1. A network algorithm for the X chromosomal exact test for Hardy-Weinberg equilibrium with multiple alleles
- Author
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Leonardo Ortoleva, Jan Graffelman, Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, and Universitat Politècnica de Catalunya. COSDA-UPC - COmpositional and Spatial Data Analysis
- Subjects
Male ,0106 biological sciences ,0301 basic medicine ,Matemàtiques i estadística::Matemàtica aplicada a les ciències [Àrees temàtiques de la UPC] ,network algorithm ,Numerical analysis--Simulation methods ,Hardy-Weinberg equilibrium ,01 natural sciences ,X chromosome ,Reduction (complexity) ,Gene Frequency ,Resampling ,Network algorithm ,Mathematics ,RESOURCE ARTICLES ,92 Biology and other natural sciences::92B Mathematical biology in general [Classificació AMS] ,Hardy–Weinberg principle ,Exact test ,indel ,Microsatellite ,Female ,Algorithms ,permutation test ,Biotechnology ,microsatellite ,Biomatemàtica ,Biology ,010603 evolutionary biology ,Matemàtiques i estadística::Anàlisi numèrica [Àrees temàtiques de la UPC] ,03 medical and health sciences ,Genetics ,Humans ,Hardy–Weinberg equilibrium ,Resource Article ,Permutation test ,65 Numerical analysis::65C Probabilistic methods, simulation and stochastic differential equations [Classificació AMS] ,Indel ,Allele ,Alleles ,Ecology, Evolution, Behavior and Systematics ,Biomathematics ,Anàlisi numèrica ,Discrete mathematics ,Chromosomes, Human, X ,Models, Genetic ,Molecular and Statistical Advances ,030104 developmental biology - Abstract
Statistical methodology for testing the Hardy-Weinberg equilibrium at X chromosomal variants has recently experienced considerable development. Up to a few years ago, testing X chromosomal variants for equilibrium was basically done by applying autosomal test procedures to females only. At present, male alleles can be taken into account in asymptotic and exact test procedures for both the bi-and multiallelic case. However, current X chromosomal exact procedures for multiple alleles rely on a classical full enumeration algorithm and are computationally expensive, and in practice not feasible for more than three alleles. In this article, we extend the autosomal network algorithm for exact Hardy-Weinberg testing with multiple alleles to the X chromosome, achieving considerable reduction in computation times for multiallelic variants with up to five alleles. The performance of the X chromosomal network algorithm is assessed in a simulation study. Beyond four alleles, a permutation test is, in general, the more feasible approach. A detailed description of the algorithm is given, and examples of X chromosomal indels and microsatellites are discussed. This work was supported by grant RTI2018‐095518‐B‐C22 (MCIU/AEI/FEDER) of the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund, and by grant R01 GM075091 from the United States National Institutes of Health. We thank three anonymous reviewers whose comments have helped us to improve the article.
- Published
- 2020
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