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Autosomal recessive retinitis pigmentosa, identification and partial characterisation of a novel gene implicated in RP25

O’Driscoll, C.A.; (2010) Autosomal recessive retinitis pigmentosa, identification and partial characterisation of a novel gene implicated in RP25. Doctoral thesis, UCL (University College London). Green open access

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Abstract

The purpose of this project is to identify the causative gene for one type of autosomal recessive retinitis pigmentosa, RP25. Through CGH (comparative genome hybridisation) and mutation screening, independent mutations were identified in arRP affected Spanish families mapping to RP25. These mutations were identified within a cluster of uncharacterised gene transcripts all which have EGF-like repeat domains; Q5T669, Q5T1H1, Q9H557_human, Q5TEL3_human, Q5TEL4_human, Q5VVG4_human, and Q5T3C8. Through 5` and 3` RACE PCR analysis, the full length gene was revealed to incorporate the EGFL11 gene. On assembling all available data we noted that RP25 gene encompasses 30 exons belonging to nine previously predicted genes and 13 newly identified exons, totaling 43 exons and spanning the interval between 64,487,835 and 66,473,839 on chromosome 6q12. The RP25 full length gene transcript is retinal specific. The genomic length covers over 2.0 MB in size and is therefore the largest eye specific gene identified to date. It is also the fifth largest gene in the human genome to date. Homologs of the RP25 gene to Drosophila eys/eys-shut (Spacemaker) were identified, leading to the annotation of the name EYS (SPAM). An apparently intact eys gene is found across the mammalian clade, including monotremes (platypus) and marsupials (opossum). However, despite the mutations and the presumed loss of function associated with human disease, this gene has been dispensed with on at least four separate occasions in the last 100 million years of mammalian evolution including in the armadillo (Dasypus novemcinctus), little brown bat (Myotis lucifugus) and ruminant (cattle and sheep) lineages. EYS has acquired several (<3) reading-frame disruptions in three rodents (mouse, rat and guinea pig) representing two of the three major rodent clades. Through immunohistochemical and electron microscopy analysis, a signal for SPAM was identified in the outer segments of photoreceptor cells.

Type:Thesis (Doctoral)
Title:Autosomal recessive retinitis pigmentosa, identification and partial characterisation of a novel gene implicated in RP25
Open access status:An open access version is available from UCL Discovery
Language:English
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology

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