PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Multifactorial Inheritance”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

fw2.2 directly affects the size of developing tomato fruit, with secondary effects on fruit number and photosynthate distribution.

fw2.2 is a quantitative trait locus responsible for approximately 30% of the difference in fruit size between large, domesticated tomatoes (Lycopersicon esculentum Mill.) and their small-fruited wild relatives. The gene underlying this quantitative trait locus was cloned recently and shown to be associated with altered cell division in ovaries (Frary et al., 2000). However, it was not known whether the change in fruit size is associated with other changes in plant morphology or overall fruit yield-changes that could potentially cause the fruit weight phenotype. To shed light on this issue, a detailed comparison was made between nearly isogenic lines differing for alleles at this locus to search for pleiotropic effects associated with fw2.2. Field observations show that although the small-fruited nearly isogenic line produced smaller ovaries and fruit as expected, this was compensated by a larger number of fruit-due mainly to a significantly greater number of inflorescences-but with no net change in total fruit mass yield. This strongly suggests that fw2.2 may have a pleiotropic effect on how the plant distributes photosynthate among fruit. In a flower removal experiment to control for differences in inflorescence size and number, fruit size remained significantly different between the nearly isogenic lines. These observations indicate that the primary effect of fw2.2 is in controlling ovary and fruit size, and that other associated phenotypic effects are secondary.

Alleles↗

Epistasis, complex traits, and mapping genes.

Using a three-locus model wherein two loci regulate a third, candidate locus, I examine physiological epistasis from the 'gene's eye view' of the regulated locus. I show that, depending upon genetic background at the regulatory loci, an allele at the candidate locus can be dominant, additive, recessive, neutral, over-dominant, or under-dominant in its effects on fitness. This kind of variation in allelic effect caused by variation in genetic background from population to population, from time to time in the same population, or sample to sample makes finding and mapping the genes underlying a complex phenotype difficult. The rate of evolution of such genes can also be slowed, especially in genetically subdivided metapopulations with migration. Nevertheless, understanding how variation in genetic background causes variation in allelic effects permits the genetic architecture of such complex traits to be dissected into the interacting component genes. While some backgrounds diminish allelic effects and make finding and mapping genes difficult, other backgrounds enhance allelic effects and facilitate gene mapping.

Alleles↗

On the genetic contribution to selected multifactorial diseases with autoimmune characteristics.

The genetics of multifactorial diseases characterized by autoimmune phenomena are elusive so far. Yet, it is clear that the genetic contribution to a given clinically defined autoimmune disease entity is mostly variable and highly complex. On the basis of two basically different model diseases, Wegener's Granulomatosis and multiple sclerosis, approaches are discussed to unravel at least certain genetic predisposition factors. Major difficulties in these analyses arise from (in)exact definition of the clinical phenotype (disease entity), the vast number of potential candidate genes, the small to modest contribution of each genetic variation to disease risk and the combinatorial possibilities.

Autoimmune Diseases↗

Investigation of the prevalence and inheritance of bronchial asthma in San Antonio de los Baños, Cuba.

A survey of bronchial asthma prevalence and inheritance patterns was carried out in the municipality of San Antonio de los Banõs, La Habana, Cuba, employing as a sample 3,295 of the area's inhabitants. These persons, selected by stratified, non-restricted sampling techniques, represented 11.02 per cent of the total population. The asthma prevalence found in this sample, which was considered representative of the local population, was 9.74 percent. No significant variations were noted in male and female prevalence rates. The occurrence of bronchial asthma is strongly influenced by inheritance. Our survey supported this view, and also showed that the age of asthma onset is influenced by whether or not the subject's family has a positive history of allergy or not. However, patients with a positive history on one side of their family had an age of onset that was not significantly different from patients with a positive history on both sides (p less than 0.35). Overall, the results tend to confirm that the inheritance of bronchial asthma is autosomal and does not conform to simple dominant or recessive inheritance patterns. Rather, asthma inheritance appears multifactorial, perhaps involving varying degrees of expression, indicating that more is involved than absence or deficiency of a single enzyme.

Adolescent↗

[Genetics study on photo- and thermo-sensitive genic male sterility of indica rice (O. satival L.)].

