Zielenski J, Fujiwara T M, Markiewicz D, Paradis A J, Anacleto A I, Richards B, Schwartz R H, Klinger K W, Tsui L C, Morgan K
Department of Genetics, Hospital for Sick Children, Toronto, Canada.
Am J Hum Genet. 1993 Mar;52(3):609-15.
The Hutterite population is a genetic isolate with an increased incidence of cystic fibrosis (CF). Previously we identified three CF haplotypes defined by polymorphisms flanking the CF transmembrane conductance regulator (CFTR) gene. delta F508 was present on one of the haplotypes in only 35% of CF chromosomes. We hypothesized that the other two CF haplotypes, one of which was the most common and the other of which is rare, each harbored different non-delta F508 mutations. Single-strand conformation polymorphism analysis detected a missense mutation, M1101K, in both chromosomes of a Hutterite patient carrying the two non-delta F508 haplotypes. M1101K appears to have originated on an uncommon CFTR allele and to be infrequent outside the Hutterite population. The presence of M1101K on two haplotypes is likely the result of a CFTR intragenic recombination which occurred since the founding, 10-12 generations ago, of the Hutterite population. The crossover was located between exons 14a and 17b, an interval of approximately 15 kbp. delta F508 and M1101K accounted for all of the CF mutations in patients from 16 CF families representing the three subdivisions of the Hutterite population.
哈特人种群是一个囊性纤维化（CF）发病率增加的遗传隔离群体。此前我们鉴定出了三种由囊性纤维化跨膜传导调节因子（CFTR）基因侧翼多态性定义的CF单倍型。ΔF508仅在35%的CF染色体的其中一种单倍型上出现。我们推测另外两种CF单倍型，其中一种是最常见的，另一种是罕见的，各自携带着不同的非ΔF508突变。单链构象多态性分析在一名携带两种非ΔF508单倍型的哈特人患者的两条染色体上检测到一个错义突变，即M1101K。M1101K似乎起源于一个不常见的CFTR等位基因，并且在哈特人种群之外很少见。M1101K在两种单倍型上的存在可能是CFTR基因内重组的结果，这种重组发生在哈特人种群大约10 - 12代前建立之时。交叉点位于外显子14a和17b之间，间隔约15千碱基对。ΔF508和M1101K占了代表哈特人种群三个分支的16个CF家族患者中所有的CF突变。
