Transposed elements constitute an attractive, useful source of phylogenetic markers to elucidate the evolutionary history of their hosts. Frequent and successive amplifications over evolutionary time are important requirements for utilizing their presence or absence as landmarks of evolution. Although transposed elements are well distributed in rodent taxa, the generally high degree of genomic sequence divergence among species complicates our access to presence/absence data. With this in mind we developed a novel, high-throughput computational strategy, called CPAL (Conserved Presence/Absence Locus-finder), to identify genome-wide distributed, phylogenetically informative transposed elements flanked by highly conserved regions. From a total of 232 extracted chromosomal mouse loci we randomly selected 14 of these plus 2 others from previous test screens and attempted to amplify them via PCR in representative rodent species. All loci were amplifiable and ultimately contributed 31 phylogenetically informative markers distributed throughout the major groups of Rodentia.

Aims Little is known about the role of genetic variants in the early stages of age-related macular degeneration (AMD). We aimed to investigate how genetic variations within five well-defined genes relate to AMD severity. Methods We analysed SNPs in the genes for complement factor H (CFH), age-related maculopathy susceptibility (ARMS2), HtrA serine peptidase 1 (HtrA1), complement factor B (CFB), and complement component 2 (C2) in 183 controls and 730 patients with increasing severity of AMD from the Muenster aging and retina study (MARS). Severity scoring was based on the Rotterdam classification of fundus photographs. Results Compared with controls, patients with very early AMD showed a significantly increased minor allele frequency (MAF) only for CFH-rs1061170. With increasing severity of AMD, SNPs in CFH-rs1061170, as well as ARMS2-rs10490924, became consistently more common (Po0.001). Likewise, HtrA1-rs11200638 was less clearly associated with AMD severity, whereas C2-rs9332739 and CFB-rs641153 showed no relation. Multifactorial models confirmed CFH and ARMS2 as major determinants of AMD severity, whereas addition of HtrA1, C2 and CFB did not improve model prediction. In the models, age did not contribute to very early but to all more severe AMD stages, whereas smoking history had a significant impact only for late AMD. ConclusionOur findings indicate that the CFH gene is involved in the onset of AMD, whereas both, the CFH and ARMS2 genes, and more weakly, the HtrA1 gene, appear to account for the advancement of AMD. The results for SNPs in the C2 and CFB genes were inconclusive. Genetic factors dominated in their impact over age and smoking history.

The findings indicate that AMD progression is differentially affected by genotypic variants. Probably, aging processes of the human retina predispose to AMD onset in the presence of genetic variation in the complement system, which alters immunoregulatory and inflammatory responses. The specific functional role of ARMS2-rs10490924 remains as yet unknown, but it appears to mainly affect the progression to late AMD stages.