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A novel statistical approach for jointly analyzing RNA-Seq data from F1 reciprocal crosses and inbred lines.

ABSTRACT: RNA sequencing (RNA-seq) not only measures total gene expression but may also measure allele-specific gene expression in diploid individuals. RNA-seq data collected from F1 reciprocal crosses in mice can powerfully dissect strain and parent-of-origin effects on allelic imbalance of gene expression. In this article, we develop a novel statistical approach to analyze RNA-seq data from F1 and inbred strains. Method development was motivated by a study of F1 reciprocal crosses derived from highly divergent mouse strains, to which we apply the proposed method. Our method jointly models the total number of reads and the number of allele-specific reads of each gene, which significantly boosts power for detecting strain and particularly parent-of-origin effects. The method deals with the overdispersion problem commonly observed in read counts and can flexibly adjust for the effects of covariates such as sex and read depth. The X chromosome in mouse presents particular challenges. As in other mammals, X chromosome inactivation silences one of the two X chromosomes in each female cell, although the choice of which chromosome to be silenced can be highly skewed by alleles at the X-linked X-controlling element (Xce) and stochastic effects. Our model accounts for these chromosome-wide effects on an individual level, allowing proper analysis of chromosome X expression. Furthermore, we propose a genomic control procedure to properly control type I error for RNA-seq studies. A number of these methodological improvements can also be applied to RNA-seq data from other species as well as other types of next-generation sequencing data sets. Finally, we show through simulations that increasing the number of samples is more beneficial than increasing the library size for mapping both the strain and parent-of-origin effects. Unless sample recruiting is too expensive to conduct, we recommend sequencing more samples with lower coverage.

SUBMITTER: Zou F

PROVIDER: S-EPMC4012495 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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A novel statistical approach for jointly analyzing RNA-Seq data from F1 reciprocal crosses and inbred lines.

Zou Fei F Sun Wei W Crowley James J JJ Zhabotynsky Vasyl V Sullivan Patrick F PF Pardo-Manuel de Villena Fernando F

Genetics 20140221 1

RNA sequencing (RNA-seq) not only measures total gene expression but may also measure allele-specific gene expression in diploid individuals. RNA-seq data collected from F1 reciprocal crosses in mice can powerfully dissect strain and parent-of-origin effects on allelic imbalance of gene expression. In this article, we develop a novel statistical approach to analyze RNA-seq data from F1 and inbred strains. Method development was motivated by a study of F1 reciprocal crosses derived from highly di ...[more]

PMID: 24561482

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Project description:Chicory, a horticultural crop cultivated worldwide, presents many botanical varieties and local biotypes. Among these, cultivars of the Italian radicchio group of the pure species Cichorium intybus L. and its interspecific hybrids with Cichorium endivia L.-as the "Red of Chioggia" biotype-includes several phenotypes. This study uses a pipeline to address the marker-assisted breeding of F1 hybrids: it presents the genotyping-by-sequencing results of four elite inbred lines using a RADseq approach and an original molecular assay based on CAPS markers for screening mutants with nuclear male sterility in the radicchio of Chioggia. A total of 2953 SNP-carrying RADtags were identified and used to compute the actual estimates of homozygosity and overall genetic similarity and uniformity of the populations, as well as to determine their genetic distinctiveness and differentiation. Molecular data were further used to investigate the genomic distribution of the RADtags among the two Cichorium species, allowing their mapping in 1131 and 1071 coding sequences in chicory and endive, respectively. Paralleling this, an assay to screen the genotype at the male sterility locus Cims-1 was developed to discriminate wild-type and mutant alleles of the causative gene myb80-like. Moreover, a RADtag mapped close to this genomic region proved the potential application of this method for future marker-assisted selection tools. Finally, after combining the genotype information of the core collection, the best 10 individuals from each inbred line were selected to compute the observed genetic similarity as a measure of uniformity as well as the expected homozygosity and heterozygosity estimates scorable by the putative progenies derived from selfing (pollen parent) and full-sibling (seed parent) or pair-wise crossing (F1 hybrids). This predictive approach was conducted as a pilot study to understand the potential application of RADseq in the fine tuning of molecular marker-assisted breeding strategies aimed at the development of inbred lines and F1 hybrids in leaf chicory.

Dataset Information

A novel statistical approach for jointly analyzing RNA-Seq data from F1 reciprocal crosses and inbred lines.

Publications

A novel statistical approach for jointly analyzing RNA-Seq data from F1 reciprocal crosses and inbred lines.

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