背景:影响配子发生的生物学机制,胚胎发育和出生后的生存能力有可能改变孟德尔遗传预期,导致可观察到的透射率失真(TRD)。尽管发现TRD病例已经存在了很长时间,目前DNA技术在畜牧业中的广泛和不断增长的使用提供了大量基因组数据的宝贵资源,包括亲本-后代基因分型三重奏,实现TRD方法的实施。在这项研究中,目的是使用SNP逐个SNP和滑动窗口方法对441,802只基因型荷斯坦牛和132,991(或47,910分期)常染色体SNP进行TRD研究。
结果:使用等位基因和基因型参数化表征TRD。在整个基因组中,总共604个染色体区域显示出强烈的显著TRD。大多数(85%)的区域呈现等位基因TRD模式,其携带者(杂合)后代的代表性不足(生存力降低)或纯合个体的完全或准完全缺失(致死性)。另一方面,具有基因型TRD模式的其余区域表现出经典的隐性遗传或杂合子后代的过量或缺乏。其中,具有强等位基因和隐性TRD模式的最相关新区域的数量分别为10个和5个。此外,功能分析揭示了调节与胚胎发育和存活相关的关键生物过程的候选基因,DNA修复和减数分裂过程,其中,提供TRD发现的其他生物学证据。
结论:我们的结果揭示了实施不同TRD参数化以捕获所有类型的扭曲并确定相应的继承模式的重要性。还确定了包含致死等位基因和对生育力和产前和产后生存能力具有功能和生物学影响的基因的新候选基因组区域。为提高牛的育种成功率提供了机会。
BACKGROUND: Biological mechanisms affecting gametogenesis, embryo development and postnatal viability have the potential to alter Mendelian inheritance expectations resulting in observable transmission ratio distortion (TRD). Although the discovery of TRD cases have been around for a long time, the current widespread and growing use of DNA technologies in the livestock industry provides a valuable resource of large genomic data with parent-offspring genotyped trios, enabling the implementation of TRD approach. In this research, the objective is to investigate TRD using SNP-by-SNP and sliding windows approaches on 441,802 genotyped Holstein cattle and 132,991 (or 47,910 phased) autosomal SNPs.
RESULTS: The TRD was characterized using allelic and genotypic parameterizations. Across the whole genome a total of 604 chromosomal regions showed strong significant TRD. Most (85%) of the regions presented an allelic TRD pattern with an under-representation (reduced viability) of carrier (heterozygous) offspring or with the complete or quasi-complete absence (lethality) for homozygous individuals. On the other hand, the remaining regions with genotypic TRD patterns exhibited the classical recessive inheritance or either an excess or deficiency of heterozygote offspring. Among them, the number of most relevant novel regions with strong allelic and recessive TRD patterns were 10 and 5, respectively. In addition, functional analyses revealed candidate genes regulating key biological processes associated with embryonic development and survival, DNA repair and meiotic processes, among others, providing additional biological evidence of TRD findings.
CONCLUSIONS: Our results revealed the importance of implementing different TRD parameterizations to capture all types of distortions and to determine the corresponding inheritance pattern. Novel candidate genomic regions containing lethal alleles and genes with functional and biological consequences on fertility and pre- and post-natal viability were also identified, providing opportunities for improving breeding success in cattle.