A gene-based radiation hybrid map of the pig chromosome 6q32 region associated with a QTL for fat deposition traits.
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Animals↗
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High blood pressure and metabolic disorders are associated in the Lyon hypertensive rat.
OBJECTIVE: A large population of F2 rats, obtained from a cross between male Lyon hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in order to assess the relationship between increased body weight, hyperlipidaemia and high blood pressure which characterize LH rats. METHODS: Mean arterial pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2 rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low-density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids, triglycerides, insulin and glucose were measured. RESULTS: In the F2 cohort it was observed that high MAP was a recessive trait that depends on several genes and was unrelated to body weight. The left ventricular weight, corrected for tibia length, was correlated with MAP. Plasma total and high-density lipoprotein-cholesterol and phospholipids concentrations were lower in the F1 rats than in the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP was related to total, high-density lipoprotein- and low-density lipoprotein-cholesterol. Plasma triglycerides, insulin and the insulin:glucose ratio, which were higher in the LH rats than in the LN rats, were also correlated with MAP in the F2 cohort. Using stepwise multiple regression analysis, MAP remained correlated with plasma total cholesterol, insulin and the insulin:glucose ratio, but not with triglycerides. CONCLUSIONS: Hypertension in LH rats is a recessive trait that is independent of body weight. In addition, the cosegregation of blood pressure with plasma cholesterol and, to a lesser degree, with insulin levels, which was observed in the present study provides the first direct evidence that these phenotypes are associated and are not due simply to genetic drift in the Lyon model.
Animals↗
Resolution of a 16.8-Mb autoimmunity-regulating rat chromosome 4 region into multiple encephalomyelitis quantitative trait loci and evidence for epistasis.
To investigate effects of a 16.8-Mb region on rat chromosome 4q42-43 on encephalomyelitis, we performed a high-resolution mapping using a 10th generation advanced intercross line between the susceptible DA strain and the MHC identical but resistant PVG.1AV1 strain. Clinical signs of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) developed in 29% of 772 F(10) rats. Three regions controlling disease, Eae20, Eae21, and Eae22, were mapped using 15 microsatellite markers spanning 16.8 Mb. Eae20 was a major genetic determinant within the region whereas Eae21 modified disease severity. Eae22 was identified as an epistatic region because it only displayed an effect together with Piebald Virol Glaxo (PVG) alleles on Eae20. Disease down-regulation by PVG alleles in the telomeric part of Eae20 was also demonstrated in DA rats made congenic for a approximately 1.44-Mb chromosomal region from PVG. As the region containing Eae20-Eae22 also regulates arthritis, together with the fact that the syntenic mouse 6F(2)-F(3) region regulates experimental lupus and diabetes, and the syntenic human 12p13.31-13.2 region regulates multiple sclerosis and rheumatoid arthritis, the present data point to genes that control several inflammatory diseases. The pairscan analyses of interaction, which here identified Eae22, are novel in the encephalomyelitis field and of importance in the design of further studies of this region in other diseases and species. The limited number of genes identified in Eae20, Eae21, and Eae22 enables focused examination of their relevance in mechanistic animal studies and screening of their association to human diseases.
Animals↗
An informative linkage map of soybean reveals QTLs for flowering time, leaflet morphology and regions of segregation distortion.
A genetic linkage map covering a large region of the genome with informative markers is essential for plant genome analysis, including identification of quantitative trait loci (QTLs), map-based cloning, and construction of a physical map. We constructed a soybean genetic linkage map using 190 F2 plants derived from a single cross between the soybean varieties Misuzudaizu and Moshidou Gong 503, based on restriction-fragment-length polymorphisms (RFLPs) and simple-sequence-repeat polymorphisms (SSRPs). This linkage map has 503 markers, including 189 RFLP markers derived from expressed sequence tag (EST) clones, and consists of 20 major linkage groups that may correspond to the 20 pairs of soybean chromosomes, covering 2908.7 cM of the soybean genome in the Kosambi function. Using this linkage map, we identified 4 QTLs--FT1, FT2, FT3, and FT4--for flowering time, the QTLs for the 5 largest principal components determining leaflet shape, 6 QTLs for single leaflet area, and 18 regions of segregation distortion. All 503 analyzed markers identified were located on the map, and almost all phenotypic variations in flowering time were explained by the detected QTLs. These results indicate that this map covers a large region of the soybean genome.
