Informativeness of D۹S۱۸۷۶ Marker Located within the TMC۱ Gene in Iranian Population

Background and Objective: TMC۱ 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 TMC۱ 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 D۹S۱۸۷۶ 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 D۹S۱۸۷۶ locus located within the TMC۱ gene region was genotyped by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis (PAGE) and fluorescent capillary electrophoresis. The genotyping data from ۱۶۵ 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 ۹ alleles of D۹S۱۸۷۶ marker in Iranian population. The most frequent allele computed for ۱۴۸bp with ۳۴.۸۵% frequency. The maximum heterozygosity observed in Arab people with ۹۰.۹%. The data of PIC value demonstrated that the D۹S۱۸۷۶ marker was found highly informative in the population examined (PIC value above ۰.۷). Conclusion: D۹S۱۸۷۶ can be suggested as a highly informative marker for possible carrier detection and prenatal diagnosis of TMC۱ gene based ARNSHL by linkage analysis in Iranian population. References ۱- 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. ۱۹۹۳ ۴۶: ۴۸۶-۹۱. ۲- Kenneson A, Braun KVN, Boyle C. GJB۲ (connexin ۲۶) variants and nonsyndromic sensorineural hearing loss: a HuGE review. Genet Med. ۲۰۰۲ ۴: ۲۵۸-۷۴. ۳- Gorlin RJ, Toriello HV, Cohen MM. Hereditary hearing loss and its syndromes: Oxford University Press ۱۹۹۵. ۴- Hilgert N, Smith RJH, Van Camp G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics. Mutat Res. ۲۰۰۹ ۶۸۱ :۱۸۹-۹۶. ۵- Tabatabaiefar MA, Hashemzadeh Chaleshtori M. Genetic linkage analysis of ۱۵ DFNB Loci in a group of Iranian families with autosomal recessive hearing loss. Iran J Public Health. ۲۰۱۱ ۳۴-۴۸. ۶- Zhao H, Pfeiffer R, Gail MH. Haplotype analysis in population genetics and association studies. Pharmacogenomics. ۲۰۰۳ ۴: ۱۷۱-۸. ۷- Rabionet R, Zelante L, Lopez-Bigas N, et al. Molecular basis of childhood deafness resulting from mutations in the GJB۲ (connexin ۲۶) gene. Hum Gene. ۲۰۰۰ ۱۰۶: ۴۰-۴ ۸- Kurima K, Peters LM, Yang Y, et al. Dominant and recessive deafness caused by mutations of a novel gene, TMC۱, required for cochlear hair-cell function. Nat Genet. ۲۰۰۲ ۳۰: ۲۷۷-۸۴. ۹- De Heer A-M, Collin RW, Huygen PL, et al. Progressive sensorineural hearing loss and normal vestibular function in a Dutch DFNB۷/۱۱ family with a novel mutation in TMC۱. Audiol Neurotol. ۲۰۱۰ ۱۶: ۹۳-۱۰۵. ۱۰- Kitajiri S, McNamara R, Makishima T, et al. Identities, frequencies and origins of TMC۱ mutations causing DFNB۷/B۱۱ deafness in Pakistan. Clin Genet. ۲۰۰۷ ۷۲: ۵۴۶-۵۰. ۱۱- Meyer CG, Gasmelseed NM, Mergani A, et al. Novel TMC۱ structural and splice variants associated with congenital nonsyndromic deafness in a Sudanese pedigree. Hum Mutat. ۲۰۰۵ ۲۵: ۱۰۰. ۱۲- Sirmaci A, Duman D, Öztürkmen-Akay H, et al. Mutations in TMC۱ contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations. Int J Pediatr Otorhinolaryngol. ۲۰۰۹ ۷۳: ۶۹۹-۷۰۵. ۱۳- Yazdanpanahi N, Chaleshtori MH, Tabatabaiefar MA, et al. The novel TMC۱ mutations in Iranian families with autosomal recessive hearing loss. Int J Pediatr Otorhinolaryngol. ۲۰۱۲ ۷۶: ۸۴۵-۵۰. ۱۴- Gibbs RA, Belmont JW, Hardenbol P, et al. The international hapmap project. Nature. ۲۰۰۳ ۴۲۶: ۷۸۹-۹۶. ۱۵- Elahi E, Kumm J, Ronaghi M. Global genetic analysis. J Biochem Mol Biol. ۲۰۰۴ ۳۷: ۱۱-۲۷. ۱۶- Hildebrand CE, David C, Torney WRP, Wagner P. Informativeness of polymorphic DNA markers. Los Alamos Science. ۱۹۹۲ ۲۰:۱۰۰-۲. ۱۷- UniSTS database. Available from: http://www.ncbi.nlm.nih.gov/probe? ۱۸- Mammalian Genotyping Service. Available from: http://research.marshfieldclinic.org ۱۹- Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. ۱۹۸۸ ۱۶: ۱۲۱۵. ۲۰- Raymond M, Rousset F. Population genetics software for exact tests and ecumenicism. Evolution. ۱۹۹۵ ۴۹:۱۲۸۰-۳. ۲۱- Weir BS. Genetic data analysis II: methods for discrete population genetic data. Sinauer associates, Inc ۱۹۹۶. ۲۲- Engels WR. Exact tests for hardy-weinberg proportions. Genetics. ۲۰۰۹ ۱۸۳: ۱۴۳۱-۴۱. ۲۳- Guo SW, Thompson EA. Performing the exact test of hardy-weinberg proportion for multiple alleles. Biometrics. ۱۹۹۲ ۴۸: ۳۶۱-۷۲. ۲۴- Park SDE. Trypanotolerance in West African cattle and the population genetic effects of selection. Ph D thesis, Dublin University. ۲۰۰۱.

Keywords:

Keywords: ARNSHL , Heterozygosity , TMC۱ gene , Microsatellite Repeats