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A genetic algorithm based method for stringent haplotyping of family data
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, The Linnaeus Centre for Bioinformatics.ORCID iD: 0000-0002-2722-5264
2009 (English)In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 10, article id 57Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 10, article id 57
National Category
Bioinformatics and Systems Biology
Research subject
Genetics
Identifiers
URN: urn:nbn:se:uu:diva-101397DOI: 10.1186/1471-2156-10-57ISI: 000270360900001PubMedID: 19761594OAI: oai:DiVA.org:uu-101397DiVA, id: diva2:212904
Note

Manuscripttitle in list of papers in thesis: A genetic algorithm based haplotyping method provides better control on haplotype error rate

Available from: 2009-04-24 Created: 2009-04-24 Last updated: 2017-12-13Bibliographically approved
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. p. 32
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
Supervisors
Available from: 2009-05-20 Created: 2009-04-24 Last updated: 2011-03-08Bibliographically approved

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Besnier, FrancoisCarlborg, Örjan

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