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Mapping of the QTL (quantitative trait locus) conferring partial resistance to leaf blast in rice cultivar Chubu 32.

The rice cultivar Chubu 32 possesses a high level of partial resistance to leaf blast. The number and chromosomal location of genes conferring this resistance were detected by restriction fragment length polymorphism (RFLP) linkage mapping and quantitative trait locus (QTL) analysis. For the mapping, 149 F(3) lines derived from the cross between rice cultivar Norin 29, with a low level of partial resistance, and Chubu 32 were used, and their partial resistance to leaf blast was assessed in upland nurseries. A linkage map covering six chromosomes and consisting of 36 RFLP markers was constructed. In the map, only one significant QTL (LOD>2.0) for partial resistance was detected on chromosome 11. This QTL explained 45.6% of the phenotypic variation. The segregation ratio of the F3 lines was 3:1 for partial resistance to susceptibility. These results suggest that the partial resistance in Chubu 32 is controlled by a major gene.

Journal Article↗

Molecular dissection of developmental behavior of plant height in rice (Oryza sativa L.).

A doubled haploid population of 123 lines from IR64/Azucena was used to dissect the developmental behavior and genotype by environment interaction for plant height by conditional and unconditional quantitative trait loci (QTL) mapping methods in rice. It was shown that the number of QTL detected was different at various measuring stages. Some QTL could be detected at all stages and some only at one or several stages. More QTL could be found on the basis of time-dependent measures of different stages. By conditional QTL mapping of time-dependent measures, it is possible to reveal dynamic gene expression for quantitative traits. Mapping QTL for genetic main effects and GE interaction effects could help us in understanding the nature of QTL x environment interaction for the development of quantitative traits.

Adaptation, Physiological↗

Genetic association mapping and genome organization of maize.

Association mapping, a high-resolution method for mapping quantitative trait loci based on linkage disequilibrium, holds great promise for the dissection of complex genetic traits. The recent assembly and characterization of maize association mapping panels, development of improved statistical methods, and successful association of candidate genes have begun to realize the power of candidate-gene association mapping. Although the complexity of the maize genome poses several significant challenges to the application of association mapping, the ongoing genome sequencing project will ultimately allow for a thorough genome-wide examination of nucleotide polymorphism-trait association.

Chromosome Mapping↗

An application of Bayesian QTL mapping to early development in double haploid lines of rainbow trout including environmental effects.

A Bayesian model and variable dimensional parameter estimation based on Markov chain Monte Carlo was applied to map quantitative trait loci (QTLs) in a doubled haploid mapping population of rainbow trout. To increase power, the analysis was performed using the multiple-QTL model, which simultaneously accounted for all the environmental and genetic main effects that influence the expression of early development life history traits. By doing so we obtained the posterior estimated effects for the environmental factors as well as the number, positions, and the effects for the QTLs. The analyses revealed QTLs for time at hatching, embryonic length and weight at swim-up stage. The posterior expectation of the number of QTLs in different linkage groups shows that at least four QTLs are needed to explain the observed differences in early development between the clonal lines. The Bayesian method effectively combined all the information available to accurately position these QTLs in the rainbow trout genome.

Animals↗

Mapping of mouse obesity genes: A generic approach to a complex trait.

Identification of genes underlying any complex trait such as obesity is an important and difficult problem in genetics. Traditional candidate gene approaches cannot be relied on to identify all of the genes influencing a complex trait, and positional cloning is very laborious. With the advent of new tools and methods, however, comprehensive approaches to the identification of any genes underlying complex traits are now available. Quantitative trait locus (QTL) mapping is a general technique to map Mendelian factors influencing complex traits. The QTL approach involves the crossing of two strains that differ in the trait of interest to produce F2 or back-cross progeny, individually phenotyping and genotyping each progeny, and statistically associating the typed markers and the phenotype. QTL mapping has been used in the last 4 years to map genes for a wide variety of traits, including body weight and growth, obesity, atherosclerosis and susceptibility to cancer in the mouse, and hypertension, hyperactivity and arthritis in the rat. QTL mapping has also been used to map genes in pigs, poultry, cows, fish and plants. Once a trait has been located in a chromosomal subregion, identifying the underlying gene remains a significant problem. A monogenic model must be developed, isolating one gene influencing a trait from other genes affecting the same phenotype. Then the positional candidate strategy, which relies on a combination of mapping to a chromosomal subregion followed by a survey of the interval to see if attractive candidates reside there, becomes practical.

