Comparatively analyzing the liver-specific transcriptomic profiles in Kunming mice afflicted with streptozotocin- and natural food-induced type 2 diabetes mellitus.

BACKGROUND: Streptozotocin is a classic drug used to induce diabetes in animal models. OBJECTIVE: The aim of this study is to investigate the liver transcriptome of Kunming mice with diabetes induced by either streptozotocin (STZ) or Non-STZ. METHODS: Forty male mice were randomly assigned into four groups: Control (Ctr, standard diet), mHH (high fat and high carbohydrate diet), mHS (high fat and high carbohydrate diet for 4 weeks followed by 60 mg/kg STZ for 3 consecutive days) and mSH (60 mg/kg STZ for 3 consecutive days followed by a high fat and high carbohydrate diet for 12 weeks). All mice injected with STZ were identified as diabetic despite the sequential feeding of high fat and high carbohydrate diets. RESULTS: Only 7 of 13 mice in the mHH group met the diagnostic criteria for diabetes. The asting blood glucose (FBG) of the mHH, mHS, mSH and Ctrl groups was 13.27 ± 1.14, 15.01 ± 2.59, 15.95 ± 4.38 and 6.28 ± 0.33 mmol/L at the 12th week, respectively. Compared with the mHH group, transcription was elevated in 85 genes in the livers of mHS mice, while 21 genes were downregulated and 97 genes were upregulated in the mSH group while 35 genes were decreased. A total of 43 co-expressed genes were identified in the mHS vs mHH and mSH vs mHH groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses showed that two corporate GO terms and two KEGG pathways were significantly annotated in the STZ-treated groups. Both the GO term and pathway were related to the metabolism mediated by p53. CONCLUSION: A high fat and high carbohydrate diet combined with a low dose of STZ can effectively induce diabetes in Kunming mice despite the abnormal expressions of genes in the liver. The differentially expressed genes were related to metabolism mediated by p53.

Reproductive traits in different Nile tilapia genetic groups / [Características reprodutivas em diferentes grupos genéticos de tilápia do Nilo]

The aim of this study was to evaluate the reproductive traits of the non-inbred and inbred AquaAmérica, GIFT and AquaAmérica × GIFTgenetic groups. Six fish from each genetic group were used (2 females:1 male). Females were examined for the presence of eggs in their mouth at every four days, for 12 weeks. Reproduction occurred in all genetic groups (GIFT: 100%; non-inbred AquaAmérica and AquaAmérica ×GIFT: 75%; inbred AquaAmérica: 50%). Female weight, female standard length, total spawning weight, absolute fecundity, relative fecundity, spawn index and hatching rate did not differ significantly between the genetic groups. However, the non-inbred AquaAmérica variety showed lower values (P<0.05) for egg diameter (2.4mm) and egg weight (4.2mg) and higher values (P<0.05) for relative number of eggs (247.6 eggs/g of egg) than GIFT (egg diameter: 2.8mm; egg weight: 5.7mg; relative number of eggs: 175.4 eggs/g of egg) and AquaAmérica ×GIFT (egg diameter: 2.8mm; egg weight: 5.9mg; relative number of eggs: 168.8 eggs/g of egg). In conclusion, the non-inbred AquaAmérica variety produces smaller, lighter eggs but a higher relative number of eggs than the GIFT variety and the AquaAmérica ×GIFT cross; and inbreeding negatively affects spawning rate.(AU)

