铁皮石斛野生居群遗传多样性的RAPD分析与鉴别

目的采用RAPD分子标记技术，对铁皮石斛8个野生居群的遗传多样性、亲缘关系以及分子鉴别等进行研究。方法筛选随机引物进行RAPD分析，通过UPGMA聚类，研究铁皮石斛各居群间的遗传关系，构建居群亲缘关系的分子系统树；利用特异性条带对铁皮石斛野生居群进行指纹分析鉴别。结果共筛选出10个有效引物，在8个野生居群材料的RAPD扩增中共得到439个位点，平均每个引物扩增出43.9个位点，每个居群扩增出54.9个位点；在所获得的104条可重现谱带中，9条是单态的，95条是多态的，多态性程度达91.35%，遗传距离在0.590～0.727之间，平均为0.686。结论铁皮石斛居群间遗传差异明显，具有较丰富的遗传多样性；RAPD可以作为铁皮石斛野生居群遗传多态性、居群亲缘关系和分子鉴别研究的有效手段；引物S412可以有效鉴别铁皮石斛的8个野生居群。     

Integration of Genotoxic and Population Genetic Endpoints in Biomonitoring and Risk Assessment

Genetic ecotoxicology is a multifaceted discipline that examines the effects of xenobiotic compounds on the structure and function of DNA. This paper discusses the role of genetic ecotoxicology in environmental biomonitoring and risk assessment. Genetic ecotoxicology may include somatic effects (e.g., DNA damage) or population genetic effects (changes in genetic diversity or gene frequencies). Traditionally, genetic ecotoxicology studies have focused on either one of these sub-disciplines, but integration of these two approaches would be advantageous for three reasons. First, at the population level, concordant responses between changes in population genetic structure and elevated levels of DNA damage may provide evidence that the population genetic changes are influenced by exposure to genotoxic chemicals. Second, if the frequencies of alleles or other genetic markers differ between genotoxicant-contaminated and reference populations, associations between relative amount of DNA damage and genotype may provide evidence that these changes are due to genotoxicant-induced selection. Third, genetic analysis of gene flow may provide insight into patterns of dispersal that could obscure differences between contaminated and reference populations. In order to demonstrate the application of these ideas, three lines of research are summarized herein. The first is a series of studies that focus on radionuclide-contaminated populations of mosquitofish (Gambusia). This research identified RAPD markers that may be indicative of genetic adaptation to radionuclide stress. Relative amounts of DNA damage among genotypes presented evidence that these markers may be indicators of relative radioresistance. The second study examined DNA damage and population genetic structure in radionuclide-contaminated kangaroo rat (Dipodomys) populations. It was found that between-population differences in genetic diversity paralleled those for DNA damage and relative levels of contamination. Also, population genetic analysis indicated that there was dispersal between contaminated and reference populations, and that between-population differences in the amount of DNA damage could not be detected until this dispersal was taken into account. In the third study, populations of redbreast sunfish (Lepomis auritis) from streams contaminated with complex mixtures of industrial chemicals were examined. It was found that the genetic distances between populations within the contaminated stream corresponded with the relative magnitude of molecular and community-level effects. It was concluded that genetic ecotoxicology could make significant contributions to the fields of environmental biomonitoring and ecological risk assessment, and that integration of genotoxicology and population genetic studies would be a definite advantage toward this end.     

Genetic Ecotoxicology III: the Relationship Between DNA Strand Breaks and Genotype in Mosquito Fish Exposed to Radiation

DNA polymorphism in mosquito fish (Gambusia affinis), as revealed by RAPD (randomly amplified polymorphic DNA) and allozyme analysis, was compared to relative amounts of DNA strand breakage in blood and liver tissues. Mosquito fish were exposed to radionuclide contamination in situ and to X-rays in the laboratory. The types of RAPD metrics used were the number of RAPD bands per individual and the frequency of certain RAPD bands. In a previous study, it was noted that in some instances the number of RAPD bands and the frequency of certain RAPD bands were elevated in radionuclide-contaminated sites relative to reference sites. In the present study, it was found that the median molecular length (MML) of the DNA (which is inversely proportional to the amount of DNA strand breakage) was correlated in several cases to the number of RAPD bands per individual. In addition, for those RAPD bands that occurred at a higher frequency in mosquito fish from radionuclide-contaminated sites, DNA strand breakage was often lower for those fish with than without these RAPD bands. RAPD data obtained on mosquito fish exposed to X-rays in the laboratory paralleled those from the field. Furthermore, analysis showed that heterozygotes for the allozyme locus nucleoside phosphorylase were more prevalent in radionuclide-contaminated sites and had fewer DNA strand breaks than did homozygotes. These results provide additional evidence that changes in population genetic structure of mosquito fish exposed to a genotoxicant (radiation) can be detected at the DNA level.     

