined by at least two nuclear genes. The mitochondrial genome is not involved in the regulation of cellular mitochondrial DNA levels. A number of purified petite clones derived from independent spontaneous petite isolates of the grande strain which contained 24% mitochondrial DNA were also studied. The mitochondrial DNA levels in all but one of these petites fell in the range 20-25% of total cell DNA. From these results we conclude that, in general, the mitochondrial DNA level in petite strains is controlled by the same mechanism as operates in grande strains. We propose a general model for the control of the cellular mitochondrial DNA level, in which the amount of mitochondrial DNA per cell is determined by regulation of the number of mitochondrial DNA molecules per cell. This regulation is mediated through the availability of a set of nuclear coded components, possibly a mitochondrial membrane site, which are required for the replication of mitochondrial DNA.

Aneuploidy↗
PubMed1977

Mucidin resistance in yeast. Isolation, characterization and genetic analysis of nuclear and mitochondrial mucidin-resistant mutants of Saccharomyces cerevisiae.

Mutants of Saccharomyces cerevisiae resistant to the antibiotic mucidin, a specific inhibitor of electron transport between cytochrome b and c, were isolated and divided into three phenotypic groups, as follows. Class 1 mutants were cross-resistant to a variety of mitochondrial inhibitors and exhibited no resistance at the mitochondrial level. Class 2 mutants were specifically resistant to mucidin exhibiting resistance also at the level of isolated mitochondria. Biochemical studies indicated that the mucidin resistance in class 2 mutants involved a modification of mucidin binding of inhibitory sites on the mitochondrial inner membrane without a significance change in the sensitivity of mitochondrial oxygen uptake to antimycin A, 2-heptyl-4-hydroxyquinoline-N-oxide, and 2,3-dimercaptopropanol. Class 3 was represented by a mutant which showed a high degree of resistance to mucidin and was cross-resistant to a variety of mitochondrial inhibitors at the cellular level but exhibited only a resistance to mucidin at the mitochondrial level. Genetic analysis of mucidin-resistant mutants revealed the presence of both nuclear and mitochondrial genes determining mucidin resistance/sensitivity in yeast. Resistance to mucidin in class 1 mutants was due to a single-gene nuclear recessive mutation (mucPR) whereas that in class 2 mutants was caused by mutations of mitochondrial genes. Resistance in class 3 mutant was determined both by single-gene nuclear and mitochondrial mutations. In the mitochondrial mutants the mucidin resistance segregated mitotically and the resistance determinant was lost upon induction of petite mutation by ethidium bromide. Allelism tests indicated that the mucidin resistance mutations fell into two genetic loci (MUC1 and MUC2) which were apparently not closely linked in the mitochondrial genome. Recombination studies showed that the two mitochondrial mucidin loci were not allelic with other mitochondrial loci RIB1, RIB2 and OLI1. An extremely high mucidin resistance at the cellular level was shown to arise from synergistic interaction of the nuclear gene mucPR and the mitochondrial mucidin-resistance gene (MR) in a cell. The results suggest that at least two mitochondrial gene products, responsible for mucidin resistance/sensitivity in yeast, take part in the formation of the cytochrome bc1 region of the mitochondrial respiratory chain.

Adenosine Triphosphatases↗
PubMed2026

Shared Genetic Basis, Biological Function and Causal Relationship Between Sleep Traits and Hypothyroidism: Evidence from a Comprehensive Genetic Analysis.

BACKGROUND: This research attempts to clarify whether there are any genetic similarities between sleep traits and hypothyroidism based on publicly accessible large-scale genomewide association studies. METHODS: The methodology included colocalization analysis, cross-phenotype association analysis, and linkage disequilibrium score regression analysis to find common genetic overlap. Through tissue function specificity and functional mapping, we were able to identify the shared genetic level. Genetic instrumental factors were used for causal inference in two-sample univariate and multivariable Mendelian randomization analyses. RESULTS: A hereditary correlation between hypothyroidism and napping during the day and getting up in the morning (rg= -0.0982, P= 0.0007; rg= -0.101, P= 0.0001). MAGI3, and HLA-DRB1 BX296568.1 may be potential targets for shared treatments. Colocalization and tissue-specific analysis demonstrated that the common genes and SNPs were identified in the thyroid, lung, brain, and lymphatic tissues. Functional analysis emphasized the importance of these common genes in processes like as protein transport, inflammatory response, and MHC class II protein synthesis. Furthermore, an association has been established between hypothyroidism and sleep duration (IVW, OR 1.5208; 95% CI 1.1142-2.0758, P=0.0082) and getting up in the morning (IVW, OR 1.8375; 95%CI: 1.4502-2.3284, P=4.73E-07). Furthermore, the reverse MR analysis revealed no causal connection between aberrant sleep traits and hypothyroidism. The enduring impact of insomnia on hypothyroidism persists despite controlling for alcohol consumption and smoking habits. CONCLUSION: Certain genetic correlations between sleep traits and hypothyroidism have been emphasized. These findings may elucidate the origin of comorbidity and have implications for future clinical trials.

