Explore the new Multiparental Populations resource at GENETICS and G3

The GSA Journals are proud to announce a brand new site for our Multiparental Populations (MPP) series. We’re celebrating this redesigned, easy-to-browse site with the addition of sixteen new papers from both journals to the series.

As the field of genetics has grown, the rapid development of genomic technologies has given researchers the ability to dissect genetic variation and complex trait inheritance in sophisticated ways. Now, the challenge is often analysis.

A growing community of plant and animal researchers have established multiparental populations as a way to more accurately capture genetic variation and its contribution to phenotypes of interest. Analysis of these populations is complex, and the clear communication of experimental design and methodology bolsters the community, paving the way for continuing advances.

The GSA Journals began the MPP series in 2014 to collect emerging data and transparent methods and to stimulate discussion. We have published work across a broad range of species—including mouse, maize, Drosophila, wheat, yeast, and others. We hope to foster a cross-disciplinary flow of information and to provide a rich resource of experimental and methodological data to the community. We welcome submissions to the MPP series on a continuous basis, and we accept presubmission inquiries.

Check out the new site and see how simple it is to browse and search the collection. Stay up to date with community news through the “Multiparental Populations in the News” sidebar. In line with our goal of encouraging communication across disciplinary boundaries, the “MPP People” profiles aim to introduce series authors working in a wide range of systems.

 

 

 

 

 

 

The newest papers added to the series are summarized below.

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GENETICS

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Back to the Future: Multiparent Populations Provide the Key to Unlocking the Genetic Basis of Complex Traits

Dirk-Jan de Koning, Lauren M. McIntyre

Epistasis: Searching for Interacting Genetic Variants Using Crosses

Ian M. Ehrenreich

Epistasis refers to situations in which combinations of genetic variants have nonadditive phenotypic effects. Epistasis between two variants is more commonly explored, but higher-order interactions involving multiple variants also occur. In this editorial, Ehrenreich makes the case for exploring epistasis in quantitative genetic crosses.

Genomes of the Mouse Collaborative Cross

Anuj Srivastava, Andrew P. Morgan, Maya L. Najarian, Vishal Kumar Sarsani, J. Sebastian Sigmon, John R. Shorter, Anwica Kashfeen, Rachel C. McMullan, Lucy H. Williams, Paola Giusti-Rodríguez, Martin T. Ferris, Patrick Sullivan, Pablo Hock, Darla R. Miller, Timothy A. Bell, Leonard McMillan, Gary A. Churchill, and Fernando Pardo-Manuel de Villena

The Collaborative Cross (CC) is a panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here, Srivastava et al. present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. This study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection.

Male Infertility Is Responsible for Nearly Half of the Extinction Observed in the Mouse Collaborative Cross

John R. Shorter, Fanny Odet, David L. Aylor, Wenqi Pan, Chia-Yu Kao, Chen-Ping Fu, Andrew P. Morgan, Seth Greenstein, Timothy A. Bell, Alicia M. Stevans, Ryan W. Feathers, Sunny Patel, Sarah E. Cates, Ginger D. Shaw, Darla R. Miller, Elissa J. Chesler, Leonard McMillian, Deborah A. O’Brien, and Fernando Pardo-Manuel de Villena

The extinction rate in the Collaborative Cross (CC) population is estimated at 95%. Shorter et al. analyzed fertility and reproductive phenotypes on the last unproductive males from 347 independent CC lines and performed the largest trait mapping experiment in the CC to date. Extinction in the CC is largely due to male infertility. The results from several experiments suggest that poor fertility and hybrid incompatibilities between subspecies contribute to breeding difficulties and strain extinction.

Increased Power to Dissect Adaptive Traits in Global Sorghum Diversity Using a Nested Association Mapping Population

Sophie Bouchet, Marcus O. Olatoye, Sandeep R. Marla, Ramasamy Perumal, Tesfaye Tesso, Jianming Yu, Mitch Tuinstra, and Geoffrey P. Morris

In crop species, adaptation to different agroclimatic regions creates useful variation, but also leads to genetic correlations that confound trait dissection. To address this challenge in sorghum, a widely adapted cereal crop, Bouchet et al. have developed and characterized a Nested Association Mapping (NAM) population, which reshuffles global genetic diversity for trait mapping. This manuscript describes the sorghum NAM resource, a population of 2214 recombinant inbred lines genotyped at 90,000 markers. The authors validated the NAM resource by mapping flowering time and plant height and used simulated traits to demonstrate that NAM is generally more powerful for dissection of traits under strong selection.