Chromosome Mapping↗
Inheritance of partial resistance against Colletotrichum lindemuthianum in Phaseolus vulgaris and co-localization of quantitative trait loci with genes involved in specific resistance.
Anthracnose, one of the most important diseases of common bean (Phaseolus vulgaris), is caused by the fungus Colletotrichum lindemuthianum. A "candidate gene" approach was used to map anthracnose resistance quantitative trait loci (QTL). Candidate genes included genes for both pathogen recognition (resistance genes and resistance gene analogs [RGAs]) and general plant defense (defense response genes). Two strains of C. lindemuthianum, identified in a world collection of 177 strains, displayed a reproducible and differential aggressiveness toward BAT93 and JaloEEP558, two parental lines of P. vulgaris representing the two major gene pools of this crop. A reliable test was developed to score partial resistance in aerial organs of the plant (stem, leaf, petiole) under controlled growth chamber conditions. BAT93 was more resistant than JaloEEP558 regardless of the organ or strain tested. With a recombinant inbred line (RIL) population derived from a cross between these two parental lines, 10 QTL were located on a genetic map harboring 143 markers, including known defense response genes, anthracnose-specific resistance genes, and RGAs. Eight of the QTL displayed isolate specificity. Two were co-localized with known defense genes (phenylalanine ammonia-lyase and hydroxyproline-rich glycoprotein) and three with anthracnose-specific resistance genes and/or RGAs. Interestingly, two QTL, with different allelic contribution, mapped on linkage group B4 in a 5.0 cM interval containing Andean and Mesoamerican specific resistance genes against C. lindemuthianum and 11 polymorphic fragments revealed with a RGA probe. The possible relationship between genes underlying specific and partial resistance is discussed.
Chromosome Mapping↗
Two blood pressure/cardiac mass quantitative trait loci on chromosome 3 in Dahl rats.
Interval mapping was used to identify putative quantitative trait loci (QTL) for blood pressure and cardiac mass on Chromosome (Chr) 3 in F1(S x R) x S population of 150 rats raised on an 8% NaCl diet. Two genetic markers 95.7 cM apart, D3Wox3 and D3Mco5 (tightly linked to Edn3), showed "suggestive" linkage to blood pressure (LOD = 2.0 and 1.8 respectively). In addition, D3Wox3 showed "suggestive" linkage to heart weight (LOD = 2.5), and D3Mco5 showed "suggestive" linkage to body weight-adjusted heart weight (LOD = 2.1). Congenic rats (designated S.R-Edn3) were constructed by introgressing the R-rat Edn3 allele (and flanking loci) into the S strain. On a 2% NaCl diet, S.R-Edn3 rats had lower blood pressure (21.4 mm Hg, P = 0. 0005) and heart weight (59 mg, P = 0.0038) compared with S rats, confirming the existence of a blood pressure QTL on Chr 3 near Edn3 even though QTL linkage analysis of blood pressure did not achieve stringent statistical criteria for significance. The results of the congenic experiment and the large distance between the two putative QTL suggest the presence of at least two independent blood pressure/cardiac mass QTL detectable on Chr 3 in the Dahl rat model of genetic hypertension.
Analysis of Variance↗
A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae).
In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The genus includes sexual diploid as well as apomictic polyploid, mostly triploid, plants. Apomictic Taraxacum is diplosporous, parthenogenetic, and has autonomous endosperm formation. Previous studies have indicated that these three apomixis elements are controlled by more than one locus in Taraxacum and that diplospory inherits as a dominant, monogenic trait ( Ddd; DIP). A bulked segregant analysis provided 34 AFLP markers that were linked to DIP and were, together with two microsatellite markers, used for mapping the trait. The map length was 18.6 cM and markers were found on both sides of DIP, corresponding to 5.9 and 12.7 cM, respectively. None of the markers completely co-segregated with DIP. Eight markers were selected for PCR-based marker development, of which two were successfully converted. In contrast to all other mapping studies of apomeiosis to date, our results showed no evidence for suppression of recombination around the DIP locus in Taraxacum. No obvious evidence for sequence divergence between the DIP and non- DIP homologous loci was found, and no hemizygosity at the DIP locus was detected. These results may indicate that apomixis is relatively recent in Taraxacum.
Chromosome Mapping↗
[Detection of quantitative trait loci for growth in large white x Meishan intercross].