O objetivo deste estudo foi avaliar as características reprodutivas dos grupos genéticos AquaAmérica não endogâmicos e endogâmicos, GIFT e AquaAmérica × GIFT. Foram utilizados seis peixes de cada grupo genético (duas fêmeas:um macho). As fêmeas foram examinadas quanto à presença de ovos na boca a cada quatro dias, durante 12 semanas. A reprodução ocorreu em todos os grupos genéticos (GIFT: 100%; AquaAmérica não endogâmica e AquaAmérica × GIFT: 75%; AquaAmérica endogâmica: 50%). Peso e comprimento padrão de fêmea, peso total de desova, fecundidade absoluta, fecundidade relativa, índice de desova e taxa de eclosão não diferiram significativamente entre os grupos genéticos. Entretanto, a variedade não endogâmica da AquaAmérica apresentou valores mais baixos (P<0,05) para diâmetro do ovo (2,4mm) e peso do ovo (4,2mg) e maiores valores (P<0,05) para número relativo de ovos (247,6 ovos/g de ovo ) que GIFT (diâmetro do ovo: 2,8mm; peso do ovo: 5,7mg; número relativo de ovos: 175,4 ovos/g de ovo) e AquaAmérica × GIFT (diâmetro do ovo: 2,8mm; peso do ovo: 5,9mg; número relativo de ovos: 168,8 ovos/g de ovo). Em conclusão, a variedade AquaAmérica não endogâmica produz ovos menores e mais leves, mas um número relativo maior de ovos que a variedade GIFT e o cruzamento AquaAmérica × GIFT; a consanguinidade afeta negativamente a taxa de desova.(AU)

Cleaning Genotype Data from Diversity Outbred Mice.

Data cleaning is an important first step in most statistical analyses, including efforts to map the genetic loci that contribute to variation in quantitative traits. Here we illustrate approaches to quality control and cleaning of array-based genotyping data for multiparent populations (experimental crosses derived from more than two founder strains), using MegaMUGA array data from a set of 291 Diversity Outbred (DO) mice. Our approach employs data visualizations that can reveal problems at the level of individual mice or with individual SNP markers. We find that the proportion of missing genotypes for each mouse is an effective indicator of sample quality. We use microarray probe intensities for SNPs on the X and Y chromosomes to confirm the sex of each mouse, and we use the proportion of matching SNP genotypes between pairs of mice to detect sample duplicates. We use a hidden Markov model (HMM) reconstruction of the founder haplotype mosaic across each mouse genome to estimate the number of crossovers and to identify potential genotyping errors. To evaluate marker quality, we find that missing data and genotyping error rates are the most effective diagnostics. We also examine the SNP genotype frequencies with markers grouped according to their minor allele frequency in the founder strains. For markers with high apparent error rates, a scatterplot of the allele-specific probe intensities can reveal the underlying cause of incorrect genotype calls. The decision to include or exclude low-quality samples can have a significant impact on the mapping results for a given study. We find that the impact of low-quality markers on a given study is often minimal, but reporting problematic markers can improve the utility of the genotyping array across many studies.

Genome-wide association for testis weight in the diversity outbred mouse population.

Testis weight is a genetically mediated trait associated with reproductive efficiency across numerous species. We sought to evaluate the genetically diverse, highly recombinant Diversity Outbred (DO) mouse population as a tool to identify and map quantitative trait loci (QTLs) associated with testis weight. Testis weights were recorded for 502 male DO mice and the mice were genotyped on the GIGAMuga array at ~ 143,000 SNPs. We performed a genome-wide association analysis and identified one significant and two suggestive QTLs associated with testis weight. Using bioinformatic approaches, we developed a list of candidate genes and identified those with known roles in testicular size and development. Candidates of particular interest include the RNA demethylase gene Alkbh5, the cyclin-dependent kinase inhibitor gene Cdkn2c, the dynein axonemal heavy chain gene Dnah11, the phospholipase D gene Pld6, the trans-acting transcription factor gene Sp4, and the spermatogenesis-associated gene Spata6, each of which has a human ortholog. Our results demonstrate the utility of DO mice in high-resolution genetic mapping of complex traits, enabling us to identify developmentally important genes in adult mice. Understanding how genetic variation in these genes influence testis weight could aid in the understanding of mechanisms of mammalian reproductive function.

Rapid genotype imputation from sequence without reference panels.

Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r(2) value of 0.98 in 2,073 outbred laboratory mice (0.15× sequencing coverage). In a sample of 11,670 Han Chinese (1.7× coverage), we achieve accuracy similar to that of alternative approaches that require a reference panel, demonstrating that our approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans.

Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing.

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations.

Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice.

Although mice are the most widely used mammalian model organism, genetic studies have suffered from limited mapping resolution due to extensive linkage disequilibrium (LD) that is characteristic of crosses among inbred strains. Carworth Farms White (CFW) mice are a commercially available outbred mouse population that exhibit rapid LD decay in comparison to other available mouse populations. We performed a genome-wide association study (GWAS) of behavioral, physiological and gene expression phenotypes using 1,200 male CFW mice. We used genotyping by sequencing (GBS) to obtain genotypes at 92,734 SNPs. We also measured gene expression using RNA sequencing in three brain regions. Our study identified numerous behavioral, physiological and expression quantitative trait loci (QTLs). We integrated the behavioral QTL and eQTL results to implicate specific genes, including Azi2 in sensitivity to methamphetamine and Zmynd11 in anxiety-like behavior. The combination of CFW mice, GBS and RNA sequencing constitutes a powerful approach to GWAS in mice.

Extensive variation between tissues in allele specific expression in an outbred mammal.

BACKGROUND: Allele specific gene expression (ASE), with the paternal allele more expressed than the maternal allele or vice versa, appears to be a common phenomenon in humans and mice. In other species the extent of ASE is unknown, and even in humans and mice there are several outstanding questions. These include; to what extent is ASE tissue specific? how often does the direction of allele expression imbalance reverse between tissues? how often is only one of the two alleles expressed? is there a genome wide bias towards expression of the paternal or maternal allele; and finally do genes that are nearby on a chromosome share the same direction of ASE? Here we use gene expression data (RNASeq) from 18 tissues from a single cow to investigate each of these questions in turn, and then validate some of these findings in two tissues from 20 cows. RESULTS: Between 40 and 100 million sequence reads were generated per tissue across three replicate samples for each of the eighteen tissues from the single cow (the discovery dataset). A bovine gene expression atlas was created (the first from RNASeq data), and differentially expressed genes in each tissue were identified. To analyse ASE, we had access to unambiguously phased genotypes for all heterozygous variants in the cow's whole genome sequence, where these variants were homozygous in the whole genome sequence of her sire, and as a result we were able to map reads to parental genomes, to determine SNP and genes showing ASE in each tissue. In total 25,251 heterozygous SNP within 7985 genes were tested for ASE in at least one tissue. ASE was pervasive, 89 % of genes tested had significant ASE in at least one tissue. This large proportion of genes displaying ASE was confirmed in the two tissues in a validation dataset. For individual tissues the proportion of genes showing significant ASE varied from as low as 8-16 % of those tested in thymus to as high as 71-82 % of those tested in lung. There were a number of cases where the direction of allele expression imbalance reversed between tissues. For example the gene SPTY2D1 showed almost complete paternal allele expression in kidney and thymus, and almost complete maternal allele expression in the brain caudal lobe and brain cerebellum. Mono allelic expression (MAE) was common, with 1349 of 4856 genes (28 %) tested with more than one heterozygous SNP showing MAE. Across all tissues, 54.17 % of all genes with ASE favoured the paternal allele. Genes that are closely linked on the chromosome were more likely to show higher expression of the same allele (paternal or maternal) than expected by chance. We identified several long runs of neighbouring genes that showed either paternal or maternal ASE, one example was five adjacent genes (GIMAP8, GIMAP7 copy1, GIMAP4, GIMAP7 copy 2 and GIMAP5) that showed almost exclusive paternal expression in brain caudal lobe. CONCLUSIONS: Investigating the extent of ASE across 18 bovine tissues in one cow and two tissues in 20 cows demonstrated 1) ASE is pervasive in cattle, 2) the ASE is often MAE but ranges from MAE to slight overexpression of the major allele, 3) the ASE is most often tissue specific and that more than half the time displays divergent allele specific expression patterns across tissues, 4) across all genes there is a slight bias towards expression of the paternal allele and 5) genes expressing the same parental allele are clustered together more than expected by chance, and there are several runs of large numbers of genes expressing the same parental allele.

Quantitative trait locus mapping methods for diversity outbred mice.