不同产地白及遗传多态性的RAPD分析

目的 研究国内不同产地白及的遗传多样性和亲缘关系。方法 利用随机扩增多态DNA （random amplified polymorphic DNA,RAPD）引物,RAPD分子标记技术分析国内50个不同产地的白及。结果 RAPD技术扩增产物经琼脂凝胶电泳检测,从50条引物中筛选出10条（S8,S9,S14,S19,S23,S25,S28,S29,S30,S31）条带清晰的引物,10条引物共扩增出88条DNA条带,其中多态性的DNA条带数目为81条,占总数的92.05%。每个引物能扩增出5~11条DNA条带,平均可扩增出8.8条;扩增最少的引物为S19,扩增出5条DNA条带;扩增最多的引物为S29,扩增出11条DNA条带。而每个引物能扩增的多态性DNA条带数为3~11条,平均可扩增出8.6条。结论 不同产地的白及具有较丰富的遗传多样性,RAPD可有效应用于白及的遗传多样性研究。     

Genetic ecotoxicology II: population genetic structure in mosquitofish exposed in situ to radionuclides

In 1977, approximately 250 mosquitofish (Gambusia affinis) from a relatively uncontaminated site (Crystal Springs) were transplanted into a small pond on the Department of Energy Oak Ridge Reservation which is heavily contaminated with radionuclides (Pond 3513). Starting in 1992, DNA polymorphism was evaluated using the RAPD (Randomly Amplified Polymorphic DNA) and allozyme genotype techniques to determine if genetic differentiation had occurred between the two populations. Fish from a second radionuclide-contaminated population (White Oak Lake) and another unrelated non-contaminated population (Wolf Creek) were also examined. For the RAPD analyes, 15 RAPD primers (from a total of 40) were found to produce polymorphic banding patterns in at least two of the four populations and subsequently were used to produce a total of 142 bands. Data generated by these RAPD primers indicated an increased genetic diversity in radionuclide-contaminated sites relative to reference sites. Furthermore, the patterns from six RAPD primers produced a higher average number of bands when using DNA from radionuclide- contaminated populations than from non-contaminated, and for three RAPD primers the average number of bands from radionuclide- contaminated populations was lower. In addition, 17 bands occurred at a higher frequency in the radionuclide-contaminated compared to the non-contaminated populations. For the allozyme analyses, it was found that there was a higher percentage of polymorphism and heterozygosity in the radionuclide-contaminated relative to non-contaminated sites. These findings contribute to our understanding of the evolutionary effects of contaminant exposure as well as to the development of population-level biomarkers     

不同居群白芍的DNA随机扩增多态性研究

目的分析6个不同居群白芍的遗传多样性,为白芍的种质鉴定及遗传多样性分析提供依据。方法运用随机扩增多态性DNA(RAPD)技术,对浙江磐安、四川中江、安徽亳州、上海崇明、江苏宿迁和山东荷泽居群白芍的基因组DNA进行随机扩增,利用NTsys2.10e软件计算遗传相似性,运用UPGMA法进行聚类分析并构建树状图。结果共筛选了70个随机引物,从中挑选出8条多态性强、重复性好的引物,共检测出215个位点,多态性位点137个,多态位点比率为63.7%,UPGMA聚类可以将不同来源的白芍很好地区分开。结论不同产地间的白芍存在丰富的遗传多样性,RAPD分子标记方法可以用来鉴定不同产地的白芍。     

Choice of Methodology for Assessing Genetic Impacts of Environmental Stressors: Polymorphism and Reproducibility of RAPD and AFLP Fingerprints

