Quantitative trait locus mapping with background control in genetic populations of clonal F1 and double cross

In this study, we considered five categories of molecular markers in clonal F₁ and double cross populations, based on the number of distinguishable alleles and the number of distinguishable genotypes at the marker locus. Using the completed linkage maps, incomplete and missing markers were imputed as fully informative markers in order to simplify the linkage mapping approaches of quantitative trait genes. Under the condition of fully informative markers, we demonstrated that dominance effect between the female and male parents in clonal F₁ and double cross populations can cause the interactions between markers. We then developed an inclusive linear model that includes marker variables and marker interactions so as to completely control additive effects of the female and male parents, as well as the dominance effect between the female and male parents. The linear model was finally used for background control in inclusive composite interval mapping (ICIM) of quantitative trait locus (QTL). The efficiency of ICIM was demonstrated by extensive simulations and by comparisons with simple interval mapping, multiple‐QTL models and composite interval mapping. Finally, ICIM was applied in one actual double cross population to identify QTL on days to silking in maize.     

Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumablyApoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.     

Quantitative trait locus mapping of yield-related components and oligogenic control of the cap color of the button mushroom, Agaricus bisporus

As in other crops, yield is an important trait to be selected for in edible mushrooms, but its inheritance is poorly understood. Therefore, we have investigated the complex genetic architecture of yield-related traits in Agaricus bisporus through the mapping of quantitative trait loci (QTL), using second-generation hybrid progeny derived from a cross between a wild strain and a commercial cultivar. Yield, average weight per mushroom, number of fruiting bodies per m(2), earliness, and cap color were evaluated in two independent experiments. A total of 23 QTL were detected for 7 yield-related traits. These QTL together explained between 21% (two-flushes yield) and 59% (earliness) of the phenotypic variation. Fifteen QTL (65%) were consistent between the two experiments. Four regions underlying significant QTL controlling yield, average weight, and number were detected on linkage groups II, III, IV, and X, suggesting a pleiotropic effect or tight linkage. Up to six QTL were identified for earliness. The PPC1 locus, together with two additional genomic regions, explained up to 90% of the phenotypic variation of the cap color. Alleles from the wild parent showed beneficial effects for some yield traits, suggesting that the wild germ plasm is a valuable source of variation for several agronomic traits. Our results constitute a key step toward marker-assisted selection and provide a solid foundation to go further into the biological mechanisms controlling productive traits in the button mushroom.     

Quantitative trait locus mapping and analysis of heritable variation in affiliative social behavior and co‐occurring traits

Humans exhibit broad heterogeneity in affiliative social behavior. Twin and family studies show that individual differences in core dimensions of social behavior are heritable, yet there are knowledge gaps in understanding the underlying genetic and neurobiological mechanisms. Animal genetic reference panels (GRPs) provide a tractable strategy for examining the behavioral and genetic architecture of complex traits. Here, using males from 50 mouse strains from the BXD GRP, 4 domains of affiliative social behavior—social approach, social recognition, direct social interaction (DSI) (partner sniffing) and vocal communication—were examined in 2 widely used behavioral tasks—the 3‐chamber and DSI tasks. There was continuous and broad variation in social and nonsocial traits, with moderate to high heritability of social approach sniff preference (0.31), ultrasonic vocalization (USV) count (0.39), partner sniffing (0.51), locomotor activity (0.54‐0.66) and anxiety‐like behavior (0.36). Principal component analysis shows that variation in social and nonsocial traits are attributable to 5 independent factors. Genome‐wide mapping identified significant quantitative trait loci for USV count on chromosome (Chr) 18 and locomotor activity on Chr X, with suggestive loci and candidate quantitative trait genes identified for all traits with one notable exception—partner sniffing in the DSI task. The results show heritable variation in sociability, which is independent of variation in activity and anxiety‐like traits. In addition, a highly heritable and ethological domain of affiliative sociability—partner sniffing—appears highly polygenic. These findings establish a basis for identifying functional natural variants, leading to a new understanding typical and atypical sociability.     

