Heterozygosity and homozygosity regions affect reproductive success and the loss of reproduction: A case study with litter traits in pigs

Runs of heterozygosity (ROHet) and homozygosity (ROH) harbor useful information related to traits of interest. There is a lack of investigating the effect of ROHet and ROH on reproductive success and the loss of reproduction in mammals. Here, we detected and characterized the ROHet and ROH patterns in the genomes of Chinese indigenous pigs (i.e., Jinhua, Chun'an, Longyou Black, and Shengxian Spotted pigs), revealing the similar genetic characteristics of indigenous pigs. Later, we highlighted the underlying litter traits-related ROHet and ROH using association analysis with linear model in these four indigenous pig breeds. To pinpoint the promising candidate genes associated with litter traits, we further in-depth explore the selection patterns of other five pig breeds (i.e., Erhualian, Meishan, Minzhu, Rongchang, and Diqing pigs) with different levels of reproduction performance at the underlying litter traitsrelated ROHet and ROH using FST and genetic diversity ratio. Then, we identified a set of known and novel candidate genes associated with reproductive performance in pigs. For the novel candidate genes (i.e., CCDC91, SASH1, SAMD5, MACF1, MFSD2A, EPC2, and MBD5), we obtained public available datasets and performed multi-omics analyses integrating transcriptome-wide association studies and comparative single-cell RNA-seq analyses to uncover the roles of them in mammalian reproductive performance. The genes have not been widely reported to be fertility-related genes and can be complementally considered as prior biological information to modify genomic selections models that benefits pig genetic improvement of litter traits. Besides, our findings provide new insights into the function of ROHet and ROH in mammals. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Automated summary

This study investigated the effects of ROHet and ROH on reproductive traits in pigs and identified candidate genes associated with reproductive performance. Through multi-omics analysis, the roles of these genes in mammalian reproductive performance were revealed. The findings are of significant importance for genetic improvement and understanding the function of ROHet and ROH in mammals.