Copy Number Variations of KLF6 Modulate Gene Transcription and Growth Traits in Chinese Datong Yak (Bos Grunniens)

SIMPLE SUMMARY: Associating copy number variations (CNVs) with growth and gene expression are a powerful approach for identifying genomic characteristics that contribute to phenotypic and genotypic variation. A previous study using next-generation sequencing illustrated that the KLF6 gene resides within CNV regions (CNVRs) of yak populations that overlap with quantitative trait loci (QTLs) of meat quality and growth. As a result, this research aimed to assess the prevalence of KLF6 CNVs in five Chinese domestic yak breeds and to determine their association with growth and gene expression level. These results confirmed the significant function of KLF6 CNVRs in determining the mRNA expression levels of this gene in Bos grunniens skeletal muscles and the expression of this gene affects quantitative growth traits in yak populations through the negative relationship between DNA copy numbers and gene expression. This work provides the first observation of the biological role of KLF6 CNVs in Chinese Datong yak breeds and might therefore provide a novel opportunity to utilize data on CNVs in designing molecular markers for the selection of animal breeding programs for larger populations of various yak breeds. ABSTRACT: Copy number variation (CNV) is a significant marker of the genetic and phenotypic diversity among individuals that accounts for complex quantitative traits of phenotype and diseases via modulating gene dosage and disrupting coding regions in the genome. Biochemically, Kruppel-like factor 6 (KLF6) genes plays a significant role in the regulation of cell differentiation and proliferation and muscle development. The aim of this study was to detect the distributions of KLF6 copy number variations (CNVs) in five breeds of domestic yak and to explore their effect on growth traits and gene expression. The data were analyzed by real-time quantitative PCR (qPCR). Our results elucidated that a decreased CNV in the KLF6 gene is more highly associated (p < 0.05) with various growth traits than increased or normal CNVs in six-month-old and five-year-old Datong yak. Nevertheless, negative correlations between the DNA copy number and KLF6 gene expression were observed in the skeletal muscle of adult Datong yak. These results suggest that CNVs of the KLF6 gene could be crucial genomic markers for growth phenotypes of Chinese Datong yak breeds and this finding constitutes the first evidence of the biological role of KLF6 CNVs in Chinese Datong yak breeds.