Copy number variation of bovine SHH gene is associated with body conformation traits in Chinese beef cattle
Sonic Hedgehog (Shh) regulates many key developmental processes during vertebrate limb development, fat formation, and skeletal tissue regeneration. Current whole genome sequencing data have identified a copy number variation mapping to bovine Sonic Hedgehog gene (SHH-CNV). The object of this study was to characterize the SHH-CNV distributions in 648 individuals from 11 Chinese cattle populations and further to investigate the associations of the copy number changes with gene expression and cattle growth traits. The SHH-CNV showed a high variance within Chinese indigenous yellow cattle. Compared to yak and dairy cattle, the beef cattle like Luxi and Xianan breed had significantly higher median copy numbers, suggesting the diversity of SHH-CNV in beef cattle selections. The negative correlation of SHH-CNV with SHH transcriptional level in adult adipose tissue (P < 0.01) indicated the dosage effects of SHH-CNV related to bovine fat formation. Association analysis of SHH-CNV and body size traits was conducted in five breeds. The results revealed that the copy number gain type of SHH-CNV exhibited significantly better chest depth in 24 months old Qinchuan cattle, and better body weight, body length, and chest girth in 18 months old Nanyang cattle, whereas the normal copy number had superior chest girth and body weight in adult Jinnan cattle (P < 0.05 or P < 0.01). In summary, this research uncovered meaningful effects of SHH-CNV on gene expression and cattle phenotypic traits, indicating its potential applications for genetic improvement of beef cattle.
KeywordsCattle Copy number variation Sonic Hedgehog Growth trait Associations
We acknowledge Dr. Yao Xu’s help in providing the RNA sample for tissues of QC cattle and the guidance for designing this research. We acknowledge Dr. Shaoqiang Wang’s help in providing the DNA sample for YAK population. We acknowledge Dr. Xinglei Qi’s help in sampling the blood sample for Xianan cattle. We acknowledge Dr. Shijun Li’s help in association analysis.
This study was funded by the National Natural Science Foundation of China (No. 31772574) and the Program of National Beef Cattle and Yak Industrial Technology System (CARS-37).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The China Council on Animal Care and the Experimental Animal Management Committee of Northwest A&F University approved the procedures and protocols of all experiments in this study.
Consent for publication
Written consent was obtained for use of all animal data.
- Bickhart DM, Xu L, Hutchison JL, Cole JB, Null DJ, Schroeder SG, Song J, Garcia JF, Sonstegard TS, Van Tassell CP, Schnabel RD, Taylor JF, Lewin HA, Liu GE (2016) Diversity and population-genetic properties of copy number variations and multicopy genes in cattle. DNA Res 23:253–262CrossRefGoogle Scholar
- Coutton C, Poreau B, Devillard F, Durand C, Odent S, Rozel C, Vieville G, Amblard F, Jouk PS, Satre V (2014) Currarino syndrome and HPE microform associated with a 2.7-Mb deletion in 7q36.3 excluding SHH gene. Mol Syndromol 5:25–31Google Scholar
- Liu M, Zhou Y, Rosen BD, Van Tassell CP, Stella A, Tosser-Klopp G, Rupp R, Palhiere I, Colli L, Sayre B, Crepaldi P, Fang L, Meszaros G, Chen H, Liu GE, Consortium AD (2018) Diversity of copy number variation in the worldwide goat population. Heredity (Edinb), 1Google Scholar
- Logan J, Logan JM, Edwards KJ, Saunders NA (2009) Real-time PCR: current technology and applications. Horizon Scientific Press, PooleGoogle Scholar
- Marchler-Bauer A, Derbyshire MK, Gonzales NR, Lu S, Chitsaz F, Geer LY, Geer RC, He J, Gwadz M, Hurwitz DI, Lanczycki CJ, Lu F, Marchler GH, Song JS, Thanki N, Wang Z, Yamashita RA, Zhang D, Zheng C, Bryant SH (2015) CDD: NCBI’s conserved domain database. Nucleic Acids Res 43:D222–D226CrossRefGoogle Scholar
- Mills RE, Walter K, Stewart C, Handsaker RE, Chen K, Alkan C, Abyzov A, Yoon SC, Ye K, Cheetham RK, Chinwalla A, Conrad DF, Fu Y, Grubert F, Hajirasouliha I, Hormozdiari F, Iakoucheva LM, Iqbal Z, Kang S, Kidd JM, Konkel MK, Korn J, Khurana E, Kural D, Lam HY, Leng J, Li R, Li Y, Lin CY, Luo R, Mu XJ, Nemesh J, Peckham HE, Rausch T, Scally A, Shi X, Stromberg MP, Stutz AM, Urban AE, Walker JA, Wu J, Zhang Y, Zhang ZD, Batzer MA, Ding L, Marth GT, McVean G, Sebat J, Snyder M, Wang J, Ye K, Eichler EE, Gerstein MB, Hurles ME, Lee C, McCarroll SA, Korbel JO, Genomes P (2011) Mapping copy number variation by population-scale genome sequencing. Nature 470:59–65CrossRefGoogle Scholar
- Mullenbach R, Lagoda PJ, Welter C (1989) An efficient salt-chloroform extraction of DNA from blood and tissues. Trends Genet 5:391Google Scholar
- Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M (1999) The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet 8:2479–2488CrossRefGoogle Scholar
- Spinella-Jaegle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P, Courtois B, Bergaud B, Ramez V, Blanchet AM (2001) Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci 114:2085–2094Google Scholar
- Zhou Y, Utsunomiya YT, Xu L, Hay el HA, Bickhart DM, Alexandre PA, Rosen BD, Schroeder SG, Carvalheiro R, de Rezende Neves HH, Sonstegard TS, Van Tassell CP, Ferraz JB, Fukumasu H, Garcia JF, Liu GE (2016) Genome-wide CNV analysis reveals variants associated with growth traits in Bos indicus. BMC Genomics 17:419CrossRefGoogle Scholar