Genetic Dissection of Nutrition-Induced Plasticity in Insulin/Insulin-Like Growth Factor Signaling and Median Life Span in a Drosophila Multiparent Population

Patrick D. Stanley, Enoch Ng’oma, Siri O’Day, and Elizabeth G. King

The insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) pathways have long been thought to be involved in how organisms respond to their nutritional environment; however, little is known about the genetic basis of naturally-occurring variation in these pathways. Stanley et al. use a multiparent population to genetically dissect diet-dependent IIS/TOR expression and connect it to diet-dependent changes in lifespan.

Structural Variation Shapes the Landscape of Recombination in Mouse

Andrew P. Morgan, Daniel M. Gatti,  Maya L. Najarian, Thomas M. Keane, Raymond J. Galante, Allan I. Pack, Richard Mott, Gary A. Churchill, and Fernando Pardo-Manuel de Villena

To study local variation in recombination rates and the impact of genetic diversity on the pattern and distribution of crossover events, Morgan et al. analyzed genotype data from 6,886 Diversity Outbred mice. They find that approximately three-quarters of crossover events occur within putative recombination hotspots. They further show that crossovers are suppressed in regions with copy number variation. They hypothesize that the epigenetic features of these regions may reflect altered chromatin structure in meiosis that results in a failure of pairing between chromosomes carrying different structural alleles.

Epistatic Networks Jointly Influence Phenotypes Related to Metabolic Disease and Gene Expression in Diversity Outbred Mice

Anna L. Tyler, Bo Ji, Daniel M. Gatti, Steven C. Munger, Gary A. Churchill, Karen L. Svenson, and Gregory W. Carter

Tyler et al. analyzed the complex genetic architecture of traits related to metabolic disease using the Diversity Outbred (DO) mouse population. By jointly analyzing epistasis across multiple phenotypes, the authors inferred a multi-scale network of quantitative trait loci (QTL) involving QTL-QTL, QTL-sex, and QTL-diet interactions that jointly influence body composition, serum markers, and transcriptome expression. They found that genetic contributions from different founder ancestries often combine to drive more extreme phenotypes, leading to the broad phenotypic diversity observed in the DO population.

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G3

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Inbred Strain Variant Database (ISVdb): A Repository for Probabilistically Informed Sequence Differences Among the Collaborative Cross Strains and Their Founders

Daniel Oreper, Yanwei Cai, Lisa M. Tarantino, Fernando Pardo- Manuel de Villena, William Valdar

The Collaborative Cross (CC) is a large panel of recently established multiparental recombinant inbred mouse strains. CC experimental design and analysis are facilitated by Oreper et al.’s newly developed Inbred Strain Variant Database (ISVdb), which provides easy-to-access CC sequence-based information. In particular, the ISVdb provides haplotype-imputed exonic variant data—an alternative and complement to direct sequencing of the CC, which is also not yet easily accessible. Additionally, the ISVdb 1) provides exonic variant consequences, 2) rapidly simulates F1 populations, and 3) maintains imputation uncertainty, allowing imputed CC data to be refined by upcoming sequencing. The ISVdb is accessible at http://isvdb.unc.edu/.

Loci Contributing to Boric Acid Toxicity in Two Reference Populations of Drosophila melanogaster

Michael A. Najarro, Jennifer L. Hackett, Stuart J. Macdonald

Boric acid is a widely-used household insecticide, but we do not fully understand how it leads to mortality. In this study, Najarro et al. assayed the genetic background for Boric Acid resistance by measuring resistance to the compound in a diverse set of Drosophila melanogaster strains and uncovered substantial trait variation. Several short genomic regions impact the phenotype, in one case implicating a member of a known family of detoxification enzymes. While the authors were unable to confidently identify DNA sequence changes leading to variation in toxicity, their work provides a platform for future genetic exploration of the mechanism of action of boric acid on metabolism and physiology in Drosophila.

The Beavis Effect in Next-Generation Mapping Panels in Drosophila melanogaster

Elizabeth G. King, Anthony D. Long

Two critical components of characterizing the genetic loci underlying complex traits are 1) to accurately estimate the relative contribution of mapped loci to the overall genetic variance of the trait and 2) to validate the mapped loci. Estimations of the contribution of mapped loci to the genetic variance are known to be upwardly biased. Here, King and Long quantify this effect for modern mapping techniques and shows how this bias can lead to false expectations for validating loci.

Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice

Lisa E. Gralinski, Vineet D. Menachery, Andrew P. Morgan, Allison L. Totura, Anne Beall, Jacob Kocher, Jessica Plante, D. Corinne Harrison-Shostak, Alexandra Schäfer, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Ralph S. Baric

SARS-Coronavirus (CoV) caused a wide range of disease during the global outbreak, from mild respiratory illness to significant morbidity and mortality. Gralinksi et al. performed an F2 cross of two Collaborative Cross (CC) recombinant inbred lines to search for host genes that contribute to SARS-CoV resistance and susceptibility. They identified five QTL with contributions from seven of eight CC founders. One QTL was associated with multiple phenotypes including weight loss, virus titer, and lung pathology. Ticam2-/- mice confirmed the role of that gene in contributing to SARS-CoV-induced weight loss and pulmonary hemorrhage, demonstrating the importance of Toll Like Receptor signaling in protecting from coronavirus-induced disease.

Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross

Richard Green, Courtney Wilkins, Sunil Thomas, Aimee Sekine, Duncan M. Hendrick, Kathleen Voss, Renee C. Ireton, Michael Mooney, Jennifer T. Go, Gabrielle Choonoo, Sophia Jeng, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Shannon McWeeney, Michael Gale

The oligoadenylate-synthetase (OAS) gene family includes Oas1b, a non-canonical OAS that lacks enzymatic activity. Full-length Oas1b is essential for protection against West Nile virus neuroinvasion and disease in inbred mouse models of infection, but how it programs innate immune defense across distinct genetic backgrounds is not defined. Green et al. examined Oas1b genetics, in vivo transcriptomics, and WNV infection among genetically distinct Collaborative Cross (CC) mouse strains. Their results reveal that Oas1b genotype and gene dosage link with novel innate immune gene expression signatures that impact specific biological pathways for WNV infection control and immunity.

Identification of Ganoderma Disease Resistance Loci Using Natural Field Infection of an Oil Palm Multiparental Population

Sébastien Tisné, Virginie Pomiès, Virginie Riou, Indra Syahputra, Benoît Cochard, Marie Denis

Stem rot caused by Ganoderma boninense is a devastating disease for oil palm, but information on the genetic architecture of Ganoderma resistance has not yet been reported. Tisné et al. implemented an original statistical modeling approach to analyze data based on 25 years of field monitoring the natural infection of an oil palm multiparental population. They identified four resistance loci in a broad genetic diversity that are relevant for breeding programs, showing that resistance is quantitative and that favorable alleles can be selected using the current reciprocal recurrent selection scheme.

Identification of Nitrogen Consumption Genetic Variants in Yeast Through QTL Mapping and Bulk Segregant RNA-Seq Analyses

Francisco A. Cubillos, Claire Brice, Jennifer Molinet, Sébastien Tisné, Valentina Abarca, Sebastián M. Tapia, Christian Oporto, Verónica García, Gianni Liti, Claudio Martínez

Nitrogen is an essential nutrient for yeast, and natural fermentation musts across the world differ in their nitrogen content. In this manuscript, Cubillos et al. studied nitrogen consumption differences under oenological conditions in the SGRP-4X, a recombinant population derived from the intercross of four parental strains. The results provided evidence of six allelic variants responsible for minor differences in consumption levels for arginine and aromatic amino acids, demonstrating the power of complex populations to unveil a larger number of small effect allelic variants.

Pedigree-Based Analysis in a Multiparental Population of Octoploid Strawberry Reveals QTL Alleles Conferring Resistance to Phytophthora cactorum

Jozer Mangandi, Sujeet Verma, Luis Osorio, Natalia A. Peres, Eric van de Weg, Vance M. Whitaker

Mangandi et al. describe the genetic locus in cultivated strawberry (Fragaria ×ananassa) that controls resistance to Phytophthora cactorum, which causes crown rots in the major strawberry production regions of the world. This locus, named FaRPc2, was discovered and analyzed in a complex breeding population arising from 139 crosses among 61 parents. The authors performed a pedigree-based analysis across families simultaneously, giving strong evidence for the presence of two different resistance alleles. The FaRPc2 locus has robust effects across a wide array of genetic backgrounds, making it an excellent target for genetic improvement of resistance.   

Approaches in Characterizing Genetic Structure and Mapping in a Rice Multiparental Population

Chitra Raghavan, Ramil Mauleon, Vanica Lacorte, Monalisa Jubay, Hein Zaw, Justine Bonifacio, Rakesh Kumar Singh, B. Emma Huang, Hei Leung

Raghavan et al. explore the genetic structure of a rice MAGIC population consisting of 1316 lines derived from eight parents. To determine the impact of missing data and errors on recombination levels and mapping resolution, they filtered the genotyping-by-sequencing data on all lines and imputed the data at varying levels of stringency. They map QTL for agronomic, biotic, and abiotic stress traits, and provide guidelines on best approaches to overall analysis pipelines, including quality control. These findings will serve as a guideline to researchers developing crop multiparent populations.