A general framework for marker-assisted selection

Early simulation studies have showed that the inclusion of epistatic components (especially the additive-by-additive effects) into marker-assisted selection (MAS) can improve selection efficiency for a short-term breeding program. In this study I extend Lande and Thompson's theory to incorporate both additive and non-additive effects into MAS with reference to the mass selection case. Four different indices are analytically examined in terms of the type of genetic components involved in the marker scores: phenotype-, general combining ability (GCA)-, and GCA and reciprocal effects-based marker scores. The phenotype-based marker index is applicable to any population of non-random mating, while the other three indices are applicable to the synthetic population derived from diallel crosses. All these indices may have higher selection efficiencies than the index with solely additive effects-associated markers as long as the detectable transient non-additive effects are present. The improvement in selection efficiency depends on the magnitude of non-additive variances and the proportion of them explained by markers. The index with the phenotype-based marker scores operates on the whole of the additive and non-additive effects, and has the largest selection efficiency. The indices with the GCA-based marker scores operate only on additive and additive-by-additive genetic variation and have relatively small selection efficiencies. Inclusion of the markers from organelle genomes can also increase selection efficiency, depending upon the proportion of the total genetic variation attributable to organelle genomes and the proportion of them explained by organelle genomic markers. Sharing of markers among different marker scores does not facilitate the improvement of selection efficiency.     

Evaluation of marker-assisted selection through computer simulation

Computer simulation was used to evaluate responses to marker-assisted selection (MAS) and to compare MAS responses with those typical of phenotypic recurrent selection (PRS) in an allogamous annual crop species such as maize (Zea mays L.). Relative to PRS, MAS produced rapid responses early in the selection process; however, the rate of these responses diminished greatly within three to five cycles. The gains from MAS ranged from 44.7 to 99.5% of the maximum potential, depending on the genetic model considered. Linkage distance between markers and quantitative trait loci (QTLs) was the factor which most limited the responses from MAS. When averaged across all models considered, flanking QTLs within two marker loci produced 38% more gain than did selection based on single markers if markers were loosely-linked to a QTL (20% recombination). Flanking markers were much less advantageous when markers were closely-linked to a QTL (5% recombination), producing an advantage over single markers of only 11%. Markers were most effective in fully exploiting the genetic potential when fewer QTLs controlled the trait. Large QTL numbers exacerbated the problem of marker-QTL recombination by requiring more generations for fixation. In annual crop species, MAS may offer a primary advantage of enabling two selection cycles per year versus the 2 years per cycle required by most PRS schemes for the evaluation of testcross progeny. MAS thus appears to allow very rapid gains for the first 2–3 years of recurrent selection, after which time conventional methods might replace MAS to achieve further responses.Publication number 19, 330 of the Minnesota Agricultural Experiment Station     

Re-evaluation of the prospects of marker-assisted selection for improving insect resistance against Diatraea spp. in tropical maize by cross validation and independent validation

Cross validation (CV) and validation with an independent sample (IV) are new biometric approaches in QTL analysis to obtain unbiased estimates of QTL effects and the proportion of the genetic variance explained by the detected marker-QTL association (p). Our objective with these methods was to obtain a realistic picture on the prospects of marker-assisted selection (MAS) for improving the resistance of maize against the tropical stem borer species Diatraea grandiosella (SWCB) and Diatraea saccharalis (SCB). Published QTL mapping studies on leaf-damage ratings (LDR) with populations of F_2:3 lines and recombinant inbred lines (RIL) from crosses CML131×CML67 and Ki3× CML139 of tropical maize inbreds were re-analyzed with CV and IV. With CV, the reduction in p for LDR compared to p obtained with the whole data set varied between 41.0 and 79.6% in the populations of F_2:3 lines and between 30.1 and 65.2% in the two populations of RIL. Estimates of p for SCB LDR were similar for CV and IV. For SWCB LDR, p estimates obtained with IV were larger than those obtained with CV in CML131× CML67. The reverse was observed for Ki3×CML139. Under the assumption of identical selection intensities, and based on the re-estimates of p, MAS using only molecular marker information is less-efficient than conventional phenotypic selection (CPS). MAS combining marker and phenotypic data increases the relative efficiency by only 4% in comparison to CPS. In conclusion, MAS for improving SWCB and SCB LDR seems not-promising unless additional QTLs with proven large effects are available or the costs of marker assays are considerably reduced. Received: 7 December 2000 / Accepted: 5 February 2001     

Molecular marker-assisted selection for enhanced yield in malting barley

Brewers are reluctant to change malting barley (Hordeum vulgare ssp. vulgare L.) cultivars due to concerns of altered flavor and brewing procedures. The U.S. Pacific Northwest is capable of producing high yielding, high quality malting barley but lacks adapted cultivars with desirable malting characteristics. Our goal was to develop high yielding near isogenic lines that maintain traditional malting quality characteristics by transferring quantitative trait loci (QTL) associated with yield, via molecular marker-assisted backcrossing, from the high yielding cv. Baronesse to the North American two-row malting barley industry standard cv. Harrington. For transfer, we targeted Baronesse chromosome 2HL and 3HL fragments presumed to contain QTL that affect yield. Analysis of genotype and yield data suggests that QTL reside at two regions, one on 2HL (ABG461C-MWG699) and one on 3HL (MWG571A-MWG961). Genotype and yield data indicate that additional Baronesse genome regions are probably involved, but need to be more precisely defined. Based on yield trials conducted over 22 environments and malting analyses from 6 environments, we selected one isogenic line (00-170) that has consistently produced yields equal to Baronesse while maintaining a Harrington-like malting quality profile. We conclude there is sufficient data to warrant experiments testing whether the 2HL and 3HL Baronesse QTL would be effective in increasing the yield of other low yielding barley cultivars.     

More on the efficiency of marker-assisted selection

 Computer simulations were used to study the efficiency of marker-assisted selection (MAS) based on an index combining the phenotypic value and the molecular score of individuals. The molecular score is computed from the effects attributed to markers by multiple regression of phenotype on marker genotype. The results show that in the first generation the ratio RE of the expected efficiency of MAS over the expected efficiency of purely phenotypic selection generally increases when considering: (1) larger population sizes, (2) lower heritability values of the trait, and (3) a higher type-I error risk of the regression. This is consistent with previously published results. However, at low heritabilities our results point out that response to MAS is more variable than response to phenotypic selection. Hence, when the difference of genetic gains is considered instead of their ratio, RE, the heritability values corresponding to maximal advantage of using MAS rather than phenotypic selection are still low, but higher than predicted based on RE. The study over several successive generations of the rate of fixation of QTLs shows that the higher efficiency of MAS on QTLs with large effects in early generations is balanced by a higher rate of fixation of unfavourable alleles at QTLs with small effects in later generations. This explains why MAS may become less efficient than phenotypic selection in the long term. MAS efficiency therefore depends on the genetic determinism of the trait. Finally, we investigate a modified MAS method involving an alternation of selection on markers with and without phenotypic evaluation. Our results indicate that such a selection method could at low cost, provide an important increase in the genetic gain per unit of time in practical breeding programs. Received: 11 July 1997 / Accepted: 4 August 1997     

Simultaneous marker-assisted selection for multiple traits in autogamous crops

A method is presented for the selection of parents with the aim of obtaining improved genotypes in the progeny of a cross. The procedure is designed to select in several unrelated traits simultaneously and is based on the selection of molecular markers that are linked to QTLs. The method was compared with conventional phenotypic selection in simulation experiments for a number of genetic structures underlying the traits and several types of parental populations. Although the method in general provides good results, some of the underlying assumptions may be violated quite easily, thereby reducing the applicability of the procedure in practice. Received: 10 September 1999 / Accepted: 24 August 2000     

Simulation of marker-assisted selection utilizing linkage disequilibrium: the effects of several additional factors

Use was made of our published model and methods to investigate the effects of several additional factors on marker-assisted selection (MAS) utilizing linkage disequilibrium. The additional factors were: size of the sample used to estimate the marker quantitative trait locus (MQTL) association effects, the method used to estimate the MQTL effects, use of the average of the top MQTL estimates in selection rather than individual estimates, size of the selection population, and the crossing of duplicate selection lines to generate further linkage disequilibrium and further selection response. The average map distance between the quantitative trait loci (QTLs) and their nearest marker was 0.15 Morgans. Use of estimates of MQTL effects derived by least squares yielded smaller selection responses than estimates derived by mixed-model methods. Selection responses were also reduced by using a smaller sample for estimating the associations because MQTL effects were less well estimated. This applied to selection on the MQTL effects themselves and to selection combining the MQTL with phenotypic information. Thus, poorly estimated MQTL effects added noise to the system and reduced selection response in combined selection. Using the average of the top MQTL estimates, rather than individual estimates, also reduced selection response. New linkage disequilibrium, generated by crossing two lines selected from the same population, did not lead to additional selection response in the cross line. These results show limitations to MAS using linkage disequilibrium until close linkages of markers and QTLs are available.     

Comparison between marker-assisted selection and phenotypical selection in a set of Arabidopsis thaliana recombinant inbred lines

 Parents were selected from a well-characterised Arabidopsis recombinant inbred line (RIL) population based on (1) their phenotype for flowering time or (2) marker and QTL information that had been assessed previously. The F₂ offspring obtained from pairs of selected RILs was analysed for these traits, and the results obtained with these two methods of selection were compared. Selection based on marker and QTL information gave approximately the same result as selection based on phenotype. The relative high heritability of flowering time in Arabidopsis facilitated successful phenotypical selection. The difference in selection result that was anticipated to be in favour of the marker-assisted approach was therefore not observed. Received: 29 November 1997 / Accepted: 8 June 1998     

Salt tolerance in Lycopersicon species. IV. Efficiency of marker-assisted selection for salt tolerance improvement

The usefulness of marker-assisted selection (MAS) to develop salt-tolerant breeding lines from a F₂ derived from L. esculentum x L. pimpinellifolium has been studied. Interval mapping methodology of quantitative trait locus (QTL) analysis was used to locate more precisely previously detected salt tolerance QTLs. A new QTL for total fruit weight under salinity (TW) near TG24 was detected. Most of the detected QTLs [3 for TW, 5 for fruit number, (FN) and 4 for fruit weight (FW)] had low R ² values, except the FW QTL in the TG180-TG48 interval, which explains 36.6% of the total variance. Dominant and overdominant effects were detected at the QTLs for TW, whereas gene effects at the QTLs for FJV and FW ranged from additive to partial dominance. Phenotypic selection of F₂ familes and marker-assisted selection of F₃ families were carried out. Yield under salinity decreased in the F₂ generation. F₃ means were similar to those of the F₁ as a consequence of phentoypic selection. The most important selection response for every trait was obtained from the F₃ to F₄ where MAS was applied. While F₃ variation was mainly due to the within-family component, in the F₄ the FN and FW between-family component was larger than the within-family one, indicating an efficient compartmentalization and fixation of QTLs into the F₄ families. Comparison of the yield of these families under control versus saline conditions showed that fruit weight is a key trait to success in tomato salt-tolerance improvement using wild Lycopersicon germplasm. The QTLs we have detected under salinity seem to be also working under control conditions, although the interaction family x treatment was significant for TW, thereby explaining the fact that the selected families responded differently to salinity.     

Md-ACS1 and Md-ACO1 genotyping of apple (<Emphasis Type="Italic">Malus</Emphasis> x <Emphasis Type="Italic">domestica</Emphasis> Borkh.) breeding parents and suitability for marker-assisted selection

