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Quantitative trait loci for spawning date and body weight in rainbow trout: testing for conserved effects across ancestrally duplicated chromosomes.

We incorporated 69 microsatellite loci into an existing data set of 132 markers to test for quantitative trait loci (QTLs) affecting spawning date and body weight in a backcross between two outbred strains of rainbow trout (Oncorhynchus mykiss). Twenty-six linkage groups were identified and synteny of duplicated microsatellite markers was used to confirm 13 homeologous chromosome pairs. Gene-centromere data were used to localize the centromeres for 13 linkage groups whose orientations were previously unknown. We applied a combination of interval mapping and single marker analysis to the segregating maternal and paternal alleles at 201 microsatellite loci. Four spawning date QTLs with suggestive evidence for an additional two QTLs were detected in female trout spawning at 3 and 4 years of age. Similarly we detected three QTLs for body weight in females at 2 years of age plus four suggestive QTLs for this trait. We found marginal evidence that three pairs of ancestral homeologues contained detectable QTLs for the same trait. In one of the three pairs of homeologues, the duplicated QTL regions mapped to the same relative chromosomal location, while the exact localization of the QTL position in one of the other pairs was difficult to infer since it was based on data from a male-derived map. The existing data were unable to refute a hypothesis that duplicated functional genes will be maintained within the telomeric regions of salmonids due to preferential male-mediated crossing over in this region. Two of the four spawning date QTLs were detected on linkage groups with unknown homeologous relationships. QTLs with possible pleiotropic effects on both spawning date and body size were localized to two linkage groups.

Animals↗

PubMed2005

Mapping the dominant wound healing and soft tissue regeneration QTL in MRL x CAST.

We have used a mouse ear punch model and the QTL (quantitative trait loci) mapping technique to identify genes that are responsible for soft tissue regeneration. In the early studies, we have identified several QTL and have shown that the inheritance of ear healing was additive in one cross (MRL x SJL), and recessive in another cross (DBA x 129). Because CAST mice are genetically distinct and have a different genetic background, CAST would facilitate the identification of common and novel QTL when crossed with common inbred lines. We made a cross between super healer MRL and poor healer CAST and collected ear punch phenotype and marker genotype data from F(2). Ear punch healing exhibited a dominant mode of inheritance in this cross. There were three main QTL on Chromosomes 4, 9, and 17, and two suggestive QTL on Chromosomes 1 (new) and 7. Taken together, these QTL accounted for about 29% of total F2 variance of MRL x CAST. Compared with another study using the same cross, we found a totally different set of QTL. Two QTL interactions were identified by a full QTL model: Chromosomes 4 x 17 and 9 x 17; the latter reached to a statistical level at p < 0.05. These interactions explained about 4% of the F2 phenotypic variance. We conclude that soft tissue regeneration is controlled by multiple genes and locus vs. locus interactions.

Animals↗

PubMed2004

Quantitative genomics: exploring the genetic architecture of complex trait predisposition.

Most phenotypes with agricultural or biomedical relevance are multifactorial traits controlled by complex contributions of genetics and environment. Genetic predisposition results from combinations of relatively small effects due to variations within a large number of genes, known as QTL. Well over 200 QTL have been reported for growth and body composition traits in the mouse, which likely represent at least 50 to 100 distinct genes. Molecular biology has yielded significant advances in understanding these traits at the metabolic and physiological levels; however, little has been learned regarding the identity and nature of the underlying polygenes. In addition to the significantly poor precision inherent to QTL localization, it is very difficult to differentiate between co-localization and coincidence when comparing QTL with other QTL and with potential candidate genes. The wide gap between our knowledge of physiological mechanisms underlying complex traits and the nature of genetic predisposition significantly impairs discovery of genes underlying QTL. Identification and genetic mapping of key transcriptional, proteomic, metabolomic, and endocrine events will uncover large lists of significant positional candidate genes for growth and body composition. However, integration of experimental approaches to jointly evaluate predisposition and physiology will increase success of QTL identification by merging the power of recombination with functional analysis. Measuring physiologically relevant subphenotypes within a structured QTL mapping population will not only facilitate pathway-specific prioritization among candidate genes, but may also directly identify genes underlying QTL. This would advance our understanding of the genetic architecture of complex traits by testing the central hypothesis that genes controlling predisposition to a quantitative trait are primarily involved in trans-regulation of the primary physiological pathways that regulate the trait.

Animals↗

PubMed1994

Multiple alleles for tuber shape in diploid potato detected by qualitative and quantitative genetic analysis using RFLPs.