Humans↗
PubMed1978

NZB/WF1 hybrid autoimmune disease: a genetic analysis.

This study analyzes the role of genetic and/or viral factors as etiologic agents in systemic lupus erythematosus in NZB/NZW F1 hybrid mouse, first by a backcross within the NZ strains. A separate study involved an outcross, production of an F2 generation, and then backcross to both NZ parents. The results were assayed by histologic evaluation of renal disease. Assay techniques for anti-DNA and proteinuria showed no evidence for segregation and were not useful. Histology of the kidney showed distinct segregation patterns consistent with the interpretation of the etiology as co-dominant genetic factors. While the virus[es] was not considered etiologic, mechanisms for relating activity to the pathogenesis were discussed.

Animals↗
PubMed1979

Multivariate behavioral genetic analysis of twin data on scholastic abilities.

Multivariate behavioral genetic analyses may employ either genetic and environmental correlations or phenotypically standardized covariances to assess the structure of genetic and environmental influences. Correlations and phenotypically standardized covariances answer different questions--correlations are appropriate for understanding the nature of genetic and environmental influences, whereas covariances are appropriate for determining the etiology of phenotypic correlations. The ratio of the genetic and environmental covariances to the phenotypic correlation yields estimates of bivariate heritability and environmentality, measures of the extent to which observed phenotypic covariance is due to genetic and environmental influences. Multivariate analyses of genetic and environmental correlations and covariances are illustrated with twin data on scholastic abilities. Factor analyses of correlations suggest that the same set of genes affects the major areas of academic achievement and that the environmental influences are similarly structured. Analyses of phenotypically standardized covariances indicate that the structures of genetic and environmental influences as they contribute to phenotypic resemblance among scholastic abilities are both similar and simple: there are one general genetic factor and one general environmental factor. Bivariate heritabilities and environmentalities are similar in magnitude, indicating that the strong phenotypic relationship among scholastic abilities is due roughly equally o genetic and environmental influences.

Analysis of Variance↗
PubMed1978

Genetic analysis of antibiotic resistance in Streptococcus pyogenes.

The genetics of antibiotic resistance in mutant strains of Streptococcus pyrogenes was studied. Utilizing a type 6 strain (9440) primarily resistant to strepttomycin (Strr), classes of mutant strains were isolated that were resistant to one of the following antibiotics: rifampin (Rifr), erythromycin (Eryr), thiostrepton (Tstr), spiramycin (Sprr), fusidic acid (Fusr), gramicidin (Grcr), ethidium bromide (Ebrr), kanamycin (Kanr), neomycin (Neor), oleandomycin (Oler), gentamicin (Genr), and novobiocin (Novr). Transduction experiments separated antibiotic resistance markers into two distinct groups: transducible markers, including Fusr, Bacr, Ksg+, Spcr, Eryr, Sprr, Rifr, Stlr, and Tstr (Bacr, Ksgr, Spcr, and Stlr refer to resistance to bacitracin, kasugamycin, spectinomycin, and streptolydigan, respectively), and nontransducible markers, including Grcr, Ebrr, Kanr, Neor, Oler, Genr, and Novr. By means of two- and three-point crosses, transducible markers (excluding tst) were located in three separate linkage groups. spr was found to be linked with ery and spc in the order spc-ery-spr, whereas in a separate linkage group the order was determined to be str-fus-bac-ksg. The third linkage group contained the rif and stl markers.

Anti-Bacterial Agents↗
PubMed1978

Gluten-sensitive enteropathy: genetic analysis and organ culture study in 35 families.

