scholarly journals Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of complex traits

2008 ◽  
Vol 32 (3) ◽  
pp. 335-342 ◽  
Author(s):  
Birger Voigt ◽  
Takashi Kuramoto ◽  
Tomoji Mashimo ◽  
Toshiko Tsurumi ◽  
Yoshiyuki Sasaki ◽  
...  

Recombinant inbred (RI) strains are formed from an outcross between two well-characterized inbred stains followed by at least 20 generations of inbreeding. RI strains can be utilized for the analysis of many complex phenotypic traits. The LEXF/FXLE RI strain set consists of 34 RI strains derived by reciprocal crossing of LE/Stm and F344/Stm. Here we report on genetic dissections of complex traits using this RI set and their parental strains. We have developed strain distribution patterns for 232 informative simple sequence length polymorphism markers. The framework map covers the rat genome except for chromosome Y. Seventy-six phenotype parameters, which included physiological and behavioral traits, were examined for these RI lines. Quantitative trait locus (QTL) analysis of these parameters revealed 27 significant and 91 suggestive QTLs, illustrating the potential of this RI resource for the detection of underlying gene functions for various phenotypes. Although this RI set was originally developed to study susceptibility to chemical-induced tumors, it has been shown to be equally powerful for a wide spectrum of traits. The LEXF/FXLE RI strains have been deposited at the National Bio Resource Project for the Rat in Japan and are maintained under specific pathogen-free conditions. They are available at http://www.anim.med.kyoto-u.ac.jp/nbr .

Genetics ◽  
1990 ◽  
Vol 124 (2) ◽  
pp. 221-236 ◽  
Author(s):  
W N Frankel ◽  
J P Stoye ◽  
B A Taylor ◽  
J M Coffin

Abstract Thirty endogenous proviruses belonging to the modified polytropic (Mpmv) class of murine leukemia virus (MLV) were identified by proviral-cellular DNA junction fragment segregation in several sets of recombinant inbred mice. Twenty-six Mpmv loci were mapped to chromosomal regions by matching proviral strain distribution patterns to those of previously assigned genes. Like other endogenous nonecotropic MLVs, Mpmv loci were present on several chromosomes in all strains examined. We pooled recombinant inbred strain linkage data from 110 MLV loci and selected marker genes in order to construct a chromosomal linkage map. Every mouse chromosome was found to harbor at least one proviral insertion, and several regions contained multiple integrations. However, the overall distribution of the 110 mapped proviruses did not deviate significantly from a random distribution. Because of their polymorphism in inbred strains of mice, and the ability to score as many as 57 proviruses per strain using only three hybridization probes, the nonecotropic MLVs mapped in common strains of mice offer a significant advantage over older methods (e.g., biochemical or individual restriction fragment polymorphisms) as genetic markers. These endogenous insertion elements should also be useful for assessing strain purity, and for studying the relatedness of common and not-so-common inbred strains.


2003 ◽  
Vol 52 (5) ◽  
pp. 415-417 ◽  
Author(s):  
Tamio OHNO ◽  
Jun-ichi KATOH ◽  
Yoshiaki KIKKAWA ◽  
Hiromichi YONEKAWA ◽  
Masahiko NISHIMURA

2020 ◽  
Author(s):  
Emily J. Yao ◽  
Richard K. Babbs ◽  
Julia C. Kelliher ◽  
Kimberly P. Luttik ◽  
M. Imad Damaj ◽  
...  