Fruit ethylene production genotypes for Md-ACS1 and Md-ACO1 were determined for 60 apple cultivars and 35 advanced breeding selections. Two alleles for each gene are commonly found in cultivated apple. Earlier studies showed that genotypes homozygous for the ACS1-2 allele produce less ethylene and have firmer fruit than ACS1-1/2 and ACS1-1/1 genotypes. ACO1 plays a minor role compared to ACS1, with homozygous ACO1-1 having lower ethylene production. In this study, ACS1-2 and ACO1-1 homozygotes had firmer fruit at harvest and after 60 days of 0–1°C cold storage compared to other genotypes. These genotypes, ACS1-2/2 and ACO1-1/1, were observed for the following 8 of 95 cultivars/selections: “Delblush”, “Fuji”, “Pacific Beauty”, “Sabina” and four breeding selections. Cultivars/selections that were homozygous ACS1-2 but not ACO1-1 were: “Ambrosia”, “Aurora Golden Gala”, “CrimsonCrisp”, “Gala”, “GoldRush”, “Huaguan”, “Pacific Rose, “Pacific Queen”, “Pinova”, “Sansa”, “Sonja”, “Sundance”, “Zestar”, and 17 breeding selections. Cultivars with the heterozygous ACS1-1/2 genotype were “Arlet”, “Braeburn”, “Cameo”, “Delicious”, “Delorgue”, “Empire”, “Enterprise”, “Ginger Gold”, “Golden Delicious”, “Granny Smith”, “Honeycrisp”, “Orin”, “Pink Lady”, “Silken”, “Suncrisp”, “Sundowner”, “Sunrise” and 11 breeding selections. No cultivars were detected homozygous for both ACS1-1 and ACO1-1, or for both ACS1-2 and ACO1-2. This study is the first large-scale allelic genotyping of both ethylene synthesis genes for a comprehensive set of apple breeding parents used in an ongoing breeding project. The data reported here are important for informative selection of parent combinations and marker-assisted selection of progeny for breeding low ethylene-producing apple cultivars for better storability and improved consumer acceptance.     

Money matters (II): costs of maize inbred line conversion schemes at CIMMYT using conventional and marker-assisted selection

This article presents selected results of a study carried out in Mexico at the International Maize and Wheat Improvement Center (CIMMYT) to compare the cost-effectiveness of conventional and biotechnology-assisted maize breeding. Costs associated with the use of conventional and marker-assisted selection (MAS) methods at CIMMYT were estimated using a spreadsheet-based budgeting approach. This information was used to compare the costs of conventional and MAS methods for a particular breeding application: introgressing an elite allele at a single dominant gene into an elite maize line (line conversion). At CIMMYT, neither method shows clear superiority in terms of both cost and speed: conventional breeding schemes are less expensive, but MAS-based breeding schemes can be completed in less time. For applications involving tradeoffs between time and money, relative profitability can be evaluated using conventional investment theory. Using a simple model of a plant breeding program, we show that the optimal choice of a breeding technology depends on the availability of operating capital. If operating capital is abundantly available, the "best" breeding method will be the one that maximizes the net present value (i.e., MAS), but if operating capital is constrained, the "best" breeding method will be the one that maximizes the internal rate of return (i.e., conventional selection). This insight may help to explain why private firms tend to invest more aggressively in biotechnology than public breeding programs, which are more likely to face budgetary constraints.     

A model for marker-assisted selection among single crosses with multiple genetic markers

 Trait means of marker genotypes are often inconsistent across experiments, thereby hindering the use of regression techniques in marker-assisted selection. Best linear unbiased prediction based on trait and marker data (TM-BLUP) does not require prior information on the mean effects associated with specific marker genotypes and, consequently, may be useful in applied breeding programs. The objective of this paper is to present a flanking-marker, TM-BLUP model that is applicable to interpopulation single crosses that characterize maize (Zea mays L.) breeding programs. The performance of a single cross is modeled as the sum of testcross additive and dominance effects at unmarked quantitative trait loci (QTL) and at marked QTL (MQTL). The TM-BLUP model requires information on the recombination frequencies between flanking markers and the MQTL and on MQTL variances. A tabular method is presented for calculating the conditional probability that MQTL alleles in two inbreds are identical by descent given the observed marker genotypes (G ^k _obs) at the kth MQTL. Information on identity by descent of MQTL alleles can then be used to calculate the conditional covariance of MQTL effects between single crosses given G ^k _obs. The inverse of the covariance matrix for dominance effects at unmarked QTL and MQTL can be written directly from the inverse of the covariance matrices of the corresponding testcross additive effects. In practice, the computations required in TM-BLUP may be prohibitive. The computational requirements may be reduced with simplified TM-BLUP models wherein dominance effects at MQTL are excluded, only the single crosses that have been tested are included, or information is pooled across several MQTL. Received: 22 June 1997 / Accepted: 25 February 1998     

