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Human Genetics

, Volume 118, Issue 5, pp 605–610 | Cite as

A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3

  • Muhammad Jawad Hassan
  • Regie Lyn P. Santos
  • Muhammad Arshad Rafiq
  • Maria H. Chahrour
  • Thanh L. Pham
  • Muhammad Wajid
  • Nadine Hijab
  • Michael Wambangco
  • Kwanghyuk Lee
  • Muhammad Ansar
  • Kai Yan
  • Wasim Ahmad
  • Suzanne M. LealEmail author
Original Investigation

Abstract

Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for ~75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants.

Keywords

Hearing Impairment Marker D2S2952 Autosomal Recessive Multipoint Linkage Analysis Autosomal Recessive Mode 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We wish to thank the family members for their invaluable participation and cooperation. This work was supported by the Higher Education Commission, Pakistan, the American Hearing Research Foundation, and the National Institutes of Health—National Institute of Deafness and other Communication Disorders grant R01-DC03594. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number N01-HG-65403.

References

  1. Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101PubMedCrossRefGoogle Scholar
  2. Broman K, Murray JC, Scheffield VC, White RL, Weber JL (1998) Comprehensive human genetic maps: individual and sex specific variation in recombination. Am J Hum Genet 63:861–869CrossRefPubMedGoogle Scholar
  3. Calzado MA, Sancho R, Munoz E (2004) Human immunodeficiency virus type 1 Tat increases the expression of cleavage and polyadenylation specificity factor 73-kilodalton subunit modulating cellular and viral expression. J Virol 78:6846–6854CrossRefPubMedGoogle Scholar
  4. Cottingham R, Indury RM, Schaffer AA (1993) Faster sequential genetic linkage computations. Am J Hum Genet 53:252–263PubMedGoogle Scholar
  5. Freimer NB, Sandkuijl LA, Blower SM (1993) Incorrect specification of marker allele frequencies: effects on linkage analysis. Am J Hum Genet 52:1102–1110PubMedGoogle Scholar
  6. Grimberg J, Nawoschik S, Bellusico L, McKee R, Turck A, Eisenberg A (1999) A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res 17:83–90Google Scholar
  7. Gudbjartsson DF, Jonasson K, Frigge ML, Kong A (2002) Allegro, a new computer program for multipoint linkage analysis. Nat Genet 25:12–13CrossRefGoogle Scholar
  8. Holme RH, Bussoli TJ, Steel KP (2002) Table of gene expression in the developing ear. URL: http://www.ihr.mrc.ac.uk/hereditary/genetable/search.shtml
  9. Ilhan A, Tuncer C, Komsuoglu SS, Kali S (1999) Jervell and Lange-Nielsen syndrome: neurologic and cardiologic evaluation. Pediatr Neurol 21:809–813CrossRefPubMedGoogle Scholar
  10. International Human Genome Sequence Consortium (2001) Initial sequence and analysis of the human genome. Nature 409:860–921CrossRefGoogle Scholar
  11. Jen Y, Manova K, Benezra R (1997) Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis. Dev Dyn 208:92–106CrossRefPubMedGoogle Scholar
  12. Kong X, Murphy K, Raj T, He C, White PS, Matise TC (2004) A combined linkage-physical map of the human genome. Am J Hum Genet 75:1143–1148CrossRefPubMedGoogle Scholar
  13. Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ (1999) KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 96:437–446CrossRefPubMedGoogle Scholar
  14. Malaspina A, Kaushik N, de Belleroche J (2000) A 14–3-3 mRNA is up-regulated in amyotrophic lateral sclerosis spinal cord. J Neurochem 75:2511–2520CrossRefPubMedGoogle Scholar
  15. Morton NE (1991) Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 630:16–31PubMedCrossRefGoogle Scholar
  16. Petit C (1996) Genes responsible for human hereditary deafness: symphony of a thousand. Nat Genet 14:385–391CrossRefPubMedGoogle Scholar
  17. O’Connell JR, Weeks DE (1998) PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63:259–266CrossRefPubMedGoogle Scholar
  18. Rozen S, Skaletsky HJ (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics methods and protocols: methods in molecular biology. Humana, NJ, pp 365–386Google Scholar
  19. Schuler GD (1997) Sequence mapping by electronic PCR. Genome Res 7:541–550PubMedGoogle Scholar
  20. Smith AN, Borthwick KJ, Karet FE (2002) Molecular cloning and characterization of novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation in autosomal recessive distal renal tubular acidosis. Gene 297:169–177CrossRefPubMedGoogle Scholar
  21. Sobel E, Lange K (1996) Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet 58:1323–1337PubMedGoogle Scholar
  22. Steel KP, Bussoli TJ (1999) Deafness genes: expressions of surprise. Trends Genet 15:207– 211PubMedCrossRefGoogle Scholar
  23. Su K, Kyaw H, Fan P, Zeng Z, Shell BK, Carter KC, Li Y (1997) Isolation, characterization, and mapping of two human potassium channels. Biochem Biophys Res Commun 241:675–681CrossRefPubMedGoogle Scholar
  24. The Hearing Research Group at Brigham & Women’s Hospital (2002) Human Cochlear cDNA library and EST database. URL: http://www.hearing.bwh.harvard.edu/estinfo.htm
  25. Van Camp G, Smith RJH (2005) Hereditary Hearing Loss Homepage. URL: http://www.webhost.ua.ac.be/hhh/
  26. Weeks DE, Sobel E, O’Connell JR, Lange K (1995) Computer programs for multilocus haplotyping of general pedigrees. Am J Hum Genet 56:1506–1507PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Muhammad Jawad Hassan
    • 1
  • Regie Lyn P. Santos
    • 2
  • Muhammad Arshad Rafiq
    • 3
  • Maria H. Chahrour
    • 2
  • Thanh L. Pham
    • 2
  • Muhammad Wajid
    • 1
  • Nadine Hijab
    • 2
  • Michael Wambangco
    • 2
  • Kwanghyuk Lee
    • 2
  • Muhammad Ansar
    • 3
  • Kai Yan
    • 2
  • Wasim Ahmad
    • 1
  • Suzanne M. Leal
    • 2
    Email author
  1. 1.Department of Biological SciencesQuaid-I-Azam UniversityIslamabadPakistan
  2. 2.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  3. 3.Department of BiosciencesCOMSATS Institute of Information TechnologyIslamabadPakistan

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