Ancestral Haplotypes: Our Genomes Have Been Shaped In The Deep Past

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9780986411502: Ancestral Haplotypes: Our Genomes Have Been Shaped In The Deep Past
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"Ancestral Haplotypes" recounts the scientific discoveries that have demonstrated the quantal structure of the human and higher mammalian genome. It is an informed and critical synthesis of the scientific work which has helped establish this new paradigm. It focuses on the research achievements of the Perth group led by Professor Roger L. Dawkins of the Immunogenetics Research Foundation (IRF) and the C.Y.O’Connor ERADE Village Foundation (CYO). Their work on the genomics of the major histocompatibility complex has played a significant role in establishing the scientific reality of the "Ancestral Haplotype" concept as an accurate description of the polymorphic frozen block structure of the human and wider mammalian genome. In different places it will also contain a corresponding account of the complementary clinical immunology and genetic studies on the MHC by the Boston Group led by Professors Chester A. Alper and Edmond J. Yunis on the same genetic regions within the MHC which they identify as Conserved Extended Haplotypes (CEHs). The book therefore tells the story of a great contemporary scientific discovery. It has been a leviathan effort to demonstrate that the most likely correct genomic structure of our chromosomes comprises strings of polymorphic frozen blocks which manifest as “ancestral haplotypes”. Such conserved sequences of megabase length should be viewed as diverse conserved pre-tested genetic modules involving potentially hundreds of genes. These variant genetic modules may be viewed in the same way as "allelic" variants of single genes have been viewed in the past as the identifiable “unit of selection”. This new view of the evolution of the genome therefore contradicts the more popular descriptions that have invaded main stream scientific thinking - through popular science writing and TV documentaries : that all our important genetic inheritance can be viewed under a simple Darwinian view of evolution based on recent and ongoing gene mutation followed by natural selection. To be more explicit, the neo-Darwinian paradigm based on Population Genetics and statistics. The discovery of Ancestral Haplotypes is a heroic tale spanning the past 35 - 40 years. It is a journey of scientific discovery which has been uncompromising in its focus. The research shows that in most, if not all, segmentally duplicated gene-rich regions of our genome many of our important genes are very old, dating to the early migration of Homo sapiens out of Africa ca 100,000 years ago. Many probably arose earlier in our primate ancestors. Large chromosomal blocks carrying tens to hundreds of "genes frozen in time" appear shuffled at each generation to produce individual human beings who for the most part are healthy and robust and well adapted. These ancestral sequences circulate in the human population "gene pool" and occur at respectable frequencies (>1%). However the down side is that many people also carry genetic disease predispositions as a legacy of our primate and early human origins and thus appear not so lucky. However they usually survive in the most part to adulthood and have children of their own - their inheritance is part of a complex beneficial integrated adaptation which has been passed down over thousands of years from our ancestors. Nevertheless if we are to do anything positive about these apparent evolutionary aberrations we need to first under-stand the most likely genetic story of how we arrived at our present condition. This book tells this story as accurately as is possible - given the "strangeness" and complexity of the new genetic data concerning "Ancestral Haplotypes."

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About the Author:

Edward J Steele was born and grew up in Darwin, NT, Australia. He gained his PhD from the University of Adelaide in 1976 under Professor Derrick Rowley for research on secretory IgA antibodies and intestinal immunity to cholera. Since then he has worked at a number of institutes and universities in Canada, UK and Australia. His main research theme has been the molecular mechanisms of the somatic and germline evolution of antibody variable genes for which he received the R.D. “Pansy” Wright Medal from the University of Melbourne (2009). He has also published or edited several books in-cluding Somatic Selection and Adaptive Evolution (1979), Somatic Hypermutation in V Regions (1991) and Lamarck’s Signature (1998). He is currently an Honorary Research Fellow with the C.Y.O’Connor ERADE Village Foundation, in Canning Vale, Perth, Western Australia

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