Rapid Communication: High-resolution quantitative trait loci analysis identifies LTBP2 encoding latent transforming growth factor beta binding protein 2 associated with thoracic vertebrae number in a large F2 intercross between Landrace and Korean native pigs1

Abstract

Number of vertebrae is associated with body size and meat productivity in pigs. The aim of this study was to identify QTL and associated positional candidate genes affecting the number of thoracic vertebrae (THO). A genomewide association study was conducted in a large resource population derived from an F intercross between Landrace and Korean native pigs using the Porcine SNP 60K BeadChip and the genomewide complex trait analysis (GCTA) program based on a linear mixed-effects model. A total of 38,385 SNP markers from 1,105 F progeny were analyzed for the THO trait after filtering for quality control. A total of 90 genomewide significant SNP markers ( < 1.30 × 10) on SSC 7 covering a 20-Mb region were identified for THO in this study. Several previous studies also mapped QTL for vertebral numbers in this region. The strongest association signals were detected at ASGA0035500 (-value = 4.46 × 10; 103,574,383 bp) and DIAS0000795 (-value = 4.46 × 10; 103,594,753 bp). The QTL region on SSC 7 for THO encompasses and , which are previously described candidate genes for vertebral number variation. To refine the QTL region, a haplotype-based linkage and linkage disequilibrium (LALD) analysis using the DualPHASE program was applied because subsequent conditional association and haplotype block analyses could not resolve the region that contains the 2 loci. The LALD analysis refined the critical region to a 533.9-kb region including ; was located outside the critical region. The gene encoding latent transforming growth factor beta binding protein 2 is involved in bone metabolisms. Based on these data, we propose as a positional candidate gene for THO in pigs. After further functional studies and verification of the association in other independent populations, these results could be useful for optimizing breeding programs that improve THO and other economically important traits in pigs.

Polymorphism of VRTN Gene g.20311_20312ins291 Was Associated with the Number of Ribs, Carcass Diagonal Length and Cannon Bone Circumference in Suhuai Pigs

“…On the one hand, it is possible that variants on LVN and TVN determine the BL. On the other hand, there may be other candidate genes including Hox A, Hox B, LTBP2, and TGFβ3 that affect the vertebral numbers of pigs [13][14][15][16].…”

“…A new candidate gene, LTBP2 (latent transforming growth factor binding protein 2), was found to affect RIB in 596 Large White × Chinese Min pigs F 2 intercrosses [14]. In addition, a missense mutation (c.4481 A > C) in the LTBP2 gene was associated with TVN in 1105 F 2 animals of a Landrace crossed with Korean native pigs [15]. Moreover, the 105179474 G > A loci in TGFβ3 (transforming growth factor beta 3) gene on SSC7 was found to be associated with RIB and TLVN in the F 2 resource population of Large White × Min pigs (n = 567) [16].…”

Genome-Wide Association Analysis Identified BMPR1A as a Novel Candidate Gene Affecting the Number of Thoracic Vertebrae in a Large White × Minzhu Intercross Pig Population

“…However, when we considered the effect of the NV, our GWAS for the NTV detected 31 SNPs with genome-wide associations and located within a 22.93-Mb region (from 80.26 to 103.19 Mb) on SSC7, one chromosome-wide association SNP at 28.24 Mb on SSC12, and five chromosome-wide association SNPs within a 104.12-kb region (from 87.80 to 87.90 Mb) on SSC14. The 22.93-Mb region on SSC7 also included a previously reported 951-kb fragment consisting of important candidate genes—namely VRTN , LTBP2 , and “Visual System Homeobox 2” ( VSX2 ) [ 13 , 15 , 16 , 17 , 24 , 25 , 26 ]. Among these candidates, VRTN g.19034 A > C [ 17 ] and LTBP2 c.4481A > C [ 15 ] have been regarded as good candidate causal mutations.…”

“…All the animals were genotyped for “Vertebrae Development Associated” ( VRTN ) g.19034 A>C, g.20311_20312ins291 [ 18 ] and “Latent Transforming Growth Factor Beta-binding Protein 2” ( LTBP2 ) c.4481A > C [ 15 ]. Through comparison with the Sus scrofa genetic variant database in Ensembl ( ), 37 missense or splice variants in a previously reported 951-kb interval on SSC7 [ 16 ] were obtained, and the animals were then genotyped for these variants as well.…”

“…Many studies have shown that the NTV is a polygenic trait influenced by many different quantitative trait loci (QTL) on Sus scrofa Chromosomes (SSCs) 1, 2, 4, 7, 11, 16, and 18 [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Genome-wide association studies (GWASs) in recent years have shown that the major genes controlling the NTV in pigs are concentrated on SSC7 [ 15 , 16 , 17 ]. It is known that the total number of vertebrae is determined during development by the number of somites, developing from the presomitic mesoderm (PSM) via the Notch, FGF, Wnt, and Retinoic acid pathways.…”