RESUMEN

The molecular bases of how host genetic variation impacts the gut microbiome remain largely unknown. Here we used a genetically diverse mouse population and applied systems genetics strategies to identify interactions between host and microbe phenotypes including microbial functions, using faecal metagenomics, small intestinal transcripts and caecal lipids that influence microbe-host dynamics. Quantitative trait locus (QTL) mapping identified murine genomic regions associated with variations in bacterial taxa; bacterial functions including motility, sporulation and lipopolysaccharide production and levels of bacterial- and host-derived lipids. We found overlapping QTL for the abundance of Akkermansia muciniphila and caecal levels of ornithine lipids. Follow-up in vitro and in vivo studies revealed that A. muciniphila is a major source of these lipids in the gut, provided evidence that ornithine lipids have immunomodulatory effects and identified intestinal transcripts co-regulated with these traits including Atf3, which encodes for a transcription factor that plays vital roles in modulating metabolism and immunity. Collectively, these results suggest that ornithine lipids are potentially important for A. muciniphila-host interactions and support the role of host genetics as a determinant of responses to gut microbes.

Asunto(s)

Microbioma Gastrointestinal , Verrucomicrobia , Ratones , Animales , Verrucomicrobia/genética , Microbioma Gastrointestinal/genética , Akkermansia/genética , Fenotipo

RESUMEN

Genetic studies often collect data using high-throughput phenotyping. That has led to the need for fast genomewide scans for large number of traits using linear mixed models (LMMs). Computing the scans one by one on each trait is time consuming. We have developed new algorithms for performing genome scans on a large number of quantitative traits using LMMs, BulkLMM, that speeds up the computation by orders of magnitude compared to one trait at a time scans. On a mouse BXD Liver Proteome data with more than 35,000 traits and 7,000 markers, BulkLMM completed in a few seconds. We use vectorized, multi-threaded operations and regularization to improve optimization, and numerical approximations to speed up the computations. Our software implementation in the Julia programming language also provides permutation testing for LMMs and is available at https://github.com/senresearch/BulkLMM.jl.

RESUMEN

Plants typically orient their organs with respect to the Earth's gravity field by a dynamic process called gravitropism. To discover conserved genetic elements affecting seedling root gravitropism, we measured the process in a set of Zea mays (maize) recombinant inbred lines with machine vision and compared the results with those obtained in a similar study of Arabidopsis thaliana. Each of the several quantitative trait loci that we mapped in both species spanned many hundreds of genes, too many to test individually for causality. We reasoned that orthologous genes may be responsible for natural variation in monocot and dicot root gravitropism. If so, pairs of orthologous genes affecting gravitropism may be present within the maize and Arabidopsis QTL intervals. A reciprocal comparison of sequences within the QTL intervals identified seven pairs of such one-to-one orthologs. Analysis of knockout mutants demonstrated a role in gravitropism for four of the seven: CCT2 functions in phosphatidylcholine biosynthesis, ATG5 functions in membrane remodeling during autophagy, UGP2 produces the substrate for cellulose and callose polymer extension, and FAMA is a transcription factor. Automated phenotyping enabled this discovery of four naturally varying components of a conserved process (gravitropism) by making it feasible to conduct the same large-scale experiment in two species.

Asunto(s)

Arabidopsis , Gravitropismo , Arabidopsis/genética , Celulosa , Gravitropismo/genética , Fosfatidilcolinas , Raíces de Plantas/genética , Polímeros , Sitios de Carácter Cuantitativo , Factores de Transcripción/genética , Zea mays/genética

RESUMEN

The Collaborative Cross and the Diversity Outbred mouse populations are related multiparental populations, derived from the same 8 isogenic founder strains. They carry >50 M known genetic variants, which makes them ideal tools for mapping genetic loci that regulate phenotypes, including physiological and molecular traits. Mapping quantitative trait loci requires statistical and computational training, which can present a barrier to access for some researchers. The QTLViewer software allows users to graphically explore Collaborative Cross and Diversity Outbred quantitative trait locus mapping and related analyses performed through the R/qtl2 package. Additionally, the QTLViewer website serves as a repository for published Collaborative Cross and Diversity Outbred studies, increasing the accessibility of these genetic resources to the broader scientific community.

