Molecular Genetic Medicine, Volume II, summarizes progress in several of the most important areas of modern molecular genetics and medicine. The chapters deal with ancient and common genetic diseases, a new infectious disease that threatens to become a world-wide scourge for all of humanity, and two of the most important and still poorly understood causes of mental retardation. The common thread winding through these separate stories is the astounding illumination of all these disorders by modern molecular genetic studies. The book opens with a chapter on the history of the molecular approach to the thalassemias, among the most common and severe of all human genetic diseases. Separate chapters follow covering the history and current state of the fragile X syndrome; the mechanisms of hepatitis B viral gene expression, its relation to liver cancer, and its prevention; and molecular genetics of Down syndrome. Subsequent chapters deal with mammalian X chromosome inactivation; the use of the human hprt locus as a model system for analyzing mutation in human cells in vivo; and the regulatory genes and factors that govern virus replication of HIV-1.
This book presents the state of the art of type 2 diabetes genetics, from the process of genetic discovery to its interpretation and clinical application, and illustrates a model for other complex human phenotypes. The first section explores genome-wide association studies, the extension of this method to less accessible phenotypes and the arrival of next-generation sequencing. A further section goes beyond genetics to illustrate how other data sources can help interpret genetic data, such as leveraging population diversity, the correlation of genetic associations with physiological measurements, gene expression modulation, environmental factors and our microbial commensals. The third section describes advances in elucidating the complex path from association to function using in-depth sequencing and functional studies of the cellular and molecular effects of genes in the loci identified by genetics. The final section links our current understanding with clinically relevant questions, such as prediction, interactions with drugs or nutrients, and disease prevention, and paints a realistic but hopeful vision of the future. ? Jose C. Florez, M.D., Ph.D. is an Assistant in Medicine (Endocrine Division) at the Massachusetts General Hospital, an Associate Professor at Harvard Medical School and an Associate Member at the Broad Institute, where he is active in the Program in Medical and Population Genetics and the Broad Metabolism Initiative. He and his group have contributed to the performance and analysis of genome-wide association studies in type 2 diabetes and related traits, in the Diabetes Genetics Initiative (formed by the Broad Institute, Lund University and Novartis), the Framingham Heart Study, and other international consortia such as MAGIC, GENIE and DIAGRAM, involving collaborators within CHGR and the Broad Institute. He is an author on 70+ original publications and 30+ reviews/book chapters. In addition to his research and teaching duties, he directs the MGH Down Syndrome Clinic for Adults and Adolescents, and is clinically active in the MGH Diabetes Center and in the Endocrine inpatient consult service. He serves on the Editorial Board for Diabetes and the Advisory Board for Diabetologia, and is the Editor-in-Chief for Current Diabetes Reports. He is the recipient of the MGH Physician Scientist Development Award, a Doris Duke Charitable Foundation Clinical Scientist Development Award, the MGH Department of Medicine Stephen Krane Award, and the 2010 Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers.