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