Asunto(s)

Ratones de Colaboración Cruzada , Sitios de Carácter Cuantitativo , Animales , Mapeo Cromosómico , Ratones de Colaboración Cruzada/genética , Ratones , Fenotipo , Programas Informáticos

RESUMEN

The Stiff Stalk heterotic pool is a foundation of US maize seed parent germplasm and has been heavily utilized by both public and private maize breeders since its inception in the 1930s. Flowering time and plant height are critical characteristics for both inbred parents and their test crossed hybrid progeny. To study these traits, a 6-parent multiparent advanced generation intercross population was developed including maize inbred lines B73, B84, PHB47 (B37 type), LH145 (B14 type), PHJ40 (novel early Stiff Stalk), and NKH8431 (B73/B14 type). A set of 779 doubled haploid lines were evaluated for flowering time and plant height in 2 field replicates in 2016 and 2017, and a subset of 689 and 561 doubled haploid lines were crossed to 2 testers, respectively, and evaluated as hybrids in 2 locations in 2018 and 2019 using an incomplete block design. Markers were derived from a practical haplotype graph built from the founder whole genome assemblies and genotype-by-sequencing and exome capture-based sequencing of the population. Genetic mapping utilizing an update to R/qtl2 revealed differing profiles of significant loci for both traits between 635 of the DH lines and 2 sets of 570 and 471 derived hybrids. Genomic prediction was used to test the feasibility of predicting hybrid phenotypes based on the per se data. Predictive abilities were highest on direct models trained using the data they would predict (0.55-0.63), and indirect models trained using per se data to predict hybrid traits had slightly lower predictive abilities (0.49-0.55). Overall, this finding is consistent with the overlapping and nonoverlapping significant quantitative trait loci found within the per se and hybrid populations and suggests that selections for phenology traits can be made effectively on doubled haploid lines before hybrid data is available.

Asunto(s)

Sitios de Carácter Cuantitativo , Zea mays , Mapeo Cromosómico , Haploidia , Vigor Híbrido , Fenotipo , Zea mays/genética

RESUMEN

A common step in the analysis of multiparent populations (MPPs) is genotype reconstruction: identifying the founder origin of haplotypes from dense marker data. This process often makes use of a probability model for the pattern of founder alleles along chromosomes, including the relative frequency of founder alleles and the probability of exchanges among them, which depend on a model for meiotic recombination and on the mating design for the population. While the precise experimental design used to generate the population may be used to derive a precise characterization of the model for exchanges among founder alleles, this can be tedious, particularly given the great variety of experimental designs that have been proposed. We describe an approximate model that can be applied for a variety of MPPs. We have implemented the approach in the R/qtl2 software, and we illustrate its use in applications to publicly available data on Diversity Outbred and Collaborative Cross mice.

Asunto(s)

Modelos Genéticos , Sitios de Carácter Cuantitativo , Animales , Mapeo Cromosómico , Genotipo , Ratones , Programas Informáticos

RESUMEN

The BXD family of mouse strains are an important reference population for systems biology and genetics that have been fully sequenced and deeply phenotyped. To facilitate interactive use of genotype-phenotype relations using many massive omics data sets for this and other segregating populations, we have developed new algorithms and code that enable near-real-time whole-genome quantitative trait locus (QTL) scans for up to one million traits. By using easily parallelizable operations including matrix multiplication, vectorized operations, and element-wise operations, our method is more than 700 times faster than a R/qtl linear model genome scan using 16 threads. We used parallelization of different CPU threads as well as GPUs. We found that the speed advantage of GPUs is dependent on problem size and shape (the number of cases, number of genotypes, and number of traits). Our approach is ideal for interactive web services, such as GeneNetwork.org that need to display results in real-time. Our implementation is available as the Julia language package LiteQTL at https://github.com/senresearch/LiteQTL.jl.

Asunto(s)

Algoritmos , Programas Informáticos , Animales , Genotipo , Ratones , Fenotipo , Sitios de Carácter Cuantitativo

RESUMEN

In a Diversity Outbred mouse project with genotype data on 500 mice, including 297 with microbiome data, we identified three sets of sample mix-ups (two pairs and one trio) as well as at least 15 microbiome samples that appear to be mixtures of pairs of mice. The microbiome data consisted of shotgun sequencing reads from fecal DNA, used to characterize the gut microbial communities present in these mice. These sequence reads included sufficient reads derived from the host mouse to identify the individual. A number of microbiome samples appeared to contain a mixture of DNA from two mice. We describe a method for identifying sample mix-ups in such microbiome data, as well as a method for evaluating sample mixtures in this context.

