bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic Transcription
Authors: Berg Lutz‐Peter
Published: September 2006

Ectopic (or illegitimate) transcription is the very low level of transcription of ‘tissue‐specific’ genes in cell types lacking obvious requirement for the gene product. Thought to be produced by every gene in every cell type, ectopic transcripts isolated from patient blood are useful for gene mutation studies if the main expressing tissue of a disease gene is inaccessible.
Alternative Promoter Usage
Authors: Ayoubi Torik
Published: September 2006

A major level at which gene expression is controlled is at the level of transcription initiation. The earlier view that transcription initiation occurs at a single site for every gene is no longer valid as many genes have more than one site of transcription initiation and, therefore, more than one promoter. The use of alternative promoters is a versatile mechanism for creating diversity and flexibility in the regulation of gene expression.
Posttranscriptional Processing
Authors: Hodges Angela Kaye
Published: September 2006

Messenger ribonucleic acid (mRNA) is an intermediate template in the process of protein production from a deoxyribonucleic acid (DNA) template. It offers the cell the means to control the production and destination of proteins in a complex, timely and transient way, and increases greatly the potential variation of protein isoforms. The number of molecules of any one mRNA species in a mammalian cell can vary from less than 1 to as many as 10000. In human cells, an average of about six copies of each mRNA are present per cell.
Developmental Psychopathology
Authors: DiLalla Lisabeth F , Caraway Rebecca
Published: September 2006

Psychopathology, or mental illness, can be studied developmentally by examining changes in the illness over time as well as childhood predictors of illness. Longitudinal family studies have yielded information about childhood predictors of schizophrenia and mood disorders by identifying high‐risk children of mentally ill parents prior to the diagnosis of illness in the children.
Alcoholism: Collaborative Study on the Genetics of Alcoholism (COGA)
Authors: Rice John P , Saccone Nancy L , Foroud Tatiana , Edenberg Howard J , Nurnberger John I , Goate Alison , Crowe Raymond R , Hesselbrock Victor , Schuckit Marc , Porjesz Bernice , Reich Theodore , Begleiter Henri
Published: September 2006

Twin, adoption and family studies provide evidence for a genetic component for the susceptibility to alcoholism. The Collaborative Study on the Genetics of Alcoholism (COGA) is a comprehensive family study aimed at identifying specific genetic risk factors.
Comparative Genomics
Authors: Jordan I King , Koonin Eugene V
Published: September 2006

Comparative genomics involves the comparison of features of completely sequenced (or nearly so) genomes. Comparative sequence analyses can facilitate both the functional annotation of genomes and whole‐genome approaches to evolutionary issues.
Orthologs, Paralogs and Xenologs in Human and Other Genomes
Authors: Olendzenski Lorraine , Zhaxybayeva Olga , Gogarten Peter
Published: September 2006

Homologous genes share a common evolutionary ancestor and can be orthologs (derived from speciation events), paralogs (derived from gene duplication events) or xenologs (derived from horizontal transfer or lineage fusion). Comparative analysis of the human genome indicates high levels of recent and ancient duplication at the level of nucleotides, genes and chromosome segments, and only very few, if any, examples of recent transfer from bacteria.
Modern Humans: Origin and Evolution
Authors: Disotell Todd R
Published: September 2006

Modern humans originated recently in geological time from a diverse African gene pool.
Male‐driven Evolution
Authors: Ellegren Hans
Published: September 2006

If the number of germ‐line cell divisions has an effect on the mutation rate, for example owing to replication errors, we might expect the mutation rate of the two sexes to differ. Recent estimates from human and other primates suggest that this difference corresponds to a male bias of a factor of approximately 5.
Genetic Databases
Authors: Attwood Teresa K
Published: September 2006

Internationally available databases contain the sequences of genes, together with related information concerning the proteins they encode, their functions, disease associations, etc. These repositories capture the data emerging from the worldwide genome sequencing projects, and make it freely available to the community for all aspects of modern biological and biomedical research.
Genome Databases
Authors: Hide Winston
Published: September 2006

A genome comprises all of the genetic material in the chromosomes of a particular organism. Genome databases are an organized collection of information that have resulted from the production or mapping of genome (sequence) or genome product (transcript, protein) information.
Gene Feature Identification
Authors: Makalowska Izabela
Published: September 2006

The identification of all genes is one of the goals of the Human Genome Project. Apart from laboratory techniques, genes can also be identified by using computational, homology‐based or
ab initio
(model‐based) methods, which differ in their performance according to the sequence being analyzed.
Spliceosome
Authors: Pomeranz Krummel Daniel A , Nagai Kiyoshi
Published: September 2006

The removal of introns and the splicing together of the protein‐coding regions or exons from precursor messenger RNA (pre‐mRNA) transcripts is fundamental to the development and maintenance of human cells. The nuclear process of pre‐mRNA splicing is a complex phenomenon catalyzed by the ‘spliceosome’, which comprises more than 100 hundred protein and RNA molecules that come on and off during its assembly and activity.
Short Interspersed Elements (SINEs)
Authors: Schmid Carl W , Rubin Carol M
Published: September 2006

Short interspersed elements (SINEs) are highly repetitive sequences that retrotranspose into eukaryotic DNA through intermediates transcribed by RNA polymerase III (pol III). In many species, SINEs are a ubiquitously dispersed feature of the whole genome, often constituting a significant (∼10%) mass fraction of total DNA. SINEs cause mutations both by their retrotransposition within genes and by unequal recombination, and are widely considered to be examples of ‘selfish’ or ‘parasitic’ DNA.
Genomic DNA: Purification
Authors: Tümmler Burkhard , Mekus Frauke
Published: September 2006

Genomic DNA can be prepared from any source by three steps: cell lysis, deproteinization and recovery of DNA. The basic protocol needs to be adapted to the demands of the application, the requested yield, purity and molecular weight of the DNA, and the amount and history of the source.
OD Unit
Authors: Dear Paul H
Published: September 2006

An OD unit is a unit of concentration or (loosely) mass, particularly of solutions of nucleic acids or suspensions of bacterial or yeast cells. It is derived from the degree of absorption of light at a specified wavelength by the solution or suspension.
DNA: Mechanical Breakage
Authors: Quail Michael Andrew
Published: September 2006

In order to fragment deoxyribonucleic acid (DNA) in a random manner, a variety of methods involving the mechanical breakage of DNA have been employed. These include sonication, needle shear, nebulization, point‐sink shearing and passage through a French pressure cell.
Capillary Electrophoresis
Authors: Righetti Pier Giorgio
Published: September 2006

Capillary zone electrophoresis is a fully automated approach to electrophoresis that uses narrow‐bore (10–100 μm) fused‐silica capillaries as a separation chamber and online detection of analytes. The increased heat dissipation allows the delivery of high field strengths (100–500 V cm
−1
). The use of minute sample amounts and volumes and the very fast analysis times make it an attractive technique in modern bioanalysis.
Polymerase Chain Reaction (PCR): Design and Optimization of Reactions
Authors: White Bruce A
Published: September 2006

Optimization of the polymerase chain reaction (PCR) includes the consideration of buffer, additives, magnesium chloride, deoxynucleotides, primer design, thermostable DNA polymerase, DNA template, reaction volume, denaturation time, annealing temperature and extension time. Nonspecific products can be further minimized by using a ‘hot start’ and a variable annealing temperature (touchdