Hazard Dominique, Plisson-Petit Florence, Moreno-Romieux Carole, Fabre Stéphane, Drouilhet Laurence
GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet Tolosan, France.
Front Genet. 2020 Dec 23;11:616960. doi: 10.3389/fgene.2020.616960. eCollection 2020.
Recent studies showed that epigenetic marks, including DNA methylation, influence production and adaptive traits in plants and animals. So far, most studies dealing with genetics and epigenetics considered DNA methylation sites independently. However, the genetic basis of the global DNA methylation rate (GDMR) remains unknown. The main objective of the present study was to investigate genetic determinism of GDMR in sheep. The experiment was conducted on 1,047 Romane sheep allocated into 10 half-sib families. After weaning, all the lambs were phenotyped for global GDMR in blood as well as for production and adaptive traits. GDMR was measured by LUminometric Methylation Analysis (LUMA) using a pyrosequencing approach. Association analyses were conducted on some of the lambs ( = 775) genotyped by using the Illumina OvineSNP50 BeadChip. Blood GDMR varied among the animals (average 70.7 ± 6.0%). Female lambs had significantly higher GDMR than male lambs. Inter-individual variability of blood GDMR had an additive genetic component and heritability was moderate ( = 0.20 ± 0.05). No significant genetic correlation was found between GDMR and growth or carcass traits, birthcoat, or social behaviors. Association analyses revealed 28 QTLs associated with blood GDMR. Seven genomic regions on chromosomes 1, 5, 11, 17, 24, and 26 were of most interest due to either high significant associations with GDMR or to the relevance of genes located close to the QTLs. QTL effects were moderate. Genomic regions associated with GDMR harbored several genes not yet described as being involved in DNA methylation, but some are already known to play an active role in gene expression. In addition, some candidate genes, , , and have previously been described to be involved in epigenetic modifications. In conclusion, the results of the present study indicate that blood GDMR in domestic sheep is under polygenic influence and provide new insights into DNA methylation genetic determinism.
近期研究表明，包括DNA甲基化在内的表观遗传标记会影响动植物的生产和适应性性状。到目前为止，大多数涉及遗传学和表观遗传学的研究都是独立考虑DNA甲基化位点的。然而，全球DNA甲基化率（GDMR）的遗传基础仍然未知。本研究的主要目的是调查绵羊中GDMR的遗传决定性。实验在1047只罗曼绵羊上进行，这些绵羊被分配到10个半同胞家系中。断奶后，对所有羔羊的血液中全球GDMR以及生产和适应性性状进行表型分析。使用焦磷酸测序方法通过发光甲基化分析（LUMA）测量GDMR。对使用Illumina OvineSNP50 BeadChip进行基因分型的部分羔羊（n = 775）进行关联分析。血液GDMR在动物之间存在差异（平均70.7±6.0%）。雌性羔羊的GDMR显著高于雄性羔羊。血液GDMR的个体间变异性具有加性遗传成分，遗传力适中（h² = 0.20±0.05）。在GDMR与生长或胴体性状、出生被毛或社会行为之间未发现显著的遗传相关性。关联分析揭示了28个与血液GDMR相关的QTL。由于与GDMR高度显著相关或与位于QTL附近的基因的相关性较高，1、5、11、17、24和26号染色体上的7个基因组区域最受关注。QTL效应适中。与GDMR相关的基因组区域包含几个尚未被描述为参与DNA甲基化的基因，但有些基因已知在基因表达中发挥积极作用。此外，一些候选基因，如 、 和 先前已被描述为参与表观遗传修饰。总之，本研究结果表明家养绵羊的血液GDMR受多基因影响，并为DNA甲基化遗传决定性提供了新的见解。
