ESTIMATING THE AGE OF p.(Phe508del) WITH FAMILY STUDIES OF GEOGRAPHICALLY DISTINCT EUROPEAN POPULATIONS AND THE EARLY SPREAD OF CYSTIC FIBROSIS. CFTR p.'Phe508del) age

We identified microsatellites spanning CFTR and reconstructed haplotypes at 10 loci to estimate the time/age of the most recent common ancestor (tMRCA) with the Estiage program. We found that the age estimates differ between northwestern populations, where the mean tMRCA values vary between 4600 and 4725 years, and the southeastern populations where c.1521_1523delCTT seems to have been introduced only about 1000 years ago. The tMRCA values of Central Europeans were intermediate. Thus, our data resolve a controversy by establishing an early Bronze Age origin of the c.1521_1523delCTT allele and demonstrating its likely spread from northwest to southeast during ancient migrations.

本研究鉴定了跨越CFTR基因的微卫星（microsatellites），针对10个位点重构单倍型（haplotypes），并借助Estiage软件估算最近共同祖先时间（tMRCA）以推断其演化年代。研究发现，西北人群与东南人群的年代估算结果存在差异：西北人群的平均tMRCA值介于4600至4725年，而东南人群中c.1521_1523delCTT等位基因的引入时间仅约1000年。中欧人群的tMRCA值处于中间水平。据此，本研究通过确立c.1521_1523delCTT等位基因的青铜时代早期起源，并证实该等位基因大概率在古代迁徙过程中由西北向东南扩散，从而解决了此前的学术争议。