ABSTRACTObjectiveBinge eating is a heritable quantitative trait associated with eating disorders (ED) and refers to the rapid consumption of a large quantity of energy-dense food that is associated with loss of control, anxiety, and depression. Binge Eating Disorder is the most common ED in adults in the US; however, the genetic basis is unknown. We previously identified robust mouse inbred strain differences between C57BL/6J and DBA/2J in binge-like eating (BLE) of sweetened palatable food (PF) in an intermittent access, conditioned place preference paradigm.MethodsTo map the genetic basis of BLE, we phenotyped and genotyped 128 C57BL/6J x DBA/2J-F2 mice.ResultsWe identified a quantitative trait locus (QTL) on chromosome 13 influencing progressive changes in body weight across training days (LOD = 5.5; 26-39 cM). We also identified two sex-combined QTLs influencing PF intake on chromosome 5 (LOD = 5.6; 1.5-LOD interval = 21-28 cM) and 6 (LOD = 5.3; 1.5-LOD interval = 50-59 cM). Furthermore, sex-specific analyses revealed that the chromosome 6 locus was driven by males (1.5-LOD interval: 52-59 cM) and identified a female-selective QTL for BLE on chromosome 18 (LOD = 4.1; 1.5-LOD interval: 23-35 cM). Systems genetic analysis of the chromosome 6 locus for BLE using GeneNetwork legacy trait datasets from BXD recombinant inbred strains identified Adipor2 and Plxnd1 as two positional, functional, biological candidate genes.DiscussionWe identified genetic loci influencing BLE. Future studies will phenotype BXD recombinant inbred strains to fine map loci and support candidate gene nomination and validation.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7008
Author(s):  
Nating Wang ◽  
Tinyi Chu ◽  
Jiangtao Luo ◽  
Rongling Wu ◽  
Zhong Wang

Quantitative trait locus (QTL) mapping has been used as a powerful tool for inferring the complexity of the genetic architecture that underlies phenotypic traits. This approach has shown its unique power to map the developmental genetic architecture of complex traits by implementing longitudinal data analysis. Here, we introduce the R package Funmap2 based on the functional mapping framework, which integrates prior biological knowledge into the statistical model. Specifically, the functional mapping framework is engineered to include longitudinal curves that describe the genetic effects and the covariance matrix of the trait of interest. Funmap2 chooses the type of longitudinal curve and covariance matrix automatically using information criteria. Funmap2 is available for download at https://github.com/wzhy2000/Funmap2.


1998 ◽  
Vol 9 (7) ◽  
pp. 503-505 ◽  
Author(s):  
Václav Zídek ◽  
Alena Musilová ◽  
Jan Pintí q ◽  
Miroslava x imáková

2005 ◽  
Vol 98 (1) ◽  
pp. 371-379 ◽  
Author(s):  
Tomoji Mashimo ◽  
Birger Voigt ◽  
Takashi Kuramoto ◽  
Tadao Serikawa

The National Bio Resource Project for the Rat in Japan collects, preserves, and distributes rat strains. More than 250 inbred strains have been deposited thus far into the National Bio Resource Project for the Rat and are maintained as specific pathogen-free rats or cryopreserved embryos. We are now comprehensively characterizing deposited strains as part of the Rat Phenome Project to reevaluate their value as models of human diseases. Phenotypic data are being collected for 7 categories and 109 parameters: functional observational battery (neurobehavior), behavior studies, blood pressure, biochemical blood tests, hematology, urology, and anatomy. Furthermore, genotypes are being determined for 370 simple sequence-length polymorphism markers distributed through the whole rat genome. Here, we report these large-scale, high-throughput screening data that have already been collected for 54 rat strains. This comprehensive, original phenotypic data can be systematically viewed by “strain ranking” for each parameter. This allows investigators to explore the relationship between several rat strains, to identify new rat models, and to select the most suitable strains for specific experiments. The discovery of several potential models for human diseases, such as hypertension, hypotension, renal diseases, hyperlipemia, hematological disorders, and neurological disorders, illustrates the potential of many existing rat strains. All deposited strains and obtained data are freely available for any interested researcher worldwide at http://www.anim.med.kyoto-u.ac.jp/nbr .


2021 ◽  
Vol 17 (9) ◽  
pp. e1009373
Author(s):  
Hidenori Tanaka ◽  
Jason F. Kreisberg ◽  
Trey Ideker

Despite the growing constellation of genetic loci linked to common traits, these loci have yet to account for most heritable variation, and most act through poorly understood mechanisms. Recent machine learning (ML) systems have used hierarchical biological knowledge to associate genetic mutations with phenotypic outcomes, yielding substantial predictive power and mechanistic insight. Here, we use an ontology-guided ML system to map single nucleotide variants (SNVs) focusing on 6 classic phenotypic traits in natural yeast populations. The 29 identified loci are largely novel and account for ~17% of the phenotypic variance, versus <3% for standard genetic analysis. Representative results show that sensitivity to hydroxyurea is linked to SNVs in two alternative purine biosynthesis pathways, and that sensitivity to copper arises through failure to detoxify reactive oxygen species in fatty acid metabolism. This work demonstrates a knowledge-based approach to amplifying and interpreting signals in population genetic studies.


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