Asunto(s)

Ratones de Colaboración Cruzada , Microbiota , Animales , Genotipo , Ratones , Microbiota/genética , Sitios de Carácter Cuantitativo

RESUMEN

Statistical methods to map quantitative trait loci (QTL) often neglect the X chromosome and may focus exclusively on autosomal loci. But the X chromosome often requires special treatment: sex and cross-direction covariates may need to be included to avoid spurious evidence of linkage, and the X chromosome may require a separate significance threshold. In multiple-QTL analyses, including the consideration of epistatic interactions, the X chromosome also requires special care and consideration. We extend a penalized likelihood method for multiple-QTL model selection, to appropriately handle the X chromosome. We examine its performance in simulation and by application to a large eQTL data set. The method has been implemented in the package R/qtl.

Asunto(s)

Epistasis Genética , Sitios de Carácter Cuantitativo , Mapeo Cromosómico , Ligamiento Genético , Cromosoma X

RESUMEN

Failure of homologous chromosomes to recombine is arguably the most important cause of human meiotic nondisjunction, having been linked to numerous autosomal and sex chromosome trisomies of maternal origin. However, almost all information on these "exchangeless" homologs has come from genetic mapping studies of trisomic conceptuses, so the incidence of this defect and its impact on gametogenesis are not clear. If oocytes containing exchangeless homologs are selected against during meiosis, the incidence may be much higher in developing germ cells than in zygotes. To address this, we initiated studies of exchangeless chromosomes in fetal ovarian samples from elective terminations of pregnancy. In total, we examined more than 7,000 oocytes from 160 tissue samples, scoring for the number of foci per cell of the crossover-associated protein MLH1. We identified a surprisingly high level of recombination failure, with more than 7% of oocytes containing at least one chromosome pair that lacked an MLH1 focus. Detailed analyses indicate striking chromosome-specific differences, with a preponderance of MLH1-less homologs involving chromosomes 21 or 22. Further, the effect was linked to the overall level of recombination in the cell, with the presence of one or two exchangeless chromosomes in a cell associated with a 10%-20% reduction in the total number of crossovers. This suggests individuals with lower rates of meiotic recombination are at an increased risk of producing aneuploid offspring.

Asunto(s)

Oogénesis/genética , Recombinación Genética/genética , Adolescente , Adulto , Aneuploidia , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 22/genética , Femenino , Humanos , Meiosis/genética , Homólogo 1 de la Proteína MutL/genética , No Disyunción Genética/genética , Oocitos/fisiología , Embarazo , Adulto Joven

RESUMEN

Despite the crucial roles of lipids in metabolism, we are still at the early stages of comprehensively annotating lipid species and their genetic basis. Mass spectrometry-based discovery lipidomics offers the potential to globally survey lipids and their relative abundances in various biological samples. To discover the genetics of lipid features obtained through high-resolution liquid chromatography-tandem mass spectrometry, we analysed liver and plasma from 384 diversity outbred mice, and quantified 3,283 molecular features. These features were mapped to 5,622 lipid quantitative trait loci and compiled into a public web resource termed LipidGenie. The data are cross-referenced to the human genome and offer a bridge between genetic associations in humans and mice. Harnessing this resource, we used genome-lipid association data as an additional aid to identify a number of lipids, for example gangliosides through their association with B4galnt1, and found evidence for a group of sex-specific phosphatidylcholines through their shared locus. Finally, LipidGenie's ability to query either mass or gene-centric terms suggests acyl-chain-specific functions for proteins of the ABHD family.

Asunto(s)

Mapeo Cromosómico , Genoma , Metabolismo de los Lípidos/genética , Lipidómica , Lípidos/química , Lípidos/genética , Animales , Gangliósidos/metabolismo , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Hidrolasas/genética , Ratones , Ratones Endogámicos C57BL , Fosfatidilcolinas/metabolismo , Fosfolipasas A2/genética , Plásmidos/genética , Caracteres Sexuales

