Rarefaction as a tool to determine variant diversity in monogenetic disorders

Abstract

Genetic diversity is a well-described concept within many biological disciplines. However, mathematical models determining genetic diversity are often applied within ecological disciplines and are rarely explored within the medical field. Given that genetically associated disorders and complications can occur at high frequency in developing countries, the primary aim of this study was to determine whether or not diversity theory could be applied to disease-associated variants. Two monogenic disorders were selected for this purpose one commonly observed disorder known as cystic fibrosis (CF), and one rare disorder known as metachromatic leukodystrophy (MLD). Despite being a common monogenic disorder, the clinical and molecular presentation of CF in the different population groups of South Africa is largely unknown. Thus, the medical records of 45 CF patients attending the Steve Biko Academic Hospital CF clinic were investigated to better understand the manifestation of this disorder in these patients. Additionally, molecular data was collected for both CF and MLD through published reports and analysed via the Shannon-Weaver, Simpson, Simpson Diversity, and rarefaction diversity methods. The rarefaction method was found to be the most informative measure of diversity and a potentially powerful tool to employ in the development and/or refinement of population-specific screening panels.