title: Validation of PDE9A Gene Identified in GWAS Showing Strong Association with Milk Production Traits in Chinese Holstein.
abstract: Phosphodiesterase9A (PDE9A) is a cyclic guanosine monophosphate (cGMP)-specific enzyme widely expressed among the tissues, which is important in activating cGMP-dependent signaling pathways. In our previous genome-wide association study, a single nucleotide polymorphism (SNP) (BTA-55340-no-rs(b)) located in the intron 14 of PDE9A, was found to be significantly associated with protein yield. In addition, we found that PDE9A was highly expressed in mammary gland by analyzing its mRNA expression in different tissues. The objectives of this study were to identify genetic polymorphisms of PDE9A and to determine the effects of these variants on milk production traits in dairy cattle. DNA sequencing identified 11 single nucleotide polymorphisms (SNPs) and six SNPs in 5' regulatory region were genotyped to test for the subsequent association analyses. After Bonferroni correction for multiple testing, all these identified SNPs were statistically significant for one or more milk production traits (p < 0.0001~0.0077). Interestingly, haplotype-based association analysis revealed similar effects on milk production traits (p < 0.01). In follow-up RNA expression analyses, two SNPs (c.-1376 G>A, c.-724 A>G) were involved in the regulation of gene expression. Consequently, our findings provide confirmatory evidences for associations of PDE9A variants with milk production traits and these identified SNPs may serve as genetic markers to accelerate Chinese Holstein breeding program.
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. yangshaohua309@126.com.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. yaning812@126.com.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Bi
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. xiey.300822@aliyun.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. li10020902@163.com.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. zhang62733697@163.com.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. qzhang@cau.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, China Agricultural University, Beijing 100193, China. sundx@cau.edu.cn.
authors.forename: Dong-Xiao
authors.initials: DX
authors.lastname: Sun
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D019143:Evolution, Molecular; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008892:Milk; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D019655:Quantitative Trait, Heritable; D012641:Selection, Genetic; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D015105:3',5'-Cyclic-AMP Phosphodiesterases
keywords: GWAS; PDE9A; association analysis; dairy cattle; gene expression; milk production traits