BRIEF NOTES doi: 10.1111/age.12237
Association mapping of the scurs locus in polled Simmental cattle – evidence for genetic heterogeneity J. Tetens*, N. Wiedemar†, A. Menoud†, G. Thaller* € gemu € ller† and C. Dro *Institute of Animal Breeding and Husbandry, ChristianAlbrechts-University Kiel, D-24118 Kiel, Germany; †Institute of Genetics, Vetsuisse Faculty, University of Bern, CH-3001 Bern, Switzerland Accepted for publication 18 September 2014
Genetically hornless or polled cattle occasionally grow scurs, small corneous growths that develop in the same area as horns but are not firmly attached to the skull. The most commonly accepted inheritance model1 assumes two alleles, Sc (scurs) and sc (no scurs), at the still unknown scurs locus. The presence of a single Sc allele is supposed to result in scurs in males, but two alleles are required in females. Inconsistent with previous models,1 we recently reported that only heterozygously polled cattle ever grow scurs and observed a phenotypic distribution principally consistent with X-linked inheritance.2 Numerous inconsistencies have previously been reported and, consequently, revised inheritance models have been proposed.3 Although 10 years ago the scurs mutation was assigned to BTA 19 by linkage mapping,4 the responsible gene has not yet been identified. Interestingly, a phenotypically
distinct form of scurs was identified in Charolais cattle, and the causative mutation was identified in the TWIST1 gene located on BTA45 In summary, the studies conducted so far indicate genetic heterogeneity of the scurs condition. Here, we conducted a GWAS in 150 heterozygously polled Simmental cattle consisting of 49 males (27 scurred, 22 smoothly polled) and 101 females (60 scurred, 41 smoothly polled) including only animals with clearly visible scurs or undoubtedly smoothly polled. Genotyping was performed with the Illumina BovineHD BeadChip. Genotypes were filtered for minor allele frequency and missingness resulting in a final set of 589 957 SNPs. A principal components approach6,7 was applied including the first three axes of variation and sex in the model. Only one clear association peak was obtained on BTA19 (Fig. 1), whereas single SNP associations on BTA1 4, and 7 are likely to be spurious associations. The best associated SNP is considerably close to the previously identified region on BTA19.4 Besides the mentioned association signals, some distinct peaks failing to achieve genome-wide significance are visible on BTA2, 9 and 10, possibly indicating genetic heterogeneity (Fig. 1). As all scurred females are assumed to be homozygous for the Sc allele,1 we performed homozygosity mapping for BTA19 SNPs but were not able to identify a shared homozygous haplotype. This could be due to the fact that the postulated inheritance model is wrong. Furthermore, there might be allelic heterogeneity, as seen for polled,2,8 with
Figure 1 Results of the GWAS for scurs in polled Simmental cattle. Shown are the negative decadic logarithms of the raw P-values. The horizontal line denotes the 5% Bonferroni threshold for genome-wide significance. The inset represents the respective Q–Q plot. The SNP name represents the Illumina SNP identifier; MAF = minor allele frequency.
