Hostname: page-component-6766d58669-h8lrw Total loading time: 0 Render date: 2026-05-18T08:03:12.361Z Has data issue: false hasContentIssue false
  • English
  • Français

No evidence of linkage between 7q33–36 locus (OTSC2) and otosclerosis in seven British Caucasian pedigrees

Published online by Cambridge University Press:  02 October 2007

F Q Alzoubi ,
W R Ollier ,
R T Ramsden  and
S R Saeed
F Q Alzoubi
Affiliation:
Otolaryngology Department, Jordan University of Science and Technology, Irbid, Jordan
W R Ollier
Affiliation:
Centre for Integrated Genomic Medical Research, University of Manchester
R T Ramsden
Affiliation:
Otolaryngology Department, Central Manchester and Manchester Children's Hospitals NHS Trust and Salford Royal Hospital NHS Trust, Manchester, UK
S R Saeed*
Affiliation:
Otolaryngology Department, Central Manchester and Manchester Children's Hospitals NHS Trust and Salford Royal Hospital NHS Trust, Manchester, UK
*
Address for correspondence: Mr S R Saeed, Consultant ENT and Skull Base Surgeon, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. E-mail: s.r.saeed@btopenworld.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

The aetiology of otosclerosis is complex, and probably involves an interaction between genes and environmental factors. Previous studies have revealed genetic linkage with a number of chromosome regions, including position 7q33–36.

Aim:

To confirm whether linkage exists between otosclerosis and chromosome region 7q33–36.

Materials and methods:

Seven multiply affected families were ascertained. Deoxyribonucleic acid from members of these families was extracted, and six markers were genotyped to cover a 16 cM region at 7q33–36. Both parametric and non-parametric multipoint linkage analyses were performed.

Results:

Parametric multipoint linkage analysis excluded any linkage at 7q33–36 (logarithm of odds score <−4.0). Non-parametric linkage analysis also failed to confirm any linkage (non-parametric linkage < 1.66). When tested individually, pedigree four was the only one to show a significant non-parametric linkage score between D7s684 and D7s2513 (non-parametric linkage = 1.96).

Conclusion:

No linkage was detected between otosclerosis and the 7q33–36 region. This could be explained by the study's lack of power, due to the limited number of families available.