Genetic mapping studies in the mouse and other model organisms are used to search for genes underlying complex phenotypes. Traditional genetic mapping studies that employ single-generation crosses have poor mapping resolution and limit discovery to loci that are polymorphic between the two parental strains. Multiparent outbreeding populations address these shortcomings by increasing the density of recombination events and introducing allelic variants from multiple founder strains. However, multiparent crosses present new analytical challenges and require specialized software to take full advantage of these benefits. Each animal in an outbreeding population is genetically unique and must be genotyped using a high-density marker set; regression models for mapping must accommodate multiple founder alleles, and complex breeding designs give rise to polygenic covariance among related animals that must be accounted for in mapping analysis. The Diversity Outbred (DO) mice combine the genetic diversity of eight founder strains in a multigenerational breeding design that has been maintained for >16 generations. The large population size and randomized mating ensure the long-term genetic stability of this population. We present a complete analytical pipeline for genetic mapping in DO mice, including algorithms for probabilistic reconstruction of founder haplotypes from genotyping array intensity data, and mapping methods that accommodate multiple founder haplotypes and account for relatedness among animals. Power analysis suggests that studies with as few as 200 DO mice can detect loci with large effects, but loci that account for <5% of trait variance may require a sample size of up to 1000 animals. The methods described here are implemented in the freely available R package DOQTL.

Effective population size and evolutionary dynamics in outbred laboratory populations of Drosophila.

Census population size, sex-ratio and female reproductive success were monitored in 10 laboratory populations of Drosophila melanogaster selected for different ages of reproduction. With this demographic information, we estimated eigenvalue, variance and probability of allele loss effective population sizes. We conclude that estimates of effective size based on genefrequency change at a few loci are biased downwards. We analysed the relative roles of selection and genetic drift in maintaining genetic variation in laboratory populations of Drosophila. We suggest that rare, favourable genetic variants in our laboratory populations have a high chance of being lost if their fitness effect is weak, e.g. 1% or less. However, if the fitness effect of this variation is 10% or greater, these rare variants are likely to increase to high frequency. The demographic information developed in this study suggests that some of our laboratory populations harbour more genetic variation than expected. One explanation for this finding is that part of the genetic variation in these outbred laboratory Drosophila populations may be maintained by some form of balancing selection. We suggest that, unlike bacteria, medium-term adaptation of laboratory populations of fruit flies is not primarily driven by new mutations, but rather by changes in the frequency of preexisting alleles.

Comparative analysis of the behavioral and biomolecular parameters of four mouse strains.

The use of mice as experimental models in pharmacological and biochemical research began over 100 years ago, during which time different mice strains with specific features were developed. Numerous studies demonstrate that the pharmacological efficacy of various compounds significantly varies among different animal strains, a factor which must be considered when analyzing experimental data. The Sabra strain, developed more than 35 years ago, is widely used for research in Israel but has an unclear origin and is not characterized as well as other strains. Comparative analyses of the molecular characteristics of Sabra and other strains should help to understand their characteristics and to enhance the validity of their experimental use. Thus, four mouse strains-outbred ICR and Sabra as well as inbred C57Bl/6J and Balb/c were compared. Animals' weight, blood corticosterone and hippocampal BDNF mRNA levels were measured, and animals' behavior was compared using the EPM, open field, FST, and hot plate tests. We found that although Sabra mice are bigger and heavier than other tested lines, this is not reflected in behavior or in biomolecular features, wherein Sabra mice lay within the diapason of other tested animals. Thus, behavioral tests of anxiety-like behavior and locomotor activity revealed that Sabra mice scored close to the mean of all tested lines. Analysis of blood corticosterone levels did not show significant differences among tested strains. We also found a correlation between general and locomotor activity of the tested strains and their hippocampal BDNF mRNA expression. In summary, we may conclude that Sabra mice have traits similar to the better known lines, and therefore they are good subjects for neuroscience research.

Commercially available outbred mice for genome-wide association studies.

