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C S Haley

Publications and source records attributed to C S Haley.

At least 19 recordsLinked to original sources
PubMed2006

A polymorphism in the 5'-untranslated region of the porcine cholecystokinin type a receptor gene affects feed intake and growth.

The location and utilization of quantitative trait loci (QTL) and candidate genes with significant effects on economically important traits are becoming increasingly important in livestock breeding programs. The porcine cholecystokinin type A receptor (CCKAR) is a candidate gene for performance traits, due to its known role in the physiological control of feed intake, satiety, and obesity. We investigated the association of CCKAR polymorphisms with feeding, growth, and efficiency traits in an F2 population derived from a cross between Meishan and Large White founder animals and in lines of Large White pigs that had been divergently selected on the basis of lean growth efficiency traits. In the F2 population, CCKAR genotype was significantly associated with daily feed intake and average daily gain. The effects of the polymorphisms were then assessed in a larger-scale analysis of segregating commercial lines. A newly discovered single-nucleotide polymorphism (SNP) within the 5'-untranslated region (5'-UTR) had highly significant effects on feed intake, average daily gain, and days to 110 kg, which were not seen for a previously reported SNP within the CCKAR gene. Furthermore, we provide evidence that the novel SNP disrupts the binding of the YY1 transcription factor, which raises the possibility that it is the causal variant. The 5'-UTR SNP could be utilized as a molecular genetic test for increased feed intake, faster lean growth, and reduced days to market weight in segregating commercial lines.

5' Untranslated Regions↗
PubMed2006

Genetic parameters for blood oxygen saturation, body weight and breast conformation in 4 meat-type chicken lines.

1. The objective of the study was to explore the genetic architecture of blood oxygen saturation (SaO) (an indicator trait, negatively correlated with ascites susceptibility), body weight (Weight) and fleshing score (Flesh, a measure of breast conformation) for 4 meat-type chicken lines reared in commercial conditions. 2. Genetic components, including heritabilities and genetic correlations, were estimated by Restricted Maximum likelihood for these traits measured at 6 weeks of age. 3. Data were collected over eight generations of selection and pedigrees comprised in excess of 130,000 birds. 4. Univariate analyses were performed to allow model definition and to obtain starting values for trivariate analyses. The basic model included a random animal effect and, in further models explored, a maternal environmental effect or a genetic maternal effect or both were fitted. Models were compared using likelihood ratio tests. 5. Estimated heritabilities for SaO ranged from 0.1 to 0.2, and there was no evidence of genetic maternal effects for SaO. The environmental maternal component was significant for one of the populations only. Estimated heritabilities for both Weight and Flesh were between 0.2 and 0.4, and there was evidence of environmental and genetic maternal effects for these traits in all populations. 6. Genetic correlations between SaO and Weight and between SaO and Flesh were low and negative. This suggests that, in principle, genetic selection to simultaneously increase SaO, and therefore decrease ascites susceptibility, and WEight and Flesh could be performed using traditional (marker-free) selection methods. We discuss how a putative interaction between ascites and production traits could jeopardise the success of such methods.

Animals↗
PubMed2006

Segregation analysis of blood oxygen saturation in broilers suggests a major gene influence on ascites.

1. Blood oxygen saturation (SaO) is a potential indicator trait for resistance to ascites in chickens. 2. The objective of the study was to investigate the genetic architecture of SaO in a meat-type chicken line reared in commercial conditions. 3. Data were collected over 15 generations of selection and were divided into two data sets on the basis of a change in recording age from 6 to 5 weeks of age, approximately halfway through the period. The resulting pedigrees comprised in excess of 90,000 birds each and, on average, 12% of these birds had SaO records. 4. Segregation analyses of SaO were carried out assuming a mixed inheritance model that included a major locus segregating in a polygenic background. 5. The analyses suggest that a major gene is involved in the genetic control of SaO in this line. The putative gene acts in a dominant fashion and has an additive effect of around 0.90 sigma(p), equivalent to a predicted difference in SaO between the two homozygous classes of more than 10%. The frequency of the allele that increases SaO changed from 0.53 to 0.65 from the first to the second set of data, consistent with selection on SaO scores. 6. Using estimated genotype probabilities at the putative major locus, we inferred that it acts in an overdominant fashion on body weight and fleshing score. If the low SaO allele leads to susceptibility to ascites, its combined effects are consistent with it being maintained in the population by a balance of natural selection on fitness nad artificial selection on growth and carcase traits. 7. Even with selection on both SaO and growth traits, the combined genotypic effects would make it difficult to remove the unfavourable low-SaO allele by means of traditional selection without the use of genetic markers.

Animals↗
PubMed2006

Genetic diversity within and between European pig breeds using microsatellite markers.

