| 1. |
- Carlborg, Örjan, et al.
(author)
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Simultaneous mapping of epistatic QTL in DU6i x DBA/2 mice.
- 2005
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In: Mammalian Genome. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 16:7
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Journal article (peer-reviewed)abstract
- We have mapped epistatic quantitative trait loci (QTL) in an F2 cross between DU6i x DBA/2 mice. By including these epistatic QTL and their interaction parameters in the genetic model, we were able to increase the genetic variance explained substantially (8.8%-128.3%) for several growth and body composition traits. We used an analysis method based on a simultaneous search for epistatic QTL pairs without assuming that the QTL had any effect individually. We were able to detect several QTL that could not be detected in a search for marginal QTL effects because the epistasis cancelled out the individual effects of the QTL. In total, 23 genomic regions were found to contain QTL affecting one or several of the traits and eight of these QTL did not have significant individual effects. We identified 44 QTL pairs with significant effects on the traits, and, for 28 of the pairs, an epistatic QTL model fit the data significantly better than a model without interactions. The epistatic pairs were classified by the significance of the epistatic parameters in the genetic model, and visual inspection of the two-locus genotype means identified six types of related genotype-phenotype patterns among the pairs. Five of these patterns resembled previously published patterns of QTL interactions.
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| 2. |
- de Koning, Dirk-Jan, et al.
(author)
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The genetic dissection of immune response using gene-expression studies and genome mapping.
- 2005
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In: Veterinary Immunology and Immunopathology. - : Elsevier BV. - 0165-2427 .- 1873-2534. ; 105:3-4
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Journal article (peer-reviewed)abstract
- Functional genomics has been applied to the genetic dissection of immune response in different ways: (1) experimental crosses between lines that differ in their (non-) specific immune response have been used to detect quantitative trait loci (QTL) underlying these differences. (2) The measurement of gene expression levels for thousands of genes using microarrays or oligonucleotide chips to identify differential expression with regard to antigen challenge: (a) before and after infection, (b) resistant versus susceptible lines, or (c) combinations of both. Interpretation of QTL results is hampered by the fact that confidence regions of the QTL are large and can contain hundreds of potential candidate genes for the QTL. At the same time, the microarray experiments tend to show large numbers of differentially expressed genes without identifying the relationships between these genes. In the recently proposed 'genetical genomics' framework, members of a segregating population are characterised for genome-wide molecular markers and for gene expression levels. This facilitates the mapping of expression-QTL (eQTL): loci in the genome that control the expression of genes. Initial applications of this approach are critically reviewed and potential applications of this approach with regard to immune response are presented.
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