Abstract
Copy number variation (CNV) of DNA sequences, functionally significant but yet fully ascertained, is believed to confer considerable increments in unexplained heritability of quantitative traits. Identification of phenotype-associated CNVs (paCNVs) therefore is a pressing need in CNV studies to speed up their exploitation in cattle breeding programs. Here, we provided a new avenue to achieve this goal that is to project the published CNV data onto meta-quantitative trait loci (meta-QTL) map which connects causal genes with phenotypes. Any CNVs overlapping meta-QTL therefore will be potential paCNVs. This study reported potential paCNVs in Bos taurus autosome 3 (BTA3). Notably, overview indexes and CNVs both highlighted a narrower region (BTA3 54,500,000–55,000,000 bp, named BTA3_INQTL_6) within one constructed meta-QTL. Then, we ascertained guanylate-binding protein 4 (GBP4) among the nine positional candidate genes was significantly associated with adult cattle stature, including body weight (BW, P < 0.05) and withers height (WHT, P < 0.05), fitting GBP4 CNV either with three levels or with six levels in the model. Although higher copy number downregulated the mRNA levels of GBP2 (P < 0.05) and GBP4 (P < 0.05) in 1-Mb window (54.0–55.0 Mb) in muscle and adipose, additional analyses will be needed to clarify the causality behind the ascertained association.
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Funding
This work was supported by the National 863 Program of China [2013AA102505], the Program of National Beef Cattle and Yak Industrial Technology System [CARS-37], the National Natural Science Foundation of China [31272408, 31601926], Bio-breeding capacity-building and industry specific projects from the National Development and Reform Commission [2014-2573], Specific Projects of Science and Technology in Henan Province [141100110200], Science and Technology Co-ordinator Innovative engineering projects of Shaanxi Province [2014KTZB02-02-02-02, 2015KTCL02-08], Project of breeding and application of Pinan Cattle, and Haixi Project of Qinghai Province: Identification of key genes of growth and high-quality meat in Yak Multi hybrids.
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Cao, XK., Huang, YZ., Ma, YL. et al. Integrating CNVs into meta-QTL identified GBP4 as positional candidate for adult cattle stature. Funct Integr Genomics 18, 559–567 (2018). https://doi.org/10.1007/s10142-018-0613-0
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DOI: https://doi.org/10.1007/s10142-018-0613-0