Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “polygenicity”

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.

At least 379 records · Page 21Linked to original sources
PubMed1995

Mapping the diabetes polygene Idd3 on mouse chromosome 3 by use of novel congenic strains.

Development of novel congenic mouse strains has allowed us to better define the location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3. Congenic strains were identified by use of published and newly developed microsatellite markers, their genomes fingerprinted by a rapid, fluorescence-based approach, and their susceptibility to type 1 diabetes evaluated. The maximum interval containing Idd3 is now approximately 4 cM.

Animals↗
PubMed1995

Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease.

Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3% of 126 middle-aged NIDDM subjects and 5.3% of 95 matched control subjects in the South Indians (p = 0.17). In elderly Finnish subjects the frequency of the mutation was 7.5% in 40 NIDDM subjects and 7% in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7% NIDDM subjects and 5.8% control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups.

Adult↗
PubMed1980

Polygenic control of interferon production induced by poly I:C in vivo. Brief report.

Poly I:C-induced interferon production shows quantitative differences in various mouse strains depending on multiple interactions among genes located both inside and outside the major histocompatibility complex. Moreover, circulating interferon levels do not appear to be under direct genetic control but, rather, to depend on the gene-coded intensity of specific recognition of the inducer.

Animals↗
PubMed1981

Polygenic control of the immune response to F antigen.

The ability to produce an autoimmune response to F antigen in mice is under H-2-linked and non-H-2-linked Ir-gene control. There is an absolute requirement for a k allele at H-2K or I-A in order to produce antiF antibodies. Low and high responsiveness is controlled by a non-H-2-linked Ir gene which behaves in a similar fashion to Ir-3, in that as the dose of F-antigen is lowered, low responders behave as high responders and vice versa. This conversion from low to high responders and vice versa. This conversion from low to high responsiveness also occurs within a month after ATX.-Most F1 hybrids derived from (responder X nonresponder) parents bearing identical F-types behave as dominant nonresponders. As a result of ATX, such F1 mice convert to high responders . This conversion occurs if the animals are not immunized before day 90. If they receive F antigen prior to that time, they remain nonresponders for 7-9 months. One F1 combination showed--AKD2--behaves as an dominant higher responder. Genetic analysis showed that the presence of a K allele at H-2K or I-A, a non-H-2-linked Ir gene inherited from the AKR mice determined dominant responsiveness. No manipulation of the immune response or combination of genes converted nonresponders lacking a k allele into responders. Such complex genetic control suggests regulation by a number of independently segregating loci whose function it is to limit the autoimmune response to F antigen.

Animals↗
PubMed1996

Polygenic control of antibody production and correlation with vaccine induced resistance to rabies virus in high and low antibody responder mice.

The amplification of "high" (H) and "low" (L) multispecific antibody responses achieved respectively by H and L lines of selection GP represents a valuable tool in the genetic study of host-infection interactions. These lines were obtained by bidirectional selective breeding for high (HGP) or low (LGP) antibody production to natural complex antigens. HGP and LGP parental lines and reciprocal F1 hybrids, as well as their F2 segregants and backcrosses were submitted to immunization and challenge with rabies virus CVS strain. Acquired resistance was 1000-fold higher in HGP than LGP mice, with a dominance effect to low antibody production observed in F1 hybrids. An association between high antibody response and acquired resistance (P < 0.001) in F2 segregant mice was noticed. The genetic study was performed in these several populations, with a single dose of 104.5-fold LD50 CVS. We could demonstrate 3 independent loci regulating the anti-rabies antibody production, that are distinct, at least in part, from the 10 genes controlling the antigen selection response (sheep erythrocytes) of selection GP.

Animals↗
PubMed2004

Phenotypic and molecular evaluation of a recurrent selection program for a polygenic resistance to Phytophthora capsici in pepper.

'Criollo de Morelos 334' (CM334) is one of the most promising sources of resistance to Phytophthora capsici in pepper. This Mexican accession is distantly related to bell pepper and its resistance displays a complex inheritance. The QTLs involved in resistance to P. capsici were previously mapped. In order to transfer the resistance factors from CM334 into a bell pepper genetic background, a modified, recurrent breeding scheme was initiated. The breeding population was divided into three sub-populations which were screened by distinct phenotypic tests of increasing severity. The plants from the first sub-population were screened with low-severity tests and backcrossed to the susceptible bell pepper; the plants from the second and third sub-populations were screened by more severe resistance tests and crossed with the plants from the first and second sub-populations, respectively. In this study, the phenotypic data for the three sub-populations during five screening/intermating cycles were analysed. In parallel, the changes in allelic frequencies at molecular markers linked to the resistance QTLs were reported. The resistance phenotype and allelic frequencies strongly depended on the sub-population and screening severity. Regarding allelic frequency changes across the selection cycles, a loss of resistant QTL alleles was observed in the first sub-population, particularly for the low-effect QTLs, whereas a better conservation of the resistant QTL alleles was observed in the two other sub-populations. The same trend was observed in the phenotypic data with an increasing resistance level from the first to the third sub-populations. The changes in the allelic frequencies of loci not linked to resistance QTLs and for horticultural traits across the breeding process indicated that the recovery of the recipient parent genome was not significantly affected by the selection for resistance.

