Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria.

Alport syndrome (ATS) and benign familial hematuria (BFH) are type IV collagen inherited disorders. Mutations in COL4A5 are generally believed to cause X-linked ATS, whereas mutations in COL4A3 and COL4A4 genes can be associated with the autosomal-recessive and -dominant type of ATS or BFH. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. This study involved screening each exon with boundary intronic sequences of COL4A3, COL4A4, and COL4A5 genes by optimized polymerase chain reaction-single-stranded conformational polymorphism analysis in 17 families with ATS and in 40 families diagnosed as having BFH. Twelve different mutations were found in the COL4A5 gene in ATS patients, comprising nine missense mutations, a splice site mutation, a mutation causing frameshift, and a nonsense mutation. One of the missense mutations (p.G624D) was present not only in one family with ATS but also in five families with suspected BFH. Three heterozygous mutations in the COL4A3 gene (two missense and one frameshift) and four heterozygous mutations in COL4A4 (two splice site, one in-frame deletion, and one missense) were identified in patients with BFH. Sixteen mutations are to the best of our knowledge new and private.

Phylogenomic analysis of chromoviruses.

Genome sequences of model organisms provide a unique opportunity to obtain insight into the complete diversity of any transposable element (TE) group. A limited number of chromoviruses, the chromodomain containing genus of Metaviridae, is known from plant, fungal and vertebrate genomes. By searching diverse eukaryotic genome databases, we have found a surprisingly large number of new, structurally intact and highly conserved chromoviral elements, greatly exceeding the number of previously known chromoviruses. In this study, we examined the diversity, origin and evolution of chromoviruses in Eukaryota. Chromoviral diversity in plants, fungi and vertebrates, as shown by phylogenetic analyses, was found to be much greater than previously expected. A novel centromere-specific chromoviral lineage was found to be widespread and highly conserved in all seed plants. The age of chromoviruses has been significantly extended by finding their representatives in the most basal plant lineages (green and red algae), in Heterokonta (oomycetes) and in Cercozoa (plasmodiophorids). The evolutionary origin of chromoviruses has been found to be no earlier than in Cercozoa, since none can be found in the basal eukaryotic lineages, despite the extensive genome data. The evolutionary dynamics of chromoviruses can be explained by a strict vertical transmission in plants and fungi, while in Metazoa it is more complex. The currently available genome data clearly show that chromoviruses are the most widespread and one of the oldest Metaviridae clade.