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At least 1,675 records · Page 93Linked to original sources
PubMed2001

Two-trait-locus linkage analyses of asthma susceptibility.

A genome-wide search was conducted to identify chromosomal regions likely to harbor genes for asthma susceptibility. One hundred and twelve Caucasian families ascertained through a proband with a diagnosis of asthma by the Collaborative Study on the Genetics of Asthma (CSGA) were used for this search. Genotype data on 323 polymorphic markers were analyzed via parametric and nonparametric linkage analysis in an initial genome scan to identify potential asthma susceptibility region(s). The regions where hold or nonparametric linkage scores were greater than 2.0 were selected for further investigation using two-trait-locus linkage analysis models.

Adult↗
PubMed2001

Using step-wise linear regression to detect "functional" sequence variants: application to simulated data.

Step-wise linear regression was used to detect the "functional" sequence variant in gene 6 responsible for phenotypic variation in traits Q1 and Q2. Prior to analysis, single-nucleotide polymorphisms (SNPs) that were in complete or near complete linkage disequilibrium were binned. In total, we identified 11 separate alleles (or allelic bins). Analyses were performed on all 50 replicates. The "functional" allele variant in gene 6 (at position 5782) accounted for 24% of the variation in Q1 and 11% of the variation in Q2. We detected a significant association between this SNP and Q1 in 90% of the replicates (i.e., in 45 of 50 replicates) and between this SNP and Q2 in 78% of the replicates. Although significant associations were also observed with some nonfunctional SNPs, our results nevertheless suggest that simple step-wise regression may play a useful role in analyzing sequence data. Some additional extensions to this approach are suggested.

Adult↗
PubMed2001

Linkage disequilibrium mapping of complex genetic diseases using multiallelic markers.

Various measures of allelic association are proposed and applied to affection status and markers in the region of major gene 6. The performance of the measures are compared in bias and efficiency to estimate the location of major gene 6. Since the aim is to find disease specific genes, corrections for covariates and environmental factors are made. Furthermore, all the measures allow for more than one allele to be associated with the trait. The location of the disease gene is estimated by fitting a quadratic curve with allelic association as dependent and the position of the marker as independent variable. Confidence intervals are obtained by applying Fieller's theorem. Two of the three proposed measures succeeded in finding the true position of gene 6. Since this is a fine mapping approach, we asked for the answers.

Alleles↗
PubMed2001

Comparison of marker intervals and number of sib pairs used for linkage analysis on simulated nuclear family data.

Using a two-stage global scan design, we analyzed general population replicates 1 and 42 of the Genetic Analysis Workshop (GAW) 12 simulated data set using three methods: revisited Haseman-Elston (HER), maximum likelihood variance estimation (ML), and variance components (VC). Three marker densities, 5-, 10-, and 15-cM intervals, were examined in the first-stage scan. We found that the 10-cM interval appears to be the most cost-effective approach in genotyping without sacrificing power when using a first stage significance level of 0.01. Subsequently, we performed the second-stage scan at 1-cM intervals for those putative positive regions identified in the first-stage scan at a significance level of 0.01. We also compared the power to detect linkage using different numbers of sib pairs for a genome-wide scan at a 10-cM interval and found that power decreases nonlinearly as the number of sib pairs decreases.

Analysis of Variance↗
PubMed2001

Assessing the effect of sampling strategies on the power of linkage analysis to identify pathway-specific loci underlying a complex disease.

Using the simulated general population data sets, we first examined the effect of sampling strategies on the power of identifying linkage by selecting samples with (A) two affected sibs in a nuclear family and (B) one affected sib and one sib with an intermediate trait value in the upper quantiles. Second, we evaluated the improvement in power when analyzing correlated traits simultaneously. Under each selection criteria, 100 replicates of 300 nuclear families were sampled and analyzed with two-point linkage analysis for ten markers (1 cM apart) from each of the candidate regions. Different genes were identified under different sampling strategies. When a gene has a pleitropic effect, it is more powerful to analyze correlated traits simultaneously, either by using a linear combination or the larger value of standardized traits, than to analyze each trait separately.

Chromosome Mapping↗
PubMed2006

A two-step procedure for constructing confidence intervals of trait loci with application to a rheumatoid arthritis dataset.

Preliminary genome screens are usually succeeded by fine mapping analyses focusing on the regions that signal linkage. It is advantageous to reduce the size of the regions where follow-up studies are performed, since this will help better tackle, among other things, the multiplicity adjustment issue associated with them. We describe a two-step approach that uses a confidence set inference procedure as a tool for intermediate mapping (between preliminary genome screening and fine mapping) to further localize disease loci. Apart from the usual Hardy-Weiberg and linkage equilibrium assumptions, the only other assumption of the proposed approach is that each region of interest houses at most one of the disease-contributing loci. Through a simulation study with several two-locus disease models, we demonstrate that our method can isolate the position of trait loci with high accuracy. Application of this two-step procedure to the data from the Arthritis Research Campaign National Repository also led to highly encouraging results. The method not only successfully localized a well-characterized trait contributing locus on chromosome 6, but also placed its position to narrower regions when compared to their LOD support interval counterparts based on the same data.

Arthritis, Rheumatoid↗
PubMed1998

Genetic analysis of dystrophic cardiac calcification in DBA/2 mice.

A DBA/2 x D2B6F1 backcross was produced in order to study the genetic background of pathological soft tissue calcification in the mouse. Calcification was assessed in the myocardium, kidney and tongue. Significant co-segregation was found with the genotype of microsatellite markers on the proximal end of Chromosome 7. This region contains a candidate gene, Hrc, coding for the histidine-rich calcium binding protein in the sarcoplasmatic reticulum. The results support the hypothesis that the gene previously reported to be responsible for DCC (dystrophic cardiac calcification) in C3H mice (1) causes generalized soft tissue calcification in DBA/2 mice.

Animals↗
PubMed1998

A new murine model for mammalian wound repair and regeneration.

Regeneration is generally considered to be a phenomenon restricted to amphibians in which amputated limbs reform and regrow. We have recently noted a strain of mouse, the MRL, which displays a remarkable capacity for cartilagenous wound closure and provides an example of a phenomenon previously considered to be a form of regeneration. Specifically, through-and-through ear punches rapidly attain full closure with normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to scarring, as usually seen in mammals. Histologically, we have demonstrated normal cell growth and microanatomy, including angiogenesis and chondrogenesis, as opposed to control C57BL/6 mice which have ear holes that contract minimally but do not close. Finally, this phenomenon is a genetically definable quantitative trait.

Amphibians↗
PubMed1999

Evolutionary branching under asymmetric competition.

I investigate the evolution of a continuous trait, such as body size or arms level, which affects the outcome of competitive contests such that the contestant with the larger trait value has a higher probability of winning. I show that a polymorphism of distinctly different strategies can evolve in an initially monomorphic population even if mutations have only small phenotypic effect. In a simple Lotka-Volterra-type model of asymmetric competition, I derive the conditions under which two strategies can gradually evolve from a single ancestral strategy; the evolution of higher level polymorphisms is studied by numerical analysis and computer simulations of specific examples. High levels of polymorphism may build up during evolution. The coevolution of strategies in polymorphic populations, however, may also lead to extinction, which decreases the level of polymorphism. I discuss whether the evolution of several haploid strategies from a single initial strategy may correspond to the evolution of several sympatric species in a diploid outbreeding population.

Animals↗
PubMed1986

Ouabain-resistant mutants of Chinese hamster ovary cells are not directly affected in Na+, K+-ATPase.

The nature of biochemical lesions in a number of independent single-step ouabain-resistant (OuaR) mutants of Chinese hamster ovary cells has been examined. The cellular uptake of 86Rb in the mutant cells was found to be resistant to inhibition by ouabain and correlated with the degree of resistance of the mutants to the drug. However, the plasma membrane Na+, K+-ATPase from all five of the OuaR mutants examined showed similar sensitivity to inhibition by ouabain as seen for the enzyme from the parental sensitive cells. These results provide evidence that, contrary to the general assumption, OuaR mutants of Chinese hamster ovary cells, which are widely used for genetic and quantitative mutagenesis studies, are not directly affected in the Na+, K+-ATPase.

Animals↗
PubMed1976

Properties of the cured oncogenic strain 37400 of Agrobacterium tumefaciens.

The properties of the 37400 oncogenic strain of Agrobacterium tumefaciens are described. This strain was derived from the VI lysogenic strain originally isolated by Hamilton from a Zinnia elegans tumour. Strain 37400 has a number of properties which render it suitable for quantitative and genetic studies. It is cured of prophages and can serve as a universal sensitive indicator for a number of phages isolated from various lysogenic strains of Agrobacterium tumefaciens. Its good growth properties in synthetic media and at elevated temperatues enable the isolation of auxotrophic mutants and temperature sensitive phage mutants. Preliminary experiments show that strain 37400 will serve as suitable starting material for conjugation experiments under defined conditions.

Bacteriophages↗
PubMed2002

QTLs for grain carbon isotope discrimination in field-grown barley.

In several crops including cereals, carbon isotope discrimination (Delta) has been associated with drought tolerance in terms of water-use efficiency and yield stability in drought-prone environments. By using a complete genetic map generated from 167 recombinant inbred lines from a cross between Tadmor and Er/Apm, QTLs associated with grain Delta have been detected in barley grown in three Mediterranean field environments, two differing only in water availability. Ten QTLs were identified: one was specific to one environment, two presented interaction with the environment, six presented main effects across three or two environments and one presented both effects. Heading date did not contribute to the environment (E) and G x E effects acting on Delta. Seasonal rainfall and the ratio of rainfall to evapo-transpiration made large contributions to the environmental effect, but their influence on G x E was weaker. Eight QTLs for Delta co-located with QTLs for physiological traits related to plant water status and/or osmotic adjustment, and/or for agronomic traits previously measured on the same population. Some perspectives in terms of characterising drought tolerance are evoked.

Biomarkers↗
PubMed2003

Efficient fine mapping of the naked caryopsis gene ( nud) by HEGS (High Efficiency Genome Scanning)/AFLP in barley.

The hulled or naked caryopsis character of barley ( Hordeum vulgare L.) is an important trait for edibility and to follow its domestication process. A single recessive gene, nud, controls the naked caryopsis character, and is located on the long arm of chromosome 7H. To develop a fine map around the nud locus efficiently, the HEGS (High Efficiency Genome Scanning) electrophoresis system was combined with amplified fragment length polymorphism (AFLP). From bulked segregant analysis of 1,894 primer combinations, 12 AFLP fragments were selected as linked markers. For mapping, an F(2 )population of 151 individuals derived from a cross between Kobinkatagi (naked type) and Triumph (hulled type) was used. Seven AFLP markers were localized near the nud region. A fine map was developed with one-order higher resolution than before, along with the seven anchor markers. Among the seven linked AFLP markers (KT1-7), KT1, KT2 and KT6 were co-dominant, and the former two were detected for their single-nucleotide polymorphisms (SNPs) in the same length of fragments after electrophoresis with the non-denaturing gels of HEGS. The nud locus has co-segregated with KT3 and KT7, and was flanked by KT2 and KT4, at the 0.3-cM proximal and the 1.2-cM distal side, respectively. Four of these AFLP markers were converted into sequence-characterized amplified region (SCAR) markers, one of which was a dominant marker co-segregating with the nud gene.

Chromosome Mapping↗
PubMed2003

Construction of a genetic map for arabica coffee.

We have used AFLPs to construct a genetic linkage map on a pseudo-F(2) population of arabica coffee ( Coffea arabica L.) derived from a cross between the cultivars Mokka hybrid and Catimor. Sixty trees from this population were selected on the basis of plant height distribution to construct a linkage map. A total of 456 dominant markers and eight co-dominant markers were generated from 288 AFLP primer combinations. Of the total number of markers generated, 68% were from cv. Catimor, 30% from cv. Mokka hybrid, and 2% were co-dominant. This distribution suggests that the heterozygosity within the cv. Catimor sub-genomes was twice that within the cv. Mokka hybrid sub-genomes. Linkage groups were constructed using MAPMAKER version 3.0, resulting in 16 major linkage groups containing 4-21 markers, and 15 small linkage groups consisting of 2-3 linked markers each. The total length of the map was 1,802.8 cM, with an average distance of 10.2 cM between adjacent markers. This genetic map will serve as the framework for mapping QTL controlling source-sink traits in the same population.

Coffee↗
PubMed2004

Demonstration of linkage and development of the first low-density genetic map of garlic, based on AFLP markers.

Garlic (Allium sativum L.) is a long-cultivated, clonally propagated diploid plant (2n=2x=16). With routine seed production now underway, we used populations (MP1 and MP2) generated by self-pollination of unrelated plants to generate two low-density genetic maps of garlic, consisting of amplified fragment length polymorphism (AFLP) and gene-specific markers. We did not observe any two plants with identical marker patterns in either population, indicating that they were the result of amphimixis rather than apomixis. This is an important finding, since several Alliums are facultative apomicts. A total of 360 markers segregated in MP1 (12.8 AFLP markers per primer combination) and 321 markers segregated in MP2 (13.9 per primer combination) to indicate a fairly high level of genetic heterozygosity in the garlic nuclear genome. Of these markers, 15.3% in MP1 and 24.3% in MP2 had segregation ratios distorted from the expected 3:1. Interestingly, 94.7% of those distorted segregations fit a 15:1 segregation ratio for duplicated loci, suggesting extensive levels of duplication in the garlic genome and supporting similar observations for onion. The genetic map for the MP1 family with 216 markers spanned 1,166 cM of the garlic genome (5.4 cM average), while 143 markers of MP2 spanned 862 cM (6.0 cM average). Gene-specific markers for alliinase, chitinase, sucrose 1-fructosyltransferase (SST-1), and chalcone synthase (CHS) were mapped, demonstrating the immediate utility of the garlic genetic map. These two garlic families had relatively few segregating AFLP markers in common, which supports their relatively distant relationship based on diversity analysis. Of those markers that were conserved, linkages were also conserved.

