Strain and sex differences in repeated ethanol treatment-induced motor activity in quasi-congenic mice

The B6.C quasi-congenic Recombinant QTL Introgression (RQI) strains of the b4i5 series have similar genetic background, but differ in about 5% of their genome from the C57BL/6ByJ (B6) background strain because they carry short chromosome segments introgressed from the BALB/cJ (C) donor strain. These RQI strains were derived from mouse lines selectively bred for high activity of mesencephalic tyrosine hydroxylase (TH/MES), therefore genetic variation in dopamine system-related behaviours, such as ethanol-induced motor activity, can be expected. Males and females of 17 RQI and two progenitor strains were tested for initial motor activity for 15 min after a habituating injection of saline, which was followed by an i.p. injection of saline or ethanol (2 g/kg) and an additional test of motor activity for 30 min. This procedure was repeated during 4 subsequent days. In all strains, the first-day ethanol treatment showed an inhibitory effect. With repetition of the treatment the inhibitory effect decreased, and a stimulatory effect could be observed with significant strain- and sex-dependent variation. Females exhibited higher activity in the saline group than males, and reached an equilibrium of inhibition and stimulation sooner than males with repetition of the ethanol treatment. The highest (> 25-fold) difference in activity after repeated ethanol treatment was detected between females of the two strains B6.Cb4i5-Alpha4/Vad and B6.Cb4i5-Beta13/Vad. These results firstly suggest that females are more sensitive to repeated ethanol exposure than males, secondly they support the observations that ethanol has both inhibitory and stimulatory effects on motor activity, which are affected by sex, genotype, and repetition of treatment, and thirdly offer new quasi-congenic animal models with highly different responses to ethanol allowing one to more quickly move to gene detection.     

Mapping of QTLs for Oral Alcohol Self-Administration in B6.C and B6.I Quasi-Congenic RQI Strains

One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle-choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (Vadasz et al. (2000) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22:25–34) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12, while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance.     

Development of Oryza rufipogon and O. sativa Introgression Lines and Assessment for Yield-related Quantitative Trait Loci

Introgression lines population was effectively used in mapping quantitative trait loci （QTLs）, identifying favorable genes, discovering hidden genetic variation, evaluating the action or interaction of QTLs in multiple conditions and providing the favorable experimental materials for plant breeding and genetic research. In this study, an advanced backcross and consecutive selfing strategy was used to develop introgression lines （ILs）, which derived from an accession of Oryza rufipogon Griff. collected from Yuanjiang County, Yunnan Province of China, as the donor, and an elite indica cultivar Teqing （O. sativa L.）, as the recipient. Introgression segments from O. rufipogon were screened using 179 polymorphic simple sequence repeats （SSR） markers in the genome of each IL. Introgressed segments carried by the introgression lines population contained 120 ILs covering the whole O. rufipogon genome. The mean number of homozygous O. rufipogon segments per introgression line was about 3.88. The average length of introgressed segments was approximate 25.5 cM, and about 20.8% of these segments had sizes less than 10 cM. The genome of each IL harbored the chromosomal fragments of O. rufipogon ranging from 0.54% to 23.7%, with an overall average of 5.79%. At each locus, the ratio of substitution of O. rufipogon alleles had a range of 1.67-9.33, with an average of 5.50. A wide range of alterations in morphological and yield-related traits were also found in the introgression lines population. Using single-point analysis, a total of 37 putative QTLs for yield and yield components were detected at two sites with 7%-20% explaining the phenotypic variance. Nineteen QTLs （51.4%） were detected at both sites, and the alleles from O. rufipogon at fifteen loci （40.5%） improved the yield and yield components in the Teqing background. These O. rufipogon-O, sativa introgression lines will serve as genetic materials for identifying and using favorable genes from common wild rice.     

