犬髋关节发育不良数量性状位点及致病基因研究进展

犬髋关节发育不良(canine hip dysplasia,CHD)是一种以髋关节松弛为主要特征的先天遗传性疾病,受环境和基因共同作用,发病率较高,但其发病机制尚未完全明了。近年来,在CHD基因组学研究方面取得了重要进展,譬如,发现数量性状位点(quantitative trait locus,QTL)与CHD中髋关节Norberg角、背外侧半脱位评分及分离指数存在联系,FBN2、LRR1、COL6A3与FN1等基因也与CHD的发生相关。为进一步明确CHD的发病机制,本文就CHD相关的QTL及相关候选致病基因的研究进展,尤其对相关QTL在染色体中的位置与功能以及候选致病基因的功能进行综述。     

Quantitative trait loci for hip dysplasia in a crossbreed canine pedigree

Canine hip dysplasia is a common developmental inherited trait characterized by hip laxity, subluxation or incongruity of the femoral head and acetabulum in affected hips. The inheritance pattern is complex and the mutations contributing to trait expression are unknown. In the study reported here, 240 microsatellite markers distributed in 38 autosomes and the X chromosome were genotyped on 152 dogs from three generations of a crossbred pedigree based on trait-free Greyhound and dysplastic Labrador Retriever founders. Interval mapping was undertaken to map the QTL underlying the quantitative dysplastic traits of maximum passive hip laxity (the distraction index), the dorsolateral subluxation score, and the Norberg angle. Permutation testing was used to derive the chromosome-wide level of significance at p < 0.05 for each QTL. Chromosomes 4, 9, 10, 11 (p < 0.01), 16, 20, 22, 25, 29 (p < 0.01), 30, 35, and 37 harbor putative QTL for one or more traits. Successful detection of QTL was due to the crossbreed pedigree, multiple-trait measurements, control of environmental background, and marked advancement in canine mapping tools.     

Quantitative trait loci for fertility traits in Finnish Ayrshire cattle

A whole genome scan was carried out to detect quantitative trait loci (QTL) for fertility traits in Finnish Ayrshire cattle. The mapping population consisted of 12 bulls and 493 sons. Estimated breeding values for days open, fertility treatments, maternal calf mortality and paternal non-return rate were used as phenotypic data. In a granddaughter design, 171 markers were typed on all 29 bovine autosomes. Associations between markers and traits were analysed by multiple marker regression. Multi-trait analyses were carried out with a variance component based approach for the chromosomes and trait combinations, which were observed significant in the regression method. Twenty-two chromosome-wise significant QTL were detected. Several of the detected QTL areas were overlapping with milk production QTL previously identified in the same population. Multi-trait QTL analyses were carried out to test if these effects were due to a pleiotropic QTL affecting fertility and milk yield traits or to linked QTL causing the effects. This distinction could only be made with confidence on BTA1 where a QTL affecting milk yield is linked to a pleiotropic QTL affecting days open and fertility treatments.     

数量性状基因座位及其在家禽中的定位

近年来随着现代分子生物学的发展 ,一些高效的分子遗传标记将各种畜禽的遗传图谱研究推向深入。为高密度、覆盖面广的连锁图谱的构建及QTL的定位奠定了基础。有关QTL的基本理论、QTL定位的步骤、QTL的检测方法以及家禽中定位的QTL已经展开了深入的研究 ,但目前QTL定位中存在诸多问题的问题     

A random model for mapping imprinted quantitative trait loci in a structured pedigree: an implication for mapping canine hip dysplasia