The development of molecular biology techniques and the application of these techniques to farm animals have progressed rapidly and have opened new vistas for investigators wishing to identify genes that control quantitative traits. Now that a comprehensive map has been developed for the porcine genome, genomic scans to detect quantitative trait loci (QTL) can begin. In order to locate the genetic regions in the swine genome that are responsible for economically important traits, a resource population was developed by intercross with three Large White and seven Meishan pigs. In subsequent generations, 66 F2 offsprings in 2000 were recorded for four growth traits including birth weight (BWT), body weight at 60 day (WT60), average daily gain from birth to 60 day (ADG1) and average daily gain from 60 day to the end of test (ADG2), and genotyped for 48 microsatellite markers spanning six chromosomes. Association analyses were performed using interval mapping by regression under an outbred line-cross model on chromosomes 1, 2, 3, 4, 6 and 7. The F threshold values were determined by permutation. A total of 12 QTL were detected at suggestive level for the four traits evaluated in this study. Of the 12 suggestive QTL, 3 and 1 QTL were significant at the chromosome-wise and genome-wise levels. There was a QTL for ADG2 at genome-wide level on chromosome 4 explained additive variance 2.19%. A chromosome-wide QTL affecting ADG1 and WT60 were detected on chromosomes 2 and 1 explained additive variance 0.01% and 26.01%, respectively.
Animals↗
A molecular marker based linkage map of Vitis.
Genetic linkage maps of Vitis (2n = 38) have been constructed from a single interspecific hybrid grape population (60 seedlings) of 'Cayuga White' X 'Aurore'. The maps were primarily based on 422 RAPD markers but also included 16 RFLP and isozyme markers. These maps had an average distance of 6.1 cM between markers and were developed using a double-pseudotestcross strategy. The 'Cayuga White' map had 214 markers covering 1196 cM and that of 'Aurore' spanned over 1477 cM with 225 markers. The 'Cayuga White' map consisted of 20 linkage groups, whereas 22 linkage groups comprised the 'Aurore' map. The number of groups reduced to 19, as in some instances two or more groups from one parent showed homology with a single group from the other parent on the basis of markers heterozygous in both parents. Each linkage group ranged in size from 14 to 135 cM in 'Aurore' and from 14 to 124 cM in 'Cayuga White'. These maps provide enough coverage of the genome to allow quantitative trait locus analysis and map-based gene cloning.
Base Sequence↗
Segregation and linkage analysis of a quantitative versus a qualitative trait in large pedigrees.
Goals of this analysis were to map loci contributing to variation in the quantitative trait, Q1, using the lod-score method on data set 1, and to explore the difference in power to map genes when considering the discrete vs. quantitative phenotype. Segregation analyses, after covariate adjustment, correctly suggested two contributing loci. The major gene on chromosome 5 was successfully mapped, but the major gene on chromosome 8 was not. Comparison of linkage analyses for the qualitative and quantitative traits confirmed that the quantitative trait is more informative, suggesting that localizing disease genes with a qualitative trait would be more difficult in these pedigrees.
Chromosome Mapping↗
Physical mapping of genes in the porcine ovarian transcriptome.
Reproductive efficiency and associated traits are of major economic importance to the swine industry and have been more difficult to improve genetically than other production traits. Integration of phenotypical data with gene mapping and expression studies provides a powerful approach for dissection of the genetic basis regulating complex traits. We developed a total of 101 polymerase chain reaction-based markers, representing 91 unique genes, for expressed sequence tags previously reported to be putatively differentially expressed in the porcine ovarian transcriptome of a swine line selected on an index of high ovulation rate and embryonic survival. These were subsequently used in physical mapping experiments with a porcine radiation hybrid and somatic cell hybrid panels. Our results increased the information content of the porcine physical map useful for comparative mapping by c. 10%. Moreover, the mapped genes are likely to be biologically relevant to the molecular mechanisms that control ovulation rate in the pig. A total of 12 differentially expressed genes were mapped to regions previously reported to contain quantitative trait loci affecting swine ovulation rate.
Animals↗
A recoding scheme for X-linked and pseudoautosomal loci to be used with computer programs for autosomal LOD-score analysis.
