May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Analysis and Evolution of the LOC387715 Gene and HTRA1 Promoter Sequence Within Primates
Author Affiliations & Notes
  • B. Appukuttan
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • C. Runckel
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • E. Simmons
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • T. J. McFarland
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • Y. Zhang
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • P. Francis
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • D. Schultz
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • J. T. Stout
    Retina, Casey Eye Institute, Biomedical Research Building, Oregon Health & Science University, Portland, Oregon
  • Footnotes
    Commercial Relationships B. Appukuttan, None; C. Runckel, None; E. Simmons, None; T.J. McFarland, None; Y. Zhang, None; P. Francis, None; D. Schultz, None; J.T. Stout, None.
  • Footnotes
    Support Clayton Foundation for Research, Research to Prevent Blindness, The Foundation Fighting Blindness, Macular Vision Research Foundation, NIH Grant EY01223-06A2
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3788. doi:
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      B. Appukuttan, C. Runckel, E. Simmons, T. J. McFarland, Y. Zhang, P. Francis, D. Schultz, J. T. Stout; Analysis and Evolution of the LOC387715 Gene and HTRA1 Promoter Sequence Within Primates. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3788.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Single nucleotide polymorphisms (SNP) within LOC387715, a transcribed locus, and the promoter of the HTRA1 gene have been shown to be strongly associated with age-related macular degeneration (AMD). The LOC387715 SNP is situated 6102bp 5’ to the HTRA1 promoter SNP on chromosome 10q26. The human LOC387715 transcript includes two exons and is presumed to be a primate specific gene. The LOC387715 SNP is expected to alter an amino acid within the predicted protein. To determine whether this AMD susceptibility region is conserved within the primate lineage, we aim to isolate and compare the DNA sequences of LOC387715 from several non-human primates.

Methods:: Consensus primers were designed to human and chimp gDNA at the relevant LOC387715 and HTRA1 loci. Primers were tested for gDNA amplification from a variety of Old (Pan paniscus, Pan troglodyte, Gorilla gorilla, Pongo pygmaeus, Macaca mulatta, Macaca nemestrina) and New (Lagothrix lagotricha, Ateles geoffroyi, Saguinus labiatus) World monkeys (OWM, NWM) and a prosimian (Lemur catta). Human gDNA was used as a control. Amplified products were purified and sequenced.

Results:: Primers designed to exon 1 of LOC387715 amplified products of the expected size from all OWM and NWM, however no product was obtained from the prosimian. All primate exon 1 products share 78% sequence identity. Chimp, bonobo, gorilla, and the NWM have the same predicted ATG start site. Orangutan has a CTG codon while rhesus and pig-tailed macaque possess a GTG codon at the equivalent site. Primers designed to exon 2 of LOC387715 amplified products of the expected size from all OWM only. The predicted TGA stop codon situated within exon 2 at codon 108 is only present within the hominid group. Cercopithecoid monkeys have a CGA at codon 108 and an alternative in frame TAA stop codon 8 codons downstream. The human and bonobo LOC387715 sequence is predicted to code for 107 amino acid protein. The gorilla sequence has a premature TGA stop at codon 38. The AMD susceptibility codon is conserved in OWM & NWM lineages.

Conclusions:: The sequence of the first of the 2 exons of LOC387715 may have arisen after the split of prosimians and anthropoids about 60-65 million years ago (mya). The 2nd exon conserved in OWM only may have evolved after the division of OWM and NWM approximately 40-50mya. The fact that the predicted ATG start and TGA stop sites are not present in all non-human primates may indicate that LOC387715 translation is restricted to humans and chimps, or that the RNA produced has an alternative function or is a pseudogene.

Keywords: age-related macular degeneration • genetics 
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