Genetic imprinting may have played a more notable role in shaping embryonic development of plants, animals, and humans than previously appreciated. Quantitative trait loci that are imprinted (iQTL) exert monoallelic effects, depending on the parent of origin, which is an exception to the laws of Mendelian genetics. In this article, we present a modified random effect-based mapping model to use in a genome-wide scan for the distribution of iQTL that contribute to genetic variance for a complex trait in a structured pedigree. This model, implemented with the maximum likelihood method, capitalizes on a network of relatedness for maternally and paternally derived alleles through identical-by-descent sharing, thus allowing for the discrimination of the genetic variances due to alleles derived from maternal and paternal parents. The model was employed to map iQTL responsible for canine hip dysplasia in a multihierarchical canine pedigree, founded with seven greyhounds and six Labrador retrievers. Of eight significant QTL detected, three, located on CFA1, CFA8, and CF28, were found to trigger significant parent-of-origin effects on the age of femoral capital ossification measured at the left and right hips of a canine. The detected iQTL provide important candidate regions for fine-mapping of imprinted genes and for studying their structure and function in the control of complex traits.     

Genetic mapping of quantitative trait loci for meat quality and muscle metabolic traits in cattle

A whole‐genome scan was carried out in New Zealand and Australia to detect quantitative trait loci (QTL) for live animal and carcass composition traits and meat quality attributes in cattle. Backcross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin backgrounds. The New Zealand cattle were reared and finished on pasture, whilst Australian cattle were reared on grass and finished on grain for at least 180 days. This paper reports on meat quality traits (tenderness measured as shear force at 4–5 ages on two muscles as well as associated traits of meat colour, pH and cooking loss) and a number of metabolic traits. For meat quality traits, 18 significant QTL (P < 0.05), located in nine linkage groups, were detected on a genome‐wise basis, in combined‐sire (seven QTL) or within‐sire analyses (11 QTL). For metabolic traits, 11 significant QTL (P < 0.05), located in eight linkage groups, were detected on a genome‐wise basis, in combined‐sire (five QTL) or within‐sire analyses (six QTL). BTA2 and BTA3 had QTL for both metabolic traits and meat quality traits. Six significant QTL for meat quality and metabolic traits were found at the proximal end of chromosome 2. BTA2 and BTA29 were the most common chromosomes harbouring QTL for meat quality traits; QTL for improved tenderness were associated with Limousin‐derived and Jersey‐derived alleles on these two chromosomes, respectively.     

Quantitative trait loci controlling water use efficiency and related traits in Quercus robur L.

Genetic variation for intrinsic water use efficiency (W _i) and related traits was estimated in a full-sib family of Quercus robur L. over 3 years. The genetic linkage map available for this F1 family was used to locate quantitative trait loci (QTL) for W _i, as estimated by leaf carbon stable isotope composition (δ ¹³C) or the ratio of net CO₂ assimilation rate (A) to stomatal conductance to water vapour (g _w) and related leaf traits. Gas exchange measurements were used to standardize estimates of A and g _w and to model the sensitivity of g _w to leaf-to-air vapour pressure deficit (sg^VPD). δ ¹³C varied by more than 3‰ among the siblings, which is equivalent to 40% variation of W _i. Most of the studied traits exhibited high clonal mean repeatabilities (>50%; proportion of clonal mean variability in global variance). Repeatabilities for δ ¹³C, leaf mass per area (LMA) and leaf nitrogen content were higher than 70%. For δ ¹³C, ten QTLs were detected, one of which was detected repeatedly for all 3 years and consistently explained more than 20% of measured variance. Four genomic regions were found in which co-localizing traits linked variation in W _i to variations in leaf chlorophyll and nitrogen content, LMA and sg^VPD. A positive correlation using clonal means between δ ¹³C and A/g _w, as well as a co-localisation of QTL detected for both traits, can be seen as validation of the theoretical model linking the genetic architecture of these two traits.     

Quantitative trait loci for yield components in oil palm (Elaeis guineensis Jacq.)

