| 1. |
- Albert, Frank W., et al.
(författare)
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Genetic architecture of tameness in a rat model of animal domestication
- 2009
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 182:2, s. 541-554
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Tidskriftsartikel (refereegranskat)abstract
- A common feature of domestic animals is tameness - i.e., they tolerate and are unafraid of human presence and handling. To gain insight into the genetic basis of tameness and aggression, we studied an intercross between two lines of rats (Rattus norvegicus) selected over >60 generations for increased tameness and increased aggression against humans, respectively. We measured 45 traits, including tameness and aggression, anxiety-related traits, organ weights, and levels of serum components in >700 rats from an intercross population. Using 201 genetic markers, we identified two significant quantitative trait loci (QTL) for tameness. These loci overlap with QTL for adrenal gland weight and for anxiety-related traits and are part of a five-locus epistatic network influencing tameness. An additional QTL influences the occurrence of white coat spots, but shows no significant effect on tameness. The loci described here are important starting points for finding the genes that cause tameness in these rats and potentially in domestic animals in general.
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| 2. |
- Albert, F. W., et al.
(författare)
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Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
- 2011
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 107:3, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.
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| 3. |
- Alexander, Michelle, et al.
(författare)
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Mitogenomic analysis of a 50-generation chicken pedigree reveals a rapid rate of mitochondrial evolution and evidence for paternal mtDNA inheritance
- 2015
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Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 x 10(-7) mutations/site/year (95% confidence interval 3.75 x 10(-8)-1.12 x 10(-6)). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods.
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| 4. |
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| 5. |
- Besnier, Francois, 1980-, et al.
(författare)
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A general and efficient method for estimating continuous IBD functions for use in genome scans for QTL
- 2007
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identity by descent (IBD) matrix estimation is a central component in mapping of Quantitative Trait Loci (QTL) using variance component models. A large number of algorithms have been developed for estimation of IBD between individuals in populations at discrete locations in the genome for use in genome scans to detect QTL affecting various traits of interest in experimental animal, human and agricultural pedigrees. Here, we propose a new approach to estimate IBD as continuous functions rather than as discrete values. Results: Estimation of IBD functions improved the computational efficiency and memory usage in genome scanning for QTL. We have explored two approaches to obtain continuous marker-bracket IBD-functions. By re-implementing an existing and fast deterministic IBD-estimation method, we show that this approach results in IBD functions that produces the exact same IBD as the original algorithm, but with a greater than 2-fold improvement of the computational efficiency and a considerably lower memory requirement for storing the resulting genome-wide IBD. By developing a general IBD function approximation algorithm, we show that it is possible to estimate marker-bracket IBD functions from IBD matrices estimated at marker locations by any existing IBD estimation algorithm. The general algorithm provides approximations that lead to QTL variance component estimates that even in worst-case scenarios are very similar to the true values. The approach of storing IBD as polynomial IBD-function was also shown to reduce the amount of memory required in genome scans for QTL. Conclusion: In addition to direct improvements in computational and memory efficiency, estimation of IBD-functions is a fundamental step needed to develop and implement new efficient optimization algorithms for high precision localization of QTL. Here, we discuss and test two approaches for estimating IBD functions based on existing IBD estimation algorithms. Our approaches provide immediately useful techniques for use in single QTL analyses in the variance component QTL mapping framework. They will, however, be particularly useful in genome scans for multiple interacting QTL, where the improvements in both computational and memory efficiency are the key for successful development of efficient optimization algorithms to allow widespread use of this methodology.
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| 6. |
- Besnier, Francois, et al.
