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1.
Individual variation in sensitivity to acute ethanol (EtOH) challenge is associated with alcohol drinking and is a predictor of alcohol abuse. Previous studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse strains differ in responses on certain measures of acute EtOH intoxication. To gain insight into genetic factors contributing to these differences, we performed quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration in a B6×S1 F2 population. We confirmed that S1 showed greater EtOH-induced hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL analysis revealed several additive and interacting loci for various phenotypes, as well as examples of genotype interactions with sex. QTLs for different EtOH phenotypes were largely non-overlapping, suggesting separable genetic influences on these behaviors. The most compelling main-effect QTLs were for hypothermia on chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with loci repeatedly linked to EtOH drinking in previous mouse studies. The architecture of the traits we examined was complex but clearly amenable to dissection in future studies. Using integrative genomics strategies, plausible functional and positional candidates may be found. Uncovering candidate genes associated with variation in these phenotypes in this population could ultimately shed light on genetic factors underlying sensitivity to EtOH intoxication and risk for alcoholism in humans.  相似文献   

2.
Nicotine is the reinforcing ingredient in tobacco. Following chronic exposure, sudden cessation of nicotine use produces negative symptoms of withdrawal that contribute to dependence. The molecular mechanisms underlying nicotine withdrawal behaviors, however, are poorly understood. Using recombinant inbred mice, chronic nicotine was delivered by minipump and withdrawal induced using mecamylamine. Somatic signs of withdrawal, and anxiety-like behavior using elevated plus maze, were then assessed. Interval mapping was used to identify associations between genetic variation and withdrawal behaviors, and with basal gene expression. Differential gene expression following nicotine exposure and withdrawal was also assessed in progenitor mice using microarrays. Quantitative trait loci mapping identified chromosome intervals with significant genetic associations to somatic signs of withdrawal or withdrawal-induced anxiety-like behavior. Using bioinformatics, and association with basal gene expression in nucleus accumbens, we implicated Rb1, Bnip3l, Pnma2, Itm2b, and Kif13b as candidate genes for somatic signs of withdrawal, and Galr1, which showed trans-regulation from a region of chromosome 14 that was associated with somatic signs of withdrawal. Candidate genes within the chromosome 9 region associated with anxiety-like withdrawal behavior included Dixdc1, Ncam1, and Sorl1. Bioinformatics identified six genes that were also significantly associated with nicotine or alcohol traits in recent human genome-wide association studies. Withdrawal-associated somatic signs and anxiety-like behavior had strong non-overlapping genetic associations, respectively, with regions of chromosome 14 and chromosome 9. Genetic, behavioral and gene expression correlations, and bioinformatics analysis identified several candidate genes that may represent novel molecular targets for modulating nicotine withdrawal symptoms.  相似文献   

3.
We report on the observation of sex-restricted, non-Mendelian inheritance over a region of mouse Chromosome (Chr) 11, occurring in the offspring of crosses between two commonly used Mus musculus-derived inbred strains, C57BL/6J and DBA/2J. In the surviving backcross progeny of reciprocal matings between (C57BL/6J × DBA/2J)F1 hybrids and the C57BL/6J parental strain, we observed the preferential appearance of C57BL/6J alleles along a region of Chr 11. The deviation from Mendelian predictions was observed only in female offspring from both reciprocal backcrosses, and not in males from either cross. The sex-specificity of the observed non-Mendelian inheritance points to an explanation based on embryonic or neonatal lethality. Our data add to previously obtained evidence for a Chr 11 locus or loci with sex-specific and allele-specific effects on viability. Received: 19 December 1997 / Accepted: 10 June 1998  相似文献   