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© 2015 Stichting International Foundation for Animal Genetics, 46, 224–226
Brief Notes different scurs alleles residing on different haplotypes or genetic heterogeneity and with various scurs loci influencing the expression of the horn-like structures. The latter seems more likely, as genetic heterogeneity has already been shown for the scurs condition.3,5 In conclusion, it is obvious that the development of scurs in Simmental cannot be explained by a single locus, as our study should have shown a stronger clear association signal. Nonetheless, our results support the existence of a scurs locus in Simmental cattle residing on BTA19 as proposed earlier, but clearly point to genetic heterogeneity as previously reported in the Charolais breed. Interestingly, there is no evidence for an X chromosome association contrary to former segregation analyses. References 1 Long C.R. et al. (1978) J Hered 69, 395–400. 2 Wiedemar N. et al. (2014) PLoS ONE 9, e93435. 3 Capitan A. et al. (2009) BMC Genet 10, 33. 4 Asai M. et al. (2004) Anim Genet 35, 34–9. 5 Capitan A. et al. (2011) PLoS ONE 6, e22242. 6 Aulchenko Y.S. et al. (2007) Bioinformatics 23, 1294–6. 7 Price A.L. et al. (2006) Nat Genet 38, 904–9. 8 Medugorac I. et al. (2012) PLoS ONE 7, e39477. Correspondence: J. Tetens ([email protected])
doi: 10.1111/age.12265
Evaluation of the causality of the zinc finger BED-type containing 6 gene (ZBED6) for six important growth traits in Nanyang beef cattle Yong-Zhen Huang*, Yu-Jia Sun*, Ming-Xun Li*, Jing Wang*, Jia-Jie Sun*, Chun-Lei Zhang†, Yu-Tang Jia‡ and Hong Chen* *Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; †Institute of Cellular and Molecular Biology, Xuzhou Normal University, Xuzhou, Jiangsu 221116, China; ‡Institute of Animal Husbandry and Veterinary, Anhui Academy of Agricultural Sciences, Hefei 230000, Anhui, China Accepted for publication 03 December 2014
Description: The zinc finger, BED-type containing 6 (ZBED6) gene has been shown to act as a repressor of IGF2 transcription in skeletal muscle myogenesis and development.1 Three single nucleotide polymorphisms (SNPs) in the promoter and coding regions may modulate the promoter
activity and protein function of bovine ZBED6 in the skeletal muscles.2 Previously, we reported that three SNPs of the bovine ZBED6 gene revealed significant effects on body weight in cattle.3 The aim of this study was to investigate their associations with five other important growth traits in a Nanyang cattle population. Sample and genotyping: Blood samples were taken from 265 Nanyang cattle in China. The traits under study were the body weight, withers height, body length, heart girth, hucklebone width and average daily gain at 6, 12, 18 and 24 months. These traits were measured following the method described in Gilbert et al.4 Nanyang cattle is an important breed for beef production in China. Calves are weaned on average at 6 months of age and raised from weaning to slaughter on a diet of corn and corn silage. The animals used for the association study came from a common ancestor, and pedigrees of core breeding population animals were traced back three generations. The three SNPs investigated, ZBED6:g.–826G>A (SNP1), ZBED6:g.680C>G (SNP2), and ZBED6:g.1043A>G (SNP3), were genotyped by forced PCR-RFLP methods.3 Association analysis: Statistical results showed that the growth traits values of homozygous wild-type animals were lower than those of homozygous mutant-type animals in the three SNPs of the bovine ZBED6 gene. The association of the three SNPS (SNP1-AA, SNP2-GG, and SNP3-GG) with body weight, withers height, body length, hucklebone width and average daily gain in the Nanyang cattle population at four different ages (followed by the P-level in parentheses) are shown in Table S1. These values suggest that these mutations are causative for variation in growth rate at different ages in Nanyang beef cattle. Comments: The analysis of candidate genes suggested that the cattle with genotypes SNP1-AA, SNP2-GG, and SNP3GG could be selected to obtain greater phenotypic traits. SNP1 has a significant effect at 12 months but generally not at the earlier or later ages, and SNP2 seems to have an effect at the earlier but not at the later ages. This holds the promise of minimizing calving difficulties caused by larger birth weights while maintaining the same final weight. Because SNP1 is situated in the promoter, it may modulate the promoter activity and gene expression of the bovine ZBED6 in this cattle breed. SNP2 and SNP3 are missense mutations in the coding region of the bovine ZBED6 gene and may affect the function of the ZBED6 protein. In conclusion, this study shows the prospects of ZBED6 as a candidate gene. Acknowledgements: This study was supported by the National Natural Science Foundation of China (Grants no. 31272408 and 30972080), Program of National Beef Cattle and Yak Industrial Technology System (Grant no.