Animals↗

Fine-mapping milk production quantitative trait loci on BTA6: analysis of the bovine osteopontin gene.

Bovine chromosome six (BTA6) harbors up to six quantitative trait loci (QTL) influencing the milk production of dairy cattle. In stark contrast to human, there is long-range linkage disequilibrium in dairy cattle, which has previously made it difficult to identify the mutations underlying these QTL. Using 38 microsatellite markers in a pedigree of 3,147 Holstein bulls, we fine mapped regions of BTA6 that had previously been shown to harbor QTL. Next, we sequenced a 12.3-kb region harboring Osteopontin, a positional candidate for the statistically most significant of the identified QTL. Nine mutations were identified, and only genotypes for the OPN3907 indel were concordant with the QTL genotypes of eight bulls that were established by segregation analysis. Four of these mutations were genotyped, and a joint linkage/linkage disequilibrium mapping analysis was used to demonstrate the existence of only two functionally distinct clusters of haplotypes within the QTL region, which were uniquely defined by OPN3907 alleles. We estimate a probability of 0.40 that no other mutation within this region is concordant with the QTL genotypes of these eight bulls. Finally, we demonstrate that the motif harboring OPN3907, which is upstream of the promoter and within a region known to harbor tissue-specific osteopontin regulatory elements, is moderately conserved among mammals. The motif was not retrieved from database queries and may be a novel regulatory element.

Alleles↗

A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor.

The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of the Trp64Arg variant in human obesity remains controversial. We performed a quantitative linkage analysis of the ADRB3 and obesity, using 12 markers (including the intragenic Trp64Arg polymorphism) spanning a 57-cM region of chromosome 8. The study population consisted of 470 individuals from 10 large multigenerational families of Mexican-American ancestry residing in San Antonio, TX. In two-point analysis, logarithm of odds (LOD) scores >1.0 were observed for six markers surrounding ADRB3 in a 33-cM region spanned by markers D8S1477 and D8S1136. The multipoint LOD score was 3.21, occurring between markers D8S1121 and ADRB3, approximately 2-3 cM from ADRB3. Adjusting for the presence of the Arg64 allele or excluding from the analysis the 11 individuals homozygous for the Arg64 allele did not reduce the evidence for linkage. A genome scan was conducted at 10 cM map density to detect other loci influencing variation in BMI. Multipoint LOD scores >1.0 were observed in four other regions, including two on chromosome 17, one on chromosome 6q, and one on chromosome 2p. These data suggest that the ADRB3 should continue to be regarded as a strong candidate gene for obesity even though evidence for an effect of the Trp64Arg polymorphism could not be established. It is also possible that a gene closely linked to ADRB3 may influence susceptibility to obesity.

Adult↗

Quantitative trait loci affecting fertility and calving traits in Swedish dairy cattle.

Impaired fertility is the main reason for involuntary culling of dairy cows in Sweden. The objective of this study was to map quantitative trait loci (QTL) influencing fertility and calving traits in the Swedish dairy cattle population. The traits analyzed were number of inseminations, 56-d nonreturn rate, interval from calving to first insemination, fertility treatments, heat intensity score, stillbirth, and calving performance. A genome scan covering 20 bovine chromosomes was performed using 145 microsatellite markers. The mapping population consisted of 10 sires and their 417 sons in a granddaughter design. Nine of the sires were of the Swedish Red Breed, and one was a Swedish Holstein. Least squares regression was used to map loci affecting the analyzed traits, and permutation tests were used to set significance thresholds. Cofactors were used in the analyses of individual chromosomes to adjust for QTL found on other chromosomes. The use of cofactors increased both the number of QTL found and the significance level. In the initial analysis, we found 13 suggestive QTL that were mapped to chromosomes 6, 7, 9, 11, 13, 15, 20, and 29. When cofactors were included, 30 QTL were detected on chromosomes 1, 3, 4, 18, 19, 22, and 25, in addition to the 8 previously mentioned chromosomes. Some of the results from the cofactor analysis may be false positives and require further validation. In conclusion, we were able to map several QTL affecting fertility and calving traits in Swedish dairy cattle.

Animals↗

Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains.

Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F(2) population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F(2) population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F(2) results, three QTLs emerged as significant (P <.00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P <.0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males.

Animals↗

Taking stock of complex trait genetics in mice.