In an elite cross of maize a major quantitative trait locus controls one-fourth of the genetic variation for grain yield

Quantitative trait loci (QTLs) for grain yield, dry matter content and test weight were identified in an F₂ segregating population derived from a single cross between two elite maize lines (B73 and A7) and testcrossed to two genetically divergent in breds. Most of the QTLs inferred were consistent across locations, indicating that the expression of the genes influencing the traits under investigation was largely independent of the environment. By using two different tester lines we found that QTLs exhibited by one tester may not necessarily be detected with the second one. Only loci with larger effects were consistent across testers, suggesting that interaction with tester alleles may contribute to the identification of QTLs in a specific fashion. Analysis across both testers revealed four significant QTLs for grain yield that explained more than 35% of the phenotypic variation and showed an overall phenotypic effect of more than 2t/ha. The major QTL for grain yield, located in the proximity of the Nucleolus Organiser Region, accounted for 24.5% of the phenotypic variation for grain yield and showed an average effect of allele substitution of approximately 1 t/ha. Marker-assisted introgression of the superior A7 allele at this locus in the B73 genetic background will not differ from qualitative trait introgression and will eventually lead to new lines having superior testcross performance.     

Shaping melons: agronomic and genetic characterization of QTLs that modify melon fruit morphology

The consistency of quantitative trait locus (QTL) effects among genetic backgrounds is a key factor for introgressing QTLs from initial mapping experiments into applied breeding programs. We have selected four QTLs (fs6.4, fw4.3, fw4.4 and fw8.1) involved in melon fruit morphology that had previously been detected in a collection of introgression lines derived from the cross between a Spanish cultivar, “Piel de Sapo,” and the Korean accession PI161375 (Songwan Charmi). Introgression lines harboring these QTLs were crossed with an array of melon inbred lines representative of the most important cultivar types. Hybrids of the introgression and inbred lines, with the appropriate controls, were evaluated in replicated agronomic trials. The effects of the QTLs were consistent among the different genetic backgrounds, demonstrating the utility of these QTLs for applied breeding programs in modifying melon fruit morphology. Three QTLs, fw4.4, fs6.4 and fs12.1 were subjected to further study in order to map them more accurately by substitution mapping using a new set of introgression lines with recombination events within the QTL chromosome region. The position of the QTLs was narrowed down to 36–5 cM, depending on the QTL. The results presented in the current study set the basis for the use of these QTLs in applied breeding programs and for the molecular characterization of the genes underlying them.     

Marker-assisted introgression of favorable alleles at quantitative trait loci between maize elite lines

This article reports the marker-assisted introgression of favorable alleles at three quantitative trait loci (QTL) for earliness and grain yield among maize elite lines. The QTL were originally detected in 1992 by means of ANOVA in a population of 96 recombinant inbred lines (RILs). Introgression started from a selected RIL, which was crossed three times to one of the original parents and then self-fertilized, leading to BC(3)S(1) progenies. Markers were used to assist both foreground and background selection at each generation. At the end of the program, the effect of introgression was assessed phenotypically in agronomic trials, and QTL detection was performed by composite interval mapping among BC(3)S(1) progenies. The marker-assisted introgression proved successful at the genotypic level, as analyzed by precision graphical genotypes, although no emphasis was put on the reduction of linkage drag around QTL. Also, QTL positions were generally sustained in the introgression background. For earliness, the magnitude and sign of the QTL effects were in good agreement with those expected from initial RIL analyses. Conversely, for yield, important discrepancies were observed in the magnitude and sign of the QTL effects observed after introgression, when compared to those expected from initial RIL analyses. These discrepancies are probably due to important genotype-by-environment interactions.     

A large QTL for fear and anxiety mapped using an F2 cross can be dissected into multiple smaller QTLs

Using chromosome substitution strains (CSS), we previously identified a large quantitative trait locus (QTL) for conditioned fear (CF) on mouse chromosome 10. Here, we used an F₂ cross between CSS‐10 and C57BL/6J (B6) to localize that QTL to distal chromosome 10. That QTL accounted for all the difference between CSS‐10 and B6. We then produced congenic strains to fine‐map that interval. We identified two congenic strains that captured some or all the QTL. The larger congenic strain (Line 1: 122.387121–129.068 Mb; build 37) appeared to account for all the difference between CSS‐10 and B6. The smaller congenic strain (Line 2: 127.277–129.068 Mb) was intermediate between CSS‐10 and B6. We used haplotype mapping followed by quantitative polymerase chain reaction to identify one gene that was differentially expressed in both lines relative to B6 (Rnf41) and one that was differentially expressed between only Line 1 and B6 (Shmt2). These cis‐eQTLs may cause the behavioral QTLs; however, further studies are required to validate these candidate genes. More generally, our observation that a large QTL mapped using CSS and F₂ crosses can be dissected into multiple smaller QTLs shows a weaknesses of two‐stage approaches that seek to use coarse mapping to identify large regions followed by fine‐mapping. Indeed, additional dissection of these congenic strains might result in further subdivision of these QTL regions. Despite these limitations, we have successfully fine‐mapped two QTLs to small regions and identified putative candidate genes, showing that the congenic approach can be effective for fine‐mapping QTLs .     