RESUMEN

BACKGROUND & AIMS: Currently, only a few genetic variants explain the heritability of fatty liver disease. Quantitative trait loci (QTL) analysis of mouse strains has identified the susceptibility locus Ltg/NZO (liver triglycerides from New Zealand obese [NZO] alleles) on chromosome 18 as associating with increased hepatic triglycerides. Herein, we aimed to identify genomic variants responsible for this association. METHODS: Recombinant congenic mice carrying 5.3 Mbp of Ltg/NZO were fed a high-fat diet and characterized for liver fat. Bioinformatic analysis, mRNA profiles and electrophoretic mobility shift assays were performed to identify genes responsible for the Ltg/NZO phenotype. Candidate genes were manipulated in vivo by injecting specific microRNAs into C57BL/6 mice. Pulldown coupled with mass spectrometry-based proteomics and immunoprecipitation were performed to identify interaction partners of IFGGA2. RESULTS: Through positional cloning, we identified 2 immunity-related GTPases (Ifgga2, Ifgga4) that prevent hepatic lipid storage. Expression of both murine genes and the human orthologue IRGM was significantly lower in fatty livers. Accordingly, liver-specific suppression of either Ifgga2 or Ifgga4 led to a 3-4-fold greater increase in hepatic fat content. In the liver of low-fat diet-fed mice, IFGGA2 localized to endosomes/lysosomes, while on a high-fat diet it associated with lipid droplets. Pulldown experiments and proteomics identified the lipase ATGL as a binding partner of IFGGA2 which was confirmed by co-immunoprecipitation. Both proteins partially co-localized with the autophagic marker LC3B. Ifgga2 suppression in hepatocytes reduced the amount of LC3B-II, whereas overexpression of Ifgga2 increased the association of LC3B with lipid droplets and decreased triglyceride storage. CONCLUSION: IFGGA2 interacts with ATGL and protects against hepatic steatosis, most likely by enhancing the binding of LC3B to lipid droplets. LAY SUMMARY: The genetic basis of non-alcoholic fatty liver disease remains incompletely defined. Herein, we identified members of the immunity-related GTPase family in mice and humans that act as regulators of hepatic fat accumulation, with links to autophagy. Overexpression of the gene Ifgga2 was shown to reduce hepatic lipid storage and could be a therapeutic target for the treatment of fatty liver disease.

Asunto(s)

Hígado Graso/genética , Proteínas de Unión al GTP/genética , Regulación de la Expresión Génica , Hepatocitos/metabolismo , Lipasa/genética , Metabolismo de los Lípidos/genética , Proteínas Asociadas a Microtúbulos/genética , Animales , Autofagia , Modelos Animales de Enfermedad , Hígado Graso/metabolismo , Hígado Graso/patología , Femenino , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Proteínas de Unión al GTP/biosíntesis , Células Hep G2 , Hepatocitos/patología , Humanos , Lipasa/biosíntesis , Lipasa/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos/biosíntesis , Fenotipo , ARN/genética

RESUMEN

Niemann-Pick disease type C1 (NPC1) is a rare, fatal neurodegenerative disorder characterized by lysosomal accumulation of unesterified cholesterol and glycosphingolipids. These subcellular pathologies lead to phenotypes of hepatosplenomegaly, neurological degeneration and premature death. NPC1 is extremely heterogeneous in the timing of clinical presentation and is associated with a wide spectrum of causative NPC1 mutations. To study the genetic architecture of NPC1, we have generated a new NPC1 mouse model, Npc1em1PavNpc1em1Pav/em1Pav mutants showed notably reduced NPC1 protein compared to controls and displayed the pathological and biochemical hallmarks of NPC1. Interestingly, Npc1em1Pav/em1Pav mutants on a C57BL/6J genetic background showed more severe visceral pathology and a significantly shorter lifespan compared to Npc1em1Pav/em1Pav mutants on a BALB/cJ background, suggesting that strain-specific modifiers contribute to disease severity and survival. QTL analysis for lifespan of 202 backcross N2 mutants on a mixed C57BL/6J and BALB/cJ background detected significant linkage to markers on chromosomes 1 and 7. The discovery of these modifier regions demonstrates that mouse models are powerful tools for analyzing the genetics underlying rare human diseases, which can be used to improve understanding of the variability in NPC1 phenotypes and advance options for patient diagnosis and therapy.This article has an associated First Person interview with the first author of the paper.

Asunto(s)

Antecedentes Genéticos , Longevidad , Enfermedad de Niemann-Pick Tipo C/patología , Índice de Severidad de la Enfermedad , Alelos , Animales , Secuencia de Bases , Cromosomas de los Mamíferos/genética , Modelos Animales de Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Lisosomas/metabolismo , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Mutantes , Degeneración Nerviosa/patología , Proteína Niemann-Pick C1 , Fenotipo , Sitios de Carácter Cuantitativo/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Supervivencia , Vísceras/patología , Pérdida de Peso

RESUMEN

The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp. and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions.

