scholarly journals Novel genomic approaches unravel genetic architecture of complex traits in apple

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 393 ◽  
Author(s):  
Satish Kumar ◽  
Dorian J Garrick ◽  
Marco CAM Bink ◽  
Claire Whitworth ◽  
David Chagné ◽  
...  
2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.


Author(s):  
Toshiyuki Sakai ◽  
Akira Abe ◽  
Motoki Shimizu ◽  
Ryohei Terauchi

Abstract Characterizing epistatic gene interactions is fundamental for understanding the genetic architecture of complex traits. However, due to the large number of potential gene combinations, detecting epistatic gene interactions is computationally demanding. A simple, easy-to-perform method for sensitive detection of epistasis is required. Due to their homozygous nature, use of recombinant inbred lines (RILs) excludes the dominance effect of alleles and interactions involving heterozygous genotypes, thereby allowing detection of epistasis in a simple and interpretable model. Here, we present an approach called RIL-StEp (recombinant inbred lines stepwise epistasis detection) to detect epistasis using single nucleotide polymorphisms in the genome. We applied the method to reveal epistasis affecting rice (Oryza sativa) seed hull color and leaf chlorophyll content and successfully identified pairs of genomic regions that presumably control these phenotypes. This method has the potential to improve our understanding of the genetic architecture of various traits of crops and other organisms.


2018 ◽  
Author(s):  
Doug Speed ◽  
David J Balding

LD Score Regression (LDSC) has been widely applied to the results of genome-wide association studies. However, its estimates of SNP heritability are derived from an unrealistic model in which each SNP is expected to contribute equal heritability. As a consequence, LDSC tends to over-estimate confounding bias, under-estimate the total phenotypic variation explained by SNPs, and provide misleading estimates of the heritability enrichment of SNP categories. Therefore, we present SumHer, software for estimating SNP heritability from summary statistics using more realistic heritability models. After demonstrating its superiority over LDSC, we apply SumHer to the results of 24 large-scale association studies (average sample size 121 000). First we show that these studies have tended to substantially over-correct for confounding, and as a result the number of genome-wide significant loci has under-reported by about 20%. Next we estimate enrichment for 24 categories of SNPs defined by functional annotations. A previous study using LDSC reported that conserved regions were 13-fold enriched, and found a further twelve categories with above 2-fold enrichment. By contrast, our analysis using SumHer finds that conserved regions are only 1.6-fold (SD 0.06) enriched, and that no category has enrichment above 1.7-fold. SumHer provides an improved understanding of the genetic architecture of complex traits, which enables more efficient analysis of future genetic data.


2018 ◽  
Author(s):  
Yizhen Zhong ◽  
Minoli Perera ◽  
Eric R. Gamazon

AbstractBackgroundUnderstanding the nature of the genetic regulation of gene expression promises to advance our understanding of the genetic basis of disease. However, the methodological impact of use of local ancestry on high-dimensional omics analyses, including most prominently expression quantitative trait loci (eQTL) mapping and trait heritability estimation, in admixed populations remains critically underexplored.ResultsHere we develop a statistical framework that characterizes the relationships among the determinants of the genetic architecture of an important class of molecular traits. We estimate the trait variance explained by ancestry using local admixture relatedness between individuals. Using National Institute of General Medical Sciences (NIGMS) and Genotype-Tissue Expression (GTEx) datasets, we show that use of local ancestry can substantially improve eQTL mapping and heritability estimation and characterize the sparse versus polygenic component of gene expression in admixed and multiethnic populations respectively. Using simulations of diverse genetic architectures to estimate trait heritability and the level of confounding, we show improved accuracy given individual-level data and evaluate a summary statistics based approach. Furthermore, we provide a computationally efficient approach to local ancestry analysis in eQTL mapping while increasing control of type I and type II error over traditional approaches.ConclusionOur study has important methodological implications on genetic analysis of omics traits across a range of genomic contexts, from a single variant to a prioritized region to the entire genome. Our findings highlight the importance of using local ancestry to better characterize the heritability of complex traits and to more accurately map genetic associations.