We present a recoding scheme that allows for a parametric multipoint X-chromosomal linkage analysis of dichotomous traits in the context of a computer program for autosomes that can use trait models with imprinting. Furthermore, with this scheme, it is possible to perform a joint multipoint analysis of X-linked and pseudoautosomal loci. It is required that (1) the marker genotypes of all female nonfounders are available and that (2) there are no male nonfounders who have daughters in the pedigree. The second requirement does not apply if the trait locus is pseudoautosomal. The X-linked marker loci are recorded by adding a dummy allele to the males' hemizygous genotypes. For modelling an X-linked trait locus, five different liability classes are defined, in conjunction with a paternal imprinting model for male nonfounders. The formulation aims at the mapping of a diallelic trait locus relative to an arbitrary number of codominant markers with known genetic distances, in cases where a program for a genuine X-chromosomal analysis is not available.
Chromosome Mapping↗
A comprehensive mouse IBD database for the efficient localization of quantitative trait loci.
Traditional fine-mapping approaches in mouse genetics that go from a linkage region to a candidate gene are very costly and time consuming. Shared ancestry regions, along with the combination of genetics and genomics approaches, provide a powerful tool to shorten the time and effort required to identify a causative gene. In this article we present a novel methodology that predicts IBD (identical by descent) regions between pairs of inbred strains using single nucleotide polymorphism (SNP) maps. We have validated this approach by comparing the IBD regions, estimated using different algorithms, to the results derived using the sequence information in the strains present in the Celera Mouse Database. We showed that based on the current publicly available SNP genotypes, large IBD regions (>1 Mb) can be identified successfully. By assembling a list of 21,514 SNPs in 61 common inbred strains, we inferred IBD regions between all pairs of strains and confirmed, for the first time, that existing quantitative trait genes (QTG) and susceptibility genes all lie outside of IBD regions. We also illustrated how knowledge of IBD structures can be applied to strain selection for future crosses. We have made our results available for data mining and download through a public website ( http://www.mouseibd.florida.scripps.edu ).
Algorithms↗
Gene actions of QTLs affecting several agronomic traits resolved in a recombinant inbred rice population and two testcross populations.
To understand the types of gene action controlling seven quantitative traits in rice, QTL mapping was performed to dissect the main effect (M-QTLs) and digenic epistatic (E-QTLs) QTLs responsible for the trait performance of 254 recombinant inbred lines (RILs) of "Lemont/Teqing", and two testcross (TC) F(1) populations derived from these RILs. The correlation analyses reveal a general pattern, i.e. trait heritability in the RILs was negatively correlated to trait heterosis in the TC hybrids. A large number of M-QTLs and E-QTLs affecting seven traits, including heading date (HD), plant height (PH), flag leaf length (FLL), flag leaf width (FLW), panicle length (PL), spikelet number per panicle (SN) and spikelet fertility (SF), were identified and could be classified into two predominant groups, additive QTLs detected primarily in the RILs, and overdominant QTLs identified exclusively in the TC populations. There is little overlap between QTLs identified in the RILs and in the TC populations. This result implied that additive gene action is largely independent from non-additive gene action in the genetic control of quantitative traits of rice. The detected E-QTLs collectively explained a much greater portion of the total phenotypic variation than the M-QTLs, supporting prior findings that epistasis has played an important role in the genetic control of quantitative traits in rice. The implications of these results to the development of inbred and hybrid cultivars were discussed.
Crosses, Genetic↗
Labile evolution of display traits in bowerbirds indicates reduced effects of phylogenetic constraint.
Bowerbirds (Ptilonorhynchidae) have among the most exaggerated sets of display traits known, including bowers, decorated display courts and bright plumage, that differ greatly in form and degree of elaboration among species. Mapping bower and plumage traits on an independently derived phylogeny constructed from mitochondrial cytochrome b sequences revealed large differences in display traits between closely related species and convergences in both morphological and behavioural traits. Plumage characters showed no effect of phylogenetic inertia, although bowers exhibited some constraint at the more fundamental level of design, but above which they appeared free of constraint. Bowers and plumage characters, therefore, are poor indicators of phylogenetic relationship in this group. Testing Gilliard's (1969) transferral hypothesis indicated some support for the idea that the focus of display has shifted from bird to bower in avenue-building species, but not in maypole-builders or in bowerbirds as a whole.
Animals↗
Toward an integrated linkage map of common bean. III. Mapping genetic factors controlling host-bacteria interactions.