Quantitative trait locus mapping using sets of near-isogenic lines: relative power comparisons and technical considerations

 The power to detect QTL using near-isogenic line (NIL) comparisons versus recombinant inbred (RI) populations was assessed. The power to detect QTL was found to be generally greater when using RI populations than when using NIL contrasts. Power to detect QTL with NIL contrasts never exceeded that of RI populations when the number of RI lines is maximized relative to replication of lines for a given number of experimental units. The relative power of NIL contrasts is highest for traits with high heritability and when a gain in precision is realized due to increased replication of entries. Although NIL populations are generally less powerful than RI populations of similar size, some practical considerations may enhance the value of these materials. Availability of NILs allows the genetic effect of a specific chromosome region to be determined by comparing two lines; all RI lines in a population need to be rescored for each new trait even if the effect of a specific chromosome region is suspected. NIL comparisons may allow genetic differences to be detected by visual inspection; genetic effects can only be expressed as means and variances with recombinant inbred populations. In summary, RI populations generally, and in some cases, substantially, provide better power for QTL detection than NIL comparisons. Practical considerations, however, indicate that many factors need to be considered when choosing a population structure to meet an experimental objective. Received: 12 December 1996 / Accepted: 21 March 1997     

Quantitative trait locus mapping of resistance to Aspergillus flavus infection using a recombinant inbred line population in maize

Aflatoxin contamination of maize (Zea mays L.) grain caused by Aspergillus flavus is a serious health hazard to animals and humans. Development of maize varieties resistant to A. flavus infection and/or aflatoxin production can reduce this contamination. This study was conducted to identify quantitative trait loci (QTL) associated with resistance to A. flavus infection. A recombinant inbred line population was developed derived from RA, a maize inbred line resistant to A. flavus infection, and M53, a susceptible inbred line. After inoculation with A. flavus under controlled conditions, the kernels from each plant line grown in three different environments were evaluated for infection level. Categorical inoculation data were collected for each plant line based on the percentage of the kernel surface covered by fungal conidia. Significant genotypic variation in infection level was observed in all environments. Based on a genetic map containing 916 polymorphic simple sequence repeat and single nucleotide polymorphism markers, the resistance QTL were initially analyzed by composite interval mapping (CIM) separately for each environment. One QTL in bin 5.03 was detected in all environments, and seven other QTL were identified in one environment. Next, a mixed model based on CIM (MCIM) was employed for QTL analysis using data from the three environments simultaneously. Significant epistasis and epistasis × environment interaction to A. flavus infection were revealed. The QTL in bin 5.03 was repeatedly detected by the MCIM. This QTL explained the largest phenotypic variation among all of the detected QTL and could be considered as a major QTL for use in breeding for A. flavus resistance.     

Quantitative trait locus mapping of resistance in apple to Cydia pomonella and Lyonetia clerkella and of two selected fruit traits

Apple, Malus×domestica, is the most important fruit grown within the temperate zonobiome. It is attacked by both fruit‐damaging and leaf‐damaging lepidopteran pest insects, which require regular control such as the carpophagous codling moth, Cydia pomonella, or frequent control such as the phyllophagous apple leaf miner, Lyonetia clerkella. As many environmentally friendly pest control tactics are only effective at low levels of infestation, host plant resistance is a promising future component of integrated pest management systems, but knowledge is still lacking on such genetically based approaches against lepidopteran pests. The aim of the study was to identify molecular markers linked to C. pomonella and L. clerkella resistance or susceptibility in commercial apple as well as markers linked to selected fruit traits. The number of C. pomonella‐infested fruits and the number of L. clerkella mines were quantified as measures of apple resistance or susceptibility to the studied moth species. Herbivore surveys on 160 apple genotypes, representing a segregating F₁ cross of the apple cultivars ‘Fiesta’ and ‘Discovery’, were carried out during two consecutive years and at two sites in Switzerland. Broad‐sense heritability was 29.9% (C. pomonella), 18.2% (L. clerkella), 21.9% (fruit number) and 16.6% (fruit diameter). A subsequent analysis identified a quantitative trait locus (QTL) associated to C. pomonella susceptibility on the Discovery linkage group 10. The closest marker to this QTL was the random amplified polymorphic marker Z19‐350. No significant QTL was identified for resistance to L. clerkella. A putative QTL associated to fruit number was identified on Fiesta linkage group 12. The presented QTL associated with C. pomonella susceptibility and the putative QTL linked to fruit number may facilitate marker‐assisted breeding of resistant apple cultivars with cropping traits desirable for optimal fruit production.     

