Genetic pesticides: Monsanto goes ahead with trials

The Monsanto Company will soon notify the Environmental Protection Agency (EPA) that it plans to conduct the first field test of a genetically-engineered microbial pesticide, thereby becoming the first company to break with the convention whereby private corporations have voluntarily sought approval for genetic engineering experiments from the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH). It is assumed that Monsanto's decision was influenced by a preliminary legal injunction blocking NIH approval of such field trials without a formal environmental assessment. EPA will allow tests, after 90 days' notice, if it raises no objections to the protocol. Although EPA will not formally call on RAC to examine the protocol, an agency spokesperson said there is "total agreement" between EPA and RAC on what data must be included.     

Data protection: UK bill improved and approved

The Data Protection Bill, which provides individuals the right of access to computerized data about themselves while preventing unauthorized disclosure of information, passed Britain's House of Commons at its third reading and returned to the House of Lords. Among the amendments added to the controversial legislation was one concerning the transfer of medical information to agencies outside the health system. After extensive lobbying by the medical community, the government agreed that a code of practice governing disclosure of medical data recently developed by an interprofessional working group should apply in principle to computerized records.     

Genetic manipulation: British watchdog reconstituted

Britain's Genetic Manipulation Advisory Group (GMAG) is to be replaced by a new body, the Advisory Committee on Genetic Manipulation (ACGM), slated to consist of representatives of employers' and employees' organizations and technical experts. ACGM will address policy issues and will not review individual experiments, as did GMAG. Those doing individual research projects will instead report to the Health and Safety Executive. One of the first issues likely to be addressed by ACGM is the proposed release of genetically-engineered organisms into the environment. Some members of GMAG have pointed out that the new system does not provide for a permanent mechanism for considering ethical problems arising from new recombinant DNA techniques.     

Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis

Following up on recent genome-wide association studies (GWAS) of Crohn's disease, we investigated 50 previously reported susceptibility loci in a German sample of individuals with Crohn's disease (n = 1,850) or ulcerative colitis (n = 1,103) and healthy controls (n = 1,817). Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection.     

A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC

The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.     

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.     

CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair

Inherited mutations in BRCA2 are associated with a predisposition to early-onset breast cancers. The underlying basis of tumorigenesis is thought to be linked to defects in DNA double-strand break repair by homologous recombination. Here we show that the carboxy-terminal region of BRCA2, which interacts directly with the essential recombination protein RAD51, contains a site (serine 3291; S3291) that is phosphorylated by cyclin-dependent kinases. Phosphorylation of S3291 is low in S phase when recombination is active, but increases as cells progress towards mitosis. This modification blocks C-terminal interactions between BRCA2 and RAD51. However, DNA damage overcomes cell cycle regulation by decreasing S3291 phosphorylation and stimulating interactions with RAD51. These results indicate that S3291 phosphorylation might provide a molecular switch to regulate RAD51 recombination activity, providing new insight into why BRCA2 C-terminal deletions lead to radiation sensitivity and cancer predisposition.