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Search Results: 1 - 10 of 115234 matches for " Daniel W Nebert "
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Designer Genes: A new Era in the Evolution of Man
Daniel W Nebert
Human Genomics , 2011, DOI: 10.1186/1479-7364-5-4-316
Abstract: The sequence of Steve's early chapters provides a simplistic and non-intimidating introduction for the lay and semi-lay reader. In the early chapters, he gives sufficient background, so that everyone might easily understand and be comfortable with the important discoveries during the past five decades in molecular developmental biology and genetics -- from DNA being transcribed to RNA, RNA spliced to messenger RNA to RNA translated to the protein (gene product).In a 'user-friendly' manner, Steve also covers recently appreciated mechanisms in the genomics field by which we now realise that such striking human diversity and variability are achieved -- including DNA base-pair changes, insertions, deletions and even 'jumping genes'. Using a few clinical diseases, dog breeding and athletic abilities as examples, Steve provides some easy-to-understand concepts about human evolution. At the end of the book, he even goes into exciting futuristic concepts about robots and computers that might extend human knowledge.To me, the most exciting thing about the book is the realisation that, because mouse and human embryos are extremely similar, everything we know about early mouse embryo development quite clearly applies to the human as well. Scientists today have the ability to make a 'transgenic human' -- just as Steve's laboratory (and my laboratory) are currently doing with transgenic mouse lines.Steve even ventures into morality and religious issues, and he does this with great capability and sensitivity. 'When does "the soul" most likely enter the developing fertilised egg?' 'How many souls are possible from one fertilised egg?' These and many other deep questions are approached with answers that can be easily comprehended and should be acceptable to the large majority of people, whether they are scientists or not, and whether they are theologians or not.Since the book was published in September 2010, my understanding is that it has already sold more than 300,000 copies. Not
Given the complexity of the human genome, can 'personalised medicine' or 'individualised drug therapy' ever be achieved?
Daniel W Nebert
Human Genomics , 2009, DOI: 10.1186/1479-7364-3-4-299
Abstract: Contrary to this point of view and opposing such hype, several of us have steadfastly insisted that the genome is far too complex for us to understand at the present time [1-5]. In fact, the 2003 Nebert et al. review[1] was initially rejected by a very high citation-indexed journal; the author suspects that one or more of the reviewers may have had financial interests in DNA-assay companies.Can some number of DNA variant sites (genotype) really be associated -- 100 per cent of the time -- with the diagnosis of a complex disease such as obesity, or schizophrenia, or coronary artery disease or type-2 diabetes (phenotype)? Can some number of single nucleotide polymorphisms (SNPs) (genotype) really be associated -- 100 per cent ofthe time -- with the prediction of a drug response (phe-notype)? Ideally, a 100 per cent level of success in genotype phenotype association studies is what physicians require for personalised medicine or individualised drug therapy to be successful.Sequencing of the entire human genome, the HapMap Consortium (Phases I, II and III, 2003-2009) has now identified more than 11 million SNPs in 1,115 individuals from 11 populations worldwide having minor allele frequencies (MAFs) of ≥5 per cent. Increasingly, cost-effective high-throughput genotyping technologies leading to genome-wide association (GWA) studies have demonstrated the requirements needed to separate true associations from the plethora of publications dealing with false positives. 'Third-generation DNA sequencing' promises, in 2009 and 2010, to be able to sequence dozens of human genomes per month.The Encyclopedia of DNA Elements (ENCODE) Pilot Project, covering ~1 per cent of the human genome (2004-2007), however, has shown us that we are no longer even certain what a 'gene' is. ENCODE discovered multiple transcription start sites, complexities of histone modifications and chromatin remodeling 'beyond our wildest expectations', regulatory elements in trans on one chromosome controlling
A new home for Human Genomics
Vasilis Vasiliou, Daniel W Nebert
Human Genomics , 2012, DOI: 10.1186/1479-7364-6-1
Update on genome completion and annotations: Protein Information Resource
Cathy Wu, Daniel W Nebert
Human Genomics , 2004, DOI: 10.1186/1479-7364-1-3-229
Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family
Vasilis Vasiliou, Daniel W Nebert
