2,3,7,8-Tetrachlorodibenzo-p-dioxin affects fluctuating asymmetry of molar shape in mice, and an epistatic interaction of two genes for molar size

Fluctuating asymmetry (FA), random variation between left and right sides in a bilaterally symmetrical character, is a commonly used measure of developmental instability that is expected to increase with increasing environmental stress. One potential stressor is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a powerful toxicant known to disturb tooth development. In this study, mice in the F(2) generation produced from an intercross between two inbred strains (C57BL/6J and AKR/J) were exposed in utero to TCDD. We hypothesized that TCDD would increase FA in the molars of exposed mice over that of the control mice. In addition, we hypothesized that we would discover genes for molar size, shape or asymmetry whose expression would be affected by TCDD. We detected a very small, but significant, increase in FA of molar shape (but not size) in the TCDD-exposed mice compared to the control mice, although molar size and shape did not differ between these groups. Although we did not uncover any genes that acted differently in the TCDD exposed and control groups, we did identify two genes whose dominance by additive epistatic effect on molar size was affected by TCDD. We concluded that although TCDD may be affecting the expression of some genes governing the development of molars in our population of mice, FA of molar size and shape is not a particularly sensitive indicator of this effect.     

An epistatic genetic basis for fluctuating asymmetry of mandible size in mice

The genetic basis of fluctuating asymmetry (FA), or nondirectional variation in the subtle differences between left and right sides of bilateral characters, continues to be of considerable theoretical interest. FA generally has been thought to arise from random noise during development and therefore to have a largely or entirely environmental origin. Whereas additive genetic variation for FA generally has been small and often insignificant, a number of investigators have hypothesized that interactions between loci, or epistasis, significantly influence FA. We tested this hypothesis by conducting a whole-genome scan to detect any epistasis in FA of centroid size in the mandibles of more than 400 mice from an F2 intercross population formed from crossing the Large (LG/J) and Small (SM/J) inbred strains. Genotypic deviations were imputed at each site 2 cM apart on all 19 autosomes, and these and centroid size asymmetry values were used in canonical correlation analyses for each of the 171 possible pairs of 19 autosomes to identify the most probable sites for epistasis. Epistasis for centroid size asymmetry was abundant, occurring far more often than was expected by chance alone (there were 30 separate instances of epistasis at the 0.001 significance level, when only two were expected by chance alone). The contributions of epistasis from 30 pairwise combinations of loci tended to suppress the additive and dominance genetic variance, but greatly increased the epistatic genetic variance for FA in centroid size given the intermediate allele frequencies of an F2 intercross population.     

A SEARCH FOR QUANTITATIVE TRAIT LOCI AFFECTING ASYMMETRY OF MANDIBULAR CHARACTERS IN MICE

An interval mapping procedure was used to search for and describe the effects of any quantitative trait loci (QTLs) for directional asymmetry (DA) and fluctuating asymmetry (FA) of 10 bilateral mandible characters in house mice. It was hypothesized that more QTLs would be found for DA than for FA, but that any discovered for FA should tend to exhibit dominance. All mandible characters were triply measured and 76 microsatellite markers were scored in an average of 471 mice from the F₂ intercross of the Large (LG/J) and Small (SM/J) inbred strains. A total of 16 QTLs significantly affected DA in nine of the 10 mandible characters, and this was more than the 9.5 expected by chance alone. These QTLs were found on seven of the 19 chromosomes, often at or near locations of QTLs affecting the mean of the two sides for various dimensions on the mandible. It was concluded that there is genetical variability for DA in these characters, although its level was low (4.4% of the total variation in this particular F₂ population). Eleven QTLs were detected for FA, suggesting that there is very little genetic variability for FA, at least as seen in the mandible characters in this particular F₂ population. As hypothesized, however, these QTLs did tend to exhibit dominance.     

