Bovine lactoferrin (Lf) is an iron absorbing whey protein with antibacterial, antiviral, and antifungal activity. Lactoferrin is economically valuable and has an extremely variable concentration in milk, partly driven by environmental influences such as milking frequency, involution, or mastitis. A significant genetic influence has also been previously observed to regulate lactoferrin content in milk. Here, we conducted genetic mapping of lactoferrin protein concentration in conjunction with RNA-seq, ChIP-seq, and ATAC-seq data to pinpoint candidate causative variants that regulate lactoferrin concentrations in milk. We identified a highly-significant lactoferrin protein quantitative trait locus (pQTL), as well as a cis lactotransferrin (LTF) expression QTL (cis-eQTL) mapping to the LTF locus. Using ChIP-seq and ATAC-seq datasets representing lactating mammary tissue samples, we also report a number of regions where the openness of chromatin is under genetic influence. Several of these also show highly significant QTL with genetic signatures similar to those highlighted through pQTL and eQTL analysis. By performing correlation analysis between these QTL, we revealed an ATAC-seq peak in the putative promotor region of LTF, that highlights a set of 115 high-frequency variants that are potentially responsible for these effects. One of the 115 variants (rs110000337), which maps within the ATAC-seq peak, was predicted to alter binding sites of transcription factors known to be involved in lactation-related pathways. Here, we report a regulatory haplotype of 115 variants with conspicuously large impacts on milk lactoferrin concentration. These findings could enable the selection of animals for high-producing specialist herds.

中文翻译：

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常见的调节单倍型使牛奶中的乳铁蛋白浓度加倍


牛乳铁蛋白 (Lf) 是一种吸收铁的乳清蛋白，具有抗菌、抗病毒和抗真菌活性。乳铁蛋白具有经济价值，并且在牛奶中的浓度变化很大，部分原因是挤奶频率、退化或乳腺炎等环境影响。先前也观察到显着的遗传影响可调节牛奶中的乳铁蛋白含量。在这里，我们结合 RNA-seq、ChIP-seq 和 ATAC-seq 数据进行乳铁蛋白浓度的遗传图谱，以查明调节牛奶中乳铁蛋白浓度的候选致病变异。我们鉴定了一个高度显着的乳铁蛋白数量性状基因座 (pQTL)，以及映射到 LTF 基因座的顺式乳铁蛋白 (LTF) 表达 QTL (cis-eQTL)。使用代表哺乳期乳腺组织样本的 ChIP-seq 和 ATAC-seq 数据集，我们还报告了许多染色质开放性受到遗传影响的区域。其中一些还显示出高度显着的 QTL，其遗传特征与通过 pQTL 和 eQTL 分析突出显示的相似。通过对这些 QTL 之间进行相关性分析，我们揭示了 LTF 推定启动子区域的 ATAC-seq 峰，突出显示了一组 115 个可能导致这些效应的高频变异。映射在 ATAC-seq 峰内的 115 个变体之一 (rs110000337) 预计会改变已知参与哺乳相关途径的转录因子的结合位点。在这里，我们报告了 115 个变异体的调节单倍型，这些变异体对牛奶乳铁蛋白浓度具有显着的巨大影响。这些发现可以为高产专业畜群选择动物。