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Biomedical subjects

O Carlborg

Publications and source records attributed to O Carlborg.

7 recordsLinked to original sources

The twofold difference in adult size between the red junglefowl and White Leghorn chickens is largely explained by a limited number of QTLs.

A large intercross between the domestic White Leghorn chicken and the wild ancestor, the red junglefowl, has been used in a Quantitative Trait Loci (QTL) study of growth and egg production. The linkage map based on 105 marker loci was in good agreement with the chicken consensus map. The growth of the 851 F2 individuals was lower than both parental lines prior to 46 days of age and intermediate to the two parental lines thereafter. The QTL analysis of growth traits revealed 13 loci that showed genome-wide significance. The four major growth QTLs explained 50 and 80% of the difference in adult body weight between the founder populations for females and males, respectively. A major QTL for growth, located on chromosome 1 appears to have pleiotropic effects on feed consumption, egg production and behaviour. There was a strong positive correlation between adult body weight and average egg weight. However, three QTLs affecting average egg weight but not body weight were identified. An interesting observation was that the estimated effects for the four major growth QTLs all indicated a codominant inheritance.

Alleles↗

Melanocortin-4 receptor (MC4R) genotypes have no major effect on fatness in a Large White x Wild Boar intercross.

The melanocortin-4 receptor (MC4R), a G-protein coupled receptor, is implicated in mediating the effect of leptin on food intake and energy balance. A previous candidate gene study reported an association between an MC4R missense mutation (Asp298Asn) and fatness, growth and feed intake in pigs. To assess this association further, we analysed the segregation of this missense mutation in relation to variation in fatness traits using a Wild Boar x Large White intercross. The Wild Boar and Large White founders were homozygous for different MC4R alleles. The MC4R was assigned to the expected region on pig chromosome 1. The statistical evaluation did not reveal any indication of a significant effect on fatness related traits in this pedigree.

Animals↗

The origin of the domestic pig: independent domestication and subsequent introgression.

The domestic pig originates from the Eurasian wild boar (Sus scrofa). We have sequenced mitochondrial DNA and nuclear genes from wild and domestic pigs from Asia and Europe. Clear evidence was obtained for domestication to have occurred independently from wild boar subspecies in Europe and Asia. The time since divergence of the ancestral forms was estimated at approximately 500,000 years, well before domestication approximately 9,000 years ago. Historical records indicate that Asian pigs were introduced into Europe during the 18th and early 19th centuries. We found molecular evidence for this introgression and the data indicated a hybrid origin of some major "European" pig breeds. The study is an advance in pig genetics and has important implications for the maintenance and utilization of genetic diversity in this livestock species.

Animals↗

The use of a genetic algorithm for simultaneous mapping of multiple interacting quantitative trait loci.

Here we describe a general method for improving computational efficiency in simultaneous mapping of multiple interacting quantitative trait loci (QTL). The method uses a genetic algorithm to search for QTL in the genome instead of an exhaustive enumerative ("step-by-step") search. It can be used together with any method of QTL mapping based on a genomic search, since it only provides a more efficient way to search the genome for QTL. The computational demand decreases by a factor of approximately 130 when using genetic algorithm-based mapping instead of an exhaustive enumerative search for two QTL in a genome size of 2000 cM using a resolution of 1 cM. The advantage of using a genetic algorithm increases further for larger genomes, higher resolutions, and searches for more QTL. We show that a genetic algorithm-based search has efficiency higher than or equal to a search method conditioned on previously identified QTL for all epistatic models tested and that this efficiency is comparable to that of an exhaustive search for multiple QTL. The genetic algorithm is thus a powerful and computationally tractable alternative to the exhaustive enumerative search for simultaneous mapping of multiple interacting QTL. The use of genetic algorithms for simultaneous mapping of more than two QTL and for determining empirical significance thresholds using permutation tests is also discussed.

Algorithms↗

High in situ rat intestinal permeability of artemisinin unaffected by multiple dosing and with no evidence of P-glycoprotein involvement.

The objective of this study was to investigate whether the decrease in artemisinin bioavailability after repeated oral dosing in humans can be a result of increased efflux of artemisinin by P-glycoprotein or decreased membrane transport at the intestinal barrier. The effective jejunal permeability (Peff) of artemisinin was investigated using an in situ rat perfusion model. Fifty-four rats were randomized to one of three treatment arms: no pretreatment, pretreatment with artemisinin emulsion for 5 days (60 mg/kg/day, p.o. ), or pretreatment with emulsion vehicle for 5 days. The rats within each treatment arm were randomized further to be jejunally perfused with either low (500 ng/ml) or high (5000 ng/ml) artemisinin concentration or low artemisinin concentration plus the P-glycoprotein inhibitor R,S-verapamil (400 microg/ml). Perfusate samples were assayed for content of artemisinin, R,S-verapamil, and perfusion viability markers. Artemisinin Peff was 1.44 +/- 0.38, 1. 17 +/- 0.32, and 1.71 +/- 0.29 (.10(-4), cm/s) in rats receiving no pretreatment and perfused with low, high, or low artemisinin concentration plus verapamil, respectively. Multiple oral dosing of artemisinin did not affect the jejunal permeability of artemisinin. R,S-verapamil Peff was similar in artemisinin-pretreated rats (1.09 +/- 0.54. 10(-4), cm/s) and rats pretreated with only vehicle (1.07 +/- 0.37. 10(-4), cm/s). The decrease in artemisinin bioavailability after multiple oral dosing in human is probably not a result of changes in P-glycoprotein expression or general intestinal transport. It seems more likely attributed to increased hepatocellular activity. Furthermore, artemisinin exhibits high jejunal permeability and is neither a substrate nor inducer of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Parallel computing in interval mapping of quantitative trait loci.

Linear regression analysis is considered the least computationally demanding method for mapping quantitative trait loci (QTL). However, simultaneous search for multiple QTL, the use of permutations to obtain empirical significance thresholds, and larger experimental studies significantly increase the computational demand. This report describes an easily implemented parallel algorithm, which significantly reduces the computing time in both QTL mapping and permutation testing. In the example provided, the analysis time was decreased to less than 15% of a single processor system by the use of 18 processors. We indicate how the efficiency of the analysis could be improved by distributing the computations more evenly to the processors and how other ways of distributing the data facilitate the use of more processors. The use of parallel computing in QTL mapping makes it possible to routinely use permutations to obtain empirical significance thresholds for multiple traits and multiple QTL models. It could also be of use to improve the computational efficiency of the more computationally demanding QTL analysis methods.

Algorithms↗