A common ancestral origin of the frequent and widespread 2299delG USH2A mutation

Bo Dreyer, Lisbeth Tranebjærg, Vigdis Brox, Thomas Rosenberg, Claes Möller, Magdalena Beneyto, Michael D. Weston, William J Kimberling, Øivind Nilssen

Research output: Contribution to journalArticle

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Abstract

Usher syndrome type IIa is an autosomal recessive disorder characterized by mild-to-severe hearing loss and progressive visual loss due to retinitis pigmentosa. The mutation that most commonly causes Usher syndrome type IIa is a 1-bp deletion, described as "2299delG," in the USH2A gene. The mutation has been identified in several patients from northern and southern Europe and from North America, and it has been found in single patients from South America, South Africa, and China. Various studies have reported a range of frequencies (.16-.44) among patients with Usher syndrome, depending on the geographic origin of the patients. The 2299delG mutation may be the one that most frequently causes retinitis pigmentosa in humans. Given the high frequencies and the wide geographic distribution of the mutation, it was of interest to determine whether the mutation resulted from an ancestral mutational event or represented a mutational hotspot in the USH2A gene. Haplotype analysis was performed on DNA samples from 116 unrelated patients with Usher syndrome type IIa; the patients were from 14 countries and represented 148 2299delG alleles. On the basis of six single-nucleotide polymorphisms within the USH2A gene, 12 core haplotypes were observed in a panel of normal chromosomes. However, in our analysis, only one core haplotype was found to be associated with the 2299delG mutation. The data indicate that the widespread geographic distribution of the 2299delG mutation is the result of an ancestral mutation that has spread throughout Europe and into the New World as a result of migration.

Original languageEnglish (US)
Pages (from-to)228-234
Number of pages7
JournalAmerican Journal of Human Genetics
Volume69
Issue number1
DOIs
StatePublished - Jan 1 2001

Fingerprint

Usher Syndromes
Mutation
Haplotypes
Retinitis Pigmentosa
Genes
South America
North America
South Africa
Hearing Loss
Single Nucleotide Polymorphism
China
Chromosomes
Alleles
DNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Dreyer, B., Tranebjærg, L., Brox, V., Rosenberg, T., Möller, C., Beneyto, M., ... Nilssen, Ø. (2001). A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. American Journal of Human Genetics, 69(1), 228-234. https://doi.org/10.1086/321269

A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. / Dreyer, Bo; Tranebjærg, Lisbeth; Brox, Vigdis; Rosenberg, Thomas; Möller, Claes; Beneyto, Magdalena; Weston, Michael D.; Kimberling, William J; Nilssen, Øivind.

In: American Journal of Human Genetics, Vol. 69, No. 1, 01.01.2001, p. 228-234.

Research output: Contribution to journalArticle

Dreyer, B, Tranebjærg, L, Brox, V, Rosenberg, T, Möller, C, Beneyto, M, Weston, MD, Kimberling, WJ & Nilssen, Ø 2001, 'A common ancestral origin of the frequent and widespread 2299delG USH2A mutation', American Journal of Human Genetics, vol. 69, no. 1, pp. 228-234. https://doi.org/10.1086/321269
Dreyer B, Tranebjærg L, Brox V, Rosenberg T, Möller C, Beneyto M et al. A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. American Journal of Human Genetics. 2001 Jan 1;69(1):228-234. https://doi.org/10.1086/321269
Dreyer, Bo ; Tranebjærg, Lisbeth ; Brox, Vigdis ; Rosenberg, Thomas ; Möller, Claes ; Beneyto, Magdalena ; Weston, Michael D. ; Kimberling, William J ; Nilssen, Øivind. / A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. In: American Journal of Human Genetics. 2001 ; Vol. 69, No. 1. pp. 228-234.
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