Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

Karyotype and chromosome banding in the reed frogHyperolius viridiflavus ommatostictus (Amphibia,Anura, Hyperoliidae)

Summary C-banding and mithramycin staining were used to characterize the karyotypes of 10 specimens of the African reed frogHyperolius viridiflavus ommatostictus from Tanzania. The diploid chromosome number is 2n=24. Although no heteromorphic sex chromosomes were present in the mitotic karyotypes, in many diakineses of male meiosis one or two bivalents exhibited an end-to-end arrangement. In the laboratory 7 out of 24 females changed sex spontaneously. This indicates that an XY/XX system of sex determination operates inH. viridiflavus ommatostictus.This study was supported by the Deutsche Forschungsgemeinschaft (Schm 484/2-4). We thank K. E. Linsenmair and C. M. Richards for helpful comments on an earlier draft.     

A frog with highly evolved sex chromosomes

Summary Highly differentiated ZZ/ZW sex chromosomes and an exceptionally low genome, size were found in the karyotypes ofPyxicephalus adspersus (Anura, Ranidae). The W-chromosome is considerably smaller than the Z-chromosome and consists to a very great proportion of constitutive heterochromatin. The DNA content of this species and the chromosome length have the lowest values determined in the Ranidae to date.This study was supported by a grant from the Deutsche Forschungsgemeinschaft. We thank Professor W. Engel for his support and interest.     

Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis

Iron is required to produce haem and iron-sulphur (Fe-S) clusters, processes thought to occur independently. Here we show that the hypochromic anaemia in shiraz (sir) zebrafish mutants is caused by deficiency of glutaredoxin 5 (grx5), a gene required in yeast for Fe-S cluster assembly. We found that grx5 was expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the assembly of grx5 yeast Fe-S, showing that the biochemical function of grx5 is evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory protein 1 (IRP1) to sense intracellular iron and regulate mRNA stability or the translation of iron metabolism genes. We found that loss of Fe-S cluster assembly in sir animals activated IRP1 and blocked haem biosynthesis catalysed by aminolaevulinate synthase 2 (ALAS2). Overexpression of ALAS2 RNA without the 5' iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS2 including the iron response element did not. Further, antisense knockdown of IRP1 restored sir embryo haemoglobin synthesis. These findings uncover a connection between haem biosynthesis and Fe-S clusters, indicating that haemoglobin production in the differentiating red cell is regulated through Fe-S cluster assembly.