Abstract:
The research of Mendel, born two centuries ago, still has many direct implications for our everyday clinical work. He introduced the terms \"dominant\" and \"recessive\" characters and determined their 3:1 ratio in the offspring of heterozygous \"hybrid\" plants. This distribution allowed calculation of the number of the phenotype-determining \"elements,\" i.e., the alleles, and has been used ever since to prove the monogenic origin of a disorder. The Mendelian inheritance of monogenic kidney disorders is still of great help in distinguishing them from those with multifactorial origin in clinical practice. Inheritance of most monogenic kidney disorders fits to Mendel\'s observations: the equal contribution of the two parents and the complete penetrance or the direct correlation between the frequency of the recessive character and the degree of inbreeding. Nevertheless, beyond the truth of these basic concepts, several observations have expanded their genetic characteristics. The extreme genetic heterogeneity, the pleiotropy of the causal genes and the role of modifiers in ciliopathies, the digenic inheritance and parental imprinting in some tubulopathies, and the incomplete penetrance and eventual interallelic interactions in podocytopathies, reflect this expansion. For all these reasons, the transmission pattern in a natural setting may depend not only on the \"character\" but also on the causal gene and the variant. Mendel\'s passion for research combined with his modest personality and meticulous approach can still serve as an example in the work required to understand the non-Mendelian universe of genetics.
摘要:
孟德尔的研究,出生于两个世纪前,对我们的日常临床工作仍有许多直接影响.他引入了术语“显性”和“隐性”字符,并在杂合“杂种”植物的后代中确定了它们的3:1比例。这种分布允许计算表型决定元素的数量,\"即,等位基因,从那以后就被用来证明疾病的单基因起源。单基因肾病的孟德尔遗传在临床实践中仍然有助于将它们与多因素起源的肾脏疾病区分开来。大多数单基因肾脏疾病的遗传符合孟德尔的观察:两个父母的同等贡献和完全外显率或隐性特征的频率与近亲繁殖程度之间的直接相关性。然而,超越这些基本概念的真理,一些观察扩大了他们的遗传特征。极端的遗传异质性,因果基因的多效性和修饰剂在纤毛病中的作用,一些肾小管疾病的双基因遗传和父母印记,足细胞病的不完全外显率和最终的等位基因间相互作用,反映了这种扩张。由于所有这些原因,自然环境中的传播模式可能不仅取决于“字符”,还取决于因果基因和变异。孟德尔对研究的热情,加上他谦虚的个性和细致的方法,仍然可以作为理解非孟德尔世界遗传学所需工作的一个例子。