Association study and expression analysis of GPC1 gene copy number variation in Chinese Datong yak (Bos grunniens) breed

Abstract

Copy number variations (CNVs) can cause radical changes in phenotype variation, gene expression and evolutionary adaptation, through gene dosage effects, disruption of transcript arrangement and regulatory polymorphisms. Therefore, the current study was undertaken to investigate the distribution of glypican1 (GPC1) CNVs in five domestic yak breeds, and their association growth traits and gene expression. The data were analysed using real-time quantitative PCR (qPCR). Loss and normal copy number types had a significant (p < .05) associated with body height, weight and length and chest girth than gain of copy number types. Population studies indicated that loss of copy number was more frequently observed in the Tianzhu, Gannan and Plateau yaks than the Polled and Datong yaks. We elucidated a moderately negative and highly significant (p < .005) correlation among DNA copy numbers and mRNA transcription levels of GPC1. From these results, we hypothesise that GPC1 CNVs could alter mRNA transcription levels of skeletal muscles which impact on quantitative of growth traits. Our study makes data available for breeders and genomics studies focussing on the fundamental function of GPC1 CNVs in gene expression and growth traits and presents the foundation for future molecular marker application in designing yak breeding programmes. HIGHLIGHTSThe GPC1 gene encompasses within CNVRs of yak individuals that overlap with growth traits. The copy number types of GPC1 had a significant associated with growth traits of yak breeds Negative and highly significant correlation among DNA copy numbers and mRNA transcription levels of GPC1 are obtained ARTICLE HISTORY

Copy Number Variations and Expression Levels of Guanylate-Binding Protein 6 Gene Associated with Growth Traits of Chinese Cattle

“…In beef cattle, 17 CNVs were identified to associate with seven different body traits [22]. Moreover, CNVs of ten genes (CYP4A11, GBP2, GPC1, KCNJ12, KLF3, KLF6, LEPR, MAPK10, MICALL2 and MYH3) were identified in correlation with transcript expression levels and growth traits (e.g., body length and body weight) of Chinese domestic cattle in the previous CNV studies [23][24][25][26][27][28][29][30][31][32].…”

“…The relative CNV copy numbers were defined by an evaluation of 2 × 2 −∆∆Ct with the average threshold cycles (Ct) in triplicate independent repeats, where ∆Ct = Ct target gene − Ct reference gene following the previous studies [26,30,31,[41][42][43][44][45][46]. The basic transcription factor 3 (BTF3) acted as the internal reference gene following the study of Bickhart et al [43], because neither CNVs nor segmental duplications were observed in BTF3.…”

“…Meanwhile, Angus cattle were treated as the reference sample for CNV identification. Moreover, CNV types were classified into three types that were gain type (Log 2 2 −∆∆Ct ≥ 0.5), loss type (Log 2 2 −∆∆Ct < −0.5) and medium type (−0.5 ≤ Log 2 2 −∆∆Ct < 0.5), thus, Log 2 2 −∆∆Ct was considered as CNV type value [26,30,31,[41][42][43][44][45][46]. Finally, the CNV results were summarized and displayed by Prism software (version 5.0.0).…”

“…The QTL database was downloaded from Animal Quantitative Trait Loci Database (Animal QTLdb) for the growth traits of cattle (https://www.animalgenome.org/cgi-bin/ QTLdb/BT/traitmap?trait_ID=1449&traitnm=Growth). Ten genes (CYP4A11, GBP2, GPC1, KCNJ12, KLF3, KLF6, LEPR, MAPK10, MICALL2 and MYH3) identified in relationship with growth traits by previous CNV studies [23][24][25][26][27][28][29][30][31][32] were used to overlap with QTL database on different chromosomes and to investigate the relationship between growth trait-related QTLs and ten CNV-related genes. The QTLs with candidate genes were visualized by R package RCircos (version 1.2.0) [50].…”

“…GBP6 was located on chromosome 3 with low QTL densities, but it probably collaborates with the neighboring GBP2 on affecting growth traits of cattle through potential strong linkage disequilibrium (LD) (Figure 5). Ten genes (CYP4A11, GBP2, GPC1, KCNJ12, KLF3, KLF6, LEPR, MAPK10, MICALL2 and MYH3) on five different chromosomes (i.e., 3, 6, 13, 19 and 25) from previous similar CNV studies [23][24][25][26][27][28][29][30][31][32] were used for the comparison of our results (Table 5). These candidate genes were mainly located on chromosome 3 and enriched in the Bos taurus 04920: Adipocytokine signaling pathway (p < 0.05).…”