Genome-wide association study for numbers of vertebrae in Dezhou donkey population reveals new candidate genes

Numbers of vertebrae is an important economic trait associated with body size and meat productivity in animals.However,the genetic basis of vertebrae number in donkey remains to be well understood.The aim of this study was to identify candidate genes affecting the number of thoracic(TVn)and the number of lumbar vertebrae(LVn)in Dezhou donkey.A genome-wide association study was conducted using whole genome sequence data imputed from low-coverage genome sequencing.For TVn,we identified 38 genome-wide significant and 64 suggestive SNPs,which relate to 7 genes(NLGN1,DCC,SLC26A7,TOX,WNT7A,LOC123286078,and LOC123280142).For LVn,we identified 9 genome-wide significant and 38 suggestive SNPs,which relate to 8 genes(GABBR2,FBXO4,LOC123277146,LOC123277359,BMP7,B3GAT1,EML2,and LRP5).The genes involve in the Wnt and TGF-βsignaling pathways and may play an important role in embryonic development or bone formation and could be good candidate genes for TVn and LVn.

Quantitative trait loci for the number of vertebrae on Sus scrofa chromosomes 1 and 7 independently influence the numbers of thoracic and lumbar vertebrae in pigs

Although quantitative trait loci（QTLs） for number of thoracic-lumbar vertebrae have been identified on Sus scrofa chromosomes（SSCs） 1 and 7, the influence of these QTLs on the thoracic and lumbar vertebrae is not clear. The aim of this study was to identify single nucleotide polymorphisms（SNPs） associated with total number of thoracic-lumbar vertebrae and for each trait（number of thoracic and lumbar vertebrae） separately. A total of 581 individuals from an F2 Large White×Minzhu population were genotyped using an SNP60 K chip. Performing a genome-wide association study（GWAS） for total number of thoracic-lumbar vertebrae, 38 significant SNPs were identified in two QTL regions located on SSC1 and SSC7. Performing a GWAS for number of thoracic vertebrae only, 72 significant SNPs were located on SSC7. While performing a GWAS for number of lumbar vertebrae only, 17 significant SNPs were identified on SSC1. Gene mining suggested that the gene encoding orphan nuclear receptor, germ cell nuclear factor（NR6A1） on SSC1 was a strong candidate affecting the number of lumbar vertebrae in pigs. Additionally, genes encoding vertnin（VRTN）, prospero homeobox 2（PROX2）, Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog（FOS）, and transforming growth factor beta 3（TGFB3） may be important candidates affecting the number of thoracic vertebrae in pigs. QTLs on SSC1 and SSC7 independently influenced the numbers of thoracic and lumbar vertebrae. These results shed light on the complex genetic background of vertebrae development in pigs.

Genome-wide search for candidate genes determining vertebrae number in pigs

Longer porcine carcasses may be expected to have more vertebrae. Therefore, vertebrae number in pigs is an economically important trait. To examine the genetic basis of this trait, we genotyped 578 F-2 Large White x Minzhu pigs using the Porcine SNP60K BeadChip. A genome-wide association study (GWAS) identified 36 significant single nucleotide polymorphisms (SNPs) on the chromosomes SSC1 (294.28-300.32 Mb) and SSC7 (102.22-109.39 Mb). A 6.04-Mb region that contained all 13 significant SNPs on SSC1 also contained the gene NR6A1, previously reported to influence the number of vertebrae in pigs. However, the reported putative casual mutation of NR6A1 c. 748C > T showed no genome-wide significant association with the trait, suggesting it was not a causal mutation in our population. The remaining 23 significant SNPs on SSC7 were concentrated in a 7.17-Mb region, which was within a quantitative trait locus interval for number of vertebrae. TMED10 was the closest gene to the most significant SNP and might be a candidate. Haplotype sharing and block analysis refined the QTL to an interval of about 3 Mb containing 29 candidate genes. Of these 29 genes, the previously reported possible casual mutation of VRTN g. 19034A > C was not found to be a causal mutation in our population. Exploration of these genes via additional genetic and functional studies in mammals revealed that TGF beta 3 could be a good candidate on SSC7. A mutation of TGF beta 3 c. 1749G > A was detected by GWAS and could be proposed as a candidate causal mutation, or as closely linked to a causal mutation, for the number of vertebrae in pigs.