Analysis of DNA elements that modulate myosin VIIA expression in humans.

D. J. Orten, M. D. Weston, P. M. Kelley, C. W. Cremers, M. Wagenaar, S. G. Jacobson, W. J. Kimberling

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Usher syndromeIb (USH1B), an autosomal recessive disorder caused by mutations in myosin VIIa (MYO7A), is characterized by congenital profound hearing loss, vestibular abnormalities and retinitis pigmentosa. Promoter elements in the 5 kb upstream of the translation start were identified using adult retinal pigment epithelium cells (ARPE-19) as a model system. A 160 bp minimal promoter within the first intron was active in ARPE-19 cells, but not in HeLa cells that do not express MYO7A. A 100 bp sequence, 5' of the first exon, and repeated with 90% homology within the first intron, appeared to modulate expression in both cell lines. Segments containing these elements were screened by heteroduplex analysis. No heteroduplexes were detected in the minimal promoter, suggesting that this sequence is conserved. A -2568 A>T transversion in the 5' 100 bp repeat, eliminating a CCAAT element, was found only in USH1B patients. However, in all 5 families, -2568 A>T was in cis with the same missense mutation in the myosin VIIa tail (Arg1240Gln), and 4 of the 5 families were Dutch. These observations suggest either 1) linkage disequilibrium or 2)that a combination of a promoter mutation with a less active myosin VIIa protein results in USH1B.

Original languageEnglish (US)
Number of pages1
JournalHuman mutation
Volume14
Issue number4
DOIs
StatePublished - Oct 1999

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Myosins
Introns
DNA
Heteroduplex Analysis
Mutation
Retinitis Pigmentosa
Retinal Pigment Epithelium
Conserved Sequence
Linkage Disequilibrium
Missense Mutation
HeLa Cells
Hearing Loss
Tail
Exons
Cell Line
myosin VIIa
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Orten, D. J., Weston, M. D., Kelley, P. M., Cremers, C. W., Wagenaar, M., Jacobson, S. G., & Kimberling, W. J. (1999). Analysis of DNA elements that modulate myosin VIIA expression in humans. Human mutation, 14(4). https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<354::AID-HUMU18>3.0.CO;2-Z

Analysis of DNA elements that modulate myosin VIIA expression in humans. / Orten, D. J.; Weston, M. D.; Kelley, P. M.; Cremers, C. W.; Wagenaar, M.; Jacobson, S. G.; Kimberling, W. J.

In: Human mutation, Vol. 14, No. 4, 10.1999.

Research output: Contribution to journalArticle

Orten, DJ, Weston, MD, Kelley, PM, Cremers, CW, Wagenaar, M, Jacobson, SG & Kimberling, WJ 1999, 'Analysis of DNA elements that modulate myosin VIIA expression in humans.', Human mutation, vol. 14, no. 4. https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<354::AID-HUMU18>3.0.CO;2-Z
Orten, D. J. ; Weston, M. D. ; Kelley, P. M. ; Cremers, C. W. ; Wagenaar, M. ; Jacobson, S. G. ; Kimberling, W. J. / Analysis of DNA elements that modulate myosin VIIA expression in humans. In: Human mutation. 1999 ; Vol. 14, No. 4.
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