Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side

Rohrer and Nonneman Genet Sel Evol (2017) 49:4 DOI 10.1186/s12711-016-0282-1 RESEARCH ARTICLE Ge n e t i c s Se l e c t i o n Ev o l u t i o n Open Access Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side Gary A. Rohrer* and Dan J. Nonneman Abstract Background: Number of functional teats is an important trait in commercial swine production. As litter size increases, the number of teats must also increase to supply nutrition to all piglets. Therefore, a genome-wide association analysis was conducted to identify genomic regions that affect this trait in a commercial swine population. Genotypic data from the Illumina Porcine SNP60v1 BeadChip were available for 2951 animals with total teat number (TTN) records. A subset of these animals (n = 1828) had number of teats on each side recorded. From this information, the following traits were derived: number of teats on the left (LTN) and right side (RTN), maximum number of teats on a side (MAX), difference between LTN and RTN (L − R) and absolute value of L − R (DIF). Bayes C option of GENSEL (version 4.61) and 1-Mb windows were implemented. Identified regions that explained more than 1.5% of the genomic variation were tested in a larger group of animals (n = 5453) to estimate additive genetic effects. Results: Marker heritabilities were highest for TTN (0.233), intermediate for individual side counts (0.088 to 0.115) and virtually nil for difference traits (0.002 for L − R and 0.006 for DIF). Each copy of the VRTN mutant allele increased teat count by 0.35 (TTN), 0.16 (LTN and RTN) and 0.19 (MAX). 15, 18, 13 and 18 one-Mb windows were detected that explained more than 1.0% of the genomic variation for TTN, LTN, RTN, and MAX, respectively. These regions cumulatively accounted for over 50% of the genomic variation of LTN, RTN and MAX, but only 30% of that of TTN. Sus scrofa chromosome SSC10:52 Mb was associated with all four count traits, while SSC10:60 and SSC14:54 Mb were associated with three count traits. Thirty-three SNPs accounted for nearly 39% of the additive genetic variation in the validation dataset. No effect of piglet sex or percentage of males in litter was detected, but birth weight was positively correlated with TTN. Conclusions: Teat number is a heritable trait and use of genetic markers would expedite selection progress. Exploiting genetic variation associated with teat counts on each side would enhance selection focused on total teat counts. These results confirm QTL on SSC4, seven and ten and identify a novel QTL on SSC14. Background Genetic selection for increased litter size in pigs has resulted in many sows giving birth to more live piglets than they are capable of nursing. The competition for teats leads to increased pre-weaning mortality due to crushing and starvation [1]. Therefore, selection on teat *Correspondence: U.S. Meat Animal Research Center, USDA, Agricultural Research Service, Clay Center, NE, USA number has begun to ensure that sows can nurture all of their piglets [2]. Number of piglets born in the largest 25% of litters in purebred Danish Large White and Landrace exceeded 18 in sows born in 2009 [3], which indicates that the number of piglets born was larger than the number of teats for a substantial proportion of litters. Number of teats in pigs is a variable and heritable trait. Number of teats differs between breeds, for example [4–6], and is moderately heritable [7–10]. Numerous © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Rohrer and Nonneman Genet Sel Evol (2017) 49:4 genome scans have been conducted for number of teats in pigs (QTLdb; http://www.animalgenome.org/cgi-bin/ QTLdb/SS/index), yet to date, few causative genes (or variants) have been discovered. Most early studies used crosses between Meishan and occidental F2 swine populations and detected the largest QTL on either Sus scrofa chromosome SSC1 or 7 [6, 11, 12]. These QTL on SSC1 and seven coincided with QTL for vertebra number or carcass length, which led to the hypothesis that vertebra and teat number were controlled by common genes [6, 13]. Putative causative genetic variations for vertebra number in the NR6A1 gene [14] on SSC1 and the VRTN gene [15] on SSC7 have been associated with variation in teat number in Meishan × occidental cross populations [6, 12]. VRTN has also been associated with teat number in commercial swine populations [13, 16, 17]. While the presence of mammary glands is a defining character of species in the class Mammalia, location and number of mammary glands across species are quite variable [18]. Mammary glands commonly exhibit bilateral symmetry [19] and variation in number of functional mammary glands within a species is relatively low. Among the farmed artiodactyl species, only pigs have thoracic/pectoral and abdominal mammary glands, in addition to the inguinal mammary glands that are present in all artiodactyls. Mice are a common model mammalian species, yet they lack abdominal mammary glands and male pups do not have any visible teats at all. A greater understanding of mammary gland development is necessary to fully exploit the genetic variation present in pigs. In early embryonic development of mammals, three separate streaks of multilayered surface ectoderm will form a mammary line that spans from the axilla to the inguen (groin) of the embryo. Mammary line cells will either group together or regress and eventually form mammary rudiments, which can later develop into functional mammary glands. As the gland continues to form, milk canals and nipples develop, completing the process. The developmental process in mice suggests that each pair of mammary glands develops at its own pace and may be regulated by different mechanisms [19, 20]. While male mouse embryos develop mammary rudiments, these structures typically regress prior to birth [19]. Studies have shown that spontaneous events and genetic mutations can result in bilateral asymmetry of mammary development in mice. Fernández et al. [9] speculated that the observed fluctuating asymmetry in the number of nipples in pigs may be caused by disruption of co-adaptive gene complexes, which results in developmental instability. Fluctuating asymmetry has been studied in numerous species and it is often Page 2 of 11 associated with increased stress or disease during critical development t (...truncated)