Genetic Effects on Bone Mechanotransduction in Congenic Mice Harboring Bone Size and Strength Quantitative Trait Loci

2007 ◽  
Vol 22 (7) ◽  
pp. 984-991 ◽  
Author(s):  
Alexander G Robling ◽  
Stuart J Warden ◽  
Kathryn L Shultz ◽  
Wesley G Beamer ◽  
Charles H Turner
Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 867-883 ◽  
Author(s):  
Nengjun Yi ◽  
Shizhong Xu ◽  
David B Allison

AbstractMost complex traits of animals, plants, and humans are influenced by multiple genetic and environmental factors. Interactions among multiple genes play fundamental roles in the genetic control and evolution of complex traits. Statistical modeling of interaction effects in quantitative trait loci (QTL) analysis must accommodate a very large number of potential genetic effects, which presents a major challenge to determining the genetic model with respect to the number of QTL, their positions, and their genetic effects. In this study, we use the methodology of Bayesian model and variable selection to develop strategies for identifying multiple QTL with complex epistatic patterns in experimental designs with two segregating genotypes. Specifically, we develop a reversible jump Markov chain Monte Carlo algorithm to determine the number of QTL and to select main and epistatic effects. With the proposed method, we can jointly infer the genetic model of a complex trait and the associated genetic parameters, including the number, positions, and main and epistatic effects of the identified QTL. Our method can map a large number of QTL with any combination of main and epistatic effects. Utility and flexibility of the method are demonstrated using both simulated data and a real data set. Sensitivity of posterior inference to prior specifications of the number and genetic effects of QTL is investigated.


2019 ◽  
Vol 36 (5) ◽  
pp. 1517-1521
Author(s):  
Leilei Cui ◽  
Bin Yang ◽  
Nikolas Pontikos ◽  
Richard Mott ◽  
Lusheng Huang

Abstract Motivation During the past decade, genome-wide association studies (GWAS) have been used to map quantitative trait loci (QTLs) underlying complex traits. However, most GWAS focus on additive genetic effects while ignoring non-additive effects, on the assumption that most QTL act additively. Consequently, QTLs driven by dominance and other non-additive effects could be overlooked. Results We developed ADDO, a highly efficient tool to detect, classify and visualize QTLs with additive and non-additive effects. ADDO implements a mixed-model transformation to control for population structure and unequal relatedness that accounts for both additive and dominant genetic covariance among individuals, and decomposes single-nucleotide polymorphism effects as either additive, partial dominant, dominant or over-dominant. A matrix multiplication approach is used to accelerate the computation: a genome scan on 13 million markers from 900 individuals takes about 5 h with 10 CPUs. Analysis of simulated data confirms ADDO’s performance on traits with different additive and dominance genetic variance components. We showed two real examples in outbred rat where ADDO identified significant dominant QTL that were not detectable by an additive model. ADDO provides a systematic pipeline to characterize additive and non-additive QTL in whole genome sequence data, which complements current mainstream GWAS software for additive genetic effects. Availability and implementation ADDO is customizable and convenient to install and provides extensive analytics and visualizations. The package is freely available online at https://github.com/LeileiCui/ADDO. Supplementary information Supplementary data are available at Bioinformatics online.


2006 ◽  
Vol 43 (11) ◽  
pp. 873-880 ◽  
Author(s):  
H Shen ◽  
J-R Long ◽  
D-H Xiong ◽  
Y-F Guo ◽  
P Xiao ◽  
...  

2008 ◽  
Vol 14 (6) ◽  
pp. 631-645 ◽  
Author(s):  
G D Gale ◽  
R D Yazdi ◽  
A H Khan ◽  
A J Lusis ◽  
R C Davis ◽  
...  

2009 ◽  
Vol 23 (7) ◽  
pp. 2142-2154 ◽  
Author(s):  
Neema Saless ◽  
Suzanne J. Litscher ◽  
Gloria E. Lopez Franco ◽  
Meghan J. Houlihan ◽  
Shaan Sudhakaran ◽  
...  

2007 ◽  
Vol 292 (1) ◽  
pp. R207-R216 ◽  
Author(s):  
K. Ganesh Kumar ◽  
Angela C. Poole ◽  
Barbara York ◽  
Julia Volaufova ◽  
Aamir Zuberi ◽  
...  

Quantitative trait loci (QTL) for carbohydrate ( Mnic1) and total energy ( Kcal2) intake on proximal mouse chromosome 17 were identified previously from a C57BL/6J (B6) X CAST/Ei (CAST) intercross. Here we report that a new congenic strain developed in our laboratory has confirmed this complex locus by recapitulating the original linked phenotypes: B6.CAST-17 homozygous congenic mice consumed more carbohydrate (27%) and total energy (17%) compared with littermate wild-type mice. Positional gene candidates with relevance to carbohydrate metabolism, glyoxalase I ( Glo1) and glucagon-like peptide-1 receptor ( Glp1r), were evaluated. Glo1 expression was upregulated in liver and hypothalamus of congenic mice when compared with B6 mice. Analyses of Glp1r mRNA and protein expression revealed tissue-specific strain differences in pancreas (congenic>B6) and stomach (B6>congenic). These results suggest the possibility of separate mechanisms for enhanced insulin synthesis and gastric accommodation in the presence of high carbohydrate intake and larger food volume, respectively. Sequence analysis of Glp1r found a G insert at nt position 1349, which results in earlier termination of the open reading frame, thus revealing an error in the public sequence. Consequently, the predicted length of GLP-1R is 463 aa compared with 489 aa, as previously reported. Also, we found a polymorphism in Glp1r between parental strains that alters the amino acid sequence. Variation in Glp1r could influence nutrient intake in this model through changes in the regulatory or protein coding regions of the gene. These congenic mice offer a powerful tool for investigating gene interactions in the control of food intake.


2007 ◽  
Vol 80 (2) ◽  
pp. 103-110 ◽  
Author(s):  
H. Yu ◽  
S. Mohan ◽  
B. Edderkaoui ◽  
G. L. Masinde ◽  
H. M. Davidson ◽  
...  

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