The sterility segregation and its genetic patterns of indica P(T)GMS rice were analyzed mainly based on the investigation of bagged seed-set of individuals in reciprocal F2 population from the crosses between P(T)GMS lines of different origin and typical indica conventional varieties of different ecotype under long day-length and high temperature condition by using the software of the maximum likelihood method. The results showed that the sterility of Annong S-1, Hengnong S-1, and W6154S, of which the sterility alteration was mainly induced by temperature fluctuation, was controlled by one major recessive gene. But the sterility of W7415S was controlled by more than two major recessive genes. Apart from the major recessive gene, there was a group of polygenes in controlling of the sterility segregation in F2 population. Moreover, the polygenic variance was different from line to line. It implied that the polygenes of W6154S or W7415S was far more complicated than that of Annong S-1 and Hengnong S-1 according to the maximum likelihood method. All the conventional indica varieties of different ecotypes possessed the major dominant fertility genes. Meanwhile, the genetic background in different ecotype conventional varieties, the essentiality of which lies in the existence of polygenes, was different and influenced the major gene expression deeply. It was also indicated that genetic background of middle-season variety Nanjing 11 was more complicated than that of early-season variety Erjiuqing and late-season variety GER-1 as well. Finally, the differences of drift in critical temperature inducing male sterility of P(T)GMS lines (for short term DCT) and the strategy of breeding practically usable P(T)GMS line with slighter DCT were discussed in the paper.

Crosses, Genetic↗

Toward positional cloning with SNPs.

Efficient methods are available for positional cloning of major genes by linkage and linkage disequilibrium (LD). The application of these methods to complex diseases is more demanding, but advances in sequencing the human genome, SNP discovery, high-throughput genotyping techniques, LD maps, and haplotype annotation are revolutionizing positional cloning of oligogenes for common multifactorial disease.

Alleles↗

[The realm of mitochondrial genetics competence].

The paper discusses the main applications of achievements of mitochondrial genetics: human pathology (mitochondrial diseases, complex disease susceptibility genes) and population genetics (evolution of mankind, demographic history, and migration ways of populations). Awareness of the physiological properties of the well-known nucleotide sequences of mitochondrial DNA is ascertained to be a strategy for studying the functional organization of nuclear genome whose structure is all but completely decoded.

Genetic Predisposition to Disease↗

A unified approach to joint modeling of multiple quantitative and qualitative traits in gene mapping.

Using graph theory, we present a theoretical basis for mapping oligogenes in the joint presence of multiple phenotypic measurements of both quantitative and qualitative types. Various statistical models proposed earlier for several traits of solely single type are special cases of the unified approach given here. Our emphasis is on the generality of the framework, without specifying explicit assumptions about a sampling design. When information about environmental factors potentially affecting the traits is available, it can be incorporated into the genetic model. We adopt the Bayesian inferential machinery due to its firm theoretical basis and its capability of handling uncertain quantities; such as unobserved model parameters, missing marker data, and even different putative genetic models, probabilistically within a single framework. It is shown here that biological hypotheses about single gene affecting simultaneously multiple traits (pleiotropy) can be intuitively imposed as parameter constraints, leading to pleiotropic models for which posterior probabilities can be calculated. Outline of the possible implementation of the Bayesian method is described using the general reversible-jump Markov chain Monte Carlo algorithm. Some future challenges and extensions are also discussed.

Animals↗

Genetic basis of neural tube defects. II. Genes correlated with folate and methionine metabolism.

Effective supplementation with folate, which prevents neural tube defect (NTD) occurrence, and high homocysteine levels in the blood of NTD children's mothers suggest that genes involved in folate and homocysteine metabolism can be involved in NTD aetiology. Genes encoding methylenetetrahydrofolate reductase (MTHFR) or methylenetetrahydrofolate dehydrogenase (MTHFD) belong to the first group. Genes encoding methionine synthase (MTR), its regulator - methionine synthase reductase (MTRR) and also cystathionine synthase (CBS) can be included in the second group. We present a current list of the folate and homocysteine metabolism genes that are known to be involved in NTD and pay special attention to primary and secondary NTD prevention.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

[Mapping genes of complex diseases in genetic isolates of Dagestan].

Original results of the analysis of genetic linkage between some genomic markers and two complex clinical phenotypes, schizophrenia and mental retardation, in pedigrees from Dagestan genetic isolates are described. Interpopulation differences in the epidemiology of the complex phenotypes were studied and in their genetic linkage was demonstrated. These differences are evidently related to the genetic structure of the isolates determined by their genetic history. The MR epidemiological index characterizing the lifetime morbid risk of schizophrenia varies in the Dagestan isolates studied from 0 to 4.95%, which is almost five times higher than the average worldwide population rate, 1%. Comparative genetic mapping permitted determination of the most probable genetic linkages and associations of loci from chromosomal regions 17p11.1-12, 3q13.3, and a locus from 22q with schizophrenia and locus 12q23 with mental retardation. There is evidence that this approach is effective for detailed study of the relationship between the genetic (allele and locus) and clinical heterogeneity of complex diseases, which favors successful identification of the genes determining them. The study of linkage disequilibrium (LD) in genetic isolates of Daghestan populations (which have a common genetic background) may be an effective methodological approach for revealing the numerous contradictory results of mapping of the same genes of complex disease performed by different researchers in different regions of the world.

