Revitalizing difference in the HapMap: race and contemporary human genetic variation research.

Through an examination of the International Haplotype Map (HapMap), this paper explores some of the ways in which relationships among categories of race and genetic variation are being reconfigured in contemporary genetic research.

DNA data sharing: research participants' perspectives.

PURPOSE: Current genomic research policy calls for public data release with specific consent for data sharing. Because most clinical investigators are not responsible for and do not anticipate data broadcast few include information about data sharing in their informed consent process. Model language is therefore urgently needed and should be responsive to research participants' attitudes and judgments. The purpose of this study was to describe research participants' attitudes and judgments about data release and their preferences for varying levels of control over decision-making. METHODS: Focus group sessions with patients and controls from a genetic study of epilepsy. RESULTS: Despite wide variation in judgments, there was general interest in receiving information and making decisions about data sharing. Participants preferred multiple data sharing options, but were more likely to consent to public data release when given fewer options. For existing samples most participants felt that genomic information should not be publicly released without explicit consent from research participants. CONCLUSIONS: Specific information about data sharing ought to be included in the consent process for all genetic research. These participants desire multiple data release options, but the effect, if any, on consent to public release deserves further investigation.

Evidence that monoclonal antibodies directed against the integrin beta subunit plexin/semaphorin/integrin domain stimulate function by inducing receptor extension.

The overall structure of integrins is that of a ligand-binding head connected to two long legs. The legs can exhibit a pronounced bend at the "knees," and it has been proposed that the legs undergo a dramatic straightening when integrins transit from a low affinity to a high affinity state. The knee region contains domains from both alpha and beta subunits, including the N-terminal plexin/semaphorin/integrin (PSI) domain of the beta subunit. The role played by the knee domains in the regulation of integrin-ligand binding is uncertain. Here we show that: (i) monoclonal antibodies (mAbs) N29 and 8E3 have epitopes in the beta(1) subunit PSI domain and stimulate ligand binding to alpha(5)beta(1); (ii) N29 and 8E3 cause long range conformational changes that alter the ligand binding activity of the head region; (iii) the stimulatory action of these mAbs is dependent on the calf-1 domain, which forms part of the alpha subunit knee; and (iv) the epitopes of 8E3 and N29 map close to the extreme N terminus of the PSI and are likely to lie on the side of this domain that faces the alpha subunit. Taken together, our data suggest that the binding of these mAbs results in a levering apart of the PSI and calf-1 domains, and thereby causes the alpha and beta subunit knees to separate. Several major inferences can be drawn from our findings. First, the PSI domain appears to form part of an interface with the alpha subunit that normally restrains the integrin in a bent state. Second, the PSI domain is important for the transduction of conformational changes from the knee to head. Third, unbending is likely to provide a general mechanism for control of integrin-ligand recognition.