Genetic variation in pleiotropy: differential epistasis as a source of variation in the allometric relationship between long bone lengths and body weight

Pleiotropy is an aspect of genetic architecture underlying the phenotypic covariance structure. The presence of genetic variation in pleiotropy is necessary for natural selection to shape patterns of covariation between traits. We examined the contribution of differential epistasis to variation in the intertrait relationship and the nature of this variation. Genetic variation in pleiotropy was revealed by mapping quantitative trait loci (QTLs) affecting the allometry of mouse limb and tail length relative to body weight in the mouse-inbred strain LG/J by SM/J intercross. These relationship QTLs (rQTLs) modify relationships between the traits affected by a common pleiotropic locus. We detected 11 rQTLs, mostly affecting allometry of multiple bones. We further identified epistatic interactions responsible for the observed allometric variation. Forty loci that interact epistatically with the detected rQTLs were identified. We demonstrate how these epistatic interactions differentially affect the body size variance and the covariance of traits with body size. We conclude that epistasis, by differentially affecting both the canalization and mean values of the traits of a pleiotropic domain, causes variation in the covariance structure. Variation in pleiotropy maintains evolvability of the genetic architecture, in particular the evolvability of its modular organization.     

Dynamic Quantitative Trait Loci Analysis of Seed Reserve Utilization during Three Germination Stages in Rice

In this study, one rice population of recombinant inbred lines (RILs) was used to determine the genetic characteristics of seed reserve utilization during the early (day 6), middle (day 10) and late (day 14) germination stages. The seedling dry weight (SDW) and weight of the mobilized seed reserve (WMSR) were increased, while the seed reserve utilization efficiency (SRUE) decreased, during the process of seed germination. The SDW and WMSR were affected by the seed weight, while the SRUE was not affected by the seed weight. A total of twenty unconditional and twenty-one conditional additive QTLs and eight epistatic QTLs were identified at three germination stages, and the more QTLs were expressed at the late germination stage. Among them, twelve additive and three epistatic QTLs for SDW, eight additive and three epistatic QTLs for WMSR and thirteen additive and two epistatic QTLs for SRUE were identified, respectively. The phenotypic variation explained by each additive QTL, epistatic QTL and QTL × development interaction ranged from 6.10 to 23.91%, 1.79 to 6.88% and 0.22 to 2.86%, respectively. Two major additive QTLs qWMSR7.1 and qSRUE4.3 were identified, and each QTL could explain more than 20% of the total phenotypic variance. By comparing the chromosomal positions of these additive QTLs with those previously identified, eleven QTLs might represent novel genes. The best four cross combinations of each trait for the development of RIL populations were selected. The selected RILs and the identified QTLs might be applicable to improve rice seed reserve utilization by the marker-assisted selection approach.     

EPISTASIS AND THE EFFECT OF FOUNDER EVENTS ON THE ADDITIVE GENETIC VARIANCE

Models of founder events have focused on the reduction in the genetic variation following a founder event. However, recent work (Bryant et al., 1986; Goodnight, 1987) suggests that when there is epistatic genetic variance in a population, the total genetic variance within demes may actually increase following a founder event. Since the additive genetic variance is a statistical property of a population and can change with the level of inbreeding, some of the epistatic genetic variance may be converted to additive genetic variance during a founder event. The model presented here demonstrates that some of the additive-by-additive epistatic genetic variance is converted to additive genetic variance following a founder event. Furthermore, the amount of epistasis converted to additive genetic variance is a function of the recombination rate and the propagule size. For a single founder event of two individuals, as much as 75% of the epistatic variance in the ancestral population may become additive genetic variance following the founder event. For founder events involving two individuals with free recombination, the relative contribution of epistasis to the additive genetic variance following a founder event is equal to its proportion of the total genetic variance prior to the founder event. Traits closely related to fitness are expected to have relatively little additive genetic variance but may have substantial nonadditive genetic variance. Founder events may be important in the evolution of fitness traits, not because they lead to a reduction in the genetic variance, but rather because they lead to an increase in the additive genetic variance.     

The Statistical Power of Inclusive Composite Interval Mapping in Detecting Digenic Epistasis Showing Common F2 Segregation Ratios

Epistasis is a commonly observed genetic phenomenon and an important source of variation of complex traits,which could maintain additive variance and therefore assure the long-term genetic gain in breeding.Inclusive composite interval mapping（ICIM） is able to identify epistatic quantitative trait loci（QTLs） no matter whether the two interacting QTLs have any additive effects.In this article,we conducted a simulation study to evaluate detection power and false discovery rate（FDR） of ICIM epistatic mapping,by considering F₂ and doubled haploid（DH） populations,different F₂ segregation ratios and population sizes.Results indicated that estimations of QTL locations and effects were unbiased,and the detection power of epistatic mapping was largely affected by population size,heritability of epistasis,and the amount and distribution of genetic effects.When the same likelihood of odd（LOD） threshold was used,detection power of QTL was higher in F₂ population than power in DH population;meanwhile FDR in F₂ was also higher than that in DH.The increase of marker density from 10 cM to 5 cM led to similar detection power but higher FDR.In simulated populations,ICIM achieved better mapping results than multiple interval mapping（MIM） in estimation of QTL positions and effect.At the end,we gave epistatic mapping results of ICIM in one actual population in rice（Oryza sativa L.）.     

Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice

The genetic basis of variation in obesity in human populations is thought to be owing to many genes of relatively small effect and their interactions. The LG/J by SM/J intercross of mouse inbred strains provides an excellent model system in which to investigate multigenic obesity. We previously mapped a large number of quantitative trait loci (QTLs) affecting adult body weight in this cross. We map body composition traits, adiposity, and skeletal size, in a replicate F₂ intercross of the same two strains containing 510 individuals. Using interval-mapping methods, we located eight QTLs affecting adiposity (Adip1–8). Two of these adiposity loci also affected tail length (Adip4 and Adip6) along with seven additional tail length QTLs (Skl1–7). A further four QTLs (Wt1–4) affect adult weight but not body composition. These QTLs have relatively small effects, typically about 0.2–0.4 standard deviation units, and account for between 3% and 10% of the variance in individual characters. All QTLs participated in epistatic interactions with other QTLs. Most of these interactions were due to additive-by-additive epistasis, which can nullify the apparent effects of single loci in our population. Adip8 interacts with all the other adiposity QTLs and seems to play a central role in the genetic system affecting obesity in this cross. Only two adiposity QTLs, Adip4 and Adip6, also affect tail length, indicating largely separate genetic control of variation in adiposity and skeletal size. Body size and obesity QTLs in the same locations as those discovered here are commonly found in mapping experiments with other mouse strains. Received: 11 January 2000 / Accepted: 17 August 2000     

Unconditional and conditional QTL analysis of kernel weight related traits in wheat (Triticum aestivum L.) in multiple genetic backgrounds

Wheat thousand kernel weight (TKW) is a complex trait, and is largely controlled by several kernel traits, including kernel length (KL) and kernel width (KW). In order to reveal the genetic relationship between TKW and these kernel traits (KW and KL) as accurate as possible, we applied both unconditional and conditional mapping analyses to three distinct genetic populations, one DH population and two RIL populations. This report describes the identifications of 36 unconditional and conditional additive QTLs and 30 pairs of unconditional and conditional epistatic QTLs, all of which are closely associated with TKW. While the conditional additive locus Qtkw1B, detected in the RIL2 population, exhibited the largest contribution, explaining 14.12 % of TKW variance, the unconditional epistatic QTLs Qtkw3A-2/Qtkw5B.1, detected in the DH population, accounted for 11.95 % of phenotypic variance. This study also showed that, compared with unconditional mapping, conditional mapping resulted in very different numbers and different extent of effects of additive and epistatic QTLs that were associated with TKW when TKW was conditioned on kernel traits (KW and KL). These data strongly suggest that KW and KL indeed play a significant role in determining TKW. Furthermore, we demonstrated that the effects of the 25 additive QTLs for TKW were either entirely or largely determined by KW, while the effects of the other 25 additive QTLs for TKW were either entirely or largely affected by KL. We conclude that the conditional mapping can be useful for a better understanding of the interrelationship between the yield contributing traits at the QTL level.     

Genetic variation underlying pod size and color traits of common bean depends on quantitative trait loci with epistatic effects

Common bean is an important vegetable legume in many regions of the world. Size and color of fresh pods are the key factors for deciding the commercial acceptance of bean as a fresh vegetable. The genetic basis of important horticultural traits of common bean is still poorly understood, which hinders DNA marker-assisted breeding in this crop. Here we report the identification of single-locus and epistatic quantitative trait loci (QTLs), as well as their environment interaction effects for six pod traits, namely width, thickness, length, size index, beak length and color, using an Andean intra-gene pool recombinant inbred line population from a cross between a cultivated common bean and an exotic nuña bean. The QTL analyses performed detected a total of 23 QTLs (single-locus QTLs and epistatic QTLs): five with only individual additive effects and six with only epistatic effects, while the remaining twelve showed both effects. These QTLs were distributed across linkage groups (LGs) 1, 2, 4, 6, 7, 8, 9, 10 and 11; particularly noteworthy are the QTLs for pod size co-located on LGs 1 and 4, indicative of tight linkage or genes with pleiotropic effects governing these traits. Overall, the results obtained showed that additive and epistatic effects are the major genetic basis of pod size and color traits. The mapping of QTLs including epistatic loci for the six pod traits evaluated provides support for implementing marker-assisted selection toward genetic improvement of common bean.     

