Genome-wide interval mapping using SNPs identifies new QTL for growth, body composition and several physiological variables in an F2 intercross between fat and lean chicken lines.

BACKGROUND: For decades, genetic improvement based on measuring growth and body composition traits has been successfully applied in the production of meat-type chickens. However, this conventional approach is hindered by antagonistic genetic correlations between some traits and the high cost of measuring body composition traits. Marker-assisted selection should overcome these problems by selecting loci that have effects on either one trait only or on more than one trait but with a favorable genetic correlation. In the present study, identification of such loci was done by genotyping an F2 intercross between fat and lean lines divergently selected for abdominal fatness genotyped with a medium-density genetic map (120 microsatellites and 1302 single nucleotide polymorphisms). Genome scan linkage analyses were performed for growth (body weight at 1, 3, 5, and 7 weeks, and shank length and diameter at 9 weeks), body composition at 9 weeks (abdominal fat weight and percentage, breast muscle weight and percentage, and thigh weight and percentage), and for several physiological measurements at 7 weeks in the fasting state, i.e. body temperature and plasma levels of IGF-I, NEFA and glucose. Interval mapping analyses were performed with the QTLMap software, including single-trait analyses with single and multiple QTL on the same chromosome. RESULTS: Sixty-seven QTL were detected, most of which had never been described before. Of these 67 QTL, 47 were detected by single-QTL analyses and 20 by multiple-QTL analyses, which underlines the importance of using different statistical models. Close analysis of the genes located in the defined intervals identified several relevant functional candidates, such as ACACA for abdominal fatness, GHSR and GAS1 for breast muscle weight, DCRX and ASPSCR1 for plasma glucose content, and ChEBP for shank diameter. CONCLUSIONS: The medium-density genetic map enabled us to genotype new regions of the chicken genome (including micro-chromosomes) that influenced the traits investigated. With this marker density, confidence intervals were sufficiently small (14 cM on average) to search for candidate genes. Altogether, this new information provides a valuable starting point for the identification of causative genes responsible for important QTL controlling growth, body composition and metabolic traits in the broiler chicken.

Complex trait subtypes identification using transcriptome profiling reveals an interaction between two QTL affecting adiposity in chicken.

BACKGROUND: Integrative genomics approaches that combine genotyping and transcriptome profiling in segregating populations have been developed to dissect complex traits. The most common approach is to identify genes whose eQTL colocalize with QTL of interest, providing new functional hypothesis about the causative mutation. Another approach includes defining subtypes for a complex trait using transcriptome profiles and then performing QTL mapping using some of these subtypes. This approach can refine some QTL and reveal new ones.In this paper we introduce Factor Analysis for Multiple Testing (FAMT) to define subtypes more accurately and reveal interaction between QTL affecting the same trait. The data used concern hepatic transcriptome profiles for 45 half sib male chicken of a sire known to be heterozygous for a QTL affecting abdominal fatness (AF) on chromosome 5 distal region around 168 cM. RESULTS: Using this methodology which accounts for hidden dependence structure among phenotypes, we identified 688 genes that are significantly correlated to the AF trait and we distinguished 5 subtypes for AF trait, which are not observed with gene lists obtained by classical approaches. After exclusion of one of the two lean bird subtypes, linkage analysis revealed a previously undetected QTL on chromosome 5 around 100 cM. Interestingly, the animals of this subtype presented the same q paternal haplotype at the 168 cM QTL. This result strongly suggests that the two QTL are in interaction. In other words, the "q configuration" at the 168 cM QTL could hide the QTL existence in the proximal region at 100 cM. We further show that the proximal QTL interacts with the previous one detected on the chromosome 5 distal region. CONCLUSION: Our results demonstrate that stratifying genetic population by molecular phenotypes followed by QTL analysis on various subtypes can lead to identification of novel and interacting QTL.

New investigations around CYP11A1 and its possible involvement in an androstenone QTL characterised in Large White pigs.

BACKGROUND: Previously, in boars with extreme androstenone levels, differential expression of the CYP11A1 gene in the testes has been characterised. CYP11A1 is located in a region where a QTL influencing boar fat androstenone levels has been detected in a Large White pig population. Clarifying the role of CYP11A1 in boar taint is important because it catalyses the initial step of androstenone synthesis and also of steroid synthesis. RESULTS: A genome-wide association study located CYP11A1 at approximately 1300 kb upstream from SNP H3GA0021967, defining the centre of the region containing the QTL for androstenone variation. In this study, we partially sequenced the CYP11A1 gene and identified several new single nucleotide polymorphisms (SNP) within it. Characterisation of one animal, heterozygous for CYP11A1 testicular expression but homozygous for a haplotype of a large region containing CYP11A1, revealed that variation of CYP11A1 expression is probably regulated by a mutation located downstream from the SNP H3GA0021967. We analysed CYP11A1 expression in LW families according to haplotypes of the QTL region's centre. Effects of haplotypes on CYP11A1 expression and on androstenone accumulation were not concordant. CONCLUSION: This study shows that testicular expression of CYP11A1 is not solely responsible for the QTL influencing boar fat androstenone levels. As a conclusion, we propose to refute the hypothesis that a single mutation located near the centre of the QTL region could control androstenone accumulation in fat by regulating the CYP11A1 expression.