4.
Moderate doses of ethanol (1–2 g/kg) markedly increase locomotor activity in some inbred mouse strains, for example, the DBA/2J (D2), but have relatively little effect in other strains, for example, the C57BL/6J (B6). In the present study, we conducted a genome-wide search in a B6D2 F2 intercross (N = 925) for quantitative trait loci (QTLs) associated with the locomotor response. A QTL with a LOD score of 8.4 was detected on Chromosome (Chr) 2; this QTL accounted for 11.4% of the phenotypic variance and approximately 30% of the genetic variance. The QTL on Chr 2 is in the same general region as QTLs previously described for ethanol preference/consumption (Rodriguez et al. Alcohol Clin Exp Res 19, 367, 1995; Melo et al. Nat Genet 13, 147, 1996; Phillips et al. Mamm Genome, in press), acute ethanol withdrawal (Buck et al. J. Neurosci 17, 3946, 1997) and nitrous oxide withdrawal severity (Belknap et al. Behav Genet 23, 213, 1993). A logical candidate gene in the region of interest is the enzyme which synthesizes GABA, glutamic acid decarboxylase 1 (GadI). Received: 15 September 1998 / Accepted: 8 October 1998  相似文献   

5.
To determine the genetic variation that contributes to body composition in the mouse, we interbred a wild-derived strain (PWK/PhJ; PWK) with a common laboratory strain (C57BL/6J; B6). The parental, F1, and F2 mice were phenotyped at 18 weeks old for body weight and composition using dual-energy X-ray absorptiometry (DEXA). A total of 479 (244 male and 235 female) F2 mice were genotyped for 117 polymorphic markers spanning the autosomes. Twenty-eight suggestive or significant linkages for four traits (body weight, adjusted lean and fat weight, and percent fat) were detected. Of these, three QTLs were novel: one on the proximal portion of Chr 5 for body weight (Bwq8; LOD = 4.7), one on Chr 3 for lean weight (Bwtq13; LOD = 3.6), and one on Chr 11 for percent fat (Adip19; LOD = 5.8). The remaining QTLs overlapped previously identified linkages, e.g., Adip5 on Chr 9. One QTL was sex-specific (present in males only) and seven were sex-biased (more prominent in one sex than the other). Most alleles that increased body weight were contributed by the B6 strain, and most alleles that increased percent fat were contributed by the PWK strain. Eight pairs of interacting loci were identified, none of which exactly overlapped the main-effect QTLs. Many of the QTLs found in the B6 × PWK cross map to the location of previously reported linkages, suggesting that some QTLs are common to many strains (consensus QTLs), but three new QTLs appear to be particular to the PWK strain. The location and type of QTLs detected in this new cross will assist in future efforts to identify the genetic variation that determines the ratio of lean to fat weight as well as body size in mice.  相似文献   

6.
Grain yield and associated agronomic traits are important factors in wheat (Triticum aestivum L.) improvement. Knowledge regarding the number, genomic location, and effect of quantitative trait loci (QTL) would facilitate marker-assisted selection and the development of cultivars with desirable characteristics. Our objectives were to identify QTLs directly and indirectly affecting grain yield expression. A population of 132 F12 recombinant inbred lines (RILs) was derived by single-seed descent from a cross between the Chinese facultative wheat Ning7840 and the US soft red winter wheat Clark. Phenotypic data were collected for 15 yield and other agronomic traits in the RILs and parental lines from three locations in Oklahoma from 2001 to 2003. Twenty-nine linkage groups, consisting of 363 AFLP and 47 SSR markers, were identified. Using composite interval mapping (CIM) analysis, 10, 16, 30, and 14 QTLs were detected for yield, yield components, plant adaptation (shattering and lodging resistance, heading date, and plant height), and spike morphology traits, respectively. The QTL effects ranged from 7 to 23%. Marker alleles from Clark were associated with a positive effect for the majority of QTLs for yield and yield components, but gene dispersion was the rule rather than the exception for this RIL population. Often, QTLs were detected in proximal positions for different traits. Consistent, co-localized QTLs were identified in linkage groups 1AL, 1B, 4B, 5A, 6A, and 7A, and less consistent but unique QTLs were identified on 2BL, 2BS, 2DL, and 6B. Results of this study provide a benchmark for future efforts on QTL identification for yield traits.  相似文献   