An important prerequisite for a conservation programme is a comprehensive description of genetic diversity. The aim of this study was to use anonymous genetic markers to assess the between- and the within-population components of genetic diversity for European pig breeds at the scale of the whole continent using microsatellites. Fifty-eight European pig breeds and lines were analysed including local breeds, national varieties of international breeds and commercial lines. A sample of the Chinese Meishan breed was also included. Eleven additional breeds from a previous project were added for some analyses. Approximately 50 individuals per breed were genotyped for a maximum of 50 microsatellite loci. Substantial within-breed variability was observed, with the average expected heterozygosity and observed number of alleles per locus being 0.56 [range 0.43-0.68] and 4.5 respectively. Genotypic frequencies departed from Hardy-Weinberg expectations (P < 0.01) in 15 European populations, with an excess of homozygotes in 12 of them. The European breeds were on average genetically very distinct, with a Wright F(ST) index value of 0.21. The Neighbour-Joining tree drawn from the Reynolds distances among the breeds showed that the national varieties of major breeds and the commercial lines were mostly clustered around their breeds of reference (Duroc, Hampshire, Landrace, Large White and Piétrain). In contrast, local breeds, with the exception of the Iberian breeds, exhibited a star-like topology. The results are discussed in the light of various forces, which may have driven the recent evolution of European pig breeds. This study has consequences for the interpretation of biodiversity results and will be of importance for future conservation programmes.

Alleles↗
PubMed2006

QTL analysis of body weight and conformation score in commercial broiler chickens using variance component and half-sib analyses.

The aim of the study was to investigate quantitative trait loci (QTL) in previously identified regions of chicken chromosomes 1, 4 and 5 relating to 40-day body weights and conformation scores. Half-sib (HS) and variance component analyses were implemented and compared using QTL Express software. Data were from a two-generation design and consisted of 100 dam families nested in 46 sire families with trait values for 2,708 offspring. Chicken chromosome 4 showed nominal significance for QTL affecting body weight and conformation, and linkage was confirmed for both traits on chromosome 5. Results varied according to method of analysis and with common parent in the HS method.

Animals↗
PubMed2005

Methodological aspects of the genetic dissection of gene expression.

MOTIVATION: Dissection of the genetics underlying gene expression utilizes techniques from microarray analyses as well as quantitative trait loci (QTL) mapping. Available QLT mapping methods are not tailored for the highly automated analyses required to deal with the thousand of gene transcripts encountered in the mapping of QTL affecting gene expression (sometimes referred to as eQTL). This report focuses on the adaptation of QTL mapping methodology to perform automated mapping of QTL affecting gene expression. RESULTS: The analyses of expression data on > 12,000 gene transcripts in BXD recombinant inbred mice found, on average, 629 QTL exceeding the genome-wide 5% threshold. Using additional information on trait repeatabilities and QTL location, 168 of these were classified as 'high confidence' QTL. Current sample sizes of genetical genomics studies make it possible to detect a reasonable number of QTL using simple genetic models, but considerably larger studies are needed to evaluate more complex genetic models. After extensive analyses of real data and additional simulated data (altogether > 300,000 genome scans) we make the following recommendations for detection of QTL for gene expression: (1) For populations with an unbalanced number of replicates on each genotype, weighted least squares should be preferred above ordinary least squares. Weights can be based on repeatability of the trait and the number of replicates. (2) A genome scan based on multiple marker information but analysing only at marker locations is a good approximation to a full interval mapping procedure. (3) Significance testing should be based on empirical genome-wide significance thresholds that are derived for each trait separately. (4) The significant QTL can be separated into high and low confidence QTL using a false discovery rate that incorporates prior information such as transcript repeatabilities and co-localization of gene-transcripts and QTL. (5) Including observations on the founder lines in the QTL analysis should be avoided as it inflates the test statistic and increases the Type I error. (6) To increase the computational efficiency of the study, use of parallel computing is advised. These recommendations are summarized in a possible strategy for mapping of QTL in a least squares framework. AVAILABILITY: The software used for this study is available on request from the authors.

Algorithms↗
PubMed2005

Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable.

Bipolar Disorder↗
PubMed2005

Marker densities and the mapping of ancestral junctions.

In any partially inbred population, 'junctions' are the loci that form boundaries between segments of ancestral chromosomes. Here we show that the expected number of junctions per Morgan in such a population is linearly related to the inbreeding coefficient of the population, with a maximum in a completely inbred population corresponding to the prediction given by Stam (1980). We further show that high-density marker maps (fully informative markers with average densities of up to 200 per cM) will fail to detect a significant proportion of the junctions present in highly inbred populations. The number of junctions detected is lower than that which would be expected if junctions were distributed randomly along the chromosome, and we show that junctions are not, in fact randomly spaced. This non-random spacing of junctions significantly increases the number of markers that is required to detect 90% of the junctions present on any chromosome: a marker count of at least 12 times the number of junctions present will be needed to detect this proportion.

Animals↗
PubMed2005

Mapping of quantitative trait loci affecting organ weights and blood variables in a broiler layer cross.

