Ongoing efforts in human genetics are accumulating a wealth of information about genetic variation in our species. Using this knowledge to benefit human health raises a diverse range of challenges.
Most genome-scale studies of human genetic variation do not provide information about the specific combinations of variants that lie on each of the two homologous chromosomes in an individual. However, such phase information is important for gaining a complete understanding of the relationship between genotype and phenotype. As discussed in the Review by Browning and Browning on p703, improvements in computational approaches for inferring phase will be crucial in this respect.
Understanding how different types of variant affect phenotype is another key challenge. In their Review on p683, Sauna and Kimchi-Sarfaty look at how non-synonymous or 'silent' mutations contribute to disease. Such variants have now been implicated in a range of conditions, and our knowledge of how they influence gene expression and protein function is steadily increasing.
The ethical issues surrounding an increased knowledge of human genetic variation are also highlighted in this issue. In their Opinion article on p730, Craig and colleagues look at issues that arise from meta-analyses of genome-wide association studies. This approach is powerful, but involves increased sharing of variation data among researchers — a development that necessitates careful consideration of privacy risks to study participants. Finally, the issues surrounding direct-to-consumer genetic testing have been widely discussed, but mostly in the context of North America. In the Ethics Watch article on p670, Kricka and colleagues discuss how these issues are playing out in Europe.
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From the editors. Nat Rev Genet 12, 665 (2011). https://doi.org/10.1038/nrg3082