Analysis of Variance↗
PubMed2000

Age-dependent changes in phenotypes and candidate gene analysis in a polygenic animal model of Type II diabetes mellitus; NSY mouse.

AIMS/HYPOTHESIS: The Nagoya-Shibata-Yasuda (NSY) mouse closely mimics human Type II (non-insulin-dependent) diabetes mellitus in that the onset is age-dependent, the animals are not severely obese, and both insulin resistance and impaired insulin response to glucose contribute to disease development. The aim of this study was to clarify the influence of age on the pathogenesis of diabetes and to analyse a candidate gene for Type II diabetes in this strain. METHODS: Several phenotypic characteristics related to diabetes mellitus were monitored longitudinally in male NSY and control C3H/He mice. The nucleotide sequence of Glut4, a candidate gene for Nidd1nsy (a susceptibility gene for Type II diabetes) on Chromosome 11, encoding insulin-sensitive glucose transporter, was determined in NSY and C3H mice. RESULTS: Glucose intolerance worsened with age, and fasting blood glucose and fasting plasma insulin concentration increased with age in NSY mice. Pancreatic insulin content increased until 24 weeks of age but then decreased at 48 weeks of age in NSY mice. The hypoglycaemic response to insulin was statistically significantly smaller in NSY than in C3H/He mice. The nucleotide sequence of GLUT4 cDNA was identical in NSY and C3H/He mice, but both were different from the sequence reported previously. CONCLUSION/INTERPRETATION: Insulin secretion and insulin resistance, as well as ageing possibly play an important part in the disease development in NSY mice. A decline of pancreatic insulin content in older age might cause the relative insulin deficiency in this strain. Nucleotide sequencing suggests that Glut4 is unlikely to be a candidate gene for Nidd1nsy.

3T3 Cells↗
PubMed1997

Multiple sclerosis: a polygenic disease involving epistatic interactions, germline rearrangements and environmental effects.

Several regions of the human genome are associated with susceptibility to multiple sclerosis (MS). We review studies of linkage of MS to germline genes using microsatellites. A modest effect on susceptibility was seen with markers in the vicinity of 6p21 (HLA) and 17q22. The influence of epistatic interactions between these genes is considered. The impact of genetic rearrangements of certain germline genes on susceptibility to MS is described. Analysis of TCR gene rearrangements has established some of the target antigens of the immune response in MS. Environmental influences on MS are described with particular attention given to how microbes might trigger demyelinating disease.

Autoimmunity↗
PubMed2006

Identification and mapping of open chromatin regions within a 140 kb polygenic locus of human chromosome 19 using E. coli Dam methylase.

Using transient expression of the E. coli Dam methylase gene and analysis of the distribution of methylated GATC sites, we studied the distribution of open chromatin regions within a 140 kb long human genome segment in HEK-293 cells. Dam methylated sites were found in gene introns, exons, and intergenic regions, and their distribution along DNA was uneven. There were regions of high and low density of Dam methylated GATC sites, presumably corresponding to "open" and "closed" chromatin regions, respectively, and to the functional profile of the genomic locus under study. The Dam methylation profile was also generally in agreement with transcriptional activity of genes in the locus. Moreover, DNA regions accessible to Dam methylase apparently coincided with those hypersensitive to DNase I.

Binding Sites↗
PubMed1999

Genetic markers to predict polygenic disease.

Many genetic markers that relate to common multifactorial disease in adults have been identified during the past 15 years. Their use as adjuncts for the diagnosis, prognosis, prediction of disease or targeting therapy for these disorders has commenced; good examples being the Factor V Leiden mutation for venous-thromboembolism, lipoprotein lipase mutations for hypertriglyceridemia and the apolipoprotein E4 variant for Alzheimer's dementia. However, extensive gene-gene interactions and gene-environment interactions make their use more complex than markers for the simpler monogenic disorders (eg, cystic fibrosis, or Duchennne's muscular dystrophy). Possible misapplications of the use of genetic markers for multifactorial disease are discussed.

Eugenics↗