Modelización de la variabilidad mutacional según la edad de los progenitores en dos especies de mamíferos

Student thesis: Doctoral thesis

Abstract

The relevance of new mutations on the infinitesimal genetic variability remains out of any doubt. Nevertheless, biological mechanisms underlying this source of genetic variance are poorly understood, even when some factors such as parents' age may play a key role. Unfortunately, we lack of appropriate analytical approaches to investigate these phenomena, this shortage being specially dramatic when departing from standard experimental designs. This Ph.D. dissertation precisely focuses on the development of a statistical methodology for mutation analysis within the context of mixed linear models. This approach accounts for the genetic background of quantitative traits by making inference on two independent compounds, the additive genetic variability holding in the founder generation, and the new additive genetic variability originated by new mutations across the whole pedigree. Moreover, the mutational component differentiates between paternal and maternal origins, and may increase (or decrease) depending on parents' age. In order to validate this methodology, two different data sets were analyzed. The first accounted for weaning weight from 12,644 C57BL/6J mice, whereas the other one relied on the birth weight of 8,130 beef calves of the Bruna dels Pirineus breed. The different parameterizations were compared on the basis of two well known comparison criteria within the context of Bayesian inference, the deviance information criterion and the Bayes factor. The analyses revealed a very similar behavior in mice and calves. Both paternal and maternal variance component were small and different from zero. Although paternal mutational variance seemed slightly bigger than the maternal one, the analyses did not reveal statistical departures. Nevertheless, clearly different patterns were observed when considering parents' age. Both C57BL/6J mice and Bruna dels Pirineus calves evidenced a relevant gain of the parental mutation variance with sire's age, even reaching a 50% increase during the first age of life. On the contrary, the maternal mutational variance was not influenced by mother's age and kept stable along reproductive life. As a whole, these results must be viewed as a relevant advance within the research framework of mutations in mammals, they contributing remarkable implications for both
Date of Award13 Dec 2017
Original languageSpanish
Awarding Institution
  • Universitat Autònoma de Barcelona (UAB)
SupervisorJoaquin Casellas Vidal (Director)

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