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Fine mapping and replication of QTL in outbred chicken advanced intercross lines
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
Swedish University of Agricultural Sciences . (Department of Animal Breeding and Genetics)
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2011 (English)In: Genetics Selection Evolution, ISSN 0999-193X, E-ISSN 1297-9686, Vol. 43, 3- p.Article in journal (Refereed) Published
Abstract [en]

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.

 

Place, publisher, year, edition, pages
2011. Vol. 43, 3- p.
National Category
Genetics
Research subject
Genetics
Identifiers
URN: urn:nbn:se:uu:diva-101398DOI: 10.1186/1297-9686-43-3ISI: 000287133300001PubMedID: 21241486OAI: oai:DiVA.org:uu-101398DiVA: diva2:212905
Available from: 2009-04-24 Created: 2009-04-24 Last updated: 2016-05-18
In thesis
1. Development of Variance Component Methods for Genetic Dissection of Complex Traits
Open this publication in new window or tab >>Development of Variance Component Methods for Genetic Dissection of Complex Traits
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 32 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 646
National Category
Bioinformatics and Systems Biology
Research subject
Genetics
Identifiers
urn:nbn:se:uu:diva-101399 (URN)978-91-554-7534-5 (ISBN)
Public defence
2009-06-12, C8:305, BMC, Husargatan 3, Uppsala, 09:00 (English)
Opponent
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Available from: 2009-05-20 Created: 2009-04-24 Last updated: 2011-03-08Bibliographically approved

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Andersson, LeifCarlborg, Örjan

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