Quantitative trait locus analysis of drought tolerance and yield in Maize in China

Drought accounts for significant yield losses in crops. Maize (Zea mays L.) is particularly sensitive to water stress at reproductive stages, and breeding to improve drought tolerance has been a challenge. By use of a linkage map with 121 single sequence repeat (SSR) markers, quantitative trait loci (QTLs) for grain yield and yield components were characterized in the population of the cross X178×B73 under water-stressed and well-watered conditions. Under the well-watered regime, 2, 4, 4, 1, 2, 2, and 3 QTLs were identified for grain yield, 100-kernel weight, kernel number per ear, cob weight per ear, kernel weight per ear, ear weight, and ear number per plant, respectively, whereas under the water-stressed conditions, 1, 5, 2, 6, 1, 3, and 2 QTLs, respectively, were found. The significant phenotypic correlations among yield and yield components to some extent were observed under both water conditions, and some overlaps between the corresponding QTLs were also found. QTLs for grain yield and kernel weight per ear under well-watered conditions and ear weight under both well-watered and water-stressed conditions over-lapped, and all were located on chromosome 1.03 near marker bnlg176. Two other noticeable QTL regions were on chromosome 9.05 and 9.07 near markers umc1657 and bnlg1525; the first corresponded to grain yield, kernel weight per ear, and ear weight under well-watered conditions and kernel number per ear under both water conditions, and the second to grain yield and cob weight per ear under water-stressed conditions and ear number per plant under both water conditions. A comparative analysis of the QTLs herein identified with those described in previous studies for yield and yield components in different maize populations revealed a number of QTLs in common. These QTLs have potential use in molecular marker-assisted selection.     

Quantitative trait locus (QTL) isogenic recombinant analysis: a method for high-resolution mapping of QTL within a single population

In the quest for fine mapping quantitative trait loci (QTL) at a subcentimorgan scale, several methods that involve the construction of inbred lines and the generation of large progenies of such inbred lines have been developed (Complex Trait Consortium 2003). Here we present an alternative method that significantly speeds up QTL fine mapping by using one segregating population. As a first step, a rough mapping analysis is performed on a small part of the population. Once the QTL have been mapped to a chromosomal interval by standard procedures, a large population of 1000 plants or more is analyzed with markers flanking the defined QTL to select QTL isogenic recombinants (QIRs). QIRs bear a recombination event in the QTL interval of interest, while other QTL have the same homozygous genotype. Only these QIRs are subsequently phenotyped to fine map the QTL. By focusing at an early stage on the informative individuals in the population only, the efforts in population genotyping and phenotyping are significantly reduced as compared to prior methods. The principles of this approach are demonstrated by fine mapping an erucic acid QTL of rapeseed at a subcentimorgan scale.     

Quantitative trait locus analysis of tolerance to temperature fluctuations in winter,fruit characteristics,flower color,and prickle-free canes in raspberry

Despite the interest in growing raspberries (Rubus idaeus) in the southeastern USA, production is limited by the lack of cultivars adapted to the climate. One of these major climate adaptations is the ability to tolerate fluctuating winter temperatures. Perennial plants have adapted to these conditions by having high chilling requirements. Breeding efforts are underway for developing adapted cultivars, but breeding improvements in Rubus is a time-consuming process. In order to expedite the breeding process, molecular breeding tools are being developed. In this work, the cross (Rubus parvifolius × Tulameen) × Qualicum was used for the construction of a genetic linkage map and for quantitative trait locus (QTL) analyses of chilling requirement, prickle density, fruit color, fruit shape, fruit size, and flower color. Chilling requirements were determined by measuring bud break in chilled cuttings; all other traits were scored visually. Seven linkage groups were constructed and compared to an established Rubus map. Four regions were associated with chilling requirement, and were mostly consistent across 3 years of evaluation. For the fruit and flower color traits, significant regions were consistent across 2 years, and either one or two QTL were found. Two QTL linked to prickle density were detected; one coincided with previous studies, while the second QTL was found in linkage group 4 and co-localized with the marker for lack of prickles. This region is proposed to contain gene s for the prickle-free trait.     