Human Genomics , 2005, DOI: 10.1186/1479-7364-2-2-138
Analysis of the glutathione S-transferase (GST) gene family
Daniel W Nebert, Vasilis Vasiliou
Human Genomics , 2004, DOI: 10.1186/1479-7364-1-6-460
The truth about mouse, human, worms and yeast
David R Nelson, Daniel W Nebert
Human Genomics , 2004, DOI: 10.1186/1479-7364-1-2-146
Update on the olfactory receptor (OR) gene superfamily
Tsviya Olender, Doron Lancet, Daniel W Nebert
Human Genomics , 2008, DOI: 10.1186/1479-7364-3-1-87
Abstract: Before 1980, the names of genes and classification of their encoded proteins were highly variable and non-systematic -- especially to anyone slightly outside a particular field or to a new graduate student entering the field. Professor Margaret Oakley Dayhoff was a pioneer in attempting to create order out of chaos in the naming of genes and gene families by means of computerised protein alignments [1]. She was widely recognised as the founder in this new field of gene/protein classification, before her untimely death in 1983.Cytochrome P450 (CYP) genes are conveniently arranged into families and subfamilies based on the percentage amino acid sequence identity [2-7]. Enzymes that share approximately ≥ 40 per cent identity are assigned to a particular family designated by an Arabic numeral, whereas those sharing approximately ≥ 55 per cent identity are grouped into a particular subfamily designated by a letter. For example, the sterol 27-hydroxylase enzyme and the 25-hydroxy-vitamin D3 1α-hydroxylase enzyme are both assigned to the CYP27 family because they share > 40 per cent sequence identity. Furthermore, the sterol 27-hydroxylase is assigned to the CYP27 'A' subfamily and the 25-hydroxy-vitamin D3 1 α-hydroxylase to the CYP27 'B' subfamily because their protein sequences are < 55 per cent identical. If an additional enzyme were to be discovered that shared > 55 per cent identity with the sterol 27-hydroxylase, then it would be named CYP27A2. If an additional enzyme were to be discovered that shared < 55 per cent but > 40 per cent identity with the sterol 27-hydroxylase as well as the 25-hydroxy-vitamin D3 1α-hydroxylase, then it would be named CYP27C1. The development and application of this delightfully logical system of nomenclature to the genes of many animals, plants and bacteria [8] has eliminated the confusion that often had plagued the naming of gene families and superfamilies. Subsequently, this 'divergent evolution' nomenclature system was adopted for se
Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family
Vasilis Vasiliou, David Ross, Daniel W Nebert
Human Genomics , 2006, DOI: 10.1186/1479-7364-2-5-329
Analysis and update of the human solute carrier (SLC) gene superfamily
Lei He, Konstandinos Vasiliou, Daniel W Nebert
Human Genomics , 2009, DOI: 10.1186/1479-7364-3-2-195
Abstract: The period between the 1980s and the early 1990s might be considered the era of 'the cloning of genes encoding enzymes and transcription factors', whereas that between the early 1990s and the present day could be regarded as focusing on 'the cloning of genes coding for transporters'. One conceivable reason for the earlier spotlight on many of the enzymes and transcription factors is that those gene products were more abundant and/or could be more easily isolated and antibodies generated against them (compared with transporters). Transporters are embedded within membranes and generally have multiple transmembrane domains. Another reason might be that the mRNA transcripts for enzymes are usually shorter than those for transporters, and early reverse transcription activities starting at the 3' end were tedious and less efficient, meaning that longer mRNA transcripts were often unsuccessful.Proteins with transport functions http://www.tcdb.org/tcdb/ webcite can roughly be divided into three categories: ATP-powered pumps, ion channels and transporters. ATP-binding cassette (ABC) pumps and other ATP-binding pumps use energy released by ATP hydrolysis to move substrates across membranes and out of cells or into cellular vesicles against their electrochemical gradient. These pumps have two states -- open and closed. By contrast, ion channels in most cases exist in the closed state. Substrates (ions or water) are transferred down their electrochemical gradient at extremely high efficiency (up to 108 s-1). There are 49 ABC-related functional genes in the human genome (including the genes encoding the cystic fibrosis transmembrane conductance regulator [CFTR] and the transporter associated with antigen processing [TAP] 1 and TAP2). Aquaporins (AQPs) are water-channel proteins, encoded by each of 13 AQP functional genes in the human genome http://www.gene-names.org/ webcite.Transporters facilitate the movement of a specific substrate -- either with or against its concentration
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