The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL-KsJ and C57BL-6J strains.
Explore the source record for details and available documents.
Age Factors↗
SEARCH · Search PubMed
Results for “Genetic background”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Genetic background of adrenocortical tumor development.
The increasing occurrence of incidentally discovered benign adrenocortical tumors has become a clinical dilemma because of the difficulties in differentiating them from their malignant counterpart. Adrenocortical tumors are associated with familial cancer syndromes such as the Beckwith-Wiedemann syndrome, the Li-Fraumeni syndrome, the Carney complex, multiple endocrine neoplasia type 1, congenital adrenal hyperplasia, and the McCune-Albright syndrome. Genetic events are known to take place on the chromosomal and gene level in sporadic adrenocortical tumors.
Adrenal Cortex↗
Hypothesis testing for the genetic background of quantitative traits.
The testing of Bayesian point null hypotheses on variance component models have resulted in a tough assigmment for which no clear and generally accepted method exists. In this work we present what we believe is a succeeding approach to such a task. It is based on a simple reparameterization of the model in terms of the total variance and the proportion of the additive genetic variance with respect to it, as well as on the explicit inclusion on the prior probability of a discrete component at origin. The reparameterization was used to bypass an arbitrariness related to the impropriety of uninformative priors onto unbounded variables while the discrete component was necessary to overcome the zero probability assigned to sets of null measure by the usual continuous variable models. The method was tested against computer simulations with appealing results.
Algorithms↗
Biochemical evidence for conversion to milder form of hereditary mouse cataract by different genetic background.
Congenic hereditary cataract mice, BALB/c-nct/nct, were established by introducing the nct gene from Nakano into BALB/c mice. These mice developed a milder cortical form of cataract which developed sporadically and later in life than in Nakano mice. Combined use of BALB/c and BALB/c-nct/nct mice enables biochemical comparison of normal clear lenses, congenic clear lenses which are destined to be opacified some time later, and opacified lenses in the same genetic and aging statuses. We compared the age-related changes in water content and water-soluble and -insoluble fractions among these three types of lenses. Congenic clear lenses and opaque lenses were more similar to BALB/c normal clear lenses and Nakano opaque ones, respectively, in these parameters. These results suggest, in addition to formation of aggregated crystallins and their accumulation in water-insoluble fractions, that decreased protein synthesis, increased protein degradation and augmented leakage of crystallin might have a significant role in the nct-induced lens opacification.
Aging↗
Comparison of sex-linked dwarf genes in chickens from two sources when introgressed into unrelated genetic backgrounds.
1. Sex-linked dwarfing genes from 2 broiler stock origins (EU and US) were each introgressed into 2 White Leghorn populations that had been divergently selected for antibody response to sheep erythrocytes. 2. When the resulting backcrossed populations were 87.5% of their respective. White Leghorn line, non-dwarf pullets were assessed for body weights, shank lengths, immunoresponsiveness, age and body weight at sexual maturity, egg production, average egg weight, and duration of fertility. For measurements where there were no differences between non-dwarf pullets from the 2 origins of the dwarfing genes, then the dwarf pullets (which were full sisters to the non-dwarfs) were compared. 3. Shank length at 8 weeks of age and mature (24-week) body weights were higher for dwarf pullets from EU than US dwarf origin. Immune response and several egg production traits were higher for dwarf pullets from the high antibody backcross than from those of the low antibody backcross. 4. There were few differences in expression of the dwarfing genes from 2 origins in the unrelated backcross populations used in this study. Also each of the dwarfing genes, when introgressed into different genomic backgrounds, was not discernibly different in its expression in terms of antibody response or egg production characteristics.
Analysis of Variance↗
Genetic background of diabetic and nondiabetic sibs in young Bangladeshis.