Asunto(s)

Ácidos y Sales Biliares/metabolismo , Variación Biológica Poblacional/genética , Microbioma Gastrointestinal/fisiología , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Sitios de Carácter Cuantitativo/genética , Simportadores/genética , Akkermansia , Animales , Ácidos y Sales Biliares/sangre , Ratones de Colaboración Cruzada , Femenino , Firmicutes/crecimiento & desarrollo , Masculino , Redes y Vías Metabólicas/genética , Ratones , Modelos Animales , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Simportadores/metabolismo , Verrucomicrobia/crecimiento & desarrollo

RESUMEN

Genetic susceptibility to type 2 diabetes is primarily due to ß-cell dysfunction. However, a genetic study to directly interrogate ß-cell function ex vivo has never been previously performed. We isolated 233,447 islets from 483 Diversity Outbred (DO) mice maintained on a Western-style diet, and measured insulin secretion in response to a variety of secretagogues. Insulin secretion from DO islets ranged >1,000-fold even though none of the mice were diabetic. The insulin secretory response to each secretagogue had a unique genetic architecture; some of the loci were specific for one condition, whereas others overlapped. Human loci that are syntenic to many of the insulin secretion QTL from mouse are associated with diabetes-related SNPs in human genome-wide association studies. We report on three genes, Ptpn18, Hunk and Zfp148, where the phenotype predictions from the genetic screen were fulfilled in our studies of transgenic mouse models. These three genes encode a non-receptor type protein tyrosine phosphatase, a serine/threonine protein kinase, and a Krϋppel-type zinc-finger transcription factor, respectively. Our results demonstrate that genetic variation in insulin secretion that can lead to type 2 diabetes is discoverable in non-diabetic individuals.

Asunto(s)

Proteínas de Unión al ADN/genética , Sitios Genéticos , Secreción de Insulina/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Fosfatasas no Receptoras/genética , Factores de Transcripción/genética , Animales , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Humanos , Ratones , Ratones Transgénicos

RESUMEN

The high mapping resolution of multiparental populations, combined with technology to measure tens of thousands of phenotypes, presents a need for quantitative methods to enhance understanding of the genetic architecture of complex traits. When multiple traits map to a common genomic region, knowledge of the number of distinct loci provides important insight into the underlying mechanism and can assist planning for subsequent experiments. We extend the method of Jiang and Zeng (1995), for testing pleiotropy with a pair of traits, to the case of more than two alleles. We also incorporate polygenic random effects to account for population structure. We use a parametric bootstrap to determine statistical significance. We apply our methods to a behavioral genetics data set from Diversity Outbred mice. Our methods have been incorporated into the R package qtl2pleio.

Asunto(s)

Cruzamientos Genéticos , Pleiotropía Genética , Genética de Población , Sitios de Carácter Cuantitativo , Algoritmos , Simulación por Computador , Escala de Lod , Modelos Genéticos , Herencia Multifactorial

RESUMEN

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.

Asunto(s)

Animales no Consanguíneos/genética , Biodiversidad , Variación Genética , Genotipo , Alelos , Animales , Cruzamientos Genéticos , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Masculino , Ratones , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo

RESUMEN

Modern quantitative trait locus (QTL) studies in multiparental populations offer opportunities to identify causal genes for thousands of clinical and molecular traits. Traditional analyses examine each trait by itself. However, to fully leverage this vast number of measured traits, the systems genetics community needs statistical tools to analyze multiple traits simultaneously (Jiang & Zeng, 1995; Korol, Ronin, & Kirzhner, 1995). A test of pleiotropy vs. separate QTL is one such tool that will aid dissection of complex trait genetics and enhance understanding of genetic architecture.

RESUMEN

R/qtl2 is an interactive software environment for mapping quantitative trait loci (QTL) in experimental populations. The R/qtl2 software expands the scope of the widely used R/qtl software package to include multiparent populations derived from more than two founder strains, such as the Collaborative Cross and Diversity Outbred mice, heterogeneous stocks, and MAGIC plant populations. R/qtl2 is designed to handle modern high-density genotyping data and high-dimensional molecular phenotypes, including gene expression and proteomics. R/qtl2 includes the ability to perform genome scans using a linear mixed model to account for population structure, and also includes features to impute SNPs based on founder strain genomes and to carry out association mapping. The R/qtl2 software provides all of the basic features needed for QTL mapping, including graphical displays and summary reports, and it can be extended through the creation of add-on packages. R/qtl2, which is free and open source software written in the R and C++ programming languages, comes with a test framework.

Asunto(s)

Mapeo Cromosómico/métodos , Estudio de Asociación del Genoma Completo/métodos , Técnicas de Genotipaje/métodos , Sitios de Carácter Cuantitativo , Programas Informáticos , Animales , Ratones