The mapping of complex trait loci in mice has recently become very popular thanks to dense genetic maps, better approaches to linkage analysis and the continued value of the mouse as a key model organism for human disease. Nevertheless, the ultimate goal remains very difficult to identify genes that underlie complex traits and to understand their function at a molecular level. In assessing the prospects of current efforts, it helps to review the findings of earlier studies of complex traits and, despite all the technology, to be reminded of the inherent benefits and limitations at the source of genetic variation: the laboratory mouse. With the right perspective it should be possible for geneticists analysing complex traits to take full advantage of the resources that the genome project will provide.

Animals↗

Statistical methods for linkage analysis of complex traits from high-resolution maps of identity by descent.

A multilocus model for complex traits is described that generalizes the additive and multiplicative models and hence allows simultaneously for both heterogeneity and gene interaction (epistasis). Statistical methods of linkage analysis are discussed under the assumption that identity by descent data from a dense set of polymorphic markers are available. Three methods, single locus search, simultaneous search and conditional search, are described and compared.

Chromosome Mapping↗

Molecular mapping of a quantitative trait locus for aluminum tolerance in wheat cultivar Atlas 66.

Genetic improvement of aluminum (Al) tolerance is one of the cost-effective solutions to improve wheat (Triticum aestivum) productivity in acidic soils. The objectives of the present study were to identify quantitative trait loci (QTL) for Al-tolerance and associated PCR-based markers for marker-assisted breeding utilizing cultivar Atlas 66. A population of recombinant inbred lines (RILs) from the cross Atlas 66/Century was screened for Al-tolerance by measuring root-growth rate during Al treatment in hydroponics and root response to hematoxylin stain of Al treatment. After 797 pairs of SSR primers were screened for polymorphisms between the parents, 131 pairs were selected for bulk segregant analysis (BSA). A QTL analysis based on SSR markers revealed one QTL on the distal region of chromosome arm 4DL where a malate transporter gene was mapped. This major QTL accounted for nearly 50% of the phenotypic variation for Al-tolerance. The SSR markers Xgdm125 and Xwmc331 were the flanking markers for the QTL and have the potential to be used for high-throughput, marker-assisted selection in wheat-breeding programs.

Aluminum↗

Mapping of provisional quantitative trait loci influencing temporal variation in locomotor activity in the LS x SS recombinant inbred strains.

The finding that stress-induced locomotor activity exhibited a significant strain x time interaction in the LS x SS RI strains prompted examination of QTL influencing this behavior as a function of time. The degree of genetic determination for locomotor activity was 0.26 for the first 5 min and decreased to 0.16 for the last 5 min of a 30-min test but the number of genetic factors stayed relatively constant (three or four) across time. A QTL point analysis revealed a total of 15 QTL, 5-8 per 5-min time block. Few of the QTL were detected across all time points and different combinations of QTL were evident for each time period. Five of the QTL were in common with those reported by other investigators for similar behaviors. The results suggest that locomotor behavior is under a greater degree of genetic control during the initial part of the test but environmental factors become increasingly important as the test progresses. Furthermore, different genetic factors appear to be mediating genetic variation in locomotor behavior at any given time point.

Analysis of Variance↗

A first-generation microsatellite-based integrated genetic and cytogenetic map for the European rabbit (Oryctolagus cuniculus) and localization of angora and albino.

Although the European rabbit (Oryctolagus cuniculus) is used both in agronomics and in research, genomic resources for this species are still limited and no microsatellite-based genetic map has been reported. Our aim was to construct a rabbit genetic map with cytogenetically mapped microsatellites so as to build an integrated genetic and cytogenetic map. A reference population of 187 rabbits comprising eight three-generation families with 10-25 offspring per family was produced. One hundred and ninety-four of 305 previously identified microsatellites were included in this study. Of these, 158 were polymorphic with two to seven alleles. The map reported here comprises 111 markers, including 104 INRA microsatellites, five microsatellites from another source and two phenotypic markers (angora and albino). Ninety markers were integrated into 20 linkage groups. The remaining 21 microsatellites mapped to separate linkage groups, 19 with a precise cytogenetic position and two with only a chromosomal assignment. The genetic map spans 2766.6 cM and covers 20 rabbit chromosomes, excluding chromosomes 20, 21 and X. The density of this map is limited, but we used it to verify the location of angora and albino on chromosomes 15q and 1q, respectively, in agreement with previously published data. This first generation genetic/cytogenetic map will help gene identification and quantitative trait loci mapping projects in rabbit.

Alleles↗

Mapping of putative quantitative trait loci controlling the total oligosaccharide and sucrose content of Glycine max seeds.