The development of an oil palm RFLP marker map has enabled marker-based QTL mapping studies to be undertaken. Information from 153 RFLP markers was used in combination with phenotypic data from an F₂ population to estimate the position and effects of quantitative trait loci (QTLs) for traits including yield of fruit and its components and measures of vegetative growth. The mapping population consisted of 84 palms segregating for the major gene influencing shell thickness. Marker data were analysed to produce a linkage map consisting of 22 linkage groups. The QTL mapping analysis was carried out by interval mapping and single-marker analysis for the unlinked markers; significance thresholds were generated by permutation. Using both single-marker and interval-mapping analysis significant marker associated QTL effects were found for 11 of the 13 traits analysed. The results of interval-mapping analysis of fruit weight, petiole cross section and rachis length, and ratios of shell:fruit, mesocarp:fruit and kernel:fruit indicated significant (P<0.05) QTLs at the genome-wide threshold. The putative QTLs were associated with between 8.2% and 44.0% of the phenotypic variation, with an average of 27% for the single-marker analysis and 19% for the interval-mapping analysis. The higher percentage of phenotypic variation explained in the single-marker analysis, when compared to the interval-mapping analysis, is likely to be due to the lower stringency associated with the single-marker analysis. Large dominance deviations were associated with a sizeable proportion of the putative QTLs. The ultimate objective of mapping QTLs in commercial populations is to utilise novel breeding strategies such as marker-assisted selection (MAS). The potential impact of MAS in oil palm breeding programmes is discussed. Received: 26 June 2000 / Accepted: 24 October 2000     

Quantitative trait loci for yield and correlated traits under high and low soil nitrogen conditions in tropical maize

The first objective of this study was to map and characterize quantitative trait loci (QTL) for grain yield (GY) and for secondary traits under varying nitrogen (N) supply. To achieve this objective, a segregating F_2:3 population previously developed for QTL mapping under water-limited conditions was used. The population was evaluated in Mexico under low N conditions in the dry winter season and under low and high N conditions in the wet summer season. From eight QTLs identified for GY under low N conditions, two were also detected under high N conditions. Five QTLs were stable across the two low N environments and five co-localized with QTLs identified for the anthesis-silking interval (ASI) or for the number of ears per plant (ENO) under low N conditions. The percentage of the phenotypic variance expressed by all QTLs for ASI and ENO was quite different when evaluated under low N conditions during the dry winter (40% for ASI and 22% for ENO) and the wet summer seasons (22% for ASI and 46% for ENO). The results suggest optimizing different breeding strategies based on selection index depending on the growing season. Good QTL colocalization was observed for ASI (four QTLs) and ENO (three QTLs) when looking at QTL identified under low N and water-limited conditions in the same population. The results suggest that that both secondary traits can be used in breeding programs for simultaneous improvement of maize against low N and drought stresses.     

Selection on domestication traits and quantitative trait loci in crop–wild sunflower hybrids

The strength and extent of gene flow from crops into wild populations depends, in part, on the fitness of the crop alleles, as well as that of alleles at linked loci. Interest in crop–wild gene flow has increased with the advent of transgenic plants, but nontransgenic crop–wild hybrids can provide case studies to understand the factors influencing introgression, provided that the genetic architecture and the fitness effects of loci are known. This study used recombinant inbred lines (RILs) generated from a cross between crop and wild sunflowers to assess selection on domestication traits and quantitative trait loci (QTL) in two contrasting environments, in Indiana and Nebraska, USA. Only a small fraction of plants (9%) produced seed in Nebraska, due to adverse weather conditions, while the majority of plants (79%) in Indiana reproduced. Phenotypic selection analysis found that a mixture of crop and wild traits were favoured in Indiana (i.e. had significant selection gradients), including larger leaves, increased floral longevity, larger disk diameter, reduced ray flower size and smaller achene (seed) mass. Selection favouring early flowering was detected in Nebraska. QTLs for fitness were found at the end of linkage groups six (LG6) and nine (LG9) in both field sites, each explaining 11–12% of the total variation. Crop alleles were favoured on LG9, but wild alleles were favoured on LG6. QTLs for numerous domestication traits overlapped with the fitness QTLs, including flowering date, achene mass, head number, and disk diameter. It remains to be seen if these QTL clusters are the product of multiple linked genes, or individual genes with pleiotropic effects. These results indicate that crop trait values and alleles may sometimes be favoured in a noncrop environment and across broad geographical regions.     