Analysis of quantitative trait locus effects on the size and shape of mandibular molars in mice

While >50 genes have been found to influence the development of teeth in mice, we still know very little about the genetic basis for the adaptive characteristics of teeth, such as size and shape. We applied interval mapping procedures to Procrustes size and shape data obtained from 10 morphological landmarks on the mandibular molar row of the F(2) progeny from a cross between the LG/J and SM/J strains of mice. This revealed many more QTL for molar shape (18) than for molar centroid size (3), although levels of dominance effects were comparable among QTL for size and shape. Comparisons of patterns of Procrustes additive and dominance shape effects and ordination of QTL effects by principal components analysis suggested that the effects of the shape QTL were dispersed among the three molars and thus that none of these molars represents a genetically distinct developmental structure. The results of an analysis of co-occurrence of QTL for molar shape, mandible shape, and cranial dimensions in these mice suggested that many of the QTL for molar shape may be the same as those affecting these other sets of characters, although in some cases this could be due to effects of closely linked genes.     

水稻生物学产量及其构成性状的QTL定位

QTL的加性效应、加性×加性上位性效应及它们与环境的互作效应是数量性状的重要遗传分量.利用IR64/Azucena的125个DH品系为群体,分析了水稻生物学产量及其两个构成性状干草产量和谷粒产量的遗传组成.用基于混合模型的复合区间作图(MCIM)方法进行QTL定位.检测到12个位点有加性主效应,27个位点涉及双位点互作,18个位点存在环境互作.结果表明水稻生物学产量和它的两个构成性状普遍存在上位性效应和QE互作效应.此外,还探讨了性状间相关的遗传基础.发现4个QTLs和一对上位性QTLs可能与生物学产量与干草产量之间的正相关有关.3个QTL可能与干草产量与谷粒产量之间的负相关有关.这些结果可能部分地解释了这3个性状相关的遗传原因.通过对水稻生物学产量及其两个构成性状所定位QTL的分析,加深了对数量性状QTL的认识.首先,QTL的上位性效应和QE互作效应是普遍存在的;其次,QTL的多效性或紧密连锁可能是遗传相关的原因,当QTL对两个性状作用的方向相同时可导致正向遗传相关,反之则为负向遗传相关,当有些QTL表现为同向作用而另一些QTL表现为反向作用时,则可削弱性状间的遗传相关性;第三,复合性状的QTL效应可分解为其组成性状的QTL效应,如果QTL对各组成性状的效应方向相反而相互抵消,可使复合性状的QTL效应不易被检测;第四,加性效应的QTL常参预构成上位性效应,而具有上位性效应的QTL并非都有加性主效应,表明忽略上位性的QTL定位方法会降低检测QTL的功效;最后,鉴别不同类型的QTL效应有利于指导育种实践,选择主效QTL适用于多环境,QE互作QTL适用于特定环境,对上位性QTL应强调选择基因组合而并非单个基因.     

Mapping QTLs with epistatic effects and QTL×environment interactions for plant height using a doubled haploid population in cultivated wheat

Quantitative trait loci (QTLs) for plant height in wheat (Triticum aestivum L.) were studied using a set of 168 doubled haploid (DH) lines, which were derived from the cross Huapei 3/Yumai 57. A genetic linkage map was constructed using 283 SSR and 22 EST-SSR markers. The DH population and the parents were evaluated for wheat plant height in 2005 and 2006 in Tai'an and 2006 in Suzhou. QTL analyses were performed using the software of QTLNetwork version 2.0 based on the mixed linear model. Four additive QTLs and five pairs of epistatic effects were detected, which were distributed on chromosomes 3A, 4B, 4D, 5A, 6A, 7B, and 7D. Among them, three additive QTLs and three pairs of epistatic QTLs showed QTLxenvironment interactions (QEs). Two major QTLs, QphAB and Qph4D, which accounted for 14.51 % and 20.22% of the phenotypic variation, were located similar to the reported locations of the dwarfing genes Rhtl and Rht2, respectively. The Qph3A-2 with additive effect was not reported in previous linkage mapping studies. The total QTL ef fects detected for the plant height explained 85.04% of the phenotypic variation, with additive effects 46.07%, epistatic effects 19.89%, and QEs 19.09%. The results showed that both additive effects and epistatic effects were important genetic bases of wheat plant height, which were subjected to environmental modifications, and caused dramatic changes in phenotypic effects. The information obtained in this study will be useful for manipulating the QTLs for wheat plant height by molecular marker-assisted selection (MAS).     