© 2015 Stichting International Foundation for Animal Genetics, 46, 224–226
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Association mapping of the scurs locus in polled Simmental cattle – evidence for genetic heterogeneity J. Tetens*, N. Wiedemar†, A. Menoud†, G. Thaller* € gemu € ller† and C. Dro *Institute of Animal Breeding and Husbandry, ChristianAlbrechts-University Kiel, D-24118 Kiel, Germany; †Institute of Genetics, Vetsuisse Faculty, University of Bern, CH-3001 Bern, Switzerland Accepted for publication 18 September 2014
Genetically hornless or polled cattle occasionally grow scurs, small corneous growths that develop in the same area as horns but are not firmly attached to the skull. The most commonly accepted inheritance model1 assumes two alleles, Sc (scurs) and sc (no scurs), at the still unknown scurs locus. The presence of a single Sc allele is supposed to result in scurs in males, but two alleles are required in females. Inconsistent with previous models,1 we recently reported that only heterozygously polled cattle ever grow scurs and observed a phenotypic distribution principally consistent with X-linked inheritance.2 Numerous inconsistencies have previously been reported and, consequently, revised inheritance models have been proposed.3 Although 10 years ago the scurs mutation was assigned to BTA 19 by linkage mapping,4 the responsible gene has not yet been identified. Interestingly, a phenotypically
distinct form of scurs was identified in Charolais cattle, and the causative mutation was identified in the TWIST1 gene located on BTA45 In summary, the studies conducted so far indicate genetic heterogeneity of the scurs condition. Here, we conducted a GWAS in 150 heterozygously polled Simmental cattle consisting of 49 males (27 scurred, 22 smoothly polled) and 101 females (60 scurred, 41 smoothly polled) including only animals with clearly visible scurs or undoubtedly smoothly polled. Genotyping was performed with the Illumina BovineHD BeadChip. Genotypes were filtered for minor allele frequency and missingness resulting in a final set of 589 957 SNPs. A principal components approach6,7 was applied including the first three axes of variation and sex in the model. Only one clear association peak was obtained on BTA19 (Fig. 1), whereas single SNP associations on BTA1 4, and 7 are likely to be spurious associations. The best associated SNP is considerably close to the previously identified region on BTA19.4 Besides the mentioned association signals, some distinct peaks failing to achieve genome-wide significance are visible on BTA2, 9 and 10, possibly indicating genetic heterogeneity (Fig. 1). As all scurred females are assumed to be homozygous for the Sc allele,1 we performed homozygosity mapping for BTA19 SNPs but were not able to identify a shared homozygous haplotype. This could be due to the fact that the postulated inheritance model is wrong. Furthermore, there might be allelic heterogeneity, as seen for polled,2,8 with
Figure 1 Results of the GWAS for scurs in polled Simmental cattle. Shown are the negative decadic logarithms of the raw P-values. The horizontal line denotes the 5% Bonferroni threshold for genome-wide significance. The inset represents the respective Q–Q plot. The SNP name represents the Illumina SNP identifier; MAF = minor allele frequency.