Chromosome Mapping↗

Type 2 diabetes mellitus--a multifactorial disease.

Type 2 diabetes is a multifactorial disease caused by both oligo- and polygenic genetic factors as well as non-genetic factors that result from a lack of balance between the energy intake and output and other life style related factors. ADA and WHO have recently reclassified diabetes on both clinical stages and aetiological grounds. There is a lot of data related to the genetics of type 2 diabetes. However, many genes and gene products as well as their interactions with the environment at the molecular, cellular, tissue, and the whole organism levels are still unknown. Changes in the frequency of diabetes occurrence in various urban and rural populations and ethnic groups prove the relationship with the transition to the 'western' life style. Understanding of diabetes pathogenesis is essential to the development of new methods of treatment and strategies of effective prevention of this disease.

Aged↗

Osteoporosis: genetic analysis of multifactorial disease.

Osteoporosis is a common disorder with a complex pathophysiology involving both endogenous and environmental factors. Family and twin studies have shown that genetic factors play an essential role in bone mass regulation and that apart from rare instances the heritability of bone mineral density (BMD) and osteoporosis is polygenic. Linkage analysis and association studies with numerous DNA markers (single nucleotide polymorphisms or microsatellites) have analysed several bone-related candidate genes encoding vitamin D, calcium-sensing, calcitonin and estrogen alpha receptors, insulin growth factor I, collagen type I alpha 1 chain and others. Despite this, the definite polymorphic marker has not been found in different populations which reflects the divergent results of association studies with their frequent limitations, and probably the fact that the relevant polymorphism is still awaiting identification. Once the genetic determinants can be defined, the clinical implications would be extensive both in diagnostics and in pharmacogenetics.

Animals↗

[Estimating family correlation of quantitative traits using generalized estimating equation].

OBJECTIVE: To study the method for measuring familial correlations of quantitative trait and analyzing family data set of body height. METHODS: Generalized estimating equation 2 (GEE2) was employed to estimating both regression coefficients and the familial correlation. Analyses was carried out on software MAREG. A example from height pedigrees illustrated the method. RESULTS: GEE2 provided robust estimations of regression coefficients and familial correlations simultaneously. In body height the correlations between parents and offspring (r = 0.459) and between siblings (r = 0.671) were significantly higher than those between two parents (r = 0.184) after adjusting gender, residence and birth age. Of the same types of relative pairs, the correlation between pairs with individuals of the same gender (eg. father-son r = 0.603, mother-daughter r = 0.456, male sibling r = 0.947, female sibling r = 0.681) was higher than those individuals of different gender (eg father-daughter r = 0.431, mother-son r = 0.364, sibling with different gender r = 0.530). CONCLUSION: GEE2 should be considered a standard method for the investigation of familial aggregation due to its flexibility and robustness.

Adult↗

Gender-specific genetic determinants of blood pressure and organ weight: pharmacogenetic approach.

A total genome scan and pharmacogenetic study were designed to search for genetic determinants of blood pressure (BP) as well as heart and kidney weights. Genome scanning was carried out in 266 F(2) intercrosses from Prague hypertensive hypertriglyceridemic rats for phenotypes of organ weights, baseline BP, BP after blockade of the renin-angiotensin system (RAS) by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide (NO) synthase by N(G)-nitro-L-arginine methyl ester. Pharmacogenetic analysis showed that, in males, BP was controlled by two loci on chromosomes 1 and 5 (Chr1, Chr5) through the SNS, and these loci showed a positive contribution for relative kidney weight (KW/BW). On the other hand, baseline BP in females was controlled by two loci on Chr3 and Chr7. The effect of these loci was not mediated by the RAS, SNS or NO system. These loci did not show any effect for KW/BW. Negatively-linked loci for KW/BW and relative heart weight (HW/BW) were identified on Chr2 in both genders. Another negatively-linked locus for KW/BW, located on Chr8 in males, affected BP through the SNS. This locus on Chr8 overlapped with a previously-reported modifier locus for polycystic kidney disease (PKD). In conclusion, this pharmacogenetic study determined two loci for BP and relative organ mass implicating sympathetic overactivity. Concordance of the identified locus for KW/BW and BP through the SNS on Chr8 with the PKD locus revealed the importance of this region for renal complications in various diseases.

Animals↗