7.
 Lodging can strongly affect both the grain yield and the quality of wheat. Lodging represents a quantitative trait and is difficult to assess on a phenotypic basis. Marker-assisted selection (MAS) could therefore become an important tool in breeding for lodging resistance. In this study, we mapped and characterised quantitative trait loci (QTLs) for lodging resistance, as well as morphological traits correlated with lodging, in a segregating population of 226 recombinant inbred lines derived from the cross of the lodging-resistant wheat variety Forno with the susceptible spelt variety Oberkulmer. Lodging, plant height, leaf width, leaf-growth habit, culm stiffness, culm swinging, culm thickness, days to ear emergence and days to flowering were assessed in field trials at two locations in 1996 and at one location in 1997. Additionally, at one location weight and length parameters were also assessed. Plant height and culm stiffness explained 77% of the phenotypic variance of lodging in a multiple regression model over all three environments. QTL analysis of lodging and morphological parameters was based on a genetic map containing 230 loci with 23 linkage groups (2469 cM). With the method of composite interval mapping nine QTLs for lodging resistance were detected, explaining 63% of the phenotypic variance in a simultaneous fit. Seven of these QTLs coincided with QTLs for morphological traits, reflecting the correlations between these traits and lodging. In our population the most efficient way to improve lodging resistance would be by a combination of indirect selection on plant height and culm stiffness together with MAS on the two QTLs for lodging resistance which did not coincide with QTLs for morphological traits. Received: 3 August 1998 / Accepted: 28 November 1998  相似文献   

8.
A highly significant cholesterol quantitative trait locus (QTL) (Cq6) was identified on chromosome 1 in C57BL/6J x RR F2 mice. The Cq6 was located over the gene for apolipoprotein A-Il (Apoa2), and the RR allele was associated with increased plasma cholesterol. C57BL/6J has Apoa2a alleles and RR has Apoa2b alleles. Three different Apoa2 alleles are known on the basis of amino acid substitutions at four residues. Analysis with partial Apoa2 congenic strains possessing Apoa2a, Apoa2b, and Apoa2C alleles revealed that the Apoa2b allele is unique in the ability to increase cholesterol among the three Apoa2 alleles, and that the Ala-to-Val substitution at residue 61 may be crucial as far as cholesterol metabolism is concerned. We also investigated the question of whether the Apoa1 gene is responsible for the cholesterol QTLs (Cq4 and Cq5) that had been identified previously on chromosome 9 in C57BL/6J x KK-Ay/a F2 and in KK x RR F2, but not in C57BL/6J x RR F2 mice. Similar to Apoa2 alleles, three different Apoal alleles with two successive amino acid substitutions were revealed among the strains. However, we could not correlate Apoal polymorphisms with the occurrence of QTLs in these three sets of F2 mice.  相似文献   

9.
Many economic losses occur in the poultry industry due to leg fragility. Knowing the genomic regions that influence traits associated with the growth and composition of the leg’s bone can help to improve the selection process leading to increased leg resistance to fracture. The present study aimed to map quantitative trait loci (QTL) for mineral composition and morphometric traits of the tibia in 478 animals from an F2 broiler × layer cross. The measurement of weight, length and width of Tibia was carried out at 42 days of age. Ash, dry matter, levels of calcium (Ca), phosphorus (P), magnesium (Mg), Zinc (Zn) and Calcium:Phosphorus (Ca:P) ratio were also recorded. The population was genotyped for 128 microsatellite markers and one single nucleotide polymorphism, covering 2630 cM of the chicken genome. A likelihood ratio test was performed to find QTLs. Additive and dominance effects of the QTLs were included in the model. In the chromosomes 2 (GGA2), 6 (GGA6), 8 (GGA8), 24 (GGA24) and 26 (GGA26) some suggestive QTLs (P<0.00276) were mapped for tibia weight (GGA2 and GGA26), ash percentage (GGA2 and GGA6), dry matter percentage (GGA2), Ca (GGA8 and GGA24) and Ca:P ratio (GGA8), many of which are close to genes already identified as good candidates for those traits. The suggestive QTL on GGA2 has a pleiotropic effect on ash percentage, dry matter and bone weight, whereas in the GGA8 there seems to be two QTLs, one for Ca and another for Ca:P ratio. Thus, this study identified at least five genomic regions, in different chromosomes, that can be targeted for further research to identify potential mutations influencing the development and composition of leg bones in Gallus gallus.  相似文献   