Detecting epistatic genetic variance with a clonally replicated design: models for lowvs high-order nonallelic interaction

A quantitative genetic model, that uses known family structure with clonal replicates to separate genetic variance into its additive, dominance and epistatic components, is available in the current literature. Making use of offspring testing, this model is based on the theory that components of variance from the linear model of an experimental design may be expressed in terms of expected covariances among relatives. However, if interactions between a pair of quantitative trait loci (QTLs) explain a large proportion of the total epistasis, it will seriously overestimate the additive and dominance variances but underestimate the epistatic variance. In the present paper, a new model is developed to manipulate this problem by combining parental and offspring material into the same test. Under the condition described above, the new model can provide an accurate estimate for additive x additive variances. Also, its accuracy in estimating dominance and total epistatic variances is much greater than the accuracy of the previous model. However, if there is obvious evidence showing the major contribution of high-order interactions, especially among 4QTLs, to the total epistasis, the previous model is more appropriate to partition the genetic variance for a quantitative trait. The re-analysis of an example from a factorial mating design in poplar shows large differences in estimating variance components between the new and previous models when two different assumptions (lowvs high-order epistatic interactions) are used. The new model will be an alternative to estimating the mode of quantitative inheritance for species, especially for longlived, predominantly outcrossing forest trees, that can be clonally replicated.     

Mapping QTL for Biomass Yield and Its Components in Rice (Oryza sativa L.)

Addicive effects, additive by additive epistatic effects, and their environmental interactions of QTLs are important genetic components of quantitative traits. Genetic architecture underlying rice biomass yield and its two component traits (straw yield and grain yield) were analyzed for a population of 125 DH lines from an inter-subspecific cross of IR64/Azucena. The mixed-model based composite interval mapping approach (MCIM) was used to detect QTLs, There were 12 QTLs detected with additive main effects, 27 QTLs involved in digenic interaction with aa and/or aae effects, and 18 QTLs affected by environments with ae and/or aae effects. It was revealed that epistatic effects and QE interaction effects existed on biomass yield and its component traits in rice. In addition, the genetic basis of relationships among these traits were investigated. Four QTLs and one pair of epistatic QTLs were detected to be responsible for the positive correlation between biomass yield and straw yield. Three QTLs might be responsible for the negative correlation between straw yield and grain yield. This result could partially explain the genetic basis of correlation among the three traits, and provide useful information for genetic improvement of these traits by marker-assisted selection.     

Mapping QTLs with epistatic effects and QTL×environment interactions for plant height using a doubled haploid population in cultivated wheat

Quantitative trait loci (QTLs) for plant height in wheat (Triticum aestivum L.) were studied using a set of 168 doubled haploid (DH) lines, which were derived from the cross Huapei 3/Yumai 57. A genetic linkage map was constructed using 283 SSR and 22 EST-SSR markers. The DH population and the parents were evaluated for wheat plant height in 2005 and 2006 in Tai’an and 2006 in Suzhou. QTL analyses were performed using the software of QTLNetwork version 2.0 based on the mixed linear model. Four additive QTLs and five pairs of epistatic effects were detected, which were distributed on chromosomes 3A, 4B, 4D, 5A, 6A, 7B, and 7D. Among them, three additive QTLs and three pairs of epistatic QTLs showed QTL×environment interactions (QEs). Two major QTLs, Qph4B and Qph4D, which accounted for 14.51% and 20.22% of the phenotypic variation, were located similar to the reported locations of the dwarfing genes Rht1 and Rht2, respectively. The Qph3A-2 with additive effect was not reported in previous linkage mapping studies. The total QTL effects detected for the plant height explained 85.04% of the phenotypic variation, with additive effects 46.07%, epistatic effects 19.89%, and QEs 19.09%. The results showed that both additive effects and epistatic effects were important genetic bases of wheat plant height, which were subjected to environmental modifications, and caused dramatic changes in phenotypic effects. The information obtained in this study will be useful for manipulating the QTLs for wheat plant height by molecular marker-assisted selection (MAS).     

