Summary of current gene-finding
studies At both the technical/molecular and statistical/conceptual levels, the science of gene discovery in complex disease selleck compound genetics is moving rapidly. By the time this paper is published, new developments are sure to have arisen. As is common in science in the state of rapid flux, the direction ahead is far from clear. How will the modest Inhibitors,research,lifescience,medical but hard-fought advances obtained in more traditional positional cloning and candidate gene work integrate with the new findings from GWAS? How will the commonvariant SNP-based approach inter-relate with the emerging rare-variant copy number variant findings? Will advances in phenotypic assessment or endophenotypes provide critical new insights? How will the burgeoning fields of bioinformatics, expression arrays, and proteomics
impact on our gene-finding efforts? One emerging consensus is that the field needs to move from a “gene-centric” approach toward one that considers “gene networks.” For example, many of the candidate genes discussed above are involved in glutamatergic neurotransmission, Inhibitors,research,lifescience,medical which may be an important systemic element in the etiology of schizophrenia. Although a detailed discussion of this theory is outside the scope of this summary, recent reviews of the genetic183 and neuroscience184 data and evidence from other studies highlight the positions of the gene products of NRG1, COMT, and possibly DTNBP1 among others, Inhibitors,research,lifescience,medical in the Inhibitors,research,lifescience,medical biochemical and functional pathways influencing the glutamatergic system. Many other possible networks may be involved in the etiology of schizophrenia that, if properly articulated, could aid in our gene-discovery efforts. Conclusion We have attempted in this article to review the rapidly evolving field of psychiatric Inhibitors,research,lifescience,medical genetics. In the section on genetic epidemiology,
we took a conceptual approach focusing on a range of the most interesting questions now being confronted by the field, with the goal of giving the reader a “feel” for the issues. While examining a wide range of disorders, we focused on substance use and externalizing STI 571 disorders because they clearly illustrated the points we wanted to make. In the section on gene-finding, we decided it would be more useful to “drill down” and illustrate our important themes by focusing on one disorder Cilengitide – schizophrenia. The major theme that cuts across these two sections is the complexity of the pathways from genetic variation to psychiatric and substance use disorders. Results of the last 20 years have shown that the early prior simple hypothesis of large effect genes that directly causes psychiatric illness was seriously misplaced. We now know that multiple gene variants (as well as – for at least some disorders – genomic rearrangements) are involved at the DNA level. These genetic risk factors then act and interact with each other and with the environment in a complex developmental “dance” to produce individuals at high versus low risk of illness.