Tuber shape in potato is commonly regarded as displaying continuous variation, yet at the diploid level phenotypes can be discerned visually, having round or long tubers. Inheritance of qualitative tuber shape can be explained by a single locus Ro, round being dominant to long. With restriction fragment length polymorphisms (RFLPs) the Ro locus was mapped on chromosome 10. Tuber shape was also studied as a quantitative trait, using the length/width ratio as trait value. The estimated broad sense heritability was h2 = 0.80. The morphologically mapped Ro locus explained 75% of the genetic variation, indicating the presence of a major quantitative trait locus (QTL) at the Ro locus and minor genetic factors. RFLP alleles linked with Ro alleles were used to divide the progeny into four genotypic classes: RofemaleRomale:Rofemalero:roRomale:roro = 1:1:1:1. The recessive ro allele is identical by descent in both parents. The significantly different effects (P = 0.0157) of the non-identical alleles Rofemale and Romale provided evidence for multiallelism at the Ro locus. Linkage mapping of the Ro locus was compared with QTL mapping. Only those markers which are polymorphic in both parents allow accurate QTL mapping when genetic factors segregate from both parents. This finding applies to QTL mapping in all outbreeders without homozygous inbred strains.

Alleles↗

PubMed2003

High-resolution mapping of quantitative trait loci by selective recombinant genotyping.

Selective recombinant genotyping (SRG) is a three-stage procedure for high-resolution mapping of a QTL that has previously been mapped to a known confidence interval (target C.I.). In stage 1, a large mapping population is accessed and phenotyped, and a proportion, P, of the high and low tails is selected. In stage 2, the selected individuals are genotyped for a pair of markers flanking the target C.I., and a group of R individuals carrying recombinant chromosomes in the target interval are identified. In stage 3, the recombinant individuals are genotyped for a set of M markers spanning the target C.I. Extensive simulations showed that: (1) Standard error of QTL location (SEQTL) decreased when QTL effect (d) or population size (N) increased, but was constant for given "power factor" (PF = d(2)N); (2) increasing the proportion selected in the tails beyond 0.25 had only a negligible effect on SEQTL; and (3) marker spacing in the target interval had a remarkably powerful effect on SEQTL, yielding a reduction of up to 10-fold in going from highest (24 cM) to lowest (0.29 cM) spacing at given population size and QTL effect. At the densest marker spacing, SEQTL of 1.0-0.06 cM were obtained at PF = 500-16,000. Two new genotyping procedures, the half-section algorithm and the golden section/half-section algorithm, allow the equivalent of complete haplotyping of the target C.I. in the recombinant individuals to be achieved with many fewer data points than would be required by complete individual genotyping.

Algorithms↗

PubMed2002

Resistance of DRH strain rats to chemical carcinogenesis of liver: genetic analysis of later progression stage.

The inbred DRH rats are highly resistant to the induction of hepatocellular carcinoma (HCC) by feeding of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Previously, we found that two quantitative trait loci (QTLs), Drh1 and Drh2, significantly reduced the number, size and area of glutathione S-transferase-placental form (GST-P)-positive foci and GST-P mRNA levels in (F344xDRH)F(2) rat livers induced by feeding 3'-Me-DAB for 8 weeks. It is unclear, however, whether these QTLs affecting pre-neoplastic lesions are also the determinants of the later stage hepatocarcinogenesis, and whether there are any additional QTLs affecting hepatocarcinogenesis in the progression stage. To answer these questions, we analyzed QTL parameters for liver tumors in 99 (F344xDRH)F(2) rats induced by feeding 3'-Me-DAB for 20 weeks. The QTL parameters examined were GST-P mRNA, ornithine decarboxylase activity, and the number and total area of HCC/nodules macroscopically detectable on the liver surface. In composite interval mapping, we observed two major QTL peaks overlapping on the map positions of Drh1 on rat chromosome 1 (RNO1) and Drh2 on RNO4, respectively. The newly mapped QTL on RNO1 affected the GST-P mRNA level at 20 weeks of 3'-Me-DAB feeding, but did not affect the number and size of tumors. The primary effect of Drh1 is, therefore, to inhibit GST-P induction and to prevent enzyme altered foci (EAF) formation. On the other hand, the QTLs on RNO4, co-mapped to Drh2, affected all parameters of liver tumors examined except for the level of GST-P mRNA. The latter QTLs influenced not only the induction of GST-P and formation of EAF but also the progression of tumors in the later stage of hepatocarcinogenesis. The GST-P induction is differentially controlled by stages of hepatocarcinogenesis and the DRH resistance to carcinogenesis is principally attributed to the QTLs on RNO4 out of two resistance QTLs identified in the pre-neoplastic stage.

Animals↗

PubMed2000

Inheritance and mapping of 2n-egg production in diploid alfalfa.

The production of eggs with the sporophytic chromosome number (2n eggs) in diploid alfalfa (Medicago spp.) is mainly associated with the absence of cytokinesis after restitutional meiosis. The formation of 2n eggs through diplosporic apomeiosis has also been documented in a diploid mutant of M. sativa subsp. falcata (L.) Arcang. (2n = 2x = 16), named PG-F9. Molecular tagging of 2n-egg formation appears to be an essential step towards marker-assisted breeding and map-based cloning strategies aimed at investigating and manipulating reproductive mutants of the M. sativa complex. We made controlled crosses between PG-F9 and three wild type plants of M. sativa subsp. coerulea (Less.) Schm. (2n = 2x = 16) and then hand-pollinated the F1 progenies with tetraploid plants of M. sativa subsp. sativa L. (2n = 4x = 32). As a triploid embryo block prevents the formation of 3x progenies in alfalfa because of endosperm imbalance, and owing to the negligible selfing rate, seed set in 2x-4x crosses was used to discriminate the genetic capacity for 2n-egg production. F1 plants that exhibited null or very low seed sets were classified as normal egg producers and plants with high seed sets as 2n-egg producers. A bulked segregant analysis (BSA) with RAPD (random amplified polymorphic DNA), ISSR (inter-simple sequence repeat), and AFLP (amplified fragment length polymorphism) markers was employed to identify a genetic linkage group related to the 2n-egg trait using one of the three F1 progenies. This approach enabled us to detect a paternal ISSR marker of 610 bp, generated by primer (CA)8-GC, located 9.8 cM from a putative gene (termed Tne1, two-n-eggs) that in its recessive form determines 2n eggs and a 30% recombination genomic window surrounding the target locus. Eight additional RAPD and AFLP markers, seven of maternal, and one of paternal origin, significantly co-segregated with the trait under investigation. The minimum number of quantitative trait loci (QTLs) controlling seed set in 2x-4x crosses was estimated by ANOVA and regression analysis. Four maternal and three paternal independent molecular markers significantly affected the trait. A paternal RAPD marker allele, mapped in the same linkage group of Tne1, explained 43% of the variation for seed set in 2x-4x crosses indicating the presence of a major QTL. A map of the PG-F9 chromosome regions carrying the minor genes that determine the expression level of 2n eggs was constructed using selected RAPD and AFLP markers. Two of these genes were linked to previously mapped RFLP loci belonging to groups 1 and 8. Molecular and genetic evidence support the involvement of at least five genes.

Chromosome Mapping↗

PubMed2005

Mapping quantitative trait loci for milk production and genetic polymorphisms of milk proteins in dairy sheep.

In this paper, we present recent advances in the molecular dissection of complex traits in dairy sheep and discuss their possible impact on breeding schemes. In the first step, we review the literature data on genetic polymorphisms and the effects of sheep alphas1-casein and beta-lactoglobulin loci. It is concluded that the results are rather inconsistent and cannot be used in dairy sheep selection. In a second step, we describe the strategy implemented in France, Italy and Spain taking advantage of the genetic maps for QTL detection. These studies were part of a European project, called "genesheepsafety", which investigated both milk production and functional traits. Preliminary QTL results are presented for production traits.

Animals↗

PubMed2001

Are contents of Rubisco, soluble protein and nitrogen in flag leaves of rice controlled by the same genetics?

Genetic relations among the contents of Rubisco, soluble protein and total leaf nitrogen (N) in leaves of rice (Oryza sativa L.) were studied by quantitative trait loci (QTL) analysis with a population of backcross inbred lines (BILs) of japonica Nipponbarexindica Kasalath. The ratio of Rubisco to total leaf N in leaves is the main target in improving photosynthetic N-use efficiency in plants. QTLs controlling Rubisco content were not detected near QTLs for total leaf N content. These results indicate that contents of Rubisco and total leaf N are controlled by different genetics. QTLs that controlled the ratio of Rubisco to total leaf N (CORNs) were detected. These results suggest that some mechanism(s) may be involved in determining this ratio, while the contents of Rubisco and total leaf N are controlled in other ways. In elite BILs, the ratios of Rubisco to total leaf N were higher than those of both parents. These results suggest a good possibility of improving N-use efficiency by CORNs in cultivated rice. A QTL controlling Rubisco content was mapped near a QTL for soluble protein content on chromosome 8 at 5 d after heading and on chromosome 9 at 25 d. In each chromosome region, the peaks of both QTLs overlapped accurately, giving a high possibility of pleiotropic effects by the same genes. Different QTLs controlling soluble protein or Rubisco were detected from those detected at 5 d or 25 d after heading. This suggests that these traits are genetically controlled depending on the growth stages of leaves.