10.
 Powdery mildew is one of the major diseases of wheat in regions with a maritime or semi-continental climate and can strongly affect grain yield. The attempt to control powdery mildew with major resistance genes (Pm genes) has not provided a durable resistance. Breeding for quantitative resistance to powdery mildew is more promising, but is difficult to select on a phenotypic basis. In this study, we mapped and characterised quantitative trait loci (QTLs) for adult-plant powdery mildew resistance in a segregating population of 226 recombinant inbred lines derived from the cross of the Swiss wheat variety Forno with the Swiss spelt variety Oberkulmer. Forno possibly contains the Pm5 gene and showed good adult-plant resistance in the field. Oberkulmer does not have any known Pm gene and showed a moderate susceptible reaction. Powdery mildew resistance was assessed in field trials at two locations in 1995 and at three locations in 1996. The high heritability (h2=0.97) for powdery mildew resistance suggests that the environmental influence did not affect the resistance phenotype to a great extent. QTL analysis was based on a genetic map containing 182 loci with 23 linkage groups (2469 cM). With the method of composite interval mapping 18 QTLs for powdery mildew resistance were detected, explaining 77% of the phenotypic variance in a simultaneous fit. Two QTLs with major effects were consistent over all five environments. One of them corresponds to the Pm5 locus derived from Forno on chromosome 7B. The other QTL on 5A, was derived from the spelt variety Oberkulmer and did not correspond to any known Pm gene. In addition, five QTLs were consistent over three environments, and six QTLs over two environments. The QTL at the Pm5 locus showed a large effect, although virulent races for Pm5 were present in the mixture of isolates. Molecular markers linked with QTLs for adult-plant resistance offer the possibility of simultaneous marker-assisted selection for major and minor genes. Received: 22 September 1998 / Accepted: 26 October 1998  相似文献   

11.
C57BL/6J小鼠超数排卵的研究   总被引:9,自引:0,他引:9  
目的 确定C57BL 6J小鼠超排的最佳激素剂量和最合适的注射间隔时间 ,提高超排率。方法  40只C57BL 6J雌鼠随机分为四组 ,分别用 5IU或 10IU的PMSG和HCG ,间隔 48h或 72h注射 ,比较排出卵母细胞的数量。结果  5IU +5IU剂量的PMSG和HCG、间隔 48h注射组超排效果最好 ;8~ 10周龄雌鼠较 6~ 8周龄雌鼠超排效果好。结论 C57BL 6J小鼠超排的最佳激素剂量为 5IUPMSG +5IUHCG ,最合适的注射间隔时间为 48h ,处于繁殖期的雌鼠超排效果好。  相似文献   

12.
Wound healing/regeneration mouse models are few, and studies performed have mainly utilized crosses between MRL/MPJ (a good healer) and SJL/J (a poor healer) or MRL/lpr (a good healer) and C57BL/6J (a poor healer). Wound healing is a complex trait with many genes involved in the expression of the phenotype. Based on data from previous studies that common and additional quantitative trait loci (QTL) were identified using different crosses of inbred strains of mice for various complex traits, we hypothesized that a new cross would identify common and additional QTL, unique modes of inheritance, and interacting loci, which are responsible for variation in susceptibility to fast wound healing. In this study, we crossed DBA/1J (DBA, a good healer) and 129/SvJ (129, a poor healer) and performed a genome-wide scan using 492 (DBA×129) F2 mice and 98 markers to identify QTL that regulate wound healing/regeneration. Four QTL on chromosomes 1, 4, 12, and 18 were identified which contributed toward wound healing in F2 mice and accounted for 17.1% of the phenotypic variation in ear punch healing. Surprisingly, locus interactions contributed to 55.7% of the phenotype variation in ear punch healing. In conclusion, we have identified novel QTL and shown that minor interacting loci contribute significantly to wound healing in DBA×129 mice cross. The authors Masinde, Li, and Nguyen contributed equally to this article.  相似文献   

