IGF1R and LOX Modules Are Related to Antler Growth Rate Revealed by Integrated Analyses of Genomics and Transcriptomics

SIMPLE SUMMARY: Previous studies on the growth rate of antlers are inconsistent, and few genes significantly related to growth traits have been obtained, which may be caused by the low-quality genome of sika deer or by the traditional genome-wide association analysis method being singly used. In this study, we conducted an integrated analysis of genome-wide association analysis and weighted gene co-expression network analysis using resequencing data identified in our previous analysis, which used antler weight and transcriptome sequencing data of faster- vs. slower-growing antlers of sika deer. The results show that a total of 49 genes related to antler growth rate were identified, and most of those genes were enriched in the IGF1R (insulin-like growth factor 1 receptor) and LOX (lysyl oxidase) modules. A gene regulation network of antler growth rate through the IGF1R pathway was constructed. We believe that our findings in the present study can provide further insight into revealing the molecular mechanism underlying the regulation of the tissue that can grow quickly without transforming into a tumor. Furthermore, the results of this study may be applied for increasing antler output for the deer industry. ABSTRACT: Deer antlers are organs of bone and have an extremely rapid growth rate. Thus far, the molecular mechanism underlying rapid antler growth has not been properly elucidated, and key genes driving this growth rate have not been fully identified. In this study, based on the newly assembled high-quality sika deer genome, we conducted an integrated analysis of genome-wide association analysis (GWAS) and weighted gene co-expression network analysis (WGCNA) using genome resequencing data from our previous GWAS, with weight and transcriptome sequencing data of faster- vs. slower-growing antlers of sika deer. The expressions of key genes were verified using Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) in different tissue zones of the antler growth center, different types of sika deer tissues and antler tissues collected from faster and slower growth rates. The results show that a total of 49 genes related to antler growth rate were identified, and most of those genes were enriched in the IGF1R and LOX modules. The gene regulation network of antler growth rate through the IGF1R pathway was constructed. In conclusion, the integration of GWAS and WGCNA analyses had great advantages in identifying regulatory genes of complex antler growth traits over using singular methods individually, and we believe that our findings in the present study can provide further insight into unveiling the mechanism underlying extraordinary fast antler growth rate in particular, as well as the regulatory mechanism of rapid tissue proliferation in general.