The prevalence of diabetes mellitus in the young is higher in Bangladesh like other Asian developing nations. Albeit, undernutrition has been shown to be associated with diabetes in the young, not all such individuals are diabetic. Diabetes Mellitus is a multigenic disease. In IDDM, DR3/4 heterozygotes were shown to have a greatly increased risk of developing the disease, suggesting the concept of genetic factor(s) being involved in the development of diabetes. Therefore, this study was undertaken to determine the distribution of HLA class II alleles (DRB) and to identify the HLA associated risk for developing diabetes mellitus in the young Bangladeshis. A total of fifty individuals were investigated. Half of them (n=25) were diabetic patients, registered in BIRDEM and half the participants were their non-diabetic sibs. A genomic DNA PCR and Enzyme Linked Probe Hybridization Assay (ELPHA, Bio-test, Germany) was used to determine HLA class II alleles (DRB1, DRB 3, 4, 5) by in vitro amplification of DRB gene. Among all the sero-equivalent antigens found in the study subjects, the prevalence of DR15 (DR2) was overrepresented, both in the diabetic subjects and in their non-diabetic sibs. Moreover, compared with the non-diabetic group the diabetic patients showed higher frequency of DR15 alleles (39 and 25%) though the difference was not significant (chisq. 1.7, p>0.05). Next to DR15, DR4 was the most prevalent HLA-DRB gene found in the study population. Interestingly, the frequency of DR4 was higher in the diabetic than in the non-diabetic group (20 vs. 14%). The study showed that the DR15 and DR4 were the most prevalent in the study population. Moreover, DR7 though not very significant, was higher in non-diabetic compared to their diabetic sibs. Comparison between the diabetic and non-diabetic sibs could have been interesting and significant but we could not confirm our findings, possibly, due to small sample size. A study in a larger paired sample of unrelated population is also needed to substantiate our findings, and also to prove the susceptibility or resistant haplotype in the young diabetic subjects.
Adult↗
Cardiovascular factors explain genetic background differences in VO2max.
The purpose of this study was to further explore factors that may be related to ethnic differences in the maximum rate at which an individual can consume oxygen (VO2max) between 20 African American (AA) and 30 European American (EA) sedentary women who were matched for body weight (kg) and fat-free mass (FFM). VO2max (l/min) was determined during a graded treadmill exercise test. Submaximal steady-state heart rate and submaximal VO2 were determined at a treadmill speed of 1.3 m/sec and a 2.5% grade. Hemoglobin (Hb) was determined by the cyanide method, muscle oxidative capacity by 31P magnetic resonance spectroscopy (ADP time constant), and FFM (kg) by dual-energy x-ray absorptiometry. Genetic classification was self-reported, and in a subset of the sample (N = 32), the determinants of ethnicity were measured by African genetic admixture. AA women had significantly reduced VO2max, Hb levels, and muscle oxidative capacity (longer ADP time constants, P < or = 0.05) than EA women. Submaximal oxygen pulse (O2Psubmax), ADP time constant, Hb, and ethnic background were all significantly related to VO2max (ml/kg/min and ml/kg FFM/min, all P < or = 0.01). By multiple regression modeling, Hb, O2Psubmax, muscle oxidative capacity, and ethnicity were found to explain 61% and 57% of the variance of VO2max in ml/kg/min and ml/kg FFM/min, respectively. Muscle oxidative capacity and O2Psubmax were both significantly and independently related to VO2max in all three models (P < or = 0.05), whereas Hb and ethnicity were not. These results suggest that mitochondrial muscle oxidative capacity and oxygen delivery capabilities, as determined by O2Psubmax, account for most if not all of the ethnic differences in VO2max.
Adenosine Diphosphate↗
Interstitial lung disease in children -- genetic background and associated phenotypes.
Interstitial lung disease in children represents a group of rare chronic respiratory disorders. There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease. Recently, mutations in the ABCA3 transporter were found as an underlying cause of fatal respiratory failure in neonates without surfactant protein B deficiency. Especially in familiar cases or in children of consanguineous parents, genetic diagnosis provides an useful tool to identify the underlying etiology of interstitial lung disease. The aim of this review is to summarize and to describe in detail the clinical features of hereditary interstitial lung disease in children. The knowledge of gene variants and associated phenotypes is crucial to identify relevant patients in clinical practice.
ATP-Binding Cassette Transporters↗
[The molecular-genetic background of spinal muscular atrophy. Diagnosis, prognosis and future treatment].
Explore the source record for details and available documents.
Alternative Splicing↗
[ Mutation of mtDNA and genetic background of hypertrophic cardiomyopathy].
The operation of the structural and functional units of the myocardial contractile apparatus relies on mutual myofilament movement, totally ATP dependent. As a consequence, cardiac action is integrally connected with the production of high energy ATP molecules, which are mainly synthesised in cellular mitochondrial structures. Mitochondrial dysfunction can lead to a reduced level of ATP, which is necessary to generate movement in the actino-myosin system. ATP insufficiencies may be a result of the genetic mitochondrial material (mtDNA) mutation, poorer expression of mitochondrial genes (at the transcription and/or translation stage), distorted import of proteins from the cytoplasm to the mitochondria or erroneous composition of mitochondrial breathing complexes. It has been proved that the efficacy of oxidative phosphorylation (mitochondrial ATP synthesis) is reduced with accumulated mutation of mitochondrial and/or nuclear DNA. The paper is a review of findings on the mutation of mitochondrial DNA discovered in patients with hypertrophy of the cardiac muscle. In many cases these changes accompany the mutations of the nuclear genes, but they may also be the only change discovered in the patient's genetic material.
Adenosine Triphosphate↗
Cell cycle and genetic background dependence of the effect of loss of BRCA2 on ionizing radiation sensitivity.
Carriers of mutations in the BRCA2 gene are at a highly elevated risk of breast and other cancers. The BRCA2 gene encodes a very large protein thought to play a role in DNA repair. To examine the effect of mutation of BRCA2 on sensitivity to ionizing radiation, we used a previously described mouse model system (Brca2(Tr)) in which the Brca2 open reading frame is truncated. Mouse embryo fibroblasts carrying this mutation have a proliferative defect, which we show here can be substantially rescued by genetic ablation of p53. Proliferating Brca2(Tr/Tr)/p53(-/-) cells, like Brca2(Tr/Tr) cells, show genomic instability. We used the clonogenic survival assay, which depends on the ability of cells to proliferate, to examine the cell cycle dependence of radiation sensitivity of Brca2(Tr/Tr)/p53(-/-) compared to p53(-/-) and wild-type cells. This showed that the Brca2 mutation had little effect on cells irradiated in quiescence but sensitized proliferating cells to ionizing radiation on a p53(-/-) background. These results suggest that the major role of Brca2 in mediating cell survival after irradiation is in the S and G(2) phases of the cell cycle.
Animals↗
Effect of genetic background on establishment of mouse embryonic stem cells.
We established 13 embryonic stem (ES) cell lines from 542 embryos crossed between various strains of mice: 10 lines from 129/Sv-ter embryos (10/48, 20.8%) and 3 lines out of other 9 combinations of intra- or inter-strain matings (1 from intracross of C57BL/6CrSlc, 1 from B6D2F1 x C57BL/6CrSlc, 1 from Yok:ddY x Slc:ICR). No ES cell line from 129/Sv-ter x Slc:ICR embryos suggests that ICR strain might have inhibitory genetic factor(s) for the ES cell formation. Some ES cell lines could be obtained from hybrids even if none or few lines from their parental strains, suggesting a heterosis effect can be expected for establishing ES cell lines in mice.
Animals↗
Genetic background affects relative nonsense mRNA accumulation in wild-type and upf mutant yeast strains.
The Saccharomyces cerevisiae nonsense-mediated mRNA decay (NMD) pathway targets mRNAs with premature stop codons and some wild-type mRNAs for accelerated decay. Upf1p, Upf2p and Upf3p are required for NMD. NMD-targeted mRNAs are degraded rapidly in wild-type cells and stabilized in upf1, upf2 or upf3 mutants. We report here that the relative CYH2 pre-mRNA/mRNA accumulation is enhanced in cells derived from a W303 background, compared with a variety of commonly used strains. The enhanced CYH2 pre-mRNA accumulation phenotype results from a larger difference in mRNA half-lives in the W303 strains than two previously used strains. This phenotype can be selected in crosses and is also seen in upf2 and upf3 mutants. These results suggest there are genes that influence the efficiency of NMD and that yeast strains derived from the W303 background may be useful for measurement of abundance and half-lives of low abundance, short-lived NMD substrates.