Quantitative genetic analysis and mapping of leaf angle in durum wheat

The leaf erectness profile has been used to optimize plant architecture since erect leaves can enhance photosynthesis and dry matter production by greater sunlight capture. Brassinosteroid is a recent class of phytohormones that has been related to a more erect profile. There are no reports in the literature of the genetic variability of leaf angle in doubled haploid durum wheat populations; most studies on leaf angle have focused on the inheritance. Our aim was to study the genetic variation in flag and penultimate leaf angle in a durum wheat doubled haploid mapping population, identifying and mapping quantitative trait loci influencing leaf angle. An F₁-derived doubled haploid population of 89 lines from the cross Strongfield/Blackbird was used to construct a genetic map using 423 molecular marker loci. Two greenhouse experiments and one field test were conducted using an alpha lattice in a randomized complete block design with three replicates. The leaf angle was measured on flag and penultimate leaf with a protractor at three different growth stages. The results indicated poor to moderate correlations between the position of the leaf angle and the growth stage. Transgressive segregation beyond Strongfield and Blackbird of leaf angle was observed for all environments. Putative trait loci were identified on chromosomes 2A, 2B, 3A, 3B, 4B, 5B and 7A. This work helps to understand the genetics of leaf angle in durum wheat.     

Characterization and genetic mapping of a new blood-flesh trait controlled by the single dominant locus DBF in peach

Anthocyanin-rich peaches, because of their antioxidant properties and their strong attractiveness to consumers, are increasingly considered in French peach varietal innovation programs that integrate plant genomics and classical breeding. In this study, we describe a new blood-flesh trait identified in the ‘Wu Yue Xian’ peach accession from China. ‘Wu Yue Xian’ exhibits a fully red mesocarp during the later stages of fruit development, both with green midrib leaf and normal growth of the tree. This blood-flesh phenotype clearly differs from that determined by a single recessive locus (bf) in ‘Harrow Blood’, a clone showing blood-flesh in both immature and mature fruit associated with red midrib leaf and reduced tree height. We have then provided genetic evidence that blood-flesh phenotype of ‘Wu Yue Xian’ was controlled by a single dominant locus, designated DBF (Dominant Blood-Flesh), in four successive families derived from this accession. A genetic linkage map of the blood-flesh parent (‘D6090’) of the fourth population was constructed, including 102 SSRs spanning a total distance of 562.3 cM in eight linkage groups. Whereas the bf locus is located to linkage group 4, we mapped DBF to the top of linkage group 5, thus proving that DBF and bf loci are not alleles. Among 64 predicted genes in the DBF region (505 kbp), three genes of the dihydroflavonol-4-reductase family were identified as good candidates for the control of the DBF trait. Furthermore, SSR markers flanking DBF, such as AMPP157 and AMPPG178, supply a good basis to implement marker-assisted selection for this trait.     

Quantitative trait locus analysis of atherosclerosis in an intercross between C57BL/6 and C3H mice carrying the mutant apolipoprotein E gene

Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) differ significantly in atherosclerosis susceptibility and plasma lipid levels on the apolipoprotein E-deficient (apoE-/-) background when fed a Western diet. To determine genetic factors contributing to the variations in these phenotypes, we performed quantitative trait locus (QTL) analysis using an intercross between the two strains carrying the apoE-/- gene. Atherosclerotic lesions at the aortic root and plasma lipid levels of 234 female F2 mice were analyzed after being fed a Western diet for 12 weeks. QTL analysis revealed one significant QTL, named Ath22 (42 cM, LOD 4.1), on chromosome 9 and a suggestive QTL near D11mit236 (20 cM, LOD 2.4) on chromosome 11 that influenced atherosclerotic lesion size. One significant QTL on distal chromosome 1, which accounted for major variations in plasma LDL/VLDL cholesterol and triglyceride levels, coincided with a QTL having strong effects on body weight. Plasma LDL/VLDL cholesterol or triglyceride levels of F2 mice were significantly correlated with body weight, but they were not correlated with atherosclerotic lesion sizes. These data indicate that atherosclerosis susceptibility and plasma cholesterol levels are controlled by separate genetic factors in the B6 and C3H mouse model and that genetic linkages exist between body weight and lipoprotein metabolism.     

Cloning and expression analysis of a novel gene, RP42, mapping to an autism susceptibility locus on 6q16

We isolated a novel mouse gene, RP42, in a systematic search for genes expressed in proliferating neuroblasts whose human orthologs map to susceptibility loci for autism. This gene is intronless and encodes a putative 259-amino-acid protein that exhibits 30-36% overall sequence identity to a fission yeast and a nematode protein (GenPept Accession Nos. CAA17006 and CAB54261). Nevertheless, no homology to any known gene was found. RP42 has developmentally regulated expression, particularly in proliferating neuroblasts from which neocortical neurons originate. Its human ortholog is located in a cluster of embryonic neuronally expressed genes on the 6q16 chromosome, making it a positional candidate susceptibility gene for autism.     

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, P _meta = 6.6×10⁻⁸, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, P _meta = 2.9×10⁻⁷, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ∼146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (P _meta = 3.2×10⁻⁷, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (P _meta = 3.5×10⁻⁴, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.     

镜鲤体长、体高、体厚性状QTL定位分析

以镜鲤全同胞家系为材料,用246个SSR和306个SNP标记构建了鲤鱼的连锁图谱,利用GridQTL软件对体长(SL)、体高(H)、体厚(BT)和体长/体高(SLH)进行了QTL定位分析。结果显示:共检测到14个相关的QTL,分布在7个连锁群上。其中,7个与体长相关的QTL——LG6、LG17、LG21、LG23和LG35连锁群上的QTL为显著水平(P<0.05),LG1和LG28上达到极显著水平(P<0.01),可解释表型变异为6.6%~12.6%;3个与体高相关的QTL均为极显著水平(P<0.01)位于LG17、LG23和LG28上,可解释表型变异分别为11.6%、12.7%和15.6%;2个与体厚相关的QTL均为显著水平(P<0.05)位于LG23和LG28上,可解释表型变异分别为8.6%和7.2%;2个与体长/体高相关的QTL均为显著水平(P<0.05)位于LG21和LG35上,可解释表型变异均为8.2%。     

Quantitative trait locus mapping identifies a locus linked to striatal dopamine and points to collagen IV alpha-6 chain as a novel regulator of striatal axonal branching in mice

Dopaminergic neurons (DA neurons) are controlled by multiple factors, many involved in neurological disease. Parkinson's disease motor symptoms are caused by the demise of nigral DA neurons, leading to loss of striatal dopamine (DA). Here, we measured DA concentration in the dorsal striatum of 32 members of Collaborative Cross (CC) family and their eight founder strains. Striatal DA varied greatly in founders, and differences were highly heritable in the inbred CC progeny. We identified a locus, containing 164 genes, linked to DA concentration in the dorsal striatum on chromosome X. We used RNAseq profiling of the ventral midbrain of two founders with substantial difference in striatal DA–C56BL/6 J and A/J—to highlight potential protein-coding candidates modulating this trait. Among the five differentially expressed genes within the locus, we found that the gene coding for the collagen IV alpha 6 chain (Col4a6) was expressed nine times less in A/J than in C57BL/6J. Using single cell RNA-seq data from developing human midbrain, we found that COL4A6 is highly expressed in radial glia-like cells and neuronal progenitors, indicating a role in neuronal development. Collagen IV alpha-6 chain (COL4A6) controls axogenesis in simple model organisms. Consistent with these findings, A/J mice had less striatal axonal branching than C57BL/6J mice. We tentatively conclude that DA concentration and axonal branching in dorsal striatum are modulated by COL4A6, possibly during development. Our study shows that genetic mapping based on an easily measured Central Nervous System (CNS) trait, using the CC population, combined with follow-up observations, can parse heritability of such a trait, and nominate novel functions for commonly expressed proteins.     

Genetic analysis of the recF pathway to genetic recombination in Escherichia coli k12: Isolation and characterization of mutants

A recombination proficient strain ofEscherichia coli which is recB^? recC^? sbcB^? has been subjected to mutagenesis by nitrosoguanidine. Among the recombination deficient mutants isolated one was sbcB⁺, three were recA^～ and 11 were mutants in at least four newrec genes: recF, recJ, recK and recL. recF143 and recL152 are cotransducible with ilv but they lie on opposite sides of the ilv operons as determined by F$\text{\$}\text{?}$studies. recF, recL and recK are not involved in the RecBC pathway of recombination since a recB⁺recC⁺sbcB^? strain carrying a mutation in one of these genes is recombination proficient. Hence the hypothesis that a RecF pathway of recombination can operate as a partially independent substitute for the RecBC pathway of recombination is supported. recF^?recB⁺ and recF⁺recB^? single mutants are sensitive to u.v. irradiation while the recF^?recB^? double mutant is more sensitive than either single mutant. The sensitivity of the recB^?recC^?sbcB^?recF^? strain approaches the sensitivity of a recA^? single mutant. This is interpreted to mean that there are partially independent RecF and RecBC pathways for the repair of u.v. damage. recJ and mutations were not mapped precisely; hence the mutant properties they confer can not be stated conclusively.