Sequence clustering for genetic mapping of binary traits

Sequence relatedness has potential application to fine-mapping genetic variants contributing to inherited traits. We investigate the utility of genealogical tree-based approaches to fine-map causal variants in three different projects. In the first project, through coalescent simulation, we compare the ability of several popular methods of association mapping to localize causal variants in a sub-region of a candidate genomic region. We consider four broad classes of association methods, which we describe as single-variant, pooled-variant, joint-modelling and tree-based, under an additive genetic-risk model. We also investigate whether differentiating case sequences based on their carrier status for a causal variant can improve fine-mapping. Our results lend support to the potential of tree-based methods for genetic fine-mapping of disease. In the second project, we develop an R package to dynamically cluster a set of single-nucleotide variant sequences. The resulting partition structures provide important insight into the sequence relatedness. In the third project, we investigate the ability of methods based on sequence relatedness to fine-map rare causal variants and compare it to genotypic association methods. Since the true gene genealogy is unknown in reality, we apply the methods developed in the second project to estimate the sequence relatedness. We also pursue the idea of reclassifying case sequences into their carrier status using the idea of genealogical nearest neighbours. We find that method based on sequence relatedness is competitive for fine-mapping rare causal variants. We propose some general recommendations for fine-mapping rare variants in case-control association studies

Using gene genealogies to localize trait-influencing variants in diploid populations

Non UBCUnreviewedAuthor affiliation: Simon Fraser UniversityGraduat

perfectphyloR: An R Package For Reconstructing Perfect Phylogenies

Background A perfect phylogeny is a rooted binary tree that recursively partitions sequences. The nested partitions of a perfect phylogeny provide insight into the pattern of ancestry of genetic sequence data. For example, sequences may cluster together in a partition indicating that they arise from a common ancestral haplotype. Results We present an R package perfectphyloR to reconstruct the local perfect phylogenies underlying a sample of binary sequences. The package enables users to associate the reconstructed partitions with a user-defined partition. We describe and demonstrate the major functionality of the package. Conclusion The perfectphyloR package should be of use to researchers seeking insight into the ancestral structure of their sequence data. The reconstructed partitions have many applications, including the mapping of trait-influencing variants. Background A perfect phylogeny is a rooted binary tree that recursively partitions sequences. The nested partitions of a perfect phylogeny provide insight into the pattern of ancestry of genetic sequence data. For example, sequences may cluster together in a partition indicating that they arise from a common ancestral haplotype. Results We present an R package perfectphyloR to reconstruct the local perfect phylogenies underlying a sample of binary sequences. The package enables users to associate the reconstructed partitions with a user-defined partition. We describe and demonstrate the major functionality of the package. Conclusion The perfectphyloR package should be of use to researchers seeking insight into the ancestral structure of their sequence data. The reconstructed partitions have many applications, including the mapping of trait-influencing variants. &nbsp

Effects of using hydrotherapy on chronic knee osteoarthritis

Millions of people around the world suffer from chronic knee osteoarthritis, also known as degenerative joint disease. There is a breakdown of cartilage and bone in the knee joint due to this degenerative disorder. This bachelor’s thesis aims to investigate the effects of hydrotherapy on chronic knee osteoarthritis. The methodology for this bachelor’s thesis was based on a literature review. It follows the key tenets of systematic search. PubMed, ScienceDirect, Wiley Library, and manual search were all thoroughly used. For this thesis, seven articles were selected, including randomized controlled trials, meta-analyses of randomized trials, and prospective intervention studies that met the inclusion criteria. According to the relevant results, hydrotherapy has been proven to be an effective treatment for chronic knee osteoarthritis. At the end of the follow-up period of four to eight weeks, hydrotherapy reduces knee pain and increases the quality of life, muscle strength, muscle power, and muscle resistance, which leads to maintaining long-term effectiveness. Based on the findings of this bachelor's thesis, hydrotherapy appears to have a positive effect on individuals with chronic knee osteoarthritis. In addition to decreasing knee discomfort, these exercises also increase muscle strength, power, and endurance. Medical professionals may suggest hydrotherapy as a potential treatment option for patients with chronic knee osteoarthritis. Key Words: Knee, Osteoarthritis, Hydrotherapy, Physiotherapy, Aquatic therapy, Exercise, Physical Therapy, Chroni