Gene conversion cetween functional trypsinogen genesPRSS1andPRSS2associated with chronic pancreatitis in a six-year-old girl
| العنوان: | Gene conversion cetween functional trypsinogen genesPRSS1andPRSS2associated with chronic pancreatitis in a six-year-old girl |
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| المؤلفون: | Niels Teich, Miklós Sahin-Tóth, Henrik Köhler, Zsofia Nemoda, Wolfram Heinritz, Volker Keim, Joachim Mössner |
| المصدر: | Human Mutation. 25:343-347 |
| بيانات النشر: | Hindawi Limited, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Adolescent, Trypsinogen, Pseudogene, Molecular Sequence Data, Gene Conversion, Biology, medicine.disease_cause, Article, chemistry.chemical_compound, Exon, Sequence Homology, Nucleic Acid, Genetics, medicine, Humans, PRSS2, Trypsin, Gene conversion, Pancreatitis, chronic, Child, Gene, Genetics (clinical), Mutation, Base Sequence, Models, Genetic, medicine.disease, Molecular biology, Pancreatitis, chemistry, Female |
| الوصف: | Gene conversion -- the substitution of genetic material from another gene -- is recognized as the underlying cause of a growing number of genetic diseases. While in most cases conversion takes place between a normal gene and its pseudogene, here we report an occurrence of disease-associated gene conversion between two functional genes. Chronic pancreatitis in childhood is frequently associated with mutations of the cationic trypsinogen gene (serine protease 1; PRSS1). We have analyzed PRSS1 in 1106 patients with chronic pancreatitis, and identified a novel conversion event affecting exon 2 and the subsequent intron. The recombination replaced at least 289 nucleotides with the paralogous sequence from the anionic trypsinogen gene (serine protease 2; PRSS2), and resulted in the PRSS1 mutations c.86A>T and c.161A>G, causing the amino acid substitutions N29I and N54S, respectively. Analysis of the recombinant N29I-N54S double mutant cationic trypsinogen revealed increased autocatalytic activation, which was solely due to the N29I mutation. In conclusion, we have demonstrated that gene conversion between two functional paralogous trypsinogen genes can occur and cause genetically determined chronic pancreatitis. |
| تدمد: | 1098-1004 1059-7794 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb7ebb6a09396455990c92b075d20ea7 https://doi.org/10.1002/humu.20148 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bb7ebb6a09396455990c92b075d20ea7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981004 10597794 |
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