Wiedemar Natalie, Tetens Jens, Jagannathan Vidhya, Menoud Annie, Neuenschwander Samuel, Bruggmann Rémy, Thaller Georg, Drögemüller Cord
Institute of Genetics, University of Bern, Bern, Switzerland.
Institute of Animal Breeding and Husbandry, Christian-Albrechts-University Kiel, Kiel, Germany.
PLoS One. 2014 Mar 26;9(3):e93435. doi: 10.1371/journal.pone.0093435. eCollection 2014.
The molecular regulation of horn growth in ruminants is still poorly understood. To investigate this process, we collected 1019 hornless (polled) animals from different cattle breeds. High-density SNP genotyping confirmed the presence of two different polled associated haplotypes in Simmental and Holstein cattle co-localized on BTA 1. We refined the critical region of the Simmental polled mutation to 212 kb and identified an overlapping region of 932 kb containing the Holstein polled mutation. Subsequently, whole genome sequencing of polled Simmental and Holstein cows was used to determine polled associated genomic variants. By genotyping larger cohorts of animals with known horn status we found a single perfectly associated insertion/deletion variant in Simmental and other beef cattle confirming the recently published possible Celtic polled mutation. We identified a total of 182 sequence variants as candidate mutations for polledness in Holstein cattle, including an 80 kb genomic duplication and three SNPs reported before. For the first time we showed that hornless cattle with scurs are obligate heterozygous for one of the polled mutations. This is in contrast to published complex inheritance models for the bovine scurs phenotype. Studying differential expression of the annotated genes and loci within the mapped region on BTA 1 revealed a locus (LOC100848215), known in cow and buffalo only, which is higher expressed in fetal tissue of wildtype horn buds compared to tissue of polled fetuses. This implicates that the presence of this long noncoding RNA is a prerequisite for horn bud formation. In addition, both transcripts associated with polledness in goat and sheep (FOXL2 and RXFP2), show an overexpression in horn buds confirming their importance during horn development in cattle.
反刍动物角生长的分子调控仍知之甚少。为了研究这一过程，我们从不同牛品种中收集了1019头无角（去角）动物。高密度SNP基因分型证实西门塔尔牛和荷斯坦牛中存在两种不同的与无角相关的单倍型，它们共定位于牛1号染色体（BTA 1）上。我们将西门塔尔牛无角突变的关键区域缩小至212 kb，并确定了一个包含荷斯坦牛无角突变的932 kb重叠区域。随后，对西门塔尔牛和荷斯坦牛无角母牛进行全基因组测序，以确定与无角相关的基因组变异。通过对更多已知角状态的动物群体进行基因分型，我们在西门塔尔牛和其他肉牛中发现了一个完全相关的插入/缺失变异，证实了最近发表的可能的凯尔特无角突变。我们总共鉴定出182个序列变异作为荷斯坦牛无角的候选突变，包括一个80 kb的基因组重复和之前报道的三个单核苷酸多态性。我们首次表明，有小角的无角牛对于其中一种无角突变是 obligate 杂合子。这与已发表的牛小角表型的复杂遗传模型形成对比。研究BTA 1上定位区域内注释基因和位点的差异表达，发现了一个仅在牛和水牛中已知的位点（LOC100848215），与无角胎儿的组织相比，该位点在野生型角芽的胎儿组织中表达更高。这意味着这种长链非编码RNA的存在是角芽形成的先决条件。此外，山羊和绵羊中与无角相关的两种转录本（FOXL2和RXFP2）在角芽中均表现出过表达，证实了它们在牛的角发育过程中的重要性。