Identification of QTLs for some agronomic traits in rice using an introgression line from Oryza minuta

Wild progenitor species provide potential gene sources for complex traits such as yield and multiple resistances to biotic and abiotic stresses, and thus are expected to contribute to sustainable food supplies. An introgression line 'IR71033-121-15' was derived from a wild species Oryza minuta (2n = 48, BBCC, Acc No. 101141) at IRRI. Introgression analysis using 530 SSR and STS markers revealed that at least 14 chromosomal segments distributed over 12 chromosomes had been introgressed from O. minuta. An F2:3 population from the cross between IR71033 and Junambyeo (a Korean japonica cultivar) consisting of 146 lines was used for quantitative trait loci (QTL) analysis of 16 agronomic traits. A total of 36 single-locus QTLs (S-QTLs) and 45 digenic epistasis (E-QTLs) were identified. In spite of it's inferiority of O. minuta for most of the traits studied, its alleles contributed positively to 57% of the QTLs. The other QTLs originated from either parent, IR71033 or Junambyeo. QTLs for phenotypically correlated traits were mostly detected on introgressed segments. Fourteen QTLs corresponded to QTLs reported earlier, indicating that these QTLs are stable across genetic backgrounds. Twenty-two QTLs controlling yield and its components had not been detected in previous QTL studies. Of these, thirteen consisted of potentially novel alleles from O. minuta. QTLs from O. minuta introgression could be new sources of natural variation for the genetic improvement of rice.     

Identification of Quantitative Trait Loci Controlling Drought Tolerance at Seedling Stage in Chinese Dongxiang Common Wild Rice (Oryza rufipogon Griff.)

Common wild rice (Oryza rufipogon Griff.) is the ancestor of cultivated rice (O. sativa L.), which has a greater genetic diversity and important traits that remain to be employed in cultivated rice. In this study, a set of introgression lines (BC₄F₅ and/or BC₄F₆) carrying various introgressed segments from common wild rice, collected from Dongxiang county, Jiangxi Province, China, in the background of an Indica (O. sativa L. ssp. indica) cultivar, Guichao 2, was used. A total of 12 drought-related quantitative trait loci (QTL) were identified by investigating drought tolerance of introgression lines under 30% PEG treatment at the young seedlings stage. Of these QTLs, the alleles of 4 QTLs on chromosome 2, 6 and 12 from Dongxiang common wild rice were responsible for increased drought tolerance of the introgression lines. In particular, a QTL qSDT12-2, near RM17 on chromosome 12, was consistently detected in different replications, and expressed stably under PEG stress throughout the study. It was also found that the QTLs located on different chromosomes might express at different stages.     

江西东乡野生稻苗期抗旱基因定位

普通野生稻是栽培稻的祖先种,其遗传多样性远远大于栽培稻,蕴涵着栽培品种中难以找到的重要性状.以江西东乡普通野生稻为供体、以桂朝2号为遗传背景的野生稻基因渗入系（BC4F5、BC4F6）为材料,利用30%的PEG人工模拟干旱环境,对渗入系二叶一心苗期进行抗旱鉴定,共定位了12个与抗旱有关的QTL,其中在第2、6和12染色体上发现了4个QTL的加性效应值为正,来自东乡野生稻的等位基因能使渗入系的抗旱性增强,特别是位于第12染色体RM17附近的qSDT12-2在多次重复中均被检测到,在PEG处理后1-8 d能稳定表达.通过对抗旱性QTL的动态分析,发现不同QTL表达时间不同.     

