Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domžale, Slovenia, 1230.
Clinical Institute for Genomic Medicine, University Medical Center Ljubljana, Šlajmerjeva 4, Ljubljana, Slovenia, 1000.
Andrology. 2022 May;10(4):720-732. doi: 10.1111/andr.13167. Epub 2022 Mar 15.
Male infertility is a disorder of the reproductive system with a highly complex genetic landscape. In most cases, the reason for male infertility remains unknown; however, the importance of genetic abnormalities in the diagnosis of subfertility/infertility is becoming increasingly recognized. Several syndromes include impaired male fertility in the clinical picture, although a comprehensive analysis of genetic causes of the syndromology perspective of male reproduction is not yet available.
(1) To develop a catalog of syndromes and corresponding genes associated with impaired male fertility and (2) to visualize an up-to-date genome-phenome network of syndromic male subfertility.
Published literature was retrieved from the Online Mendelian Inheritance in Man, Orphanet, Human Phenotype Ontology and PubMed databases using keywords "male infertility," "syndrome," "gene," and "case report"; time period from 1980 to September, 2021. Retrieved data were organized as a catalog and complemented with identification numbers of syndromes (MIM ID) and genes (Gene ID). The genome-phenome network and the phenome network were visualized using Cytoscape and Gephi software platforms. Protein-protein interaction analysis was performed using STRING tool.
Retrieved syndromes were presented as (1) a catalog containing 63 syndromes and 93 associated genes, (2) a genome-phenome network including CHD7 and WT1 genes and Noonan and Kartagener syndromes, and (3) a phenome network including 63 syndromes, and 25 categories of clinical features.
The developed catalog will contribute to the advances and translational impact toward understanding the factors of syndromic male infertility. Visualized networks provide simple, flexible tools for clinicians and researchers to quickly generate hypotheses and gain a deeper understanding of underlying mechanisms affecting male reproduction.
Recognition of the significance of genome-phenome visualization as part of network medicine can help expedite efforts toward unravelling molecular mechanisms and enable advances personal/precision medicine of male reproduction and other complex traits.
男性不育是一种生殖系统疾病，具有高度复杂的遗传特征。在大多数情况下，男性不育的原因仍然未知；然而，遗传异常在不育/不孕诊断中的重要性正日益得到认可。有几种综合征包括在临床表现中男性生育力受损，尽管从综合征学的角度对男性生殖的遗传原因进行全面分析尚未实现。
（1）编制一个与男性生育力受损相关的综合征和相应基因目录；（2）可视化最新的综合征性男性生殖力低下的基因组-表型网络。
使用“男性不育症”、“综合征”、“基因”和“病例报告”等关键词，从在线孟德尔遗传数据库、孤儿网、人类表型本体和 PubMed 数据库中检索已发表的文献，检索时间从 1980 年到 2021 年 9 月。检索到的数据被组织成目录，并补充了综合征（MIM ID）和基因（Gene ID）的识别号码。使用 Cytoscape 和 Gephi 软件平台可视化基因组-表型网络和表型网络。使用 STRING 工具进行蛋白质-蛋白质相互作用分析。
检索到的综合征以（1）包含 63 种综合征和 93 个相关基因的目录、（2）包含 CHD7 和 WT1 基因以及 Noonan 和 Kartagener 综合征的基因组-表型网络、和（3）包含 63 种综合征和 25 种临床特征类别的表型网络呈现。
开发的目录将有助于推进对综合征性男性不育相关因素的理解，并产生转化影响。可视化网络为临床医生和研究人员提供了简单、灵活的工具，可快速生成假说，并深入了解影响男性生殖的潜在机制。
认识到基因组-表型可视化作为网络医学的一部分的重要性，可以帮助加快揭示分子机制的努力，并推动男性生殖和其他复杂特征的个体化/精准医学的进展。