1. A genome scan was performed to locate genomic regions associated with traits that are known to vary in birds (most commonly broilers) suffering from heart, lung or muscular dysfunction and for weight of the dressed carcass and some internal organs. 2. The F2 population studied was derived from a cross between a broiler and a layer line and consisted of over 460 birds that were genotyped for 101 markers. 3. There was strong support for segregation of quantitative trait loci (QTL) for carcass and organ weights and blood variables. We identified 11 genome-wide significant QTL (most of them for dressed carcass weight) and several genome-wide suggestive QTL. 4. The results point to some genome regions that may be associated with health-related traits and merit further study, with the final aim of identifying linked genetic markers that could be used in commercial breeding programmes to decrease the incidence of muscular and metabolic disorders in broiler populations.

Animals↗
PubMed2005

Detection of quantitative trait loci for androstenone, skatole and boar taint in a cross between Large White and Meishan pigs.

'Boar taint' is a strong perspiration-like, urine-like unpleasant odour given off upon heating or cooking of meat from some intact (uncastrated) male pigs. Data from the F(2) generation of a Large White (LW) x Meishan (MS) crossbred population were analysed to detect quantitative trait loci (QTL) for traits associated with boar taint. Fat samples from 178 intact male pigs slaughtered at 85 +/- 5 kg were analysed for the major contributors to boar taint (androstenone, indole and skatole). Fat and lean samples from cooked meat were scored for boar, abnormal and pork flavour and odour by a trained sensory panel (SP). A scan with 117 markers covering the whole genome was performed in the F(2) individuals, together with their F(1) parents and purebred grandparents. At the 5% chromosomal significance threshold (approximately equal to the genome-wide suggestive significance threshold), QTL were detected for the laboratory estimate of androstenone on chromosomes 2, 4, 6, 7 and 9. However, only on chromosome 6 were there QTL for boar flavour (BF) traits in the same or adjacent marker intervals as a QTL for the laboratory estimate of androstenone. On chromosome 14, QTL were detected for the laboratory estimates of indole and skatole, the SP score for skatole and the scores for BF in lean and BF in fat. In all five cases, the MS allele generally increased the estimate or score, compared with the LW allele, but it appeared that desirable and undesirable alleles were present in both breeds. This locus on chromosome 14 has considerable potential for use to reduce the incidence of boar taint, especially if further research can identify the causative polymorphism or strongly associated markers.

Androsterone↗
PubMed2005

Cloning and mapping of the porcine cytochrome-p450 2E1 gene and its association with skatole levels in the domestic pig.

The porcine cytochrome-p450 2E1 (CYP2E1) gene was isolated by screening a pig BAC library and partially sequenced. This sequence information was used to identify six single nucleotide polymorphisms (SNPs) within the CYP2E1 gene and its promoter. In addition, a microsatellite marker tightly linked to the CYP2E1 gene was subcloned from the BAC. One of these markers was used to map the CYP2E1 gene distal of SWC27 on SSC14, well outside reported quantitative trait loci on SSC14 for skatole, indole and taste test measures of boar taint. However, in a population of commercial pigs scored for backfat skatole levels, there was evidence of association between a SNP in the CYP2E1 promoter and skatole deposition, although there was no significant association between this SNP and skatole levels in the experimental cross.

Adipose Tissue↗
PubMed2004

Segregation of QTL for production traits in commercial meat-type chickens.

This study investigated whether quantitative trait loci (QTL) identified in experimental crosses of chickens provide a short cut to the identification of QTL in commercial populations. A commercial population of broilers was targeted for chromosomal regions in which QTL for traits associated with meat production have previously been detected in extreme crosses. A three-generation design, consisting of 15 grandsires, 608 half-sib hens and over 15 000 third-generation offspring, was implemented within the existing breeding scheme of a broiler breeding company. The first two generations were typed for 52 microsatellite markers spanning regions of nine chicken chromosomes and covering a total of 730 cM, approximately one-fifth of the chicken genome. Using half-sib analyses with a multiple QTL model, linkage was studied between these regions and 17 growth and carcass traits. Out of 153 trait x region comparisons, 53 QTL exceeded the threshold for genome-wide significance while an additional 23 QTL were significant at the nominal 1% level. Many of the QTL affect the carcass proportions and feed intake, for which there are few published studies. Given intensive selection for efficient growth in broilers for more than 50 generations it is surprising that many QTL affecting these traits are still segregating. Future fine-mapping efforts could elucidate whether ancestral mutations are still segregating as a result of pleiotropic effects on fitness traits or whether this variation is due to new mutations.

Analysis of Variance↗
PubMed2003

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

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 > 1sigma(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.

Animals↗
PubMed2003

Identification of quantitative trait loci for production traits in commercial pig populations.

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.

Adipose Tissue↗
PubMed2003

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

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.

Animals↗
PubMed2003

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

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.

Analysis of Variance↗