2018 ◽  
Author(s):  
Sini Nagpal ◽  
Xiaoran Meng ◽  
Michael P. Epstein ◽  
Lam C. Tsoi ◽  
Matthew Patrick ◽  
...  

AbstractThe transcriptome-wide association studies (TWAS) that test for association between the study trait and the imputed gene expression levels from cis-acting expression quantitative trait loci (cis-eQTL) genotypes have successfully enhanced the discovery of genetic risk loci for complex traits. By using the gene expression imputation models fitted from reference datasets that have both genetic and transcriptomic data, TWAS facilitates gene-based tests with GWAS data while accounting for the reference transcriptomic data. The existing TWAS tools like PrediXcan and FUSION use parametric imputation models that have limitations for modeling the complex genetic architecture of transcriptomic data. Therefore, we propose an improved Bayesian method that assumes a data-driven nonparametric prior to impute gene expression. Our method is general and flexible and includes both the parametric imputation models used by PrediXcan and FUSION as special cases. Our simulation studies showed that the nonparametric Bayesian model improved both imputation R2 for transcriptomic data and the TWAS power over PrediXcan. In real applications, our nonparametric Bayesian method fitted transcriptomic imputation models for 2X number of genes with 1.7X average regression R2 over PrediXcan, thus improving the power of follow-up TWAS. Hence, the nonparametric Bayesian model is preferred for modeling the complex genetic architecture of transcriptomes and is expected to enhance transcriptome-integrated genetic association studies. We implement our Bayesian approach in a convenient software tool “TIGAR” (Transcriptome-Integrated Genetic Association Resource), which imputes transcriptomic data and performs subsequent TWAS using individual-level or summary-level GWAS data.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Wei ◽  
Paula S. Ramos ◽  
Kelly J. Hunt ◽  
Bethany J. Wolf ◽  
Gary Hardiman ◽  
...  

Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Gertrud Grilz-Seger ◽  
Thomas Druml ◽  
Markus Neuditschko ◽  
Max Dobretsberger ◽  
Michaela Horna ◽  
...  

2014 ◽  
Vol 23 (22) ◽  
pp. 5893-5905 ◽  
Author(s):  
Xu Zhang ◽  
Erika L. Moen ◽  
Cong Liu ◽  
Wenbo Mu ◽  
Eric R. Gamazon ◽  
...  

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 259-260
Author(s):  
Ashley Ling ◽  
Romdhane Rekaya

Abstract Gene editing (GE) is a form of genetic engineering in which DNA is removed, inserted or replaced. For simple monogenic traits, the technology has been successfully implemented to create heritable modifications in animals and plants. The benefits of these niche applications are undeniable. For quantitative traits the benefits of GE are hard to quantify mainly because these traits are not genetic enough (low to moderate heritability) and their genetic architecture is often complex. Because its impact on the gene pool through the introduction of heritable modifications, the potential gain from GE must be evaluated within reasonable production parameters and in comparison, with available tools used in animal selection. A simulation was performed to compare GE with genomic selection (GS) and QTN-assisted selection (QAS) under four experimental factors: 1) heritability (0.1 or 0.4), 2) number of QTN affecting the trait (1000 or 10000) and their effect distribution (Gamma or uniform); 3) Percentage of selected females (100% or 33%); and 4) fixed or variable number of edited QTNs. Three models GS (M1), GS and GE (M2), and GS and QAS (M3) were implemented and compared. When the QTN effects were sampled from a Gamma distribution, all females were selected, and non-segregating QTNs were replaced, M2 clearly outperformed M1 and M3, with superiority ranging from 19 to 61%. Under the same scenario, M3 was 7 to 23% superior to M1. As the complexity of the genetic model increased (10000 QTN; uniform distribution), only one third of the females were selected, and the number of edited QTNs was fixed, the superiority of M2 was significantly reduced. In fact, M2 was only slightly better than M3 (2 to 6%). In all cases, M2 and M3 were better than M1. These results indicate that under realistic scenarios, GE for complex traits might have only limited advantages.


Sign in / Sign up

Export Citation Format

Share Document