- Genome-wide association analyses identify known and novel loci for teat number in Duroc pigs using single-locus and multi- locus models. - Previous studies have reported the strong effect of an insertion mutation in the Vertebrae Development Associated ( VRTN ) gene on Sus scrofa chromosome 7 (SSC7) that increased the number of thoracic vertebrae and teat number in pigs. - We used genome-wide association studies (GWAS) to map genetic markers and genes associated with teat number in two Duroc pig populations with different genetic backgrounds. - We also performed association tests between the VRTN insertion and teat number in the same populations.. - Results: A total of 97 SNPs were found to be associated with teat number. - Moreover, 26 SNPs were newly found by multi-locus methods to be associated with teat number. - Notably, we detected one consistent quantitative trait locus (QTL) on SSC7 for teat number using single-locus and meta-analysis of GWAS and the top SNP (rs692640845) explained 8.68% phenotypic variance of teat number in the Canadian Duroc pigs. - The associations between the VRTN insertion and teat number in two Duroc pig populations were substantially weaker. - Further analysis revealed that the effect of VRTN on teat number may be mediated by its LD with the true causal mutation.. - Conclusions: Our study suggested that VRTN insertion may not be a strong or the only candidate causal mutation for the QTL on SSC7 for teat number in the analyzed Duroc pig populations. - The identified SNPs will be useful for the genetic improvement of teat number in pigs by assigning higher weights to associated SNPs in genomic selection.. - Teat number is an important trait for a sow to rear a large number of piglets. - Therefore, applying selection on teat number is a useful breeding strategy to improve the reproductive performance of sows in the pig industry [2]. - Previous genome-wide association studies (GWAS) in a cross between Landrace and Ko- rean pigs [3], Duroc pigs [4], Erhualian pigs [5], and Large White pigs [7] found that several single nucleotide polymorphisms (SNPs) near or within the Vertebrae De- velopment Associated ( VRTN ) gene on Sus scrofa chromosome 7 (SSC7) were associated with teat number.. - [12] showed that the 291 bp insertion of VRTN has associations with ver- tebral number, carcass length, and teat number in Chin- ese indigenous Erhualian pigs, Duroc, Landrace, and Large White pigs. - These findings suggested that the 291 bp insertion (g ins291) of the VRTN gene seemingly has pleiotropic effects on teat number and several other traits in pigs.. - Teat number is a typical polygenic quantitative trait.. - Almost all GWAS for teat number to date employed single-locus models, such as single variant mixed linear model (MLM . - In this study, we dissected the underlying genetic architecture of teat number in two Duroc pig popula- tions with different genetic backgrounds using single- and multi-locus GWAS in a total 5356 Duroc pigs. - 20312ins291 insertion of the VRTN gene, we also specif- ically tested its association with teat number.. - The descriptive statistics of teat number for the 5356 pigs are listed in Table 1. - In brief, the average numbers (mean ± standard deviation) of teat number in the American and Canadian Duroc pigs were and respectively. - No significant difference in mean teat number was found between the two Duroc pig populations. - The coefficient of variation (CV) values for teat number in the American and Canadian Duroc pigs were 10.64 and 10.44%, respectively. - the SNP-based heritability ( h 2 [standard error]) of teat number were in the American Duroc pigs and in the Canadian Duroc pigs.. - Single-locus and meta-analysis GWAS for teat number Significant SNPs detected by single-locus GWAS (MLM) for teat number of the American and Canadian Duroc pigs are shown in Table 2 and Table 3, and Fig. - In brief, 28 SNPs were identified as associated with teat number with the threshold of P = 1.21E-04. - Of these, 27 SNPs were previ- ously highlighted in the single-locus GWAS of the two Duroc pigs and one SNP on SSC18 was newly found to be associated with teat number by meta-analysis of GWAS. - Notably, we detected one consistent QTL (rs692640845) on SSC7 for teat number using single- locus and meta-analysis of GWAS.. - Multi-locus GWAS for teat number. - In the American. - Table 1 Summary statistics of teat number in two Duroc pig populations. - American Duroc Teat number . - Canadian Duroc Teat number . - Duroc pigs, the