Genome-wide association studies using commercially available outbred mice can detect genes involved in phenotypes of biomedical interest. Useful populations need high-frequency alleles to ensure high power to detect quantitative trait loci (QTLs), low linkage disequilibrium between markers to obtain accurate mapping resolution, and an absence of population structure to prevent false positive associations. We surveyed 66 colonies for inbreeding, genetic diversity, and linkage disequilibrium, and we demonstrate that some have haplotype blocks of less than 100 Kb, enabling gene-level mapping resolution. The same alleles contribute to variation in different colonies, so that when mapping progress stalls in one, another can be used in its stead. Colonies are genetically diverse: 45% of the total genetic variation is attributable to differences between colonies. However, quantitative differences in allele frequencies, rather than the existence of private alleles, are responsible for these population differences. The colonies derive from a limited pool of ancestral haplotypes resembling those found in inbred strains: over 95% of sequence variants segregating in outbred populations are found in inbred strains. Consequently it is possible to impute the sequence of any mouse from a dense SNP map combined with inbred strain sequence data, which opens up the possibility of cataloguing and testing all variants for association, a situation that has so far eluded studies in completely outbred populations. We demonstrate the colonies' potential by identifying a deletion in the promoter of H2-Ea as the molecular change that strongly contributes to setting the ratio of CD4+ and CD8+ lymphocytes.

Inbred decorated crickets exhibit higher measures of macroparasitic immunity than outbred individuals.

Inbreeding is assumed to have negative effects on fitness, including the reduced ability to withstand immune challenges. We examined the immunological consequences of inbreeding in decorated crickets, Gryllodes sigillatus, by comparing lytic activity, phenoloxidase (PO) activity, and encapsulation ability of crickets from eight inbred lines with that of crickets from the outbred founder population. Surprisingly, crickets from inbred lines had a greater encapsulation ability compared with crickets from the outbred population. We suggest that because inbred crickets have reduced reproductive effort, they may, therefore, have the option of devoting more resources to this form of immunity than outbred individuals. We also found that both inbred and outbred females had higher immunity than males in PO activity and implant darkness. This result supports the hypothesis that females should devote more effort to somatic maintenance and immunity than males. PO activity and implant darkness were heritable in both males and females, but lytic activity was only heritable in females. Males and females differed in the heritability of, and genetic correlations among, immune traits, suggesting that differences in selective pressures on males and females may have resulted in a sexual conflict over optimal immune trait values.

Bayesian shrinkage mapping for multiple QTL in half-sib families.

Recently, an effective Bayesian shrinkage estimation method has been proposed for mapping QTL in inbred line crosses. However, with regard to outbred populations, such as half-sib populations with maternal information unavailable, it is not straightforward to utilize such a shrinkage estimation for QTL mapping. The reasons are: (1) the linkage phase of markers in the outbred population is usually unknown; and (2) only paternal genotypes can be used for inferring QTL genotypes of offspring. In this article, a novel Bayesian shrinkage method was proposed for mapping QTL under the half-sib design using a mixed model. A simulation study clearly demonstrated that the proposed method was powerful for detecting multiple QTL. In addition, we applied the proposed method to map QTL for economic traits in the Chinese dairy cattle population. Two or more novel QTL harbored in the chromosomal region were detected for each trait of interest, whereas only one QTL was found using traditional maximum likelihood analyses in our earlier studies. This further validated that our shrinkage estimation method could perform well in empirical data analyses and had practical significance in the field of linkage studies for outbred populations.

Outbreeding and possibly inbreeding depression in a pollinating fig wasp with a mixed mating system.

Mixed mating systems are somewhat of an enigma as most models predict that organisms should either inbreed when inbreeding depression is low, or outbreed when inbreeding depression is high. Many wasps mix routine inbreeding with a little random mating. This random mating is most common when all local sibmating opportunities are exhausted and dispersal is the only way males can further increase their fitness. The males of the pollinating fig wasp, Platyscapa awekei, are slightly different in that they disperse before all sibmating opportunities have been exhausted. To see if this is a response to inbreeding depression we quantify inbreeding depression by comparing females' life time reproductive success to their heterozygosity at multiple microsatellite loci. We find that a female wasp's heterozygosity is an accurate predictor of her inbreeding coefficient and that P. awekei females actually seem to suffer from outbreeding depression and possibly from a little inbreeding depression. Male dispersal is thus not a means to effect the optimal mating system, but more likely a mechanism to reduce competition among brothers. The number of mature offspring a female produces depends on her own heterozygosity and not on that of the offspring, and may be determined by egg and gall quality.

Development of a Chinese-Indian hybrid (Chindian) rhesus macaque colony at the California National Primate Research Center by introgression.

BACKGROUND: Fullbred Chinese and Indian rhesus macaques represent genetically distinct populations. The California National Primate Research Center introduced Chinese founders into its Indian-derived rhesus colony in response to the 1978 Indian embargo on exportation of animals for research and the concern that loss of genetic variation in the closed colony would hamper research efforts. The resulting hybrid rhesus now number well over a thousand animals and represent a growing proportion of the animals in the colony. METHODS: We characterized the population genetic structure of the hybrid colony and compared it with that of their pure Indian and Chinese progenitors. RESULTS: The hybrid population contains higher genetic diversity and linkage disequilibrium than their full Indian progenitors and represents a resource with unique research applications. CONCLUSIONS: The genetic diversity of the hybrids indicates that the strategy to introduce novel genes into the colony by hybridizing Chinese founders and their hybrid offspring with Indian-derived animals was successful.

A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock.

The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance.

Choosing the right wild type: behavioral and neurochemical differences between 2 populations of Sprague-Dawley rats from the same source but maintained at different sites.

Sprague-Dawley rats are often the background stock for transgenic rats, and rats from various sources may differ in their physical development and behavior. In 1990, the Institute of Cytology and Genetics in Novosibirsk obtained Sprague-Dawley rats from a commercial vendor and bred them in a closed colony. To study various aspects of the physical development and behavior of male F1 progeny of the Novosibirsk colony (Nov:SD) and commercial colony (Crl:SD) raised in identical environments, we evaluated body weight; food and water consumption; behavior in the elevated-plus maze (X maze), open field, free exploration paradigm, hole board, and the rotarod; and serotonin content in brain regions. Crl:SD rats were heavier and consumed more food than did the Nov:SD rats, which displayed a higher level of motor activity in all tests without displaying differences in anxiety-related behavior in the X maze or open-field test. In the free exploration paradigm, more Nov:SD rats explored the outside and started exploration earlier; they also were more active and showed less habituation in the hole-board test. Brain serotonin content was higher in the Crl:SD rats. In conclusion, prolonged isolated breeding of 2 stocks of Sprague-Dawley rats led to populations that differed in their exploratory and anxiety-related behavior, physical development, and serotonergic neurotransmission. Therefore, rats of the same stock but obtained from different breeders should be used with caution in research involving these measures.

[Analysis of quantitative trait loci using hybrid pedigrees: quantitative traits of animals].

A method is proposed for analysis of quantitative traits in animal hybrid pedigrees formed by crosses between outbred lines differing in allele frequencies of the genes controlling the trait studied. The method is based on the decomposition of trait variances into components and uses maximization of the likelihood function for estimating model parameters, which allows the estimation of additive and dominance effects of the gene involved in trait determination and its allele frequencies, as well as determination of the chromosomal position of this gene relative to genotyped markers. To test the linkage of this gene with markers, a statistic with the noncentral chi(2) distribution has been chosen. Analytical expressions for the power of this method have been derived. The method has been tested on small model hybrid pedigrees. Phenotypic values of the trait and information on marker genotypes for each individual in hybrid pedigrees are original data for the analysis of a quantitative trait.

[Microsatellite DNA monitoring in inbred cultivation of outbred rats].

Microsatellite DNA was used to monitor the gene inheritance of successive generations of rats. It is useful in selective breeding to quickly bring genes to homozygosity and to shorten the cultivation periods of new inbreeding of rats. Thirty microsatellite DNA loci were PCR amplified to analyze the DNA polymorphism in generational crosses between the outbred Wistar and SD rats. Rats in F generations with a moderate to high coefficient of similarity with the female F0 SD rats were crossed. All loci in the F2 generation were heterozygous and polymorphic. By F9, 27 loci have become homozygotic, with a homozygosity rate of 90%. The coefficient of similarity tended to increase at a rate of 6%-20% with each successive generation. Skin grafting confirmed no rejection among the F9 generation of rats. Therefore we have established a novel method for rapid cultivation of inbred rats.