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Evidence for a novel glaucoma locus at chromosome 3p21-22


Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the world. It is a clinically variable group of diseases with the majority of cases presenting as the late onset adult type. Several chromosomal loci have been implicated in disease aetiology, but causal mutations have only been identified in a small proportion of glaucoma. We have previously described a large six-generation Tasmanian family with POAG exhibiting genetic heterogeneity. In this family, approximately one third of affected individuals presented with a glutamine-368-STOP (Q368STOP) mutation in the myocilin gene. We now use a Markov Chain Monte Carlo (MCMC) method to identify a second disease region in this family on the short arm of chromosome 3. This disease locus was initially mapped to the marker D3S1298 and a subsequent minimum disease region of 9 cM between markers D3S1298 and D3S1289 was identified through additional mapping. The region did not overlap with any previously described locus for POAG. Using a multiplicative relative risk model, we identified a positive association between this region and the Q368STOP mutation of myocilin on chromosome 1 in affected individuals. These findings provide evidence of a new autosomal dominant glaucoma locus on the short arm of chromosome 3.

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We thank the members of the GIST team for their help in contacting and collecting family members for this study. We thank Cathy Green and Andrew McNaught for additional phenotyping, Maree Ring for genealogy and Dianne Beck, Pamela Sim, Lara Fitzgerald, Diane Arnold, Lynne Roe and Andrea Richardson for help with genotyping. This work was supported by the National Health and Medical Research Council of Australia, grant 128202 and the Dorothy Edols bequest.

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Correspondence to Paul N. Baird.

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Baird, P.N., Foote, S.J., Mackey, D.A. et al. Evidence for a novel glaucoma locus at chromosome 3p21-22. Hum Genet 117, 249–257 (2005). https://doi.org/10.1007/s00439-005-1296-x

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  • Glaucoma
  • Markov Chain Monte Carlo
  • Affected Individual
  • Primary Open Angle Glaucoma
  • Marker D3S1298