Although oligosaccharides and sucrose are very important nutritional components of soybean seeds, little information is available about inheritance of oligosaccharide and sucrose content. The objective of this study was to identify quantitative trait loci (QTLs) that determine the oligosaccharide and sucrose content of soybean. The 117 F(2:10) recombinant inbred lines developed from a cross of "Keunolkong" and "Shinpaldalkong" were used. Narrow-sense heritability estimates, on a plot mean basis, of oligosaccharide and sucrose content were 79.07 and 74.84%, respectively. Four QTLs for oligosaccharide content were located on linkage groups (LG) C2, H, J, and L. Sucrose content was related with two QTLs located on LG H and J. Total oligosaccharide and sucrose content have two common QTLs on LG H and J.

Chromosome Mapping↗

Chromosomal mapping of a quantitative trait locus for the development of albuminuria in diabetic KK/Ta mice.

BACKGROUND: The KK/Ta mouse strain serves as a suitable polygenic model for human type 2 diabetes. We previously reported a genome-wide linkage analysis of KK/Ta alleles contributing to type 2 diabetes and related phenotypes such as fasting hyperglycaemia, glucose intolerance, hyperinsulinaemia, obesity and dyslipidaemia. METHODS: Since KK/Ta mice spontaneously develop renal lesions closely resembling those in human diabetic nephropathy, we investigated the susceptibility loci using the KK/Ta x (BALB/c x KK/Ta) F1 backcross progeny in the present study. RESULTS: A genome-wide analysis of susceptibility loci for albuminuria with microsatellite-based chromosomal maps showed a contributing KK/Ta locus, provisionally designated UA-1, with a significant linkage with the interval on chromosome 2 at 83.0 cM close to the microsatellite marker D2Mit311 with a maximum LOD of 3.5 (chi(2) = 13.2, P = 0.0003). UA-1 was different from the susceptibility loci contributing to type 2 diabetes, which we earlier identified. The mode of inheritance differed from that of hypertension. The progeny homozygous for UA-1 showed significantly higher urinary albumin levels. CONCLUSIONS: Although there were no significant correlations between urinary albumin levels and other diabetic phenotypes, the group of progeny homozygous for both UA-1 and alleles for fasting hyperglycaemia showed the highest urinary albumin levels. Thus, UA-1 appears to increase the risk of diabetic nephropathy, particularly in individuals susceptible to fasting hyperglycaemia, in a gene dosage-dependent manner. There are potentially important candidate genes that may be relevant to diabetic nephropathy.

Albuminuria↗

Admixture mapping as a gene discovery approach for complex human traits and diseases.

Admixture mapping (AM) is a special form of conventional meiotic or recombination mapping for disease gene discovery in humans that exploits naturally occurring genetic and phenotypic differences existing in populations between which recent gene flow has occurred. Essentially, mates from two different "parental" populations with different allelic and disease-predisposing mutation profiles will produce "admixed" offspring whose genomes will be mixtures of the genomes associated with the parental populations. Strong linkage disequilibrium (LD) will exist for several generations between neighboring loci of admixed individuals and can be exploited for identifying the genomic location of trait-influencing loci. Although it may be a very clever strategy for identifying genes that influence human traits and diseases, AM can be problematic. We review the foundations, basic strategies, resources, and settings necessary for AM. We conclude that AM has potential in the identification of disease-predisposing loci, but this potential may only exist in a limited number of realistic settings.

Chromosome Mapping↗

The extent and distribution of linkage disequilibrium in a multi-hierarchic outbred canine pedigree.

A canine integrated linkage-radiation map has been recently constructed by using microsatellite markers. This map, with a good coverage of the canine genome, allows for a genome-wide search for the extent and distribution of linkage disequilibrium derived from linkage and evolutionary forces. In this study, we genotyped an outbred pedigree between Labrador retriever and Greyhound breeds with a set of microsatellite markers (240) from the canine linkage map. Linkage disequilibrium was measured between all syntenic and nonsyntenic marker pairs. Analysis of syntenic pairs revealed a significant correlation (-0.229, P < 0.001) between linkage disequilibrium and genetic distance (log transformed). Significant linkage disequilibria were observed more frequently between syntenic pairs spaced <40 cM than those paced >40 cM. There is a clear trend for linkage disequilibrium to decline with marker distance. From our results, a genome-wide screen with markers at low to moderate density (1-2 per 10 cM) should take full advantage of linkage disequilibrium for quantitative trait locus mapping in dogs. This study supports the appropriateness of linkage disequilibrium analysis to detect and map quantitative trait loci underlying complex traits in dogs.

Animals↗