Interval mapping of quantitative trait loci for reproductive,morphological, and seed traits of soybean (Glycine max L.)

Quantitative trait loci (QTL) were mapped in segregating progeny from a cross between two soybean (Glycine max (L.) Merr.) cultivars: Minsoy (PI 27.890) and Noir 1 (PI 290.136). The 15 traits analyzed included reproductive, morphological, and seed traits, seed yield and carbon isotope discrimination ratios (¹³C/¹²C). Genetic variation was detected for all of the traits, and transgressive segregation was a common phenomenon. One hundred and thirty-two linked genetic markers and 24 additional unlinked markers were used to locate QTL by interval mapping and one-way analysis of variance, respectively. Quantitative trait loci controlling 11 of the 15 traits studied were localized to intervals in 6 linkage groups. Quantitative trait loci for developmental and morphological traits (R1, R5, R8, plant height, canopy height, leaf area, etc.) tended to be clustered in three intervals, two of which were also associated with seed yield. Quantitative trait loci for seed oil were separated from all the other QTL. Major QTL for maturity and plant height were linked to RFLP markers R79 (31% variation) and G173 (53% variation). Quantitative trait loci associated with unlinked markers included possible loci for seed protein and weight. Linkage between QTL is discussed in relation to the heritability and genetic correlation of the traits.     

AFLP mapping and detection of quantitative trait loci (QTLs) for economically important traits in Pinus sylvestris: a preliminary study

We have applied a two-way pseudo-testcross strategy in an analysis of Pinus sylvestris for genetic mapping and detection of quantitative trait loci (QTLs) associated with economically important traits targeted in the Swedish tree-breeding programme. Based on 94 full-sib progeny of a cross between two plus-trees from northern Sweden we generated two parental maps using AFLP markers. The female map was comprised of 94 markers assigned to 15 linkage groups giving a size of 796 cM. On the male map 155 markers were assigned to 15 linkage groups, giving a total size of 1335 cM. The recombination frequency was found to be sex-dependent, being 29.3% higher in male than in female gametes. On the female map, 12 QTLs were detected (but none for branch diameter or wood density). Three QTLs for tree height accounted for 25.8% of the total phenotypic variation of this trait. When the QTLs detected for all the traits were taken independently, the percentages of phenotypic variance ranged from 9.3% to 22.7%. The highest value was observed for frost hardiness, an important trait in northern Sweden for which a major gene seemed to be involved. A cluster of QTLs for tree height, trunk diameter and volume was located on one linkage group. On the male map, four QTLs for trunk diameter and volume were detected. Due to the reduced number of individuals under study, the results are preliminary and have to be validated on more trees.     

Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas-fir. IV. Cold-hardiness QTL verification and candidate gene mapping

Quantitative trait locus (QTL) analyses are used by geneticists to characterize the genetic architecture of quantitative traits, provide a foundation for marker-aided-selection (MAS), and provide a framework for positional selection of candidate genes. The most useful QTL for breeding applications are those that have been verified in time, space, and/or genetic background. In this study, spring cold-hardiness of Douglas-fir foliar tissues was evaluated in two clonally replicated (n=170 and 383 clones) full-sib cohorts derived from the same parental cross in two different years (made 5 years apart). The cohorts were established in widely separated forest test sites and tissues were artificially freeze tested using different cold injury assessment methods. Four of six unique QTL detected for spring cold-hardiness in needles of Cohort 1 were tentatively verified in the second cohort. Four additional QTL were detected in Cohort 2, two on linkage groups (LGs) not previously represented in the smaller cohort. In total, 10 unique QTL were identified across both cohorts. Seventeen of twenty-nine putative cold-hardiness candidate genes (Douglas-fir ESTs) placed on the Douglas-fir linkage map locate within the 95% confidence intervals of spring needle cold-hardiness QTL from the two cohorts and thus represent priority targets for initiating association mapping in Douglas-fir.     