Chromosome Mapping↗

PubMed2003

X-linked and lineage-dependent inheritance of coping responses to stress.

Coping-or how one routinely deals with stress-is a complex behavioral trait with bearing on chronic disease and susceptibility to psychiatric disorders. This complexity is a result of not only underlying multigenic factors, but also important non-genetic ones. The defensive burying (DB) test, although originally developed as a test of anxiety, can accurately measure differences in coping strategies by assaying an animal's behavioral response to an immediate threat with ethological validity. Using offspring derived from reciprocal crosses of two inbred rat strains differing in DB behaviors, we provide convergent phenotypic and genotypic evidence that coping styles are inherited in an X-linked fashion. We find that first-generation (F(1)) males, but not females, show maternally derived coping styles, and second-generation (F(2)) females, but not males, show significant differences in coping styles when separated by grandmaternal lineage. By using a linear modeling approach to account for covariate effects (sex and lineage) in QTL analysis, we map three quantitative trait loci (QTL) on the X Chromosome (Chr) ( Coping-1, Approach-1, and Approach-2) associated with coping behaviors in the DB paradigm. Distinct loci were associated with different aspects of coping, and their effects were modulated by both the sex and lineage of the animals, demonstrating the power of the general linear modeling approach and the important interplay of allelic and non-allelic factors in the inheritance of coping behaviors.

Adaptation, Psychological↗

PubMed2005

Structured antedependence models for functional mapping of multiple longitudinal traits.

In this article, we present a statistical model for mapping quantitative trait loci (QTL) that determine growth trajectories of two correlated traits during ontogenetic development. This model is derived within the maximum likelihood context, incorporated by mathematical aspects of growth processes to model the mean vector and by structured antedependence (SAD) models to approximate time-dependent covariance matrices for longitudinal traits. It provides a quantitative framework for testing the relative importance of two mechanisms, pleiotropy and linkage, in contributing to genetic correlations during ontogeny. This model has been employed to map QTL affecting stem height and diameter growth trajectories in an interspecific hybrid progeny of Populus, leading to the successful discovery of three pleiotropic QTL on different linkage groups. The implications of this model for genetic mapping within a broader context are discussed.

Journal Article↗

PubMed2002

Simultaneous detection and fine mapping of quantitative trait loci in mice using heterogeneous stocks.

We describe a method to simultaneously detect and fine map quantitative trait loci (QTL) that is especially suited to the mapping of modifier loci in mouse mutant models. The method exploits the high level of historical recombination present in a heterogeneous stock (HS), an outbred population of mice derived from known founder strains. The experimental design is an F(2) cross between the HS and a genetically distinct line, such as one carrying a knockout or transgene. QTL detection is performed by a standard genome scan with approximately 100 markers and fine mapping by typing the same animals using densely spaced markers over those candidate regions detected by the scan. The analysis uses an extension of the dynamic-programming technique employed previously to fine map QTL in HS mice. We show by simulation that a QTL accounting for 5% of the total variance can be detected and fine mapped with >50% probability to within 3 cM by genotyping approximately 1500 animals.

Animals↗

PubMed2002

Identification of QTLs controlling tissue-culture traits in barley ( Hordeum vulgare L.).

Quantitative trait loci (QTLs) controlling callus growth (CG), subsequent shoot differentiation ratio (SD) and green shoot ratio (GS) in immature embryo culture were identified in barley. A base map was developed from 99 recombinant inbred lines (RILs) of 'Azumamugi' x 'Kanto Nakate Gold'. The tissue-culture traits were evaluated at the F(7) and F(10) generations of the RILs. The RILs showed wide and continuous variations in each of the three tissue-culture traits. Three QTLs for CG, three QTLs for SD and two QTLs for GS were detected by using composite interval mapping. A QTL for SD on chromosome 3H had a large effect, and 'Kanto Nakate Gold', which has a high differentiation ability, contributed to this QTL. The location of this QTL is identical to, or very close to, the uzu locus. We discuss the relationships between tissue-culture loci in 'Azumamugi' x 'Kanto Nakate Gold' and those in other mapping populations.

Journal Article↗

PubMed2002

Plant molecular diversity and applications to genomics.

Surveys of nucleotide diversity are beginning to show how genomes have been shaped by evolution. Nucleotide diversity is also being used to discover the function of genes through the mapping of quantitative trait loci (QTL) in structured populations, the positional cloning of strong QTL, and association mapping.

