Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
University Children's Hospital, Mother Theresa 17 St., 1000 Skopje, North Macedonia.
Genes (Basel). 2020 Nov 20;11(11):1377. doi: 10.3390/genes11111377.
Genetic studies of population isolates have great potential to provide a unique insight into genetic differentiation and phenotypic expressions. Galičnik village is a population isolate located in the northwest region of the Republic of North Macedonia, established around the 10th century. Alport syndrome-linked nephropathy with a complex inheritance pattern has been described historically among individuals in the village. In order to determine the genetic basis of the nephropathies and to characterize the genetic structure of the population, 23 samples were genotyped using a custom-made next generation sequencing panel and 111 samples using population genetic markers. We compared the newly obtained population data with fifteen European population data sets. NGS analysis revealed four different mutations in three different collagen genes in twelve individuals within the Galičnik population. The genetic isolation and small effective population size of Galičnik village have resulted in a high level of genomic homogeneity, with domination of R1a-M458 and R1b-U106* haplogroups. The study explains complex autosomal digenic and X-linked inheritance patterns of nephropathy in the isolated population of Galičnik and describes the first case of Alport syndrome family with three different collagen gene mutations.
人群隔离体的遗传研究具有提供遗传分化和表型表达独特见解的巨大潜力。加利奇尼克村是位于北马其顿共和国西北部的一个人群隔离体，成立于 10 世纪左右。历史上，该村庄的个体中曾描述过具有复杂遗传模式的 Alport 综合征相关肾病。为了确定肾病的遗传基础，并描述人群的遗传结构，我们使用定制的下一代测序面板对 23 个样本进行了基因分型，并使用群体遗传标记对 111 个样本进行了基因分型。我们将新获得的人群数据与 15 个欧洲人群数据集进行了比较。NGS 分析在加利奇尼克人群中的 12 个人中三个不同的胶原基因中发现了四个不同的突变。加利奇尼克村的遗传隔离和小有效种群规模导致了高水平的基因组同质性，R1a-M458 和 R1b-U106*单倍群占主导地位。该研究解释了加利奇尼克隔离人群中肾病的复杂常染色体双基因和 X 连锁遗传模式，并描述了首例具有三个不同胶原基因突变的 Alport 综合征家族病例。
