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.     

Regulation of Parkin E3 ubiquitin ligase activity

Parkin is an E3 ubiquitin ligase mutated in autosomal recessive juvenile Parkinson's disease. In addition, it is a putative tumour suppressor, and has roles outside its enzymatic activity. It is critical for mitochondrial clearance through mitophagy, and is an essential protein in most eukaryotes. As such, it is a tightly controlled protein, regulated through an array of external interactions with multiple proteins, posttranslational modifications including phosphorylation and S-nitrosylation, and self-regulation through internal associations. In this review, we highlight some of the recent studies into Parkin regulation and discuss future challenges for gaining a full molecular understanding of the regulation of Parkin E3 ligase activity.     

Changes in fisheries discard rates and seabird communities

It is clear that discards from commercial fisheries are a key food resource for many seabird species around the world. But predicting the response of seabird communities to changes in discard rates is problematic and requires historical data to elucidate the confounding effects of other, more 'natural' ecological processes. In the North Sea, declining stocks, changes in technical measures, changes in population structure and the establishment of a recovery programme for cod (Gadus morhua) will alter the amount of fish discarded. This region also supports internationally important populations of seabirds, some of which feed extensively, but facultatively, on discards, in particular on undersized haddock (Melanogrammus aeglefinus) and whiting (Merlangius merlangus). Here we use long-term data sets from the northern North Sea to show that there is a direct link between discard availability and discard use by a generalist predator and scavenger--the great skua (Stercorarius skua). Reduced rates of discarding, particularly when coupled with reduced availability of small shoaling pelagic fish such as sandeel (Ammodytes marinus), result in an increase in predation by great skuas on other birds. This switching of prey by a facultative scavenger presents a potentially serious threat to some seabird communities.     

Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome

In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task.