PCR-based multi-locus DNA fingerprints represent one of the most informative and cost-effective measures of genetic diversity and are useful population-level biomarkers of toxicologic and other anthropogenic impacts. However, concerns about reproducibility of DNA fingerprints have limited their wider use in environmental biology. We assessed polymorphism and reproducibility of two common fingerprinting techniques, RAPD (randomly amplified polymorphic DNA) and AFLP (amplified fragment length polymorphism), in pedigreed populations of rainbow trout (Oncorhynchus mykiss) to derive general rules for selective removal of problematic fingerprint bands. We found that by excluding bands that comprised less than 1% of total intensity, and by excluding the largest and smallest 10% of the bands, we could achieve nearly 100% reproducibility of AFLP fingerprints. Similar application of band exclusion criteria to RAPD fingerprints did not significantly enhance their reproducibility, and at least 15% of RAPD bands were not fully repeatable, heritable, or transmittable. The RAPD technique produced more polymorphic fingerprints than AFLP; however, considering that a substantial proportion of RAPD markers did not demonstrate Mendelian inheritance patterns, the AFLP methodology is to be preferred for future research.     

Utilization of RAPD markers to assess genetic diversity of wild populations of North American ginseng (Panax quinquefolium)

The Catskill Mountains of New York State are an important source of wild-collected American ginseng (Panax quinquefolium) and, increasingly, of woods-cultivated ginseng. The objective of this study was to assess genetic diversity among 9 different wild ginseng populations in and adjacent to the Catskill Mountain region of New York State and to compare these to wild populations from other states including Kentucky, Tennessee, North Carolina, Pennsylvania, and Virginia, and one cultivated population from Wisconsin. Randomly amplified polymorphic DNA (RAPD) markers were used to estimate the genetic distance among samples from the 15 populations. Pooled DNA from 10 plants of each of 8 New York populations was initially screened with 64 random primers; subsequently, the 15 primers that exhibited the greatest number of reproducible polymorphic markers were selected for further experimentation. Gel electrophoresis with the selected 15 primers produced 124 highly reproducible polymorphic bands. The ratio of discordant bands to total bands scored was used to estimate the genetic distance within and among populations. Multidimensional scaling (MDS) of the relation matrix showed distinctly separate clusters between New York and non-New York populations, indicating separation between these two groupings. The MDS analysis was confirmed using pooled chi-square tests for fragment homogeneity. This study shows that RAPD markers can be used as population-specific markers for Panax quinquefolium, and may eventually be utilized as markers for ginsenoside assessment.     

鱼腥草种质资源的RAPD分析

目的分析鱼腥草种质资源在分子水平上的遗传多样性。方法应用RAPD技术对92份鱼腥草种质资源进行检测。结果34个随机引物中有32个引物(94.1%)扩增产物具多态性。34个引物共得到200条扩增DNA片段,其中93.5%的片段具多态性。每个多态性引物平均可扩增出5.8个多态性片段。峨眉蕺菜和蕺菜种内平均遗传相似系数(genetic similarity,GS)分别为0.521和0.572,二者种间GS值为0.517。峨眉蕺菜与蕺菜中染色体数目为36的细胞型间相似程度最高,其平均GS值达0.530。栽培蕺菜类群比其野生类群遗传多样性相对较高。聚类分析表明,利用RAPD技术可将全部供试材料区分开,所有材料共划分为14类。其中,绝大多数(62个)聚为一类,且根据RAPD遗传相似系数划分的类群同地理分布有一定关系。结论(1) 鱼腥草种质资源在分子水平上确实存在较大遗传差异。(2) RAPD标记可作为构建鱼腥草DNA指纹图谱的有效工具。(3) 鱼腥草药材道地性与环境因素有关,但更大程度上由其遗传因素所决定。     

人参和其他中草药的遗传学鉴定(英文)

The main objective of this paper is to review the chemical and genetic methods used in authentication of ginseng, especially the recent advances in microsatellite genotyping and its application to the authentication of other traditional Chinese medicines (TCM). The standardization and modernization of TCM hinge on the authentication of their botanical identities. Analysis of well-characterized marker compounds is now the most popular method for identifying the herbal materials and quality control of TCM, eg, ginsenoside profiling for authentication of Panax species. However, in many herbal species the chemical composition of the plant changes with the external environment and processing conditions, which lowers the reliability of these authentication methods. In the light of the advances in molecular biotechnology in the past few decades, genetic tools are now considered to provide more standardized and reliable methods for authentication of herbal materials at the DNA level. These genetic tools include     

Endocrine disruption in male mosquitofish (Gambusia holbrooki) inhabiting wetlands in Western Australia

