Showing papers by "Chris Haley published in 2003"

A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig

Abstract: Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation. A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region. Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation.

Mapping Quantitative Trait Loci Affecting Female Reproductive Traits on Porcine Chromosome 8

Abstract: An understanding of the genetic control of porcine female reproductive performance would offer the opportunity to utilize natural variation and improve selective breeding programs through marker-assisted selection. The Chinese Meishan is one of the most prolific pig breeds known, farrowing three to five more viable piglets per litter than the European Large White breed. This difference in prolificacy is attributed to the Meishan's superior prenatal survival levels. The present study utilized a three-generation cross in which the founder grandparental animals were purebred Meishan and Large White pigs in a scan for quantitative trait loci (QTL) on porcine chromosome 8 (SSC8) associated with reproductive performance. Reproductive traits, including number of corpora lutea (ovulation rate), teat number, litter size, and prenatal survival, were recorded for as many as 220 F2 females. Putative QTL for the related traits of litter size and prenatal survival were identified at the distal end of the long arm of SSC8. A physiological candidate gene, SPP1, was found to lie within the 95% confidence interval of these QTL. A suggestive QTL for teat number was revealed on the short arm of SSC8. The present study demonstrates, to our knowledge, the first independent confirmation of QTL for fecundity on SSC8, and these QTL regions provide a crucial starting point in the search for the causal genetic variants.

Identification of Quantitative Trait Loci for Production Traits in Commercial Pig Populations

Abstract: The aim of this study was to investigate methods for detecting QTL in outbred commercial pig populations. Several QTL for back fat and growth rate, previously detected in experimental resource populations, were examined for segregation in 10 different populations. Two hundred trait-by-population-by-chromosome tests were performed, resulting in 20 tests being significant at the 5% level. In addition, 53 QTL tests for 11 meat quality traits were declared significant, using a subset of the populations. These results show that a considerable amount of phenotypic variance observed in these populations can be explained by major alleles segregating at several of the loci described. Thus, despite a relatively strong selection pressure for growth and back fat traits in these populations, these alleles have not yet reached fixation. The approaches used here demonstrate that it is possible to verify segregation of QTL in commercial populations by limited genotyping of a selection of informative animals. Such verified QTL may be directly exploited in marker-assisted selection (MAS) programs in commercial populations and their molecular basis may be revealed by positional candidate cloning.

Quantitative trait locus detection in commercial broiler lines using candidate regions.

Abstract: A QTL that explained a large proportion of the phenotypic difference between broiler and layer chickens in an experimental cross was evaluated in a commercial broiler line. A three-generation design, consisting of 15 grandsires, 608 half-sib hens, and more than 50,000 third-generation offspring, was implemented within the existing breeding scheme of a broiler breeding company. Four markers from a candidate region on chicken chromosome 4 were selected for their informativeness in the grandsires and used to genotype the first two generations. Using half-sib analyses, linkage was studied between these markers and 13 growth and carcass traits. The QTL analyses confirmed the presence of significant QTL for body weight (P < 0.01) and residual feed intake (P < 0.05) on chicken chromosome 4. Furthermore, evidence was found for QTL affecting the relative weight of bone and muscle in the thigh. Four more markers were added to increase resolution of the QTL positions. This increased the significance of the QTL for body weight (P < 0.001) and residual feed intake (P < 0.01) and showed evidence (P < 0.05) for additional QTL affecting carcass weight and conformation score. This study showed for the first time that a QTL that explains differences between broilers and layers was segregating in lines that have been selected for body weight over 50 generations. A possible explanation could be a pleiotropic or closely linked effect on fitness-related traits that are not part of the present study. The results demonstrate the feasibility of QTL detection and the potential for marker-assisted selection within a commercial broiler line without altering the existing breeding scheme.

Candidate gene analysis for quantitative traits using the transmission disequilibrium test: the example of the melanocortin 4-receptor in pigs.

Abstract: Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal or in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.

Quantitative Trait Loci Variation for Growth and Obesity Between and Within Lines of Pigs (Sus scrofa)

Abstract: The hypothesis that quantitative trait loci (QTL) that explain variation between divergent populations also account for genetic variation within populations was tested using pig populations. Two regions of the porcine genome that had previously been reported to harbor QTL with allelic effects that differed between the modern pig and its wild-type ancestor and between the modern pig and a more distantly related population of Asian pigs were studied. QTL for growth and obesity traits were mapped using selectively genotyped half-sib families from five domesticated modern populations. Strong support was found for at least one QTL segregating in each population. For all five populations there was evidence of a segregating QTL affecting fatness in a region on chromosome 7. These findings confirm that QTL can be detected in highly selected commercial populations and are consistent with the hypothesis that the same chromosome locations that account for variation between populations also explain genetic variation within populations.