13.
We have mapped epistatic quantitative trait loci (QTL) in an F2 cross between DU6i × DBA/2 mice. By including these epistatic QTL and their interaction parameters in the genetic model, we were able to increase the genetic variance explained substantially (8.8%–128.3%) for several growth and body composition traits. We used an analysis method based on a simultaneous search for epistatic QTL pairs without assuming that the QTL had any effect individually. We were able to detect several QTL that could not be detected in a search for marginal QTL effects because the epistasis cancelled out the individual effects of the QTL. In total, 23 genomic regions were found to contain QTL affecting one or several of the traits and eight of these QTL did not have significant individual effects. We identified 44 QTL pairs with significant effects on the traits, and, for 28 of the pairs, an epistatic QTL model fit the data significantly better than a model without interactions. The epistatic pairs were classified by the significance of the epistatic parameters in the genetic model, and visual inspection of the two-locus genotype means identified six types of related genotype–phenotype patterns among the pairs. Five of these patterns resembled previously published patterns of QTL interactions.  相似文献   

14.
High-yielding capacity of the modern barley varieties is mostly dependent on the sources of semi-dwarfness associated with the sdw1/denso locus. The objective of the study was to identify quantitative trait loci (QTLs) associated with the plant height and yield potential of barley recombinant inbred lines (RILs) grown under various soil moisture regimes. The plant material was developed from a hybrid between the Maresi (European cv.) and CamB (Syrian cv.). A total of 103 QTLs affecting analysed traits were detected and 36 of them showed stable effects over environments. In total, ten QTLs were found to be significant only under water shortage conditions. Nine QTLs affecting the length of main stem were detected on 2H-6H chromosomes. In four of the detected QTLs, alleles contributed by Maresi had negative effects on that trait, the most significant being the QLSt-3H.1-1 in the 3H.1 linkage group. The close linkage between QTLs identified around the sdw1/denso locus, with positive alleles contributed by Maresi, indicates that the semi-dwarf cv. Maresi could serve as a donor of favourable traits resulting in grain yield improvement, also under water scarcity. Molecular analyses revealed that the Syrian cv. also contributed alleles which increased the yield potential. Available barley resources of genomic annotations were employed to the biological interpretation of detected QTLs. This approach revealed 26 over-represented Gene Ontology terms. In the projected support intervals of QGWSl-5H.3-2 and QLSt-5H.3 on the chromosome 5H, four genes annotated to ‘response to stress’ were found. It suggests that these QTL-regions may be involved in a response of plant to a wide range of environmental disturbances.  相似文献   

15.
R T Gentry  V P Dole 《Life sciences》1987,40(22):2191-2194
To determine why animals reject alcohol when offered palatable solutions of sucrose, male C57BL/6J mice were challenged first with 5% sucrose then with 10% sucrose, while given continuous free-access to alcohol and water. The 5% sucrose dramatically reduced the intake of alcohol and increased the intake of total fluid by an average of 7.3 ml/day. The suppression of alcohol intake could not be attributed to a volumetric ceiling since access to 10% sucrose produced a further large increase in total intake (8.8 ml/day). The results support the interpretation that animals consume alcohol for characteristics it shares with sucrose.  相似文献   

16.
目的:观察电磁脉冲Electromagnetic Pulse(EMP)对C57BL/6J小鼠胸腺的影响。方法:50只C57BL/6J小鼠按体重区组随机化分为对照组和辐照组,每组25只。EMP每天照射400次,连续照射7天,照后1d(天)、3d、7d、14d、28d共5个时间点杀取胸腺。2只辐照组和2只对照组杀取的胸腺做HE染色,观察其病理改变;3只辐照与3只对照组的小鼠,杀后称取小鼠的体重和胸腺的重量,计算胸腺指数;然后提取T淋巴细胞进行计数;同时取小鼠外周血检测其中的IL-4的水平。结果:照后1d胸腺的切片没有明显改变。7天后,胸腺开始有出血,结构不清;胸腺指数呈现递减的趋势,但辐照组与对照组没有的差异没有统计学意义;T淋巴细胞数的变化也呈现先减后增的趋势,在第1d、14d、28d辐照组与对照组的差异没有统计学意义,在第3d和7d辐照组的细胞数小于对照组的细胞数(P<0.05);辐照组与对照组的外周血IL-4水平的差异也没有统计学意义。结论:电磁脉冲对雄性Balb/c小鼠胸腺结构造成一定的损伤,但胸腺指数改变不显著,T淋巴细胞数量增加。表明EMP对胸腺有一定的作用,但是胸腺不是EMP作用的敏感器官。  相似文献   

