A scan for genes associated with cancer mortality and longevity in pedigree dog breeds

  • PDF / 2,342,781 Bytes
  • 13 Pages / 595.276 x 790.866 pts Page_size
  • 46 Downloads / 157 Views

DOWNLOAD

REPORT


A scan for genes associated with cancer mortality and longevity in pedigree dog breeds Aoife Doherty1 · Inês Lopes1 · Christopher T. Ford1 · Gianni Monaco1 · Patrick Guest2 · João Pedro de Magalhães1 Received: 4 March 2020 / Accepted: 29 June 2020 © The Author(s) 2020

Abstract Selective breeding of the domestic dog (Canis lupus familiaris) rigidly retains desirable features, and could inadvertently fix disease-causing variants within a breed. We combine phenotypic data from > 72,000 dogs with a large genotypic dataset to search for genes associated with cancer mortality and longevity in pedigree dog breeds. We validated previous findings that breeds with higher average body weight have higher cancer mortality rates and lower life expectancy. We identified a significant positive correlation between life span and cancer mortality residuals corrected for body weight, implying that long-lived breeds die more frequently from cancer compared to short-lived breeds. We replicated a number of known genetic associations with body weight (IGF1, GHR, CD36, SMAD2 and IGF2BP2). Subsequently, we identified five genetic variants in known cancer-related genes (located within SIPA1, ADCY7 and ARNT2) that could be associated with cancer mortality residuals corrected for confounding factors. One putative genetic variant was marginally significantly associated with longevity residuals that had been corrected for the effects of body weight; this genetic variant is located within PRDX1, a peroxiredoxin that belongs to an emerging class of pro-longevity associated genes. This research should be considered as an exploratory analysis to uncover associations between genes and longevity/cancer mortality.

Background The World Health Organization predicts that the proportion of the world’s population over the age of 60 will nearly double from 12 to 22% between 2015 and 2050 (WHO 2016). Ageing is the biggest risk factor for cancer (de Magalhães 2013), which is a leading cause of deaths worldwide. For example, in 2018, approximately 18.1 million new cancer cases and 9.6 million cancer-related deaths were recorded globally (Bray et al. 2018). The biological complexity of human conditions such as cancer mortality and longevity has stimulated an intense search for experimental models Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0033​5-020-09845​-1) contains supplementary material, which is available to authorized users. * João Pedro de Magalhães [email protected] 1



Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK



School of Biology, Medical and Biological Sciences Building, University of St. Andrews, North Haugh, St. Andrews KY16 9TF, UK

2

that closely resemble the pathophysiological aspects of these processes (Kuningas et al. 2008; Alvarez 2014; de Magalhães 2014). As demonstrated previously for cancer and other traits (for example, Sutter et al. 2007; Paoloni et al. 2009; Pinho et al. 2012; Fenger et al. 2014;