The use of gonopodial indices as potential indicators of endocrine disruption in the mosquitofish Gambusia holbrooki inhabiting south west Australian wetlands was investigated. A minimum of 50 mature males was collected from each of five water-bodies in the Swan Coastal Plain, Western Australia, in order to measure morphological features related to reproduction. A set of morphological measurements were used to derive the following indices: gonopodium length/standard body length, pre-anal length/standard body length, the index of elongation and the percentage of male fish with hooks on the distal end of the gonopodium. Indices of male mosquitofish collected from Jack Finney Lake, located in the Curtin University campus, suggest the presence of endocrine disrupting chemicals (EDCs) in this water-body, while those from Lake Kulinup suggest this is a site of concern. Indices of male fish from the Wagerup wetland, Lake Monger and Loch McNess indicate that fish inhabiting these wetlands are not affected by EDCs. This preliminary study suggests that EDCs may be present in a number of wetlands of the Swan Coastal Plain. Further study using EDC specific markers such as vitellogenin induction in male mosquitofish is required to confirm whether EDCs are present in these water-bodies.     

Genotoxic effects of 8-hydroxylquinoline in loach (Misgurnus anguillicaudatus) assessed by the micronucleus test,comet assay and RAPD analysis

This study was a preliminary step in evaluating the genotoxic effects of 8-hydroxylquinoline (8-HOQ) in loach (Misgurnus anguillicaudatus) using the micronucleus, comet and RAPD assays. In the micronucleus test and comet assay, the micronuclei rate (%) and three comet parameters (trailing rate, tail length and tail moment) in treated fish increased with increasing 8-HOQ concentration and treatment time. These results showed that exposure to 8-HOQ significantly induced genetic toxicity in loach blood cells. A subsequent RAPD assay also showed that 8-HOQ induced a genotoxic effect in loach. Among the 23 tested RAPD primers, 11 primers produced unique polymorphic band patterns and generated RAPD profile variations that displayed the band intensity, disappearance of bands and appearance of new bands of amplified DNA in the 8-HOQ-treated genomic DNA samples. In addition, the variation in RAPD profiles was time- and concentration-dependent. These results suggested that 8-HOQ is potentially harmful to fish and may be a toxic contaminant in the aquatic environment.     

Use of RAPD to detect sodium arsenite-induced DNA damage in human lymphoblastoid cells

Inorganic arsenic is a known human carcinogen, yet its mechanism of action remains unclear. Our previous study showed that arsenite significantly induces oxidative DNA adducts and DNA-protein cross-links in several mammalian cell lines. In the present study, we used the random amplified polymorphic DNA (RAPD) assay to evaluate the possible target in the genomic DNA of human lymphoblastoid cells that were exposed to sodium arsenite. Treatment with both 10 and 80 microM arsenite for 4h induced significant changes in RAPD profiles compared with the control pattern. Two 10-mer RAPD primers (D11 and F1) produced the most distinguishable banding profiles between arsenite-treated and control genomic DNA. The sequencing of four arsenite-sensitive RAPD bands showed that the RB1CC1 and PACE4 genes might be the DNA targets of sodium arsenite treatment. We propose that arsenite may induce sequence- or gene-specific damage and then change the RAPD profile in human lymphoblastoid cells. The results of our study also show that RAPD combined with other techniques is a good tool for detecting alterations in genomic DNA and for the direct screening of new molecular markers related to arsenite-induced carcinogenesis.     

紫苏属药用植物的rDNA ITS区SNP分子标记与位点特异性PCR鉴别

目的分析单种属——紫苏属各变种间rDNA ITS区的序列以及存在的单核苷酸多态性(SNP)现象，设计出位点特异性PCR引物，用于紫苏属各变种间的分子标记鉴别。方法对紫苏属各变种多个体的rDNA ITS区全序列进行了准确测定，运用Clustral X 1.8，MEGA 3.0进行排序并进行SNP分析，从而设计出鉴别各变种的等位基因位点特异性PCR鉴别引物。结果紫苏属各变种(紫苏、白苏、鸡冠苏和耳齿紫苏等)的rDNA ITS区全序列共有615～618 bp的长度，ITS1为233～235 bp，5.8S为179 bp，ITS2为203～204 bp，GC含量为61.5%～61.9%。从rDNA ITS区碱基变异的整体情况来看，紫苏属各变种间不仅在非编码的转录间隔区ITS1和ITS2内存在非编码区单核苷酸多态性(ncSNP)，而且在保守的5.8S编码区内也存在3个位点的单核苷酸多态性，即编码区SNP(cSNP)，所有的SNP均只具2等位多态性。5.8S区cSNP的出现与产生该变异的变种出现的显著形态差异关联。本文还利用这些SNP位点设计出了鉴别紫苏属各变种的位点特异性PCR引物，无需测序即可对紫苏属的原植物及“苏子”、“苏叶”等药材进行有效准确的分子鉴别。结论紫苏属药用植物rDNA ITS区存在的SNP可用作紫苏属各变种鉴别的分子标记。     