Genetic mapping of Sorghum bicolor (L.) Moench QTLs that control variation in tillering and other morphological characters

Grain yield of Sorghum bicolor (L.) Moench is significantly influenced by genetically controlled variation in the number of tillers, plant height, time of anthesis, and various other morphological and physiological characters. In this study, a minimum of 27 unique QTLs that control variation in nine morphological traits, including the presence versus the absence and the height of basal tillers, were mapped, and the percentage of additive genetic variance explained by the QTLs was determined in a population of 137 recombinant inbred lines in two environments. Four QTLs explained from 86.3% to 48.9% (depending upon the environment) of the additive genetic variance in the number of basal tillers with heads, and seven QTLs explained from 85.9% to 47.9% of the additive genetic variance in panicle width. It is unlikely that different alleles were segregating in the mapping population at any of the major dwarfing loci, but five QTLs that explained from 65.8% to 52.0% of the additive genetic variance in main-culm height were mapped. QTLs controlling variation in height of the tallest basal tiller, number of basal tillers per basal-tillered plant, panicle length, leaf angle, maturity, and awn length also were mapped. Three or more QTLs were mapped in linkage groups A, E, G, and I, while none were mapped in linkage groups B and D. Several of the QTLs mapped in this study are likely candidates for marker-assisted selection in breeding programs. Received: 20 September 2000 / Accepted: 26 October 2000     

Dynamic quantitative trait locus analysis of seed dormancy at three development stages in rice

In this study, a rice population of recombinant inbred lines (RILs) was used to determine the genetic characteristics of seed dormancy (SD) at 4 (early), 5 (middle) and 6 (late) weeks after heading stages. Dynamic analysis showed that the indica IR28 variety tended to have deeper dormancy than the japonica Daguandao at the middle and late development stages. The level of SD decreased with the process of seed development. The significant interaction between heading date (HD) and SD occurred only in those seeds collected at the early development stage. A total of nine additive quantitative trait loci (QTLs) and eight epistatic QTLs for SD were identified at three seed development stages. Of them, one additive and four epistatic QTLs were identified for the early stage, six additive and one epistatic QTL for the middle stage and two additive and three epistatic QTLs for the late stage. The phenotypic variation explained by each additive and epistatic QTL ranged from 5.8 to 30.6 % and from 3.8 to 13.1 %, respectively. Compared with the additive QTLs, epistatic interactions were much more important for SD at the early and late development stages. Two major additive QTLs, qSD3.1 and qSD4.1, were identified; each QTL could explain more than 20 % of the total phenotypic variance and each dormancy-enhancing allele could decrease the germination percentage by about 10 %. By comparing the chromosomal positions of these additive QTLs with those previously identified, five additive QTLs, qSD1.2, qSD2.1, qSD3.2, qSD4.1 and qSD9.1, might represent novel genes. One QTL identified here, qHD1, and nine QTLs identified in previous studies for HD were co-located with our QTLs for SD, which indicated that the significant correlation between SD and HD might be due to the linkage of QTLs for SD and HD. Four RILs with deep dormancy at development stages but non-dormancy after post-ripening under different germination conditions were selected. Using the selected RILs, three cross combinations of SD for the development of RIL populations were predicted. The selected RILs and the identified QTLs might be applicable for the improvement of pre-harvest sprouting tolerance by marker-assisted selection in rice.     

Quantitative trait loci for directional but not fluctuating asymmetry of mandible characters in mice

Non-directional variation in right minus left differences in bilateral characters, referred to as fluctuating asymmetry (FA), often has been assumed to be largely or entirely environmental in origin. FA increasingly has been used as a measure of developmental stability, and its presumed environmental origin has facilitated the comparisons of populations believed to differ in their levels of stability. Directional asymmetry (DA), in which one side is consistently larger than the other, has been assumed to be at least partially heritable. Both these assumptions were tested with interval mapping techniques designed to detect any quantitative trait loci (QTLs) affecting FA or DA in 15 bilateral mandible characters in house mice resulting from a cross of the F1 between CAST/Ei (wild strain) and M16i (selected for rapid growth rate) back to M16i. For purposes of the analysis, all mandibles were triply measured and 92 microsatellite markers were scored in a total of 350 mice. No significant QTLs were found for FA, but three QTLs significantly affected DA in several characters, confirming both assumptions. The QTLs for DA were similar in location to those affecting the size of several of the mandible characters, although they accounted for an average of only 1% of the total phenotypic variation in DA.