Porcine adrenergic receptor beta 2 (ADRB2) gene exhibits differential allelic expression in skeletal muscle, and its genetic variation has been associated with muscle pH. Exploring the molecular–genetic background of expression variation for porcine ADRB2 will provide insight into the mechanisms driving its regulatory divergence and may also contribute to unraveling the genetic basis of muscle-related traits in pigs. In the present study, we therefore examined haplotype effects on the expression of porcine ADRB2 in four tissues: longissimus dorsi muscle, liver, subcutaneous fat, and spleen. The diversity and structure of haplotypes of the proximal gene region segregating in German commercial breeds were characterized. Seven haplotypes falling into three clades were identified. Two clades including five haplotypes most likely originated from introgression of Asian genetics during formation of modern breeds. Expression analyses revealed that the Asian-derived haplotypes increase expression of the porcine ADRB2 compared to the major, wild-type haplotype independently of tissue type. In addition, several tissue-specific differences in the expression of the Asian-derived haplotypes were found. Inspection of haplotype sequences showed that differentially expressed haplotypes exhibit polymorphisms in a polyguanine tract located in the core promoter region. These findings demonstrate that expression variation of the porcine ADRB2 has a complex genetic basis and suggest that the promoter polyguanine tract is causally involved. This study highlights the challenges of finding causal genetic variants underlying complex traits.
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The authors thank Angela Garve, Hannelore Tychsen, and Marlies Fuchs for excellent technical help. The authors are also grateful to Aline Foury and Pierre Morméde (INRA, France) and Do Van Khoa for providing Meishan and Muong Khuong tissue samples, respectively. This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, Grant MU2965/2-1) and by matched funding from the FBN.
Communicated by M. Fredholm.
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Figure S1. Position of polymorphisms in the porcine ADRB2 and flanking regions. Coding region is shown in blue, untranslated regions in yellow. Vertical arrows show position of polymorphisms. Horizontal double-headed arrows depict amplicons used for resequencing. STR – short tandem repeat, I – insertion/deletion, A – nonsynonymous variant (TIFF 267 kb)
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Murani, E., Ponsuksili, S., Reyer, H. et al. Expression variation of the porcine ADRB2 has a complex genetic background. Mol Genet Genomics 288, 615–625 (2013). https://doi.org/10.1007/s00438-013-0776-2
- Haplotype structure
- Differential allelic expression
- Regulatory variation