four multi-locus GWAS identified 33 teat-number-associated SNPs with at LOD score >. - In the Canadian Duroc pigs, the four multi- locus GWAS identified a total of 26 teat-number- associated SNPs at LOD score >. - Table 2 Significant SNPs associated with teat number in American Duroc pigs SSC a SNP ID Position. - The bold data represent the model that explained largest phenotypic variance e Underline indicates that the gene was newly identified as a candidate for teat number f The SNP located upstream/downstream of the nearest gene. - Table 3 Significant SNPs associated with teat number in Canadian Duroc pigs. - 36.46 and explained the 9.31% of phenotypic variance of teat number, implying its strong influence on the teat number trait. - Moreover, marker rs345307243 on SSC14, which was found in both populations, was associated with teat number based on FASTmrEMMA and ISIS EM-BLASSO. - Notably, the results of multi-locus GWAS for teat number in both Duroc pig populations revealed the 26 SNPs newly associated with teat number that were not pre- viously known (Additional file 7: Table S4).. - Effects of the QTL on SSC7 in two Duroc pig populations Associations between the VRTN mutation and teat num- ber in the two Duroc pig populations were analyzed using single-locus model (MLM), which revealed that no associ- ation ( P = 0.032) between the VRTN genotype and teat number in the American Duroc pigs. - Although the VRTN insertion was strongly associated with teat number in the Canadian Duroc pigs, the effect was weaker than the top SNP (rs692640845) identified in this population (Fig. - 6b and c, association between the significant SNPs in this QTL region and teat number was greatly diminished in the presence of the VRTN mutation or rs692640845 as a covariate. - Table 3 Significant SNPs associated with teat number in Canadian Duroc pigs (Continued). - In the Canadian Duroc pigs, the mutant allele ( ins ) had an increasing ef- fect relative to the wild-type allele ( del ) on teat number.. - The average teat number of the ins/ins pigs was which was 0.88 more than that of del/del individ- uals with average teat number of . - In the American Duroc pigs, the average teat number of ins/ins and del/del pigs was and respectively. - These find- ings suggested that VRTN may not be a strong or the only candidate causal gene for teat number in the two pig populations.. - Gene set enrichment analysis re- vealed many terms might be relevant with teat number (Additional file 10: Table S7). - and Apoptosis Resistant E3 Ubiqui- tin Protein Ligase 1 ( AREL1 ) were further highlighted as promising candidates for teat number in pigs.. - In this study, we carried out GWAS of teat number with a panel of 5356 Duroc pigs using one single- locus model (MLM) and four multi-locus models (mrMLM, FASTmrMLM, FASTmrEMMA and ISIS EM-BLASSO). - 2 Manhattan plots of the single-locus GWAS for teat number in American (a) and Canadian Duroc pigs (b). - The dashed lines indicate the thresholds for teat number in American ( P = 1.08E-04) and Canadian ( P = 8.35E-05) Duroc pigs, respectively. - The findings pro- vide new insight into further deciphering the genetic architecture of teat number in pigs. - 3 Manhattan plots of the four multi-locus GWAS for teat number in American Duroc pigs. - Superiority of multi-locus GWAS and new SNPs for teat number. - 4 Manhattan plots of the four multi-locus GWAS for teat number in Canadian Duroc pigs. - 6 Regional plots of VRTN mutation and rs692640845 at Mb on SSC7 for teat number in Canadian Duroc pigs. - The plots of a and b shows the association results for teat number before and after conditional analysis on VRTN mutation. - The plots of a and c shows the association results for teat number before and after conditional analysis on rs692640845. - To improve the efficiency of the study, we performed multi-locus GWAS on teat number of the two Duroc pig populations. - The combination of single- locus and multi-locus GWAS detected additional SNPs in comparison with that using only one model, i.e., 33 SNPs were associated with teat number by mrMLM, FASTmrMLM, FASTmrEMMA, and ISIS EM-BLASSO, and two SNPs identified by MLM were also highlighted in the American Duroc pigs. - 36.46 accounted for 9.31% phenotypic variance of teat number. - Many QTLs or SNPs related to teat number have been identified using linkage mapping and GWAS in pigs [2, 33–35]. - To evaluate whether SNPs associated with the teat number in the present study replicate any previously known QTLs, we compared the significant SNPs from this study with SNPs in the pigQTLdatabase (https://. - The 28 SNPs newly associated with teat number were not found in any previously known QTLs (Additional file 7: Table S4) using single- locus, multi-locus, and meta-analysis methods, and the genes nearest to these SNPs were considered to be promising candidates for teat number in pigs (under- lined gene names in Table 2 and Table 3). - These SNPs each ex- plained a small proportion of the phenotypic variance of teat number ranged from 0.17 to 3.59%, suggesting that sample size and multi-locus methods of GWAS may have played an important role in detecting SNPs with small effects on teat number than previous studies that used smaller sample size and single-locus models.. - Consistent QTL for teat number on SSC7 detected by GWAS. - The 27 SNPs associated with teat number were located in a consistent QTL hotpot on SSC7 between 96.1 Mb and 98.2 Mb ( Sscrofa 11.1). - However, they did not directly perform association analyses between VRTN mutation and teat number. - Here, we examined VRTN mutation genotypes in a larger sample size (3521 Duroc pigs) than in a previous study [12] and conducted associ- ation analysis between VRTN mutation and teat number.. - Association analysis between VRTN mutation and teat number in the present two Duroc pig populations dem- onstrated that VRTN mutation was not the peak site for teat number. - Further analysis implied that the effect of VRTN on teat number may be induced by the presence of high LD with the true causal mutation in this QTL region. - Recently, VRTN has been characterized as a novel DNA-binding transcrip- tion factor and is essential for the development of thor- acic vertebrae at somitogenesis stage in pigs and mice Table 4 The frequencies and associations of the VRTN mutation (g ins291) with teat number in two Duroc pig. - a Frequency of each genotype and the mutant allele (ins) associated with increased teat number at the VRTN mutation site are shown in this table. - In an attempt to uncover the promising candidate genes of teat number for this con- sistent QTL, we searched several genes based on the LD decay distance of the SNPs in the QTL region. - [6] have previously reported YLPM1 as a candidate gene for teat number in a commercial pig line.. - However, a previous study reported that many SNPs within or near the PTGR2 and AREL1 genes showing the largest contribu- tions to the genomic heritability and prediction accuracy for teat number in a Duroc pig populations [14]. - In fur- ther analyses, large-scale transcriptome data and prote- ome data, as well as laboratory functional experiments, are necessary to pinpoint the causal gene(s) for nipple formation and teat number.. - In conclusion, 37 and 52 SNPs were found to be associ- ated with teat number by only using single-locus and multi-locus methods, respectively, combining the results of both Duroc pigs. - Furthermore, the associations between the VRTN inser- tion and teat number in two Duroc pig populations were substantially weaker. - In this study, teat number was the sum of teat numbers on both sides. - In the present study, the GEMMA software [16] was used to implement MLM for single-locus GWAS of teat number. - The model that tested the allelic effect of each SNP on teat number invoked by GEMMA was as follows:. - where y is the vector of teat number in these two Duroc pig populations. - where y is the vector of teat number. - Manhattan plot of meta-analysis of GWAS for teat number in American and Canadian Duroc pigs. - The dashed line indicates the FDR (0.01) thresholds for teat number ( P = 1.18E-04).. - Significant SNPs and genes associated with teat number in American Duroc pigs.. - Significant SNPs and genes associated with teat number in Canadian Duroc pigs.. - Significant KEGG pathways and GO terms associated with teat number. - Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side. - Genome-wide association QTL mapping for teat number in a purebred population of Duroc pigs. - Genotyping by sequencing reveals a new locus for pig teat number. - Possible introgression of the VRTN mutation increasing vertebral number, carcass length and teat number from Chinese pigs into European pigs. - Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing.. - Heritability of teat number in swine. - Genome-wide QTL mapping for three traits related to teat number in a white Duroc x Erhualian pig resource population
Xem thử không khả dụng, vui lòng xem tại trang nguồn hoặc xem
Tóm tắt