Bayesian joint mapping of quantitative trait loci for Gaussian and categorical characters in line crosses

Methodology for joint mapping of quantitative trait loci (QTL) affecting continuous and binary characters in experimental crosses is presented. The procedure consists of a Bayesian Gaussian-threshold model implemented via Markov chain Monte Carlo, which bypasses bottlenecks due to high-dimensional integrals required in maximum likelihood approaches. The method handles multiple binary traits and multiple QTL. Modeling of ordered categorical traits is discussed as well. Features of the method are illustrated using simulated datasets representing a backcross design, and the data are analyzed using mixed-trait and single-trait models. The mixed-trait analysis provides greater detection power of a QTL than a single-trait analysis when the QTL affects two or more traits. The number of QTL inferred in the mixed-trait analysis does not pertain to a specific trait, but the roles of each QTL on specific traits can be assessed from estimates of its effects. The impacts of varying incidence level and sample size on the mixed-trait QTL mapping analysis are investigated as well.     

Quantitative trait loci (QTL) mapping of resistance to strongyles and coccidia in the free-living Soay sheep (Ovis aries)

A genome-wide scan was performed to detect quantitative trait loci (QTL) for resistance to gastrointestinal parasites and ectoparasitic keds segregating in the free-living Soay sheep population on St. Kilda (UK). The mapping panel consisted of a single pedigree of 882 individuals of which 588 were genotyped. The Soay linkage map used for the scans comprised 251 markers covering the whole genome at average spacing of 15cM. The traits here investigated were the strongyle faecal egg count (FEC), the coccidia faecal oocyst count (FOC) and a count of keds (Melophagus ovinus). QTL mapping was performed by means of variance component analysis so that the genetic parameters of the study traits were also estimated and compared with previous studies in Soay and domestic sheep. Strongyle FEC and coccidia FOC showed moderate heritability (h(2)=0.26 and 0.22, respectively) in lambs but low heritability in adults (h(2)<0.10). Ked count appeared to have very low h(2) in both lambs and adults. Genome scans were performed for the traits with moderate heritability and two genomic regions reached the level of suggestive linkage for coccidia FOC in lambs (logarithm of the odds=2.68 and 2.21 on chromosomes 3 and X, respectively). We believe this is the first study to report a QTL search for parasite resistance in a free-living animal population and therefore may represent a useful reference for similar studies aimed at understanding the genetics of host-parasite co-evolution in the wild.     

Quantitative trait loci associated with traits determining grain and stover yield in pearl millet under terminal drought-stress conditions

Drought stress during the reproductive stage is one of the most important environmental factors reducing the grain yield and yield stability of pearl millet. A QTL mapping approach has been used in this study to understand the genetic and physiological basis of drought tolerance in pearl millet and to provide a more-targeted approach to improving the drought tolerance and yield of this crop in water-limited environments. The aim was to identify specific genomic regions associated with the enhanced tolerance of pearl millet to drought stress during the flowering and grain-filling stages. Testcrosses of a set of mapping-population progenies, derived from a cross of two inbred pollinators that differed in their response to drought, were evaluated in a range of managed terminal drought-stress environments. A number of genomic regions were associated with drought tolerance in terms of both grain yield and its components. For example, a QTL associated with grain yield per se and for the drought tolerance of grain yield mapped on linkage group 2 and explained up to 23% of the phenotypic variation. Some of these QTLs were common across stress environments whereas others were specific to only a particular stress environment. All the QTLs that contributed to increased drought tolerance did so either through better than average maintenance (compared to non-stress environments) of harvest index, or harvest index and biomass productivity. It is concluded that there is considerable potential for marker-assisted backcross transfer of selected QTLs to the elite parent of the mapping population and for their general use in the improvement of pearl millet productivity in water-limited environments. Received: 15 November 2000 / Accepted: 12 April 2001     

Quantitative trait loci for grain quality, productivity, morphological and agronomical traits in sorghum (Sorghum bicolor L. Moench)