Chromosome Mapping↗
PubMed2005

QTL analysis of seed yield components in red clover (Trifolium pratense L.).

Cultivars of red clover (Trifolium pratense L.), an important forage crop in temperate regions, are often characterised by an unsatisfactory level of seed yield, leading to high production costs. This complex trait is influenced by many components and negatively correlated with other important traits, such as forage yield or persistence. Therefore, seed yield has proven to be difficult to improve. Thus, the objectives of this study were to assess association among seed yield components and to provide the basis for identifying molecular markers linked to QTLs for seed yield components to assist breeding for improved red clover cultivars. A total of 42 SSR and 216 AFLP loci were used to construct a molecular linkage map with a total map length of 444.2 cM and an average distance between loci of 1.7 cM. A total of 38 QTLs were identified for eight seed yield components. The traits seed number per plant, seed yield per head, seed number per head, head number per plant and percent seed set were highly correlated with seed yield per plant, and QTLs for several of these traits were often detected in the same genome region. Head number per plant may present a particularly useful character for the improvement of seed yield since it can easily be determined before seed maturity. In addition, two genome regions containing four or five QTLs for different seed yield components, respectively, were identified representing candidate regions for further characterisation of QTLs. This study revealed several key components which may facilitate further improvement of seed yield. The QTLs identified represent an important first step towards marker-assisted breeding in red clover.

Analysis of Variance↗
PubMed2006

Genetic mapping of a major gene affecting onion bulb fructan content.

The non-structural dry matter content of onion bulbs consists principally of fructose, glucose, sucrose and fructans. The objective of this study was to understand the genetic basis for the wide variation observed in the relative amounts of these carbohydrates. Bulb carbohydrate composition was evaluated in progeny from crosses between high dry matter storage onion varieties and sweet, low dry matter varieties. When samples were analysed on a dry weight basis, reducing sugar and fructan content exhibited high negative correlations and bimodal segregation suggestive of the action of a major gene. A polymorphic SSR marker, ACM235, was identified which exhibited strong disequilibrium with bulb fructan content in F(2:3) families from the 'W202A' x 'Texas Grano 438' mapping population evaluated in two environments. This marker was mapped to chromosome 8 in the interspecific population 'Allium cepa x A. roylei'. Mapping in the 'Colossal Grano PVP' x 'Early Longkeeper P12' F2 population showed that a dominant major gene conditioning high-fructan content lay in the same genomic region. QTL analysis of total bulb fructan content in the intraspecific mapping population 'BYG15-23' x 'AC43' using a complete molecular marker map revealed only one significant QTL in the same chromosomal region. This locus, provisionally named Frc, may account for the major phenotypic differences in bulb carbohydrate content between storage and sweet onion varieties.

Breeding↗
PubMed2006

Pi35(t), a new gene conferring partial resistance to leaf blast in the rice cultivar Hokkai 188.

The japonica rice cultivar Hokkai 188 shows a high level of partial resistance to leaf blast. For mapping genes conferring the resistance, a set of 190 F2 progeny/F3 families was developed from the cross between the indica rice cultivar Danghang-Shali, with a low level of partial resistance, and Hokkai 188. Partial resistance to leaf blast in the F3 families was assessed in upland nurseries. From a primary microsatellite (SSR) linkage map and QTL analysis using a subset of 126 F2 progeny/F3 families randomly selected from the above set, one major QTL located on chromosome 1 was detected in the vicinity of SSR marker RM1216. This QTL was responsible for 69.4% of the phenotypic variation, and Hokkai 188 contributed the resistance allele. Segregation analysis in the F3 families for partial resistance to leaf blast was in agreement with the existence of a major gene, and the gene was designated as Pi35(t). Another QTL detected on chromosome 8 was minor, explained 13.4% of the phenotypic variation, and an allele of Danghang-Shali increased the level of resistance in this QTL. Additional SSR markers of the targeted Pi35(t) region were further surveyed in the 190 F2 plants, and Pi35(t) was placed in a 3.5-cM interval flanked by markers RM1216 and RM1003.

Ascomycota↗