Human RPS19 blocking peptide

We report here the first mitogenome sequences for the chlorophyte class Chlorodendrophyceae. The mitogenomes of Tetraselmis sp. CCMP 881 and Scherffelia dubia (SAG 17.86) are 46,904 bp and 78,958 bp long, respectively, but their gene repertoires are almost identical. Each genome harbors an inverted repeat (IR). The 14,105-bp IR of S. dubia encodes seven genes in addition to a part of rps19, whereas the 2445-bp IR of Tetraselmis sp. CCMP 881 contains a single gene. Considering that an IR has also been found in the mitogenomes of certain earlier-diverging chlorophytes, the IRs of chlorodendrophycean algae probably represent ancestral features.

Mutations in the RPS19 gene have been identified in 25% of individuals affected by Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia characterized by an aregenerative anemia and a variety of malformations. More than 60 mutations in the five coding exons of RPS19 have been described to date. We previously reported a mutation (c.-1 + 26G>T) and an insertion at -631 upstream of ATG (c.-147_-146insGCCA) in the noncoding region. Because DBA phenotype is extremely heterogeneous from silent to severe and because haploinsufficiency seems to play a role in this process, it is likely that genetic variations in the noncoding regions affecting translation of RPS19 can modulate the phenotypic expression of DBA. However, to date, very few studies have addressed this question comprehensively. In this study, we performed detailed sequence analysis of the RPS19 gene in 239 patients with DBA and 110 of their relatives. We found that 6.2% of the patients with DBA carried allelic variations upstream of ATG: 3.3% with c.-1 + 26G>T; 2.5% with c.-147_-146insGCCA; and 0.4% with c.-174G>A. Interestingly, the c.-147_-146insGCCA, which has been found in a black American and French Caribbean control population, was not found in 500 Caucasian control chromosomes we studied. However, it was found in association with the same haplotype distribution of four intronic polymorphisms in our patients with DBA. Although a polymorphism, the frequency of this variant in the patients with DBA and its association with the same haplotype raises the possibility that this polymorphism and the other genetic variations in the noncoding region could play a role in DBA pathogenesis. Am. J. Hematol. 85:111-116, 2010. (C) 2009 Wiley-Liss, Inc.