 Quantitative trait loci (QTLs) for grain quality, yield components and other traits were investigated in two Sorghum caudatum×guinea recombinant inbred line (RIL) populations. A total of 16 traits were evaluated (plant height, panicle length, panicle compactness, number of kernels/panicle, thousand-kernel weight, kernel weight/panicle, threshing percentage, dehulling yield, kernel flouriness, kernel friability, kernel hardness, amylose content, protein content, lipid content, germination rate and molds during germination and after harvest) and related to two 113- and 100-point base genetic maps using simple (SIM) and composite (CIM) interval mapping. The number, effects and relative position of QTLs detected in both populations were generally in agreement with the distributions, heritabilities and correlations among traits. Several chromosomal segments markedly affected multiple traits and were suspected of harbouring major genes. The positions of these QTLs are discussed in relation to previously reported studies on sorghum and other grasses. Many QTLs, depending on their relative effects and position, could be used as targets for marker-assisted selection and provide an opportunity for accelerating breeding programmes. Received: 14 February 1998 / Accepted: 4 March 1998     

Quantitative trait loci mapping for fatty acid composition traits in perirenal and back fat using a Japanese wild boar x Large White intercross

Here, we analysed quantitative trait loci (QTL) for fatty acid composition, one of the factors affecting fat quality, in a Japanese wild boar x Large White cross. We found 25 significant effects for 17 traits at 13 positions at the 5% genome-wise level, of which 16 effects for 12 traits at 10 positions were significant at the 1% level. QTL for saturated fatty acids (SFA) in back fat were mapped to swine (Sus scrofa) chromosomes (SSC) 1p, 9 and 15. QTL for unsaturated fatty acids in back fat were mapped to SSC1p, 1q, 4, 5, 9, 15 and 17. Using a regression model that fits back fat thickness as a covariate, two of the QTL for linoleic acid content on SSC4 and SSC17 were not significant, but one QTL for total SFA composition was detected on SSC5 with correction for back fat thickness. Wild boar alleles at six of seven QTL tended to increase SFAs and to decrease unsaturated fatty acids. QTL for fatty acid composition in perirenal fat were mapped on SSC2, 3, 4, 5, 6, 14, 16 and X. QTL for melting point (in back fat samples) were mapped on SSC1, 2 and 15. Wild boar alleles in QTL on SSC1 and SSC15 were associated with elevated melting points whereas those on SSC2 were associated with lower melting point measurements.     

Fine linkage mapping enables dissection of closely linked quantitative trait loci for seed dormancy and heading in rice

Two quantitative trait loci (QTLs) for seed dormancy (tentatively designated Sdr1) and heading date (Hd8) have been mapped to approximately the same region on chromosome 3 by interval mapping of backcross inbred lines derived from crosses between the rice cultivars Nipponbare (japonica) and Kasalath (indica). To clarify whether Sdr1 and Hd8 could be dissected genetically, we carried out fine-scale mapping with an advanced backcross progeny. We selected a BC₄F₁ plant, in which a small chromosomal region including Sdr1 and Hd8, on the short arm of chromosome 3, remained heterozygous, whereas all the other chromosomal regions were homozygous for Nipponbare. Days-to-heading and seed germination rate in the BC₄F₂ plants showed continuous variation. Ten BC₄F₂ plants with recombination in the vicinity of Sdr1 and Hd8 were selected on the basis of the genotypes of the restriction fragment length polymorphism (RFLP) markers flanking both QTLs. Genotypes of those plants for Sdr1 and Hd8 were determined by advanced progeny testing of BC₄F₄ families. Sdr1 was mapped between the RFLP markers R10942 and C2045, and co-segregated with C1488. Hd8 was also mapped between C12534S and R10942. Six recombination events were detected between Sdr1 and Hd8. These results clearly demonstrate that Sdr1 and Hd8 were tightly linked. Nearly isogenic lines for Sdr1 and Hd8 were selected by marker-assisted selection.Communicated by D. Mackill