Development of congenics for hypnotic sensitivity to ethanol by QTL-marker-assisted counter selection

Mouse strains congenic for individual quantitative trait loci (QTLs) conferring hypnotic sensitivity to ethanol were constructed by backcrossing genotypically selected ILS × ISS N₂ individuals to either inbred Long Sleep (ILS) or inbred Short Sleep (ISS) mice. We used a novel ``speed congenic' approach in which N<sub>2</sub> mice were genotyped for markers flanking each of the five originally identified QTLs. Genotypic selection for ISS regions at four of the five QTLs, and for ILS/ISS at the fifth QTL, allowed rapid fixation of the genetic background. We call this strategy ``QTL-Marker-Assisted Counter Selection' or QMACS. By the N₄ generation, phenotypic assessments showed that in some sublines the QTL had not been captured; these sublines were discarded and positive lines split to create new replicate sublines. One QTL, on Chromosome (Chr) 8, was not confirmed. At the N₈, virtually all sublines on the remaining QTLs retained the phenotypic difference between heterozygotes and ISS homozygotes. Small numbers of interim congenics were produced at the N₆ and later generations in which the ILS QTL was made homozygous on the ISS background; as expected, these congenic mice showed an increased sleep time. For later backcrosses (after the N₄), the parents were selected on the basis of phenotype as well as genotype. The parent-offspring correlation over all QTLs was significant, supporting the use of phenotypic selection in congenic construction. Received: 15 September 1998 / Accepted: 8 October 1998     

Individual QTLs controlling quantitative variation in blood pressure inherited in a Mendelian mode

We studied three possible genotypes at 10 well-defined blood pressure (BP) QTLs using congenic rat lines. The central question was whether the hypertensive or normotensive allele is dominant, or whether there is partial dominance. The congenic strains were employed to investigate the BP effects of alleles originating from normotensive rats in the background of hypertensive Dahl salt-sensitive (DSS) rats. The normotensive alleles at eight QTLs were fully dominant over DSS alleles, which we tentatively interpreted as indicating that DSS rats incurred a loss of function at these loci and that the QTLs produced BP-reducing agents. In contrast, the normotensive allele of only one QTL was recessive over its DSS counterpart, implying a gain of function at this QTL or a null allele involved in generating a BP-elevating agent. Only one locus, C17QTL, had alleles exhibiting partial dominance. These estimates of dominance differ considerably from those obtained by QTL analysis in a F2 cross. This disagreement demonstrates the importance of establishing a cause-effect relationship between a QTL and its phenotypic effect via congenic strains. The dominance relationships suggest pertinent strategies for gene identification and pharmaceutical intervention.     

Marker-assisted introgression of Trypanotolerance QTL in mice

A marker-assisted introgression (MAI) experiment was conducted to use genetic markers to transfer each of the three trypanotolerance QTL from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. We used a backcross strategy that consisted of selecting two lines, each carrying two of the donor QTL alleles through the backcross (BC) phase. At the fourth BC generation, single-carrier animals were selected for the production of homozygous animal in the intercross phase. The QTL regions (QTLR) were located on chromosomes MMU1, MMU5, and MMU17. Groups of mice with different genotypes and the parental lines were subjected to a challenge with Trypanosoma congolense. The results show that trypanotolerance QTL was successfully moved into the recipient background genotype, yielding a longer survival time. The mean estimated survival time was 57.9, 49.5, and 46.8 days for groups of mice carrying the donor QTL on MMU1, MMU5, and MMU17 on A/J background. The mean estimated survival time was 29.7 days for the susceptible A/J line and 68.8 days for the resistant C57BL/6 line. The estimated QTLR effects are close to 30% smaller than those in the original mapping population which was likely caused by the difference in the background on which the effects of QTLR are tested. This is the first report of successful marker-assisted introgression of QTL in animals. It is experimental proof of the use of genetic markers for marker-assisted introgression in animal breeding.Institut National des Recherches Agricoles du Bénin, 01 BP 884 COTONOU, République du Bénin     

Efficient QTL detection for nonhost resistance in wild lettuce: backcross inbred lines versus F2 population