蝙蝠蛾拟青霉与冬虫夏草关系的分子系统学研究

以5月和6月两个不同时段采集的分别产于青海省化隆县和四川省康定县的冬虫夏草(Cordyceps sinensis)新鲜子实体为材料，采用分子生物学方法，以rDNA-ITS序列为分子标记，对蝙蝠蛾拟青霉(Paecilomyces hepiali)与冬虫夏草之间的关系进行了探讨。以真菌通用引物ITS1/ITS4分别对蝙蝠蛾拟青霉及冬虫夏草子座和僵虫基因组DNA进行PCR扩增，获得的片段克隆到pMD18-T Vector上进行测序，结果表明，随机挑取的46个克隆与某些已在GenBank中注册的中国被毛孢(Hirsutella sinensis) 或冬虫夏草的rDNA-ITS序列的一致性均在99%以上，但与蝙蝠蛾拟青霉的rDNA-ITS序列的一致性约为72%。根据蝙蝠蛾拟青霉的rDNA-ITS序列设计了两对特异引物，分别以不同产地及不同生长时期共4个批次的冬虫夏草子座和僵虫基因组DNA为模板，进行PCR及巢式PCR扩增，均得到了相应片段，该片段与蝙蝠蛾拟青霉的rDNA-ITS序列具有100%的一致性。在GenBank中注册号为AB067740的另一个标明为冬虫夏草的rDNA-ITS序列与注册号为AJ309353的中国被毛孢的rDNA-ITS序列一致性仅为87.3%，但根据AB067740序列设计特异引物，也从冬虫夏草基因组DNA中扩增到其相应序列。研究结果表明，在天然冬虫夏草中除了中国被毛孢之外，还普遍存在着蝙蝠蛾拟青霉等内寄生菌。     

Using RAPD in Neisseria gonorrhoeae genotyping and transmission detection

The aim of this paper is to develop an applicable Random Amplified Polymorphic DNAs (RAPD) method for genotyping Neisseria gonorrhoeae strain, and discuss the possibility of using the RAPD method to trace N. gonorrhoeae strain transmission route. Four different pretreatment methods were used on the N. gonorrhoeae genomic DNA component, and the best adaptive extract method was selected for RAPD. Different RAPD primers sequence was used for amplification and their differentiating capabilities for N. gonorrhoeae strains were compared. Applicable RAPD primer was selected for N. gonorrhoeae genotyping and then applied into transmission detection. The results show that the so called cetyl-trimethylammonium bromide (CTAB) method for extracting genomic DNA could give integrated genomic DNA and give out relatively better RAPD fingerprint maps, subsequently, using selected RAPD primer could give out a group of amplification polymerase chain reaction bands. The fingerprint maps from different N. gonorrhoeae strains were distinctive. Some main segments were common to all the N. gonorrhoeae strains tested. Some segments were different among the N. gonorrhoeae strains. According to the fingerprint maps and similarity index of different N. gonorrhoeae isolates, isolates from a pair of sex-partners were very similar. Based on these findings, the best extracting method and suitable RAPD primer were chosen. The RAPD fingerprint maps could type N. gonorrhoeae effectively and could be used as an additional approach in molecular epidemiology for tracing infection sources.     

Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes

The present study was conducted to explore the following hypotheses: (i) do scorpions (Scorpio maurus palmatus) from different biotopes exhibit intraspecific diversity in their venom? (ii) if so, is this variation associated with ecological or genetic factors, geographical distance, and/or multiple interrelated parameters? To address these questions, scorpions were collected from four geographically isolated localities in Egypt. Three of these locations are from mutually isolated pockets in the arid biotope of Southern Sinai (Wadi Sahab, El-Agramia and Rahaba plains). The fourth population was sampled from the semiarid biotope of Western Mediterranean Costal Desert (WMCD). Using reducing gel electrophoresis (SDS-PAGE), we have shown biotope-specific variation in the expression of peptides from scorpions collected from these distinct areas. WMCD sourced venom samples contain higher molecular weight protein components (219, 200, 170, 139, 116 kDa) than Southern Sinai scorpion venom samples. The Southern Sinai venom is characterized by the presence of 11 protein bands (93-0.58 kDa) that are not mirrored in the individual venom samples of WMCD. Bands of 33 and 3.4 kDa were characteristics of all individual venom samples of the scorpion populations. Even within Southern Sinai area, Sahab venom contains five fractions that are not detected in both El-Agramia and Rahaba venom samples. Moreover, male and female venom analysis revealed some sex-related proteomic similarities and differences between scorpion populations. Female venom appears to be more complicated than the male venom. Female venom samples showed bands of 219, 200, 77.5, 55.5, 45, 39, 37, 24 and 16 kDa which were absent in the male venom. The random amplified polymorphic DNA (RAPD) technique was used to estimate the genetic distance between the four scorpion populations. The RAPD data confirmed the genetic diversity at molecular level among the sampled populations. More than 77 RAPD bands (ranging in size from 125 to 15,000 bp) were defined from the four scorpion populations. Of the 77 bands, 57 (76.2%) were polymorphic and 20 were monomorphic among the populations. The similarity coefficient data of venom and DNA were used to construct separate dendrograms, which grouped together the Southern Sinai populations and these were some distance away from the WMCD population. Taken together, we suspect that a combination of local environmental conditions, geographical separation and genetic separation may play a major role in the intraspecific variation of venom of S. m. palmatus.     

Molecular markers as a tool to verify sexual and apomictic off-spring of intraspecific crosses in Hypericum perforatum.

The aim of this project was to establish RAPD markers to determine the percentage of sexual off-spring of the facultative apomictic plant species H. perforatum. We did reciprocal crosses between four different accessions (A x B, B x A, C x D, D x C) by mechanical emasculation and hand pollination. Genomic DNA of the parents and the off-spring was isolated and PCR conditions were optimized in order to obtain reproducible bands with RAPD markers. Of the 260 screened RAPD primers 127 revealed polymorphism between the parental lines of A and B, whereas 53 revealed no amplification products. Each progeny was tested for the presence of paternal bands with three primers. We found no sexual off-spring among the 22 progenies of A x B, the nine progenies of B x A and the ten progenies of D x C. However, we detected six sexual off-spring among the 45 progenies of C x D. We have proved that RAPD markers can be used to distinguish between sexual and apomictic off-spring in H. perforatum and that sexual off-spring can be obtained from intraspecific crosses. The percentage of sexual progeny might depend on the genotype of the parental lines.     

Molecular differentiation ofPanax species by RAPD analysis

Traditional taxonomic methods used for the identification and differentiation of ginsengs rely primarily on morphological observations or physiochemical methods, which cannot be used efficiently when only powdered forms or shredded material is available. Randomly amplified polymorphic DNA (RAPD) was used to determine the unique DNA profiles that are characteristic not only of the genus Panax but also of various Panax subgroups collected from five different countries. RAPD results of OP-5A primer showed a specific single band that is characteristic of all ginseng samples. RAPD results of OP-13B primer demonstrated that OP-13B primer could be used as a unique RAPD marker to differentiate Panax species. These results support that this approach could be applied to distinguish Korean Ginseng (Panax ginseng) from others at the molecular level.     

Quantitative trait loci and psychopharmacology

Unlike simple Mendelian characteristics, individual differences in behavior, including behavioral responses to drugs, are generally distributed continuously, show substantial non-genetic as well as genetic influence, and appear to be influenced by many genes rather than one or two major genes. For these reasons, application of techniques of molecular biology to identify DNA sequences responsible for behavioral variation requires strategies that can detect genes that account for small amounts of variation, so-called quantitative trait loci (QTL). One such strategy involves analyses of association using recombinant inbred (RI) strains of mice. The RI QTL approach is especially valuable when researchers use the same RI series, such as BXD, which has 26 strains and more than 300 mapped genetic markers. Even when the progenitor inbred strains do not differ and when the strain distribution pattern of the RI strains is continuous, the approach can be used to identify and map QTL and estimate the extent to which the QTL account for genetic variance for a particular phenotype. A multivariate extension of this approach can assess genetic correlations among measures as well as the QTL underpinnings of these genetic correlations. The cumulative and integrative nature of such a program of research is the major benefit of the RI QTL approach for molecular genetic analysis of psychopharmacological processes, their physiological infrastructure, and their interface with other biological and behavioural systems.