Molecular Biology Reports 31: 97–105, 2004. © 2004 Kluwer Academic Publishers. Printed in the Netherlands. 97 Refining the DFNB17 interval in consanguineous Indian families Yingshi Guo 1 , Valentina Pilipenko 1 , Lynne H.Y. Lim 1 , Hongwei Dou 1 , Liane Johnson 1 , C.R. Srikumari Srisailapathy 2 , Arabandi Ramesh 2 , Daniel I. Choo 1 , Richard J.H. Smith 4 & John H. Greinwald 1,∗ 1 Center for Hearing and Deafness Research, Department of Otolaryngology, Cincinnati, Children’s Hos- pital Cincinnati, OH, USA; 2 Department of Genetics, University of Madras, Madras, India; 3 Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA, USA; ∗ Author for correspondence (Phone: 513-636-4870; Fax: 513-636-2886; E-mail: chdr@chdr.org) Accepted 5 January 2004 Key words: Deafness, genetic, Indian, nonsyndromic, DFNB17 Abstract We previously mapped the DFNB17 locus to a 3-4 cM interval on human chromosome 7q31 in a large consan- guineous Indian family with congenital profound sensorineural hearing loss. To further refine this interval, 30 new highly polymorphic markers and 8 SNPs were analyzed against the pedigree. Re-analysis in the original DFNB17 family and additional data from a second unrelated consanguineous family with congenital deafness found to map to the interval, limited the area of shared homozygosity-by-descent (HBD) to approximately 4 megabase (Mb) between markers D7S2453 and D7S525. Nineteen known genes and over 20 other cDNAs have been identified in the refined DFNB17 interval, including the SLC26A4 gene. We have analyzed 4 other cochlear-expressed genes that map to the DFNB17 interval as candidate genes. Analysis of coding and splice site regions of these cochlear expressed genes did not reveal any disease causing mutations. Further study of other candidate genes is currently underway. Introduction Hearing impairment is the most commonly diagnosed sensory deficit. Approximately 1 child in every 1500 is born with severe-to-profound sensorineural hearing loss (SNHL) [1]. With increasing age, the relative pre- valence of hearing loss increases to such an extent that 50% of octogenarians have an auditory deficit of at least a 25 dB SPL [2]. Although the etiology of hear- ing impairment is multifactoral, heredity plays a major role. In the neonatal population, hereditary hearing impairment (HHI) is responsible for at least 50% of cases of severe-to-profound hearing loss [3]. Identifying and understanding the genetic factors in patients and families with hearing impairment provides an excellent method to study the genes in- volved in the auditory system. In an attempt to fur- ther the understanding of HHI, the gene responsible for DFNB17 was mapped to chromosome 7q31 in a consanguineous Indian family [4]. Recombination events at markers D7S2529 and D7S486 defined a 4cM interval. Linkage analysis showed that markers homozygous-by-descent in this interval had a mul- tipoint LOD score of 4.24. Another deafness locus has been mapped to this region in a Lebanese family (DFNB14) and may represent the same gene [5]. In this report, we refine the DFNB17 interval to a more centromeric location after the additional analysis of closely placed polymorphic markers, reanalysis of the affected phenotype in the original family and the inclusion of a previously mapped family to the new DFNB17 interval. The refined interval is 3.98 Mb in physical length and contains over 40 known or pre- dicted genes. Cochlear expression and mutation ana- lysis of 3 known genes (SLC26A4, SLC26A3, LAMB1 [Locus link nos. 5172 , 1811 , 3912 , respectively]) and 2 previously uncharacterized genes (HBP1 and SYPL