Combining bacterial blight resistance and Basmati quality characteristics by phenotypic and molecular marker-assisted selection in rice

Bacterial Blight (BB) caused by Xanthomonas oryzae pv. oryzae is a major disease of rice in tropical Asia. Since all the Basmati varieties are highly susceptible and the disease is prevalent in the entire Basmati growing region of India, BB is a severe constraint in Basmati rice production. The present study was undertaken with the objective of combining the important Basmati quality traits with resistance to BB by a combination of phenotypic and molecular marker-assisted selection (MAS). Screening of 13 near-isogenic lines of rice against four isolates of the pathogen from Basmati growing regions identified the Xa4, xa8, xa13 and Xa21 effective against all the isolates tested. Two or more of these genes in combination imparted enhanced resistance as expressed by reduced average lesion length in comparison to individual genes. The two-gene pyramid line IRBB55 carrying xa13 and Xa21 was found equally effective as three/four gene pyramid lines. The two BB resistance genes present in IRBB55 were combined with the Basmati quality traits of Pusa Basmati-1 (PB-1), the most popular high yielding Basmati rice variety used as recurrent parent. Phenotypic selection for disease resistance, agronomic and Basmati quality characteristics and marker-assisted selection for the two resistance genes were carried out in BC₁F₁, BC₁F₂ and BC₁F₃ generations. Background analysis using 252 polymorphic amplified fragment length polymorphism (AFLP) markers detected 80.4 to 86.7% recurrent parent alleles in BC₁F₃ selections. Recombinants having enhanced resistance to BB, Basmati quality and desirable agronomic traits were identified, which can either be directly developed into commercial varieties or used as immediate donors of BB resistance in Basmati breeding programs.     

玉米抗甘蔗花叶病毒分子标记开发

由甘蔗花叶病毒引起的玉米矮花叶病是我国黄淮海地区玉米生产的重要病害,开发抗矮花叶病基因分子标记是开展抗病分子标记辅助育种的基础。本文基于玉米6．00-6．01区域的“一致性抗甘蔗花叶病毒QTL区间”寻找抗病基因的功能保守域,依据序列多态性开发出抗病分子标记InDel-130和InDel-110,在已知抗性的102份玉米自交系中进行验证。通过分析标记抗病带型和感病带型中的抗病和感病自交系数目,卡平方测验表明标记InDel-130在供试自交系中与抗病性的表现独立无关．而标记InDel-110与甘蔗花叶病毒抗性高度相关,为共显性标记,可用于玉米抗甘蔗花叶病毒种质筛选和分子标记辅助育种。     

Utilization of DNA marker-assisted selection in Korean native animals

The recent progress of DNA technologies including DNA fingerprinting (DFP) and random amplified DNA polymorphism (RAPD) analysis make it possible to identify the specific genetic traits of animals and to analyze the genetic diversity and relatedness between or within species or populations. Using those techniques, some efforts to identify and develop the specific DNA markers based on DNA polymorphism, which are related with economic traits for Korean native animals, Hanwoo (Korean native cattle), Korean native pig and Korean native chicken, have been made in Korea for recent a few years. The developed specific DNA markers successfully characterize the Korean native animals as the unique Korean genetic sources, distinctively from other imported breeds. Some of these DNA markers have been related to some important economic traits for domestic animals, for example, growth rate and marbling for Hanwoo, growth rate and back fat thickness for native pig, and growth rate, egg weight and egg productivity for native chicken. This means that those markers can be used in important marker-assisted selection (MAS) of Korean native domestic animals and further contribute to genetically improve and breed them.     