The genetic marker histocompatibility antigen HLA-B8 is present in 80% of patients with gluten-sensitive enteropathy (GSE). We studied 35 families with at least one affected member to determine whether an HLA-region gene alone could determine susceptibility to GSE. The incidence of HLA-B8 in the patients was 69% vs 22% for normals (P less than 0.001). The incidence of GSE in HLA-genotype-identical siblings of patients was only 8%, and in HLA-B8-haplotype-identical siblings and parents of patients was only 14% and 5%, respectively. In addition, intestinal biopsies of HLA-identical or partially identical relatives of patients were studied in an in vitro organ culture system capable of detecting gluten sensitivity in subjects ingesting a normal diet. The results confirmed the low incidence of gluten sensitivity in these individuals. The organ culture system could not differentiate mucosa obtained from unaffected parents or siblings of patients with GSE (who presumably carry the HLA-associated genetic information) from mucosa obtained from normals. We conclude that the genetic material inherited with HLA-B8 alone is not sufficient to produce clinical or subclinical disease. Other genetic and environmental factors appear to be important for disease pathogenesis.

Adolescent↗
PubMed2025

Genetic analysis of Schistosoma mansoni in a low-transmission area in Brazil suggests population sharing between wild-hosts and humans and geographical isolation.

BACKGROUND: The fluke Schistosoma mansoni is the causative agent of intestinal schistosomiasis, a neglected tropical disease, and remains prevalent in certain regions of Brazil. In the municipality of Sumidouro, state of Rio de Janeiro, Brazil, a low-endemic area for S. mansoni, water rats (Nectomys squamipes) are naturally infected by this trematode. The S. mansoni populations infecting humans and water-rats in Sumidouro exhibit distinct patterns of cercarial emergence (chronotypes) and phenotypic differences between hosts. Previous studies have shown that the adaptation of S. mansoni populations to human hosts (diurnal chronotype) and water rats (nocturnal chronotype) could result in prezygotic isolation. To test this hypothesis, we employed the mitochondrial cytochrome c oxidase subunit 1 gene (MT-CO1) and microsatellite loci as genetic markers. PRINCIPAL FINDINGS: We assessed the population structure between the definitive host species and geographically distant isolates collected from two endemic localities (Pamparrão-PAM and Encanto-Soledade-ENC-SOL) in Sumidouro. Additionally, we evaluated the phylogenetic relationships between S. mansoni from Sumidouro and those from other countries. Five haplotypes of the MT-CO1 gene were identified, with haplotypes 3 and 4 exclusive to ENC-SOL, and haplotypes 1, 2, and 3 were shared between humans and water rats. Haplotype 1 was also shared with other Brazilian localities, South American countries and a single locality in West Africa. The remaining haplotypes were exclusive to Sumidouro, indicating local genetic diversity. Population structure analysis revealed no genetic differentiation associated with host species but rather geographical structuring, probably due to the sedentary habits of rodents and the limited movement of humans between localities. This finding indicates that S. mansoni populations with different chronotypes are not genetically isolated and that significant gene flow occurs between them. CONCLUSIONS: In conclusion, our findings confirm that wild rodents contribute to the maintenance of the S. mansoni life cycle in Sumidouro and can serve as indicators of local transmission hotspots.

Animals↗
PubMed1978

A herpes simplex virus 1 integration site in the mouse genome defined by somatic cell genetic analysis.

Transfection experiments with HSV 1 in which one uses herpes simplex virus (HSV) thymidine kinase (TK) as a selectable prototrophic marker yield two classes of transformed cells: stable and unstable. In this report, we test the hypothesis that the stability phenotype can be explained by virus genome integration into a recipient cell chromosome. The method of analysis is by means of somatic cell genetics. We have isolated a series of microcell hybrids between a TK- Chinese hamster cell line and a transformed mouse cell line expressing the TK encoded by HSV 1. Several of the hybrid lines contain a single murine chromosome and express only the viral TK. Karyotypic analysis of these hybrids and of TK- derivatives generated by BrdUrd counterselection reveals that the TK+ phenotype is correlated with the presence of the terminal portion of the long arm of a specific murine chromosome. Results of extensive isozyme analyses of the hybrids and their TK- segregants fully corroborate the karyologic data. The results are consistent with the hypothesis that the viral tk gene is covalently integrated into this chromosomal region which itself does not appear to carry the endogenous murine tk locus. Other more complicated models are discussed. Our findings also show that somatic cell genetics can be used to localize viral integration sites in host chromosomes with high resolution.

Animals↗