Chromosome Mapping↗

PubMed2002

[Construction the RFLP linkage map and location the NCBL QTL of maize].

There exists the race differential phenomenon in Exserohilum turcicum (namely NCBL). At present, there are 5 identified races of NCBL and some un-known races in China. For improvement of maize resistance to NCBL, a basic method is to improve maize quantitative resistance. To identify the numbers and effects of the quantitative resistant loci to NCBL in maize, we constructed F2:3 population from resistant line P138 as male parent cross with sensitive line Z3 as female parent. Using RFLP marker technique, the RFLP linkage map of maize was cons cracted covering 1999. 8 cM, and the average distance between markers was 16.5 cM. Identified QTL of NCBL lesion length, width, and area were 3, 3, 2, respectively. The combined contribution ratios of these QTL were 58.1%, 71.5%, 27.5%, respectively. No QTL was identified NCBL lesion number per leaf, it was a trait that might be controlled by one- or oligo-genes. Finally, authors discussed and prospected the maize NCBL research in future.

Ascomycota↗

PubMed2003

Distribution of temperature tolerance quantitative trait loci in Arctic charr (Salvelinus alpinus) and inferred homologies in rainbow trout (Oncorhynchus mykiss).

We searched for quantitative trait loci (QTL) affecting upper temperature tolerance (UTT) in crosses between the Nauyuk Lake and Fraser River strains of Arctic charr (Salvelinus alpinus) using survival analysis. Two QTL were detected by using two microsatellite markers after correcting for experiment-wide error. A comparative mapping approach localized these two QTL to homologous linkage groups containing UTT QTL in rainbow trout (Oncorhynchus mykiss). Additional marginal associations were detected in several families in regions homologous to those with QTL in rainbow trout. Thus, the genes underlying UTT QTL may antedate the divergence of these two species, which occurred by approximately 16 MYA. The data also indicate that one pair of homeologs (ancestrally duplicated chromosomal segments) have contained QTL in Arctic charr since the evolution of salmonids from a tetraploid ancestor 25-100 MYA. This study represents one of the first examples of comparative QTL mapping in an animal polyploid group and illustrates the fate of QTL after genome duplication and reorganization.

Adaptation, Physiological↗

PubMed2005

Mapping of QTLS for ferrous iron toxicity tolerance in rice (Oryza sativa L.).

Ferrous iron toxicity is the main factor limiting the productivity of rice in gleyic paddy soils. In this study, an F2 and an equivalent F3 populations derived from a japonica/indica cross of rice, Longza8503/IR64, were raised under iron-enriched solution cultures, and used to map QTLs controlling ferrous iron toxicity tolerance. A genetic linkage map consisting of 101 SSR markers was constructed to determine the position and nature of quantitative trait loci (QTLs) affecting Fe2+ toxicity tolerance. Three characters, i.e., leaf bronzing index (LBI), plant height (PH) and maximum root length (MRL) were evaluated for the F2 plants and F3 lines and the parents at the seedling stage in nutrient solution. A total of 20 QTLs for LBI, PH and MRL under the Fe2+ stress were detected over 10 of the 12 rice chromosomes, reflecting multigenic control of these traits. QTLs controlling LBI were located at the region of RM315-RM212 on chromosome 1, RM6-RM240 on chromosome 2 and RM252-RM451 on chromosome 4. Compared with other mapping results: (1) the QTL for LBI located at the region of RM252-RM451 on chromosome 4 was identical with the QTL for decreased chlorophyll content on a rice function map. Another QTL for LBI located at the region of RM315-RM212 on chromosome 1 was linked with the QTL for chlorophyll content which located at the region of C178-R2635 on a rice function map. (2) The third QTL for LBI located at the region of RM6-RM240 on choromosome 2 was linked with the QTL for potassium uptake located at the region of RZ58-CDO686 under potassium deficiency stress.

Chromosome Mapping↗

PubMed2002

Seven suggestive quantitative trait loci influence hygienic behavior of honey bees.

In 1964, Walter Rothenbuhler proposed a two-gene model to explain phenotypic variance in the remarkable behavior in which honey bee workers remove dead brood from their colonies. Rothenbuhler's model proposed that one locus controls the uncapping of brood cells containing dead pupae, while a second controls the removal of the cell contents. We show here, through molecular techniques and quantitative trait loci (QTL) linkage mapping, that the genetic basis of hygienic behavior is more complex, and that many genes are likely to contribute to the behavior. In our cross, we detected seven suggestive QTLs associated with hygienic behavior. Each detected QTL controlled only 9-15% of the observed phenotypic variance in the character.

Animals↗