Full pedigree quantitative trait locus analysis in commercial pigs using variance components.

Abstract: In commercial livestock populations, QTL detection methods often use existing half-sib family structures and ignore additional relationships within and between families. We reanalyzed the data from a large QTL confirmation experiment with 10 pig lines and 10 chromosome regions using identity-by-descent (IBD) scores and variance component analyses. The IBD scores were obtained using a Monte Carlo Markov Chain method, as implemented in the LOKI software, and were used to model a putative QTL in a mixed animal model. The analyses revealed 61 QTL at a nominal 5% level (out of 650 tests). Twenty-seven QTL mapped to areas where QTL have been reported, and eight of these exceeded the threshold to claim confirmed linkage (P < 0.01). Forty-two of the putative QTL were detected previously using half-sib analyses, whereas 46 QTL previously identified by half-sib analyses could not be confirmed using the variance component approach. Some of the differences could be traced back to the underlying assumptions between the two methods. Using a deterministic approach to estimate IBD scores on a subset of the data gave very similar results to LOKI. We have demonstrated the feasibility of applying variance component QTL analysis to a large amount of data, equivalent to a genome scan. In many situations, the deterministic IBD approach offers a fast alternative to LOKI.

Detection of quantitative trait loci for locomotion and osteochondrosis-related traits in Large White ✕ Meishan pigs

Abstract: Data from the F 2 generation of a Large White (LW) ✕ Meishan (MS) crossbred population were analysed to detect quantitative trait loci (QTL) for leg and gait scores, osteochondrosis and physis scores. Legs, feet and gait score were assessed in 308 F 2 animals at 85 ( + 5) kg and osteochondrosis and physis scores were recorded for the right foreleg after slaughter. A genome scan was performed using 111 genetic markers chosen to span the genome that were genotyped on the F 2 animals and their F 1 parents and purebred grandparents. A QTL on chromosome 1 affecting gait score was significant at the genome-wide significance level. Additional QTL significant at the chromosomewide 5% threshold level (approx. equivalent to the genome-wide suggestive level) were detected on chromosome 1 for front feet and back legs scores, on chromosome 13 for front legs and front feet scores, on chromosome 14 for front legs, front feet and back legs scores and on chromosome 15 for back feet score. None of the QTL for osteochondrosis score exceeded the chromosome-wide suggestive level, but one chromosome-wide QTL for physis score was found on chromosome 7. On chromosome 1, gait and front feet scores mapped to the middle of the chromosome and showed additive effects in favour of the LW alleles and no dominance effects. The QTL for back legs score mapped to the distal end of the chromosome and showed a dominant effect and no additive effect. On chromosomes 14 and 15, the LW allele was again superior to the MS allele. On chromosome 13, there were both additive and dominance effects in favour of the MS allele. The MS alleles on chromosome 13 may have potential for introgression into a commercial LW population. The other putative QTLs identified may have value in marker-assisted selection in LW or MSsynthetic populations.

Analyses for the presence of a major gene affecting uterine capacity in unilaterally ovariectomized rabbits

Abstract: The presence of a major gene for uterine capacity (UC), ovulation rate (OR), number of implanted embryos (IE), embryo survival (ES), fetal survival (FS), and prenatal survival (PS) was investigated in a population of rabbits divergently selected for UC for 10 generations. Selection was performed on estimated breeding values for UC up to four parities. UC was estimated as litter size in the remaining overcrowded horn of unilaterally ovariectomized does. OR and IE were counted by means of laparoscopy. Bartlett’s test, Fain’s test, and a complex segregation analysis using Bayesian methods were used to test for the presence of a major gene. All three tests showed that the data appeared consistent with the presence of a major gene affecting UC and IE. The results of the complex segregation analysis suggested the presence of a major gene with large effect on IE and ES ( a > 1σ p ), at high frequency ( p = 0.70 and 0.68, respectively), and with a large contribution to the total variance ( R g = 0.39 and 0.47, respectively); and the presence of a major gene with moderate effect on each of OR, FS, PS, and UC. The results suggest that the studied reproductive traits are determined genetically by at least one gene of large effect.

Caracterización de la variabilidad genética en las razas de cerdos chinos y europeos. El proyecto PIGBIODIV2

Abstract: El proyecto PigBioDiv2 evaluara y comparara la diversidad genetica entre las razas de China y de Europa. Al menos 50 razas chinas seran muestreadas y comparadas con 59 razas europeas previamente estudiadas en el proyecto PigBioDiv1. La base de datos sobre la biodiversidad porcina europea se extendera hasta al menos 100 razas, un tercio del total de las razas porcinas europeas. Seran determinadas las relaciones entre razas por medio de la estimacion de las distancias geneticas basadas en marcadores microsatelites y relaciones haplotipicas desde los polimorfismos del ADN mitocondrial y del cromosoma Y. El proyecto tambien determinara las relaciones entre medidas generales de la diversidad genetica, tales como la distancia genetica, y diferencias funcionales entre razas por la caracterizacion de TGL (marcadores tipo I) y regiones QTL. Las medidas de la diversidad derivadas desde marcadores anonimos (microsatelites) seran comparadas con las medidas derivadas desde los genes de caracteres. Tambien seran desarrollados nuevos avances utilizando datos de marcadores (geneticos) del ADN para identificar genes relacionados con diferencias funcionales entre razas.

The use of mc1r and kit genotypes for breed characterisation el uso de los genotipos mc1r y kit para la caracterización racial

Abstract: Describimos la caracterizacion de dos loci determinantes del color de la capa en cerdos y demostramos como esta informacion puede ser utilizada para la identificacion racial. Estos avances pueden ser utiles en esquemas para asegurar la calidad y la trazabilidad cuya demanda se esta incrementando en los consumidores.

The pig genetic diversity database and the www

Abstract: La base de datos sobre la diversidad genetica porcina (PigDbase) y su sitio Web asociado (http://www.projects.roslin.ac.uk/pigbiodiv/) provee de un almacen de datos seguro para los estudios sobre la diversidad genetica de los cerdos incluyendo los genotipos de microsatelites y AFLPs. El diseno de la base de datos es tal que podria ser aplicado a cualquier especie y, con adecuados protocolos de estandarizacion, podria extenderse a cualquier laboratorio que deseara aportar datos. El acceso a PigDbase se efectua via WWW utilizando el browser diversidad. La informacion almacenada incluye detalles de los marcadores microsatelites, muestra y detalles de contacto. La informacion completa sobre datos no procesados, asi como informacion resumida sobre medidas geneticas y formatos de exportacion tambien estan disponibles.

The use of mc1r and kit genotypes for breed characterisation

Abstract: Describimos la caracterizacion de dos loci determinantes del color de la capa en cerdos y demostramos como esta informacion puede ser utilizada para la identificacion racial. Estos avances pueden ser utiles en esquemas para asegurar la calidad y la trazabilidad cuya demanda se esta incrementando en los consumidores.

What can the genetics revolution offer the meat industry

Abstract: The basic technology is now available to undertake genetic modification in farm animals - adding new genes or modifying existing genes. However, the procedures are inefficient and costly, or lack precision, or both. The technologies also raise both welfare and ethical concerns. Thus, the traits to which this technology might be applied need to be chosen with care. High-impact traits could include enhanced resistance to disease and improvements in product quality. Genome research is revealing some of the genes controlling these and other traits and could inform the choice of genes for genetic modification.

Power of QTL detection using association tests with family controls.

Abstract: The power of testing for a population-wide association between a biallelic quantitative trait locus and a linked biallelic marker locus is predicted both empirically and deterministically for several tests. The tests were based on the analysis of variance (ANOVA) and on a number of transmission disequilibrium tests (TDT). Deterministic power predictions made use of family information, and were functions of population parameters including linkage disequilibrium, allele frequencies, and recombination rate. Deterministic power predictions were very close to the empirical power from simulations in all scenarios considered in this study. The different TDTs had very similar power, intermediate between one-way and nested ANOVAs. One-way ANOVA was the only test that was not robust against spurious disequilibrium. Our general framework for predicting power deterministically can be used to predict power in other association tests. Deterministic power calculations are a powerful tool for researchers to plan and evaluate experiments and obviate the need for elaborate simulation studies.

Power of QTL detection using association tests with family controls

Abstract: The power of testing for a population-wide association between a biallelic quantitative trait locus and a linked biallelic marker locus is predicted both empirically and deterministically for several tests. The tests were based on the analysis of variance (ANOVA) and on a number of transmission disequilibrium tests (TDT). Deterministic power predictions made use of family information, and were functions of population parameters including linkage disequilibrium, allele frequencies, and recombination rate. Deterministic power predictions were very close to the empirical power from simulations in all scenarios considered in this study. The different TDTs had very similar power, intermediate between one-way and nested ANOVAs. One-way ANOVA was the only test that was not robust against spurious disequilibrium. Our general framework for predicting power deterministically can be used to predict power in other association tests. Deterministic power calculations are a powerful tool for researchers to plan and evaluate experiments and obviate the need for elaborate simulation studies.