17.
A considerable number of fatness QTL have been identified in growing pigs, but there is a lack of knowledge about the genetic architecture of this trait in gilts and sows. We have performed a genome scan, in 255 Iberian × Meishan F(2) sows, for backfat thickness (BF) at 150 (BF(150) ) and 210 (BF(210)) days of age, 30 days after conception (BF(30)) and 7-10 days before farrowing (BF(bf)). We have found one BF150 QTL in SSC6 (120 cM) that was highly significant (P < 0.001) at the chromosome-wide level and suggestive at the genome-wide level (P < 0.1). Ten additional chromosome-wide significant QTL were found for sow BF(150) (SSC1, SSC13), BF(210) (SSC6, SSC8, SSC15), BF(30) (SSC5, SSC6) and BF(bf) (SSC1, SSC6, SSC13). The location of several of the BF QTL varied depending on the growing and reproductive status of the sow, suggesting that part of these genetic effects may have a temporal pattern of phenotypic expression.  相似文献   

18.
Baseline erythroid indices are increasingly involved as risk factors for common complex diseases in humans. However, little is known about the genetic architecture of baseline erythroid traits in pigs. In this study, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell (RBC), and red cell distribution width (RDW) were measured in 1420 (day 18), 1410 (day 46), and 1033 (day 240) F(2) pigs from a White Duroc x Erhualian intercross resource population. The entire resource population was genotyped for 183 microsatellite loci across the pig genome, and the quantitative trait loci (QTL) analysis was performed for all erythroid-related traits measured with QTL Express based on a least-squares method. A total of 101 QTL, including 46 genome-wide significant QTL and 55 chromosome-wide significant QTL, regulating erythroid traits were found on all pig chromosomes (SSC) except for SSC15 and SSC18. The genome-wide significant QTL were mainly localized on SSC1, 7, 8, 10, and X. These results confirmed most of QTL previously identified in the swine. More importantly, this study detected age-specific QTL for baseline erythroid traits in pigs for the first time. Notably, the QTL for MCV and MCH on day 18 on SSC8 with small intervals of 3 and 4 cM, respectively, provided a good starting point for identifying causal genes underlying MCV and MCH in the future.  相似文献   

19.
A quantitative trait locus (QTL) analysis of female reproductive data from a three-generation experimental cross between Meishan (MS) and Large White (LW) pig breeds is presented. Six F1 boars and 23 F1 sows, progeny of six LW boars and six MS sows, produced 573 F2 females and 530 F2 males. Six traits, i.e. teat number (TN), age at puberty (AP), ovulation rate (OR), weight at mating (WTM), number of viable embryos (NVE) and embryo survival (ES) at 30 days of gestation were analysed. Animals were genotyped for a total of 137 markers covering the entire porcine genome. Analyses were carried out based on interval mapping methods, using a line-cross (LC) regression and a half-full sib (HFS) maximum likelihood test. Genome-wide (GW) highly significant (P < 0.001) QTL were detected for WTM on SSC 7 and for AP on SSC 13. They explained, respectively, 14.5% and 8.9% of the trait phenotypic variance. Other GW significant (P < 0.05) QTL were detected for TN on SSC 3, 7, 8, 16 and 17, for OR on SSC 4 and 5, and for ES on SSC 9. Two additional chromosome-wide significant (P < 0.05) QTL were detected for TN, three for WTM, four for AP, three for OR, three for NVE and two for ES. With the exception of the two above-mentioned loci, the QTL explained from 1.2% to 4.6% of trait phenotypic variance. QTL alleles were in most cases not fixed in the grand-parental populations and Meishan alleles were not systematically associated with higher reproductive performance.  相似文献   

20.
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