Restriction fragment length polymorphism (RFLP)-based genetic linkage maps allow us to dissect the genetic control of quantitative traits (QT) by locating individual quantitative trait loci (QTLs) on the linkage map and determining their type of gene action and the magnitude of their contribution to the phenotype of the QT. We have performed such an analysis for two traits in common bean, involving interactions between the plant host and bacteria, namely Rhizobium nodule number (NN) and resistance to common bacterial blight (CBB) caused by Xanthomonas campestris pv. phaseoli. Analyses were conducted in the progeny of a cross between BAT93 (fewer nodules; moderately resistant to CBB) and Jalo EEP558 (more nodules; susceptible to CBB). An RFLP-based linkage map for common bean based on 152 markers had previously been derived in the F2 of this cross. Seventy F2-derived F3 families were inoculated in separate greenhouse experiments with Rhizobium tropici strain UMR1899 or X. c. pv. phaseoli isolate isolate W18. Regression and interval mapping analyses were used to identify genomic regions involved in the genetic control of these traits. These two methods identified the same genomic regions for each trait, with a few exceptions. For each trait, at least four putative QTLs were identified, which accounted for approximately 50% and 75% of the phenotypic variation in NN and CBB resistance, respectively. A chromosome region on linkage group D7 carried factor(s) influencing both traits. In all other cases, the putative QTLs affecting NN and CBB were located in different linkage groups or in the same linkage group, but far apart (more than 50 cM). Both BAT93 and Jalo EEP558 contributed alleles associated with higher NN, whereas CBB resistance was always associated with BAT93 alleles. Further investigations are needed to determine whether the QTLs for NN and CBB on linkage group D7 represent linked genes or the same gene with pleiotropic effects. Identification of the QTLs raises the possibility of initiating map-based cloning and marker-assisted selection for these traits.
Alleles↗
A high-resolution comparative radiation hybrid map of equine chromosome 4q12-q22.
In this study, we present a comprehensive 5000-rad radiation hybrid map of a 40-cM region on equine chromosome 4 (ECA4) that contains quantitative trait loci for equine osteochondrosis. We mapped 29 gene-associated sequence tagged site markers using primers designed from equine expressed sequence tags or BAC clones in the ECA4q12-q22 region. Three blocks of conserved synteny, showing two chromosomal breakpoints, were identified in the segment of ECA4q12-q22. Markers from other segments of HSA7q mapped to ECA13p and ECA4p, and a region of HSA7p was homologous to ECA13p. Therefore, we have improved the resolution of the human-equine comparative map, which allows the identification of candidate genes underlying traits of interest.
Animals↗
Two NOTCH4 polymorphisms and their relation to schizophrenia susceptibility and different personality traits.
BACKGROUND: Recently, linkage disequilibrium mapping of the major histocompatibility complex region on the short arm of human chromosome 6 suggested that the NOTCH4 locus is highly associated with schizophrenia. OBJECTIVES AND METHODS: We analysed two polymorphisms in this gene in Swedish schizophrenic patients ( =74) and control subjects ( =135). The NOTCH4 variants were also analysed in schizophrenic patients with regard to subdiagnosis, age at first hospitalization, abuse/dependence of alcohol, solvents, or drugs, previous suicide attempts, extrapyramidal symptoms, treatment with anticholinergic drugs, and response to anti-psychotic drug treatment. Control subjects were scrutinized with regard to personality, another partially heritable trait suggested being of importance in schizophrenia. In addition, two intermediate endophenotypes suggested being of importance in schizophrenia, dopamine D(2) receptor density in striatum and monoamine metabolites in cerebrospinal fluid, respectively, were investigated with regard to the two NOTCH4 variants. RESULTS: There was no significant association between the patients and the controls for the two investigated polymorphisms neither for the parameters analysed in the schizophrenia material. The NOTCH4 SNP2 variant, an A-->G substitution, was associated with the Karolinska Scales of Personality Irritability scale. The NOTCH4 (CTG)(n) variant was associated with the revised NEO personality inventory Extraversion and Activity (E4) scales. However, after correction for multiple testing, no difference remained significant. The results for the endophenotypes and the polymorphisms were non-significant. CONCLUSIONS: The present study does not support that the investigated NOTCH4 variants have a major influence on susceptibility to schizophrenia or related neurobiological traits.
Biogenic Monoamines↗