224
© 2015 Stichting International Foundation for Animal Genetics, 46, 224–226
Brief Notes different scurs alleles residing on different haplotypes or genetic heterogeneity and with various scurs loci influencing the expression of the horn-like structures. The latter seems more likely, as genetic heterogeneity has already been shown for the scurs condition.3,5 In conclusion, it is obvious that the development of scurs in Simmental cannot be explained by a single locus, as our study should have shown a stronger clear association signal. Nonetheless, our results support the existence of a scurs locus in Simmental cattle residing on BTA19 as proposed earlier, but clearly point to genetic heterogeneity as previously reported in the Charolais breed. Interestingly, there is no evidence for an X chromosome association contrary to former segregation analyses. References 1 Long C.R. et al. (1978) J Hered 69, 395–400. 2 Wiedemar N. et al. (2014) PLoS ONE 9, e93435. 3 Capitan A. et al. (2009) BMC Genet 10, 33. 4 Asai M. et al. (2004) Anim Genet 35, 34–9. 5 Capitan A. et al. (2011) PLoS ONE 6, e22242. 6 Aulchenko Y.S. et al. (2007) Bioinformatics 23, 1294–6. 7 Price A.L. et al. (2006) Nat Genet 38, 904–9. 8 Medugorac I. et al. (2012) PLoS ONE 7, e39477. Correspondence: J. Tetens ([email protected])
doi: 10.1111/age.12265
Evaluation of the causality of the zinc finger BED-type containing 6 gene (ZBED6) for six important growth traits in Nanyang beef cattle Yong-Zhen Huang*, Yu-Jia Sun*, Ming-Xun Li*, Jing Wang*, Jia-Jie Sun*, Chun-Lei Zhang†, Yu-Tang Jia‡ and Hong Chen* *Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; †Institute of Cellular and Molecular Biology, Xuzhou Normal University, Xuzhou, Jiangsu 221116, China; ‡Institute of Animal Husbandry and Veterinary, Anhui Academy of Agricultural Sciences, Hefei 230000, Anhui, China Accepted for publication 03 December 2014
Description: The zinc finger, BED-type containing 6 (ZBED6) gene has been shown to act as a repressor of IGF2 transcription in skeletal muscle myogenesis and development.1 Three single nucleotide polymorphisms (SNPs) in the promoter and coding regions may modulate the promoter
activity and protein function of bovine ZBED6 in the skeletal muscles.2 Previously, we reported that three SNPs of the bovine ZBED6 gene revealed significant effects on body weight in cattle.3 The aim of this study was to investigate their associations with five other important growth traits in a Nanyang cattle population. Sample and genotyping: Blood samples were taken from 265 Nanyang cattle in China. The traits under study were the body weight, withers height, body length, heart girth, hucklebone width and average daily gain at 6, 12, 18 and 24 months. These traits were measured following the method described in Gilbert et al.4 Nanyang cattle is an important breed for beef production in China. Calves are weaned on average at 6 months of age and raised from weaning to slaughter on a diet of corn and corn silage. The animals used for the association study came from a common ancestor, and pedigrees of core breeding population animals were traced back three generations. The three SNPs investigated, ZBED6:g.–826G>A (SNP1), ZBED6:g.680C>G (SNP2), and ZBED6:g.1043A>G (SNP3), were genotyped by forced PCR-RFLP methods.3 Association analysis: Statistical results showed that the growth traits values of homozygous wild-type animals were lower than those of homozygous mutant-type animals in the three SNPs of the bovine ZBED6 gene. The association of the three SNPS (SNP1-AA, SNP2-GG, and SNP3-GG) with body weight, withers height, body length, hucklebone width and average daily gain in the Nanyang cattle population at four different ages (followed by the P-level in parentheses) are shown in Table S1. These values suggest that these mutations are causative for variation in growth rate at different ages in Nanyang beef cattle. Comments: The analysis of candidate genes suggested that the cattle with genotypes SNP1-AA, SNP2-GG, and SNP3GG could be selected to obtain greater phenotypic traits. SNP1 has a significant effect at 12 months but generally not at the earlier or later ages, and SNP2 seems to have an effect at the earlier but not at the later ages. This holds the promise of minimizing calving difficulties caused by larger birth weights while maintaining the same final weight. Because SNP1 is situated in the promoter, it may modulate the promoter activity and gene expression of the bovine ZBED6 in this cattle breed. SNP2 and SNP3 are missense mutations in the coding region of the bovine ZBED6 gene and may affect the function of the ZBED6 protein. In conclusion, this study shows the prospects of ZBED6 as a candidate gene. Acknowledgements: This study was supported by the National Natural Science Foundation of China (Grants no. 31272408 and 30972080), Program of National Beef Cattle and Yak Industrial Technology System (Grant no.
© 2015 Stichting International Foundation for Animal Genetics, 46, 224–226
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