A factor model to analyze heterogeneity in gene expression.

BACKGROUND: Microarray technology allows the simultaneous analysis of thousands of genes within a single experiment. Significance analyses of transcriptomic data ignore the gene dependence structure. This leads to correlation among test statistics which affects a strong control of the false discovery proportion. A recent method called FAMT allows capturing the gene dependence into factors in order to improve high-dimensional multiple testing procedures. In the subsequent analyses aiming at a functional characterization of the differentially expressed genes, our study shows how these factors can be used both to identify the components of expression heterogeneity and to give more insight into the underlying biological processes. RESULTS: The use of factors to characterize simple patterns of heterogeneity is first demonstrated on illustrative gene expression data sets. An expression data set primarily generated to map QTL for fatness in chickens is then analyzed. Contrarily to the analysis based on the raw data, a relevant functional information about a QTL region is revealed by factor-adjustment of the gene expressions. Additionally, the interpretation of the independent factors regarding known information about both experimental design and genes shows that some factors may have different and complex origins. CONCLUSIONS: As biological information and technological biases are identified in what was before simply considered as statistical noise, analyzing heterogeneity in gene expression yields a new point of view on transcriptomic data.

Using transcriptome profiling to characterize QTL regions on chicken chromosome 5.

BACKGROUND: Although many QTL for various traits have been mapped in livestock, location confidence intervals remain wide that makes difficult the identification of causative mutations. The aim of this study was to test the contribution of microarray data to QTL detection in livestock species. Three different but complementary approaches are proposed to improve characterization of a chicken QTL region for abdominal fatness (AF) previously detected on chromosome 5 (GGA5). RESULTS: Hepatic transcriptome profiles for 45 offspring of a sire known to be heterozygous for the distal GGA5 AF QTL were obtained using a 20 K chicken oligochip. mRNA levels of 660 genes were correlated with the AF trait. The first approach was to dissect the AF phenotype by identifying animal subgroups according to their 660 transcript profiles. Linkage analysis using some of these subgroups revealed another QTL in the middle of GGA5 and increased the significance of the distal GGA5 AF QTL, thereby refining its localization. The second approach targeted the genes correlated with the AF trait and regulated by the GGA5 AF QTL region. Five of the 660 genes were considered as being controlled either by the AF QTL mutation itself or by a mutation close to it; one having a function related to lipid metabolism (HMGCS1). In addition, a QTL analysis with a multiple trait model combining this 5 gene-set and AF allowed us to refine the QTL region. The third approach was to use these 5 transcriptome profiles to predict the paternal Q versus q AF QTL mutation for each recombinant offspring and then refine the localization of the QTL from 31 cM (100 genes) at a most probable location confidence interval of 7 cM (12 genes) after determining the recombination breakpoints, an interval consistent with the reductions obtained by the two other approaches. CONCLUSION: The results showed the feasibility and efficacy of the three strategies used, the first revealing a QTL undetected using the whole population, the second providing functional information about a QTL region through genes related to the trait and controlled by this region (HMGCS1), the third could drastically refine a QTL region.

Homeologous recombination plays a major role in chromosome rearrangements that occur during meiosis of Brassica napus haploids.

Chromosomal rearrangements can be triggered by recombination between distinct but related regions. Brassica napus (AACC; 2n = 38) is a recent allopolyploid species whose progenitor genomes are widely replicated. In this article, we analyze the extent to which chromosomal rearrangements originate from homeologous recombination during meiosis of haploid B. napus (n = 19) by genotyping progenies of haploid x euploid B. napus with molecular markers. Our study focuses on three pairs of homeologous regions selected for their differing levels of divergence (N1/N11, N3/N13, and N9/N18). We show that a high number of chromosomal rearrangements occur during meiosis of B. napus haploid and are transmitted by first division restitution (FDR)-like unreduced gametes to their progeny; half of the progeny of Darmor-bzh haploids display duplications and/or losses in the chromosomal regions being studied. We demonstrate that half of these rearrangements are due to recombination between regions of primary homeology, which represents a 10- to 100-fold increase compared to the frequency of homeologous recombination measured in euploid lines. Some of the other rearrangements certainly result from recombination between paralogous regions because we observed an average of one to two autosyndetic A-A and/or C-C bivalents at metaphase I of the B. napus haploid. These results are discussed in the context of genome evolution of B. napus.