Trends Genet
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Recent surveillance data of multidrug-resistant tuberculosis (MDR-TB) reported the highest rates of resistance ever documented. As further amplification of resistance in MDR strains of Mycobacterium tuberculosis occurs, extensively drug-resistant (XDR) and totally drug-resistant (TDR) TB are beginning to emerge. ⋯ Herein, we review recent findings on how bacterial factors, such as persistence, hypermutation, the complex interrelation between drug resistance and fitness, compensatory evolution, and epistasis affect the evolution of multidrug resistance in M. tuberculosis. Improved knowledge of these factors will help better predict the future trajectory of MDR-TB, and contribute to the development of new tools and strategies to combat this growing public health threat.
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Chronic pain is a classic example of gene × environment interaction: inflammatory and/or nerve injuries are known or suspected to be the etiology of most chronic pain syndromes, but only a small minority of those subjected to such injuries actually develop chronic pain. Once chronic pain has developed, pain severity and analgesic response are also highly variable among individuals. ⋯ Here, I review recent and accelerating progress in, and continuing challenges to, the identification of genes contributing to such variability. Success in this endeavor will hopefully lead to both better management of pain using currently available therapies and the development and/or prioritizing of new ones.
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Family and twin studies attest to the importance of genetic factors influencing susceptibility to bipolar disorder and to its genetic and phenotypic complexity. Although linkage and candidate gene association studies have repeatedly implicated some chromosome regions and certain genes, they have not produced the level of unambiguous support required to confirm the involvement of any specific gene or sequence variant in the pathogenesis of bipolar disorder. However, strong associations have recently been reported in meta-analyses of genome-wide association studies and the systematic study of structural variation is ongoing. These findings indicate that the study of large, phenotypically well-characterized samples will make an important contribution to delineating the etiology and pathogenesis of bipolar disorder and thereby pave the way for major improvements in clinical management.