بررسی اطلاعدهندگی مارکر D9S1876 واقع در ناحیه ژنTMC1 در جمعیت ایرانی
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Abstract:
Background and Objective: TMC1 gene mutations are known as the most common causes of autosomal recessive non-syndromic hearing loss (ARNSHL) in different populations. According to large size of the TMC1 gene and the large number of identified mutations in this gene, application of polymorphic markers is suggested for carrier detection and prenatal diagnosis in families. In this study, informativeness of D9S1876 STR marker with CA repeat was evaluated in five various ethnic groups of the Iranian population including Fars, Azeri, Turkmen, Gilak and Arab. Materials and Methods: The D9S1876 locus located within the TMC1 gene region was genotyped by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis (PAGE) and fluorescent capillary electrophoresis. The genotyping data from 165 unrelated healthy individuals were analyzed by GeneMarker HID Human STR Identity software, GenePop program and Microsatellite Tools software. Results: The obtained results via GenePop indicated the presence of 9 alleles of D9S1876 marker in Iranian population. The most frequent allele computed for 148bp with 34.85% frequency. The maximum heterozygosity observed in Arab people with 90.9%. The data of PIC value demonstrated that the D9S1876 marker was found highly informative in the population examined (PIC value above 0.7). Conclusion: D9S1876 can be suggested as a highly informative marker for possible carrier detection and prenatal diagnosis of TMC1 gene based ARNSHL by linkage analysis in Iranian population. References 1- Marazita ML, Ploughman LM, Rawlings B, Remington E, Arnos KS, Nance WE. Genetic epidemiological studies of early-onset deafness in the US school-age population. Am J Med Genet. 1993 46: 486-91. 2- Kenneson A, Braun KVN, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review. Genet Med. 2002 4: 258-74. 3- Gorlin RJ, Toriello HV, Cohen MM. Hereditary hearing loss and its syndromes: Oxford University Press 1995. 4- Hilgert N, Smith RJH, Van Camp G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics. Mutat Res. 2009 681 :189-96. 5- Tabatabaiefar MA, Hashemzadeh Chaleshtori M. Genetic linkage analysis of 15 DFNB Loci in a group of Iranian families with autosomal recessive hearing loss. Iran J Public Health. 2011 34-48. 6- Zhao H, Pfeiffer R, Gail MH. Haplotype analysis in population genetics and association studies. Pharmacogenomics. 2003 4: 171-8. 7- Rabionet R, Zelante L, Lopez-Bigas N, et al. Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. Hum Gene. 2000 106: 40-4 8- Kurima K, Peters LM, Yang Y, et al. Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet. 2002 30: 277-84. 9- De Heer A-M, Collin RW, Huygen PL, et al. 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The international hapmap project. Nature. 2003 426: 789-96. 15- Elahi E, Kumm J, Ronaghi M. Global genetic analysis. J Biochem Mol Biol. 2004 37: 11-27. 16- Hildebrand CE, David C, Torney WRP, Wagner P. Informativeness of polymorphic DNA markers. Los Alamos Science. 1992 20:100-2. 17- UniSTS database. Available from: http://www.ncbi.nlm.nih.gov/probe? 18- Mammalian Genotyping Service. Available from: http://research.marshfieldclinic.org 19- Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 16: 1215. 20- Raymond M, Rousset F. Population genetics software for exact tests and ecumenicism. Evolution. 1995 49:1280-3. 21- Weir BS. Genetic data analysis II: methods for discrete population genetic data. Sinauer associates, Inc 1996. 22- Engels WR. Exact tests for hardy-weinberg proportions. Genetics. 2009 183: 1431-41. 23- Guo SW, Thompson EA. 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volume 23 issue 97
pages 61- 71
publication date 2015-04
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