Adaptor Proteins, Signal Transducing↗
The tonsils and pustulosis palmaris et plantaris as viewed against the genetic background.
In spite of considerable research so far made on the etiology of pustulosis palmaris et plantaris (PPP), several points remain obscure. However, since tonsillectomy has been found to improve the symptoms and cure the disease, some researchers have suspected PPP to be a tonsillar focal infection. Another well-known fact is that Streptococci too are associated with tonsillar focal infection, and that even in patients with PPP, high antibody titres against Streptococci have been observed. The authors have obtained results suggesting the existence of a genetic origin in patients with chronic tonsillitis in terms of the production of antibody against Streptococci. Proceeding from these results, we have tried HL-A typing by the microcytotoxicity (NIH) method, using HL-AA and HL-AB for determination. HL-A typing was performed on 43 PPP patients, but no results were obtained which would indicate a close correlation between PPP and HL-A antigens.
Adult↗
Genetic background increases the risk of hip osteoarthritis.
Using a cohort of 49 families with at least one affected female sibling pair who had total hip arthroplasty for end-stage primary osteoarthritis, we determined the prevalence and relative risk of symptomatic and radiographic osteoarthritis in 145 children. The relative risk of symptomatic radiographic osteoarthritis in these 145 offspring was 3.5 times greater than in 119 age-matched controls (95% confidence interval; range, 2.0-6.2). Most symptoms and radiographic changes involved the hip. Results of this study showed vertical transmission of primary osteoarthritis and that genetic influences play a major role in osteoarthritis of the hip in the Caucasian population.
Arthroplasty, Replacement, Hip↗
Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait.
Congenital chloride diarrhea (CLD) is an inherited intestinal disorder caused by mutations in the down-regulated in adenoma gene. In Finland, the disease is prevalent because of a founder effect, and all but one of the CLD-associated chromosomes carry the same mutation, V317del. In Poland, another area with a high incidence of CLD, as many as seven different mutations have been detected so far. A third known cluster of CLD, around the Persian Gulf, has not been genetically studied. We studied the allelic diversity of CLD in Poland, in Saudi Arabia and Kuwait, and in three isolated families from North America and Hong Kong. Altogether, eight novel mutations were identified, making a total of 19 known CLD gene mutations. The Polish major mutation I675-676ins was found in 47% of the Polish CLD-associated chromosomes. Haplotype analysis and clustering of the I675-676ins mutation supported a founder effect and common ancestral origin. As in Finland, a major founder effect was observed in Arab patients: 94% of the CLD-associated chromosomes carried a nonsense mutation, G187X, which occurred in either a conserved ancestral haplotype or its derivative. Our data confirm that the same locus is mutated in all cases of CLD studied so far. In Poland, a relatively common founder mutation is likely to highlight a set of rare mutations that would very rarely produce homozygosity alone. This suggests that mutations in the CLD locus are not rare events. Although the disease is thought to be rare, undiagnosed patients may not be uncommon.
Chlorides↗
Genetic background of apparently idiopathic sporadic cerebellar ataxia.
Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.
Age of Onset↗
Effects of genetic background on transmission of incompatibility resulting from mutant minor histocompatibility genes.
A mutant minor histocompatibility gene, H(KH-11), was earlier reported to be unable to generate a skin allograft response unless the graft donor carried both the mutant gene and H-2Db. H(KH-11) and H-2 are unlinked, so animals heterozygous at the two relevant loci transmitted the mutant phenotype to only 25% of their progeny when backcrossed to an appropriate partner, although 50% actually inherited the mutant gene. To examine the generality of the requirement for multiple loci to generate graft incompatibility, we investigated the transmission of mutant (incompatible) phenotypes for 24 different mutant non-H-2 histocompatibility genes. Approximately half the mutant phenotypes were transmitted in frequencies suggesting that multiple loci may be involved. In certain cases, an individual mutation was transmitted at different frequencies when backcrossed onto different inbred strain backgrounds--as if the mutant phenotype were due to a single segregating locus on one background, but required two unlinked segregating loci on another. In cases in which multiple loci were involved, the relevant H-2 complex often seemed to be coselected in the backcross progeny along with the mutant minor H-gene.
Animals↗