Dachs Nina, Upadhyay Maulik, Hannemann Elisabeth, Hauser Andreas, Krebs Stefan, Seichter Doris, Russ Ingolf, Gehrke Lilian Johanna, Thaller Georg, Medugorac Ivica
Population Genomics Group, Department of Veterinary Sciences, LMU Munich, Lena-Christ-Str. 48, 82152 Martinsried, Germany; Tierzuchtforschung e.V. München, Senator-Gerauer-Str, 23, 85586 Poing, Germany.
Population Genomics Group, Department of Veterinary Sciences, LMU Munich, Lena-Christ-Str. 48, 82152 Martinsried, Germany.
J Dairy Sci. 2023 Mar;106(3):1925-1941. doi: 10.3168/jds.2021-21625. Epub 2023 Jan 27.
Although the quantitative trait locus (QTL) on chromosome 18 (BTA18) associated with paternal calving ease and stillbirth in Holstein Friesian cattle and its cross has been known for over 20 years, to our knowledge, the exact causal genetic sequence has yet escaped identification. The aim of this study was to re-examine the region of the published QTL on BTA18 and to investigate the possible reasons behind this elusiveness. For this purpose, we carried out a combined linkage disequilibrium and linkage analysis using genotyping data of 2,697 German Holstein Friesian (HF) animals and subsequent whole-genome sequencing (WGS) data analyses and genome assembly of HF samples. We confirmed the known QTL in the 95% confidence interval of 1.089 Mbp between 58.34 and 59.43 Mbp on BTA18. Additionally, these 4 SNPs in the near-perfect linkage disequilibrium with the QTL haplotype were identified: rs381577268 (on 57,816,137 bp, C/T), rs381878735 (on 59,574,329 bp, A/T), rs464221818 (on 59,329,176 bp, C/T), and rs472502785 (on 59,345,689 bp, T/C). Search for the causal mutation using short and long-read sequences, and methylation data of the BTA18 QTL region did not reveal any candidates though. The assembly showed problems in the region, as well as an abundance of segmental duplications within and around the region. Taking the QTL of BTA18 in Holstein cattle as an example, the data presented in this study comprehensively characterize the genomic features that could also be relevant for other such elusive QTL in various other cattle breeds and livestock species as well.
尽管与荷斯坦弗里生奶牛及其杂交品种的父系产犊难易度和死产相关的18号染色体（BTA18）上的数量性状基因座（QTL）已被知晓20多年，但据我们所知，确切的因果遗传序列仍未被确定。本研究的目的是重新审视已发表的BTA18上QTL的区域，并调查其难以捉摸的可能原因。为此，我们利用2697头德国荷斯坦弗里生（HF）动物的基因分型数据，以及随后的全基因组测序（WGS）数据分析和HF样本的基因组组装，进行了连锁不平衡和连锁分析的联合研究。我们在BTA18上58.34至59.43 Mbp之间1.089 Mbp的95%置信区间内确认了已知的QTL。此外，还鉴定出与QTL单倍型处于近乎完美连锁不平衡状态的4个单核苷酸多态性（SNP）：rs381577268（位于57,816,137 bp，C/T）、rs381878735（位于59,574,329 bp，A/T）、rs464221818（位于59,329,176 bp，C/T）和rs472502785（位于59,345,689 bp，T/C）。不过，使用短读长和长读长序列以及BTA18 QTL区域的甲基化数据搜索因果突变并未发现任何候选基因。组装显示该区域存在问题，并且该区域内及周围存在大量的片段重复。以荷斯坦奶牛BTA18上的QTL为例，本研究中呈现的数据全面描述了基因组特征，这些特征可能也与其他各种牛品种和家畜物种中其他此类难以捉摸的QTL相关。