(författare)
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A genetic algorithm based method for stringent haplotyping of family data
- 2009
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Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The linkage phase, or haplotype, is an extra level of information that in addition to genotype and pedigree can be useful for reconstructing the inheritance pattern of the alleles in a pedigree, and computing for example Identity By Descent probabilities. If a haplotype is provided, the precision of estimated IBD probabilities increases, as long as the haplotype is estimated without errors. It is therefore important to only use haplotypes that are strongly supported by the available data for IBD estimation, to avoid introducing new errors due to erroneous linkage phases.Results: We propose a genetic algorithm based method for haplotype estimation in family data that includes a stringency parameter. This allows the user to decide the error tolerance level when inferring parental origin of the alleles. This is a novel feature compared to existing methods for haplotype estimation. We show that using a high stringency produces haplotype data with few errors, whereas a low stringency provides haplotype estimates in most situations, but with an increased number of errors.Conclusion: By including a stringency criterion in our haplotyping method, the user is able to maintain the error rate at a suitable level for the particular study; one can select anything from haplotyped data with very small proportion of errors and a higher proportion of non-inferred haplotypes, to data with phase estimates for every marker, when haplotype errors are tolerable. Giving this choice makes the method more flexible and useful in a wide range of applications as it is able to fulfil different requirements regarding the tolerance for haplotype errors, or uncertain marker-phases.
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| 7. |
- Besnier, Francois, et al.
(författare)
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Applying QTL analysis to conservation genetics
- 2010
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 11, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- Both analytical and molecular tools currently exist that can be used to prolifically apply quantitative trait loci (QTL) analysis to the study of natural populations. In this communication, we review and exemplify the use of QTL mapping tools and genetic modeling for conservation geneticists. We simulate populations inspired by relevant cases that can be encountered in the field and analyze them using the recently developed flexible intercross analysis (FIA) method. We then reanalyze these results with the also recently developed natural and orthogonal interactions (NOIA) model of genetic effects. Next, we further exemplify the potential of genetic modeling for the interpretation of the output of QTL analyses by reviewing studies on hybrids between wild individuals and their domesticated relatives. Based on the results here presented we emphasize several points that are pertinent in conservation genetics including (i) the advantages of FIA as a powerful tool to be applied to line crosses in which the parental lines are not inbred, (ii) the importance of obtaining estimates of genetic effects that are adequate to address the research issue under consideration, (iii) the versatility of genetic modeling, particularly NOIA, to dissect complex genetic architectures and (iv) the possibility of using currently available methods to address non-equilibrium multiallelic systems.
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| 8. |
- Besnier, Francois, 1980-
(författare)
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Development of Variance Component Methods for Genetic Dissection of Complex Traits
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents several developments on Variance component (VC) approach for Quantitative Trait Locus (QTL) mapping. The first part consists of methodological improvements: a new fast and efficient method for estimating IBD matrices, have been developed. The new method makes a better use of the computer resources in terms of computational power and storage memory, facilitating further improvements by resolving methodological bottlenecks in algorithms to scan multiple QTL. A new VC model have also been developed in order to consider and evaluate the correlation of the allelic effects within parental lines origin in experimental outbred crosses. The method was tested on simulated and experimental data and revealed a higher or similar power to detect QTL than linear regression based QTL mapping. The second part focused on the prospect to analyze multi-generational pedigrees by VC approach. The IBD estimation algorithm was extended to include haplotype information in addition to genotype and pedigree to improve the accuracy of the IBD estimates, and a new haplotyping algorithm was developed for limiting the risk of haplotyping errors in multigenerational pedigrees. Those newly developed methods where subsequently applied for the analysis of a nine generations AIL pedigree obtained after crossing two chicken lines divergently selected for body weight. Nine QTL described in a F2 population were replicated in the AIL pedigree, and our strategy to use both genotype and phenotype information from all individuals in the entire pedigree clearly made efficient use of the available genotype information provided in AIL.
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| 9. |
- Besnier, Francois, et al.
(författare)
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Fine mapping and replication of QTL in outbred chicken advanced intercross lines
- 2011
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Ingår i: Genetics Selection Evolution. - Paris : Springer Science and Business Media LLC. - 0999-193X .- 1297-9686. ; 43, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.METHODS: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.RESULTS: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.
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