Keywords

OtosclerosisGeneticsGenetic LinkageLod ScoreChromosomesHumanPair 7

Information

Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 121 , Issue 12 , December 2007 , pp. 1140 - 1147
Copyright
Copyright © JLO (1984) Limited 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1 Gordon, MA. The genetics of otosclerosis: a review. Am J Otol 1989;10:426–38Google ScholarPubMed
2 Dahlqvist, A, Beckman, G, Beckman, L, Sikstrom, C. GC serum groups and otosclerosis. Acta Otolaryngol 1991;111:1105–8Google Scholar
3 Declau, F, Van Spaendonck, M, Timmermans, JP, Michaels, L, Liang, J, Qiu, JP et al. Prevalence of otosclerosis in a non-selected series of temporal bones. Otol Neurotol 2001;22:596–602CrossRefGoogle Scholar
4 Somers, T, Govaerts, P, Marquet, T, Offeciers, E. Statistical analysis of otosclerosis surgery performed by Jean Marquet. Ann Otol Rhinol Laryngol 1994;103:945–51Google Scholar
5 Browning, GG, Gatehouse, S. Sensorineural hearing loss in stapedial otosclerosis. Ann Otol Rhinol Laryngol 1984;93:13–16CrossRefGoogle ScholarPubMed
6 Ramsay, HA, Linthicum, FH Jr. Mixed hearing loss in otosclerosis: indication for long-term follow-up. Am J Otol 1994;15:536–9Google Scholar
7 Morrison, AW. Genetic factors in otosclerosis. Ann R Coll Surg Engl 1967;41:202–37Google ScholarPubMed
8 Causse, JR, Causse, JP. Otospongiosis as a genetic disease. Early detection, medical management, and prevention. Am J Otol 1984;5:211–23Google Scholar
9 Ben Arab, S, Bonaiti-Pellie, C, Belkahia, A. A genetic study of otosclerosis in a population living in the north of Tunisia. Ann Genet 1993;36:111–16Google Scholar
10 Cawthorn, T. Otosclerosis. J Laryngol Otol 1955;69:437–56CrossRefGoogle Scholar
11 Shambaugh, GE. Otosclerosis. In: Coates, GM, Schenk, HP, Miller, MV, eds. Otolaryngology. Hagerstown: WF Prior, 1956;2:1–17Google Scholar
12 Arnold, W, Friedmann, I. Immunohistochemistry of otosclerosis. Acta Otolaryngol Suppl 1990;470:124–9Google Scholar
13 Tomek, MS, Brown, MR, Mani, SR, Ramesh, A, Srisailapathy, CR, Coucke, P et al. Localization of a gene for otosclerosis to chromosome 15q25–q26. Hum Mol Genet 1998;7:285–90CrossRefGoogle ScholarPubMed
14 Van Den Bogaert, K, Govaerts, PJ, Schatteman, I, Brown, MR, Caethoven, G, Offeciers, FE et al. A second gene for otosclerosis, OTSC2, maps to chromosome 7q34–36. Am J Hum Genet 2001;68:495–500CrossRefGoogle ScholarPubMed
15 Chen, W, Campbell, CA, Green, GE, Van Den Bogaert, K, Komodikis, C, Manolidis, LS et al. Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3–22.3. J Med Genet 2002;39:473–7Google Scholar
16 Brownstein, Z, Goldfarb, A, Levi, H, Frydman, M, Avraham, KB. Chromosomal mapping and phenotypic characterization of hereditary otosclerosis linked to the OTSC4 locus. Arch Otolaryngol Head Neck Surg 2006;132:416–24CrossRefGoogle Scholar
17 Van Den Bogaert, K, De Leenheer, EM, Chen, W, Lee, Y, Nurnberg, P, Pennings, RJ et al. A fifth locus for otosclerosis, OTSC5, maps to chromosome 3q22–24. J Med Genet 2004;41:450–3Google Scholar
18 Van Den Bogaert, K, Govaerts, PJ, De Leenheer, EM, Schatteman, I, Verstreken, M, Chen, W et al. Otosclerosis: a genetically heterogeneous disease involving at least three different genes. Bone 2002;30:624–30Google Scholar
19 Di Leva, F, D'Adamo, AP, Strollo, L, Auletta, G, Caravelli, A, Carella, M et al. Otosclerosis: exclusion of linkage to the OTSC1 and OTSC2 loci in four Italian families. Int J Audiol 2003;42:475–80CrossRefGoogle Scholar
20 Govaerts, PJ, Somers, T, Offeciers, FE. Box and whisker plots for graphic presentation of audiometric results of conductive hearing loss treatment. Otolaryngol Head Neck Surg 1998;118:892–5Google Scholar
21 Marshfield Medical Research Foundation. http://research.marshfieldclinic.org/genetics/MarkerSearch/searchMarkers.asp [15 December 2006]Google Scholar
22 Ploughman, LM, Boehnke, M. Estimating the power of a proposed linkage study for a complex genetic trait. Am J Hum Genet 1989;44:543–51Google Scholar
23 GAS program http://users.ox.ac.uk/~ayoung/gas.html. [15 December 2006]Google Scholar
24 O'Connell, JR, Weeks, DE. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998;63:259–66CrossRefGoogle ScholarPubMed
25 SPLINK Linkage analysis program. http://www-gene.cimr.cam.ac.uk/clayton/software/ [15 December 2006]Google Scholar
26 Kruglyak, L, Daly, MJ, Reeve-Daly, MP, Lander, ES. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 1996;58:1347–63Google Scholar
27 Morton, NE. Sequential tests for the detection of linkage. Am J Hum Genet 1955;7:277–318Google Scholar
28 Larsson, A. Otosclerosis. A genetic and clinical study. Acta Otolaryngol Suppl 1960;154:1–86Google ScholarPubMed
29 Morrison, AW, Bundey, SE. The inheritance of otosclerosis. J Larygol Otol 1970;84:921–32Google Scholar
30 Hernandez-Orozco, F, Courtney, GT. Genetic aspects of clinical otosclerosis. Ann Otol Rhinol Laryngol 1964;73:632–44Google Scholar