In plants, several population types [F₂, recombinant inbred lines, backcross inbred lines (BILs), etc.] are used for quantitative trait locus (QTL) analyses. However, dissection of the trait of interest and subsequent confirmation by introgression of QTLs for breeding purposes has not been as successful as that predicted from theoretical calculations. More practical knowledge of different QTL mapping approaches is needed. In this recent study, we describe the detection and mapping of quantitative resistances to downy mildew in a set of 29 BILs of cultivated lettuce (L. sativa) containing genome segments introgressed from wild lettuce (L. saligna). Introgression regions that are associated with quantitative resistance are considered to harbor a QTL. Furthermore, we compare this with results from an already existing F₂ population derived from the same parents. We identified six QTLs in our BIL approach compared to only three in the F₂ approach, while there were two QTLs in common. We performed a simulation study based on our actual data to help us interpret them. This revealed that two newly detected QTLs in the BILs had gone unnoticed in the F₂, due to a combination of recessiveness of the trait and skewed segregation, causing a deficit of the wild species alleles. This study clearly illustrates the added value of extended genetic studies on two different population types (BILs and F₂) to dissect complex genetic traits.     

Identification of novel mouse genes conferring posthypoxic pauses

Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects. Fine-mapping reduced the genomic intervals and gene content, and the introgression of one QTL region back onto the C57BL/6J-Chr 1(A/J)/NaJ restored the trait. mRNA expression of non-synonymous genes in the introgressed region in the medulla and pons found evidence for differential expression of three genes, the highest of which was apolipoprotein A2, a lipase regulator; the apo a2 peptide fragment (THEQLTPLVR), highly expressed in the liver, was expressed in low amounts in the medulla but did not correlate with trait expression. This work directly demonstrates the impact of elements on mouse chromosome 1 in respiratory rhythmogenesis.     

Stability over genetic backgrounds, generations and years of quantitative trait locus (QTLs) for organoleptic quality in tomato

The efficiency of marker-assisted backcross for the introgression of a quantitative trait locus (QTL) from a donor line into a recipient line depends on the stability of QTL expression. QTLs for six quality traits in tomato (fruit weight, firmness, locule number, soluble solid content, sugar content and titratable acidity) were studied in order to investigate their individual effect and their stability over years, generations and genetic backgrounds. Five chromosome regions carrying fruit quality QTLs were transferred following a marker-assisted backcross scheme from a cherry tomato line into three modern lines with larger fruits. Three sets of genotypes corresponding to three generations were compared: (1) an RIL population, which contained 50% of each parental genome, (2) three BC3S1 populations which segregated simultaneously for the five regions of interest but were almost fully homozygous for the recipient genome on the eight chromosomes carrying no QTL and (3) three sets of QTL-NILs (BC3S3 lines) which differed from the recipient line only in one of the five regions. QTL detection was performed in each generation, in each genetic background and during 2 successive years for QTL-NILs. About half of the QTLs detected in QTL-NILs were detected in both years. Eight of the ten QTLs detected in RILs were recovered in the QTL-NILs with the genetic background used for the initial QTL mapping experiment, with the exception of two QTLs for fruit firmness. Several new QTLs were detected. In the two other genetic backgrounds, the number of QTLs in common with the RILs was lower, but several new QTLs were also detected in advanced generations.     

Genetic Analysis of a New Mouse Model for Non-Insulin-Dependent Diabetes

The TallyHo (TH) mouse strain is a newly established model for non-insulin-dependent diabetes mellitus (NIDDM). TH mice show obesity, hyperinsulinemia, hyperlipidemia, and male-limited hyperglycemia. A genetic dissection of the diabetes syndrome has been carried out using male backcross 1 progeny obtained from crosses between (C57BL/6J x TH)F1 and TH mice or (CAST/Ei x TH)F1 and TH mice. A genome-wide scan reveals three quantitative trait loci (QTLs), Tanidd1-3 (TH-associated NIDDM) linked to hyperglycemia. The major QTL (common in both crosses), Tanidd1, maps to chromosome (Chr) 19. Additionally, gene-gene interactions contributing to hyperglycemia have been observed between Tanidd1 and a locus on Chr 18 as well as between Tanidd2 and a locus on Chr 16. The overt hyperglycemia in TH mice is, therefore, likely due to a mutation in a major diabetes susceptibility locus on Chr 19, which interacts with additional genes to lead to an observable phenotype.     

粳稻蒸煮食味品质相关性状的QTL分析

以沈农265和丽江新团黑谷杂交衍生的重组自交系群体(RILs)为实验材料,对12个粳稻(Oryza sativa subsp.japonica)蒸煮食味品质相关性状进行QTL分析。共检测到29个蒸煮食味品质相关的QTLs,分布于除第8染色体外的11条染色体上,LOD值介于2.50–16.47之间,加性效应值为–132.69–471.85,单个QTL贡献率为10.36%–73.24%。在第6染色体RM508–RM253区域检测到1个蒸煮营养食味品质多效性QTL簇,其中q AC6表型贡献率最大,解释73.24%的表型变异;在第10染色体PM166–RM258区域检测到2个与蒸煮食味品质相关的QTLs,分别是控制口感的q CTS10和综合评分的q CCS10。此外,检测到15个与RVA特征谱相关的QTLs,在第6染色体RM253–RM402区域检测到3个与RVA谱特征值相关的QTLs,表型贡献率均大于12%。这些定位结果将为粳稻蒸煮食味相关品质的分子遗传机理研究奠定基础。     

Identification of salt-tolerant QTLs with strong genetic background effect using two sets of reciprocal introgression lines in rice

Effect of genetic background on detection of quantitative trait locus (QTL) governing salinity tolerance (ST) was studied using two sets of reciprocal introgression lines (ILs) derived from a cross between a moderately salinity tolerant japonica variety, Xiushui09 from China, and a drought tolerant but salinity susceptible indica breeding line, IR2061-520-6-9 from the Philippines. Salt toxicity symptoms (SST) on leaves, days to seedling survival (DSS), and sodium and potassium uptake by shoots were measured under salinity stress of 140?mmol/L of NaCl. A total of 47 QTLs, including 26 main-effect QTLs (M-QTLs) and 21 epistatic QTLs (E-QTLs), were identified from the two sets of reciprocal ILs. Among the 26?M-QTLs, only four (15.4%) were shared in the reciprocal backgrounds while no shared E-QTLs were detected, indicating that ST QTLs, especially E-QTLs, were very specific to the genetic background. Further, 78.6% of the M-QTLs for SST and DSS identified in the reciprocal ILs were also detected in the recombinant inbred lines (RILs) from the same cross, which clearly brings out the background effect on ST QTL detection and its utilization in ST breeding. The detection of ILs with various levels of pyramiding of nonallelic M-QTL alleles for ST from Xiushui09 into IR2061-520-6-9 allowed us to further improve the ST in rice.     

Healing quantitative trait loci in a combined cross analysis using related mouse strain crosses

Inbred mouse strains MRL and LG share the ability to fully heal ear hole punches with the full range of appropriate tissues without scarring. They also share a common ancestry, MRL being formed from a multi-strain cross with two final backcrosses to LG before being inbred by brother-sister mating. Many gene-mapping studies for healing ability have been performed using these two strains, resulting in the location of about 20 quantitative trait loci (QTLs). Here, we combine two of these crosses (N = 638), MRL/lpr × C57BL/6NTac and LG/J × SM/J, in a single combined cross analysis to increase the mapping power, decrease QTL support intervals, separate multiple QTLs and establish allelic states at individual QTL. The combined cross analysis located 11 QTLs, 6 affecting only one cross (5 LG × SM and 1 MRL × B6) and 5 affecting both crosses, approximately the number of common QTLs expected given strain SNP similarity. Amongst the five QTLs mapped in both crosses, three had significantly different genetic effects, additive in one cross and over or underdominant in the other. It is possible that allelic states at these three loci are different in SM and B6 because they lead to differences in dominance interactions with the LG and MRL alleles. QTL support intervals are 40% smaller in the combined cross analysis than in either of the single crosses. Combined cross analysis was successful in enhancing the interpretation of earlier QTL results for these strains.