Within-family marker-assisted selection for aquaculture species

A within-family marker-assisted selection scheme was designed for typical aquaculture breeding schemes, where most traits are recorded on sibs of the candidates. Here, sibs of candidates were tested for the trait and genotyped to establish genetic marker effects on the trait. BLUP breeding values were calculated, including information of the markers (MAS) or not (NONMAS). These breeding values were identical for all family members in the NONMAS schemes, but differed between family members in the MAS schemes, making within-family selection possible. MAS had up to twice the total genetic gain of the corresponding NONMAS scheme. MAS was somewhat less effective when heritability increased from 0.06 to 0.12 or when the frequency of the positive allele was < 0.5. The relative efficiency of MAS was higher for schemes with more candidates, because of larger fullsib family sizes. MAS was also more efficient when male:female mating ratio changed from 1:1 to 1:5 or when the QTL explained more of the total genetic variation. Four instead of two markers linked to the QTL increased genetic gain somewhat. There was no significant difference in polygenic genetic gain between MAS and NONMAS for most schemes. The rates of inbreeding were lower for MAS than NON-MAS schemes, because fewer full-sibs were selected by MAS.     

Hg浸种对玉米种子萌发过程中几种酶活性的影响

1　引　　言Hg是环境污染的重要因素,有关Hg对植物生长发育的影响及危害机制已有报导[1,3],但Hg对玉米种子萌发作用尚未见报道.种子萌发依靠自身储存的淀粉、脂肪和蛋白质的分解来提供物质和能量,合成新的生命物质.因此环境对种子萌发的影响首先表现在对这些大物质分解代谢的影     

The accuracy of prediction of genomic selection in elite hybrid rye populations surpasses the accuracy of marker-assisted selection and is equally augmented by multiple field evaluation locations and test years

Background

Marker-assisted selection (MAS) and genomic selection (GS) based on genome-wide marker data provide powerful tools to predict the genotypic value of selection material in plant breeding. However, case-to-case optimization of these approaches is required to achieve maximum accuracy of prediction with reasonable input.

Results

Based on extended field evaluation data for grain yield, plant height, starch content and total pentosan content of elite hybrid rye derived from testcrosses involving two bi-parental populations that were genotyped with 1048 molecular markers, we compared the accuracy of prediction of MAS and GS in a cross-validation approach. MAS delivered generally lower and in addition potentially over-estimated accuracies of prediction than GS by ridge regression best linear unbiased prediction (RR-BLUP). The grade of relatedness of the plant material included in the estimation and test sets clearly affected the accuracy of prediction of GS. Within each of the two bi-parental populations, accuracies differed depending on the relatedness of the respective parental lines. Across populations, accuracy increased when both populations contributed to estimation and test set. In contrast, accuracy of prediction based on an estimation set from one population to a test set from the other population was low despite that the two bi-parental segregating populations under scrutiny shared one parental line. Limiting the number of locations or years in field testing reduced the accuracy of prediction of GS equally, supporting the view that to establish robust GS calibration models a sufficient number of test locations is of similar importance as extended testing for more than one year.

Conclusions

In hybrid rye, genomic selection is superior to marker-assisted selection. However, it achieves high accuracies of prediction only for selection candidates closely related to the plant material evaluated in field trials, resulting in a rather pessimistic prognosis for distantly related material. Both, the numbers of evaluation locations and testing years in trials contribute equally to prediction accuracy.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-556) contains supplementary material, which is available to authorized users.     

Ultra-simple DNA extraction method for marker-assisted selection using microsatellite markers in rice

We prevent an ultra-simple DNA extraction method for microsatellite analysis of rice. Each extraction requires only one microtube, one disposable pipette tip, TE buffer and few pieces (about 5 mm) of rice leaf tissue. This is sufficient for 200 PCR reactions. The extract can be kept in the freezer for long-term storage. Also, DNA can be extracted from 200–300 individuals in a few hours. These features enabled us to perform rapid largescale seedling genotyping required for marker-assisted selection. We have also examined the applicability of this method for other PCR-based markers: RAPDs, nuclear STS, chloroplast STS and chloroplast microsatellites.     

Marker-assisted selection and marker-QTL associations in hybrid populations

A detailed analysis is presented of the relationship between genetic markers and quantitative trait loci (QTLs) in the process of marker-assisted selection (MAS). We simulated MAS employing a multiple linear regression to chose from among all of the markers in the genome those to be utilized by selection and to estimate their associated effects on the trait. The simulations demonstrate that, even when such selection is quite effective, the markers utilized by selection are not necessarily the most tightly linked to the QTLs controling the trait. Moreover, the additive effects associated with the markers estimated by the regression may not accurately reflect the contributions to the trait by the most tightly linked QTLs.