Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds

Alex W. Hewitt, John R. Samples, R. Rand Allingham, Irma Järvelä, George Kitsos, Subbaiah R. Krishnadas, Julia E. Richards, Paul R. Lichter, Michael B. Petersen, Periasamy Sundaresan, Janey L. Wiggs, David A. Mackey, Mary Wirtz

Research output: Contribution to journalArticle

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Abstract

Purpose: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. Methods: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. Results: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. Conclusions: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies.

Original languageEnglish (US)
Pages (from-to)487-492
Number of pages6
JournalMolecular Vision
Volume13
StatePublished - 2007

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Founder Effect
Glaucoma
Greece
Mutation
HapMap Project
Linkage Disequilibrium
Haplotypes
Macedonia (Republic)
Information Storage and Retrieval
Finland
Pedigree
Microsatellite Repeats
Single Nucleotide Polymorphism
India
trabecular meshwork-induced glucocorticoid response protein
DNA
Population
Genes

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Hewitt, A. W., Samples, J. R., Allingham, R. R., Järvelä, I., Kitsos, G., Krishnadas, S. R., ... Wirtz, M. (2007). Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds. Molecular Vision, 13, 487-492.

Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds. / Hewitt, Alex W.; Samples, John R.; Allingham, R. Rand; Järvelä, Irma; Kitsos, George; Krishnadas, Subbaiah R.; Richards, Julia E.; Lichter, Paul R.; Petersen, Michael B.; Sundaresan, Periasamy; Wiggs, Janey L.; Mackey, David A.; Wirtz, Mary.

In: Molecular Vision, Vol. 13, 2007, p. 487-492.

Research output: Contribution to journalArticle

Hewitt, AW, Samples, JR, Allingham, RR, Järvelä, I, Kitsos, G, Krishnadas, SR, Richards, JE, Lichter, PR, Petersen, MB, Sundaresan, P, Wiggs, JL, Mackey, DA & Wirtz, M 2007, 'Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds', Molecular Vision, vol. 13, pp. 487-492.
Hewitt AW, Samples JR, Allingham RR, Järvelä I, Kitsos G, Krishnadas SR et al. Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds. Molecular Vision. 2007;13:487-492.
Hewitt, Alex W. ; Samples, John R. ; Allingham, R. Rand ; Järvelä, Irma ; Kitsos, George ; Krishnadas, Subbaiah R. ; Richards, Julia E. ; Lichter, Paul R. ; Petersen, Michael B. ; Sundaresan, Periasamy ; Wiggs, Janey L. ; Mackey, David A. ; Wirtz, Mary. / Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds. In: Molecular Vision. 2007 ; Vol. 13. pp. 487-492.
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AU - Kitsos, George

AU - Krishnadas, Subbaiah R.

AU - Richards, Julia E.

AU - Lichter, Paul R.

AU - Petersen, Michael B.

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AU - Wiggs, Janey L.

AU - Mackey, David A.

AU - Wirtz, Mary

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N2 - Purpose: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. Methods: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. Results: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. Conclusions: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies.

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