Chen J M, Ferec C
Centre de Biogenetique, University Hospital, ETSBO, Brest, France.
Hum Genet. 2000 Jan;106(1):125-6. doi: 10.1007/s004390051019.
The N21I missense mutation in the cationic trypsinogen gene is the second most frequent mutation in hereditary pancreatitis (HP). In this article, we suggest that the N21I mutation most likely arose as a gene conversion event in which the functional anionic trypsinogen gene acted as the donor sequence. This hypothesis is supported by the unique presence of Ile at residue 21 of the anionic gene amongst the several highly homologous trypsinogen genes; a single unbroken tract of nucleotides of up to 113 bp flanking the I21 residue in the anionic trypsinogen gene; and the presence of a chi-like sequence in the 5' proximity and a palindromic sequence in the 3' vicinity of the N21I mutation. Furthermore, a multiple alignment of the partial amino acid sequence of vertebrate trypsins around residue 21 indicated that N21 and I21 may represent advantageously selected mutations of the two functional human trypsinogen genes in evolutionary history. These observations, which are complementary to the previous findings, provide further insights into the genetic mechanism and pathogenic role of the N21I mutation in HP.
阳离子胰蛋白酶原基因中的N21I错义突变是遗传性胰腺炎（HP）中第二常见的突变。在本文中，我们认为N21I突变很可能是作为一种基因转换事件出现的，其中功能性阴离子胰蛋白酶原基因充当了供体序列。这一假说得到了以下几点的支持：在几个高度同源的胰蛋白酶原基因中，阴离子基因第21位残基处独特地存在异亮氨酸；阴离子胰蛋白酶原基因中I21残基两侧有长达113 bp的单一不间断核苷酸序列；以及在N21I突变的5'端附近存在一个类chi序列，在3'端附近存在一个回文序列。此外，对脊椎动物胰蛋白酶第21位残基周围部分氨基酸序列的多重比对表明，N21和I21可能代表了在进化史上两种功能性人类胰蛋白酶原基因经有利选择的突变。这些观察结果与之前的发现相互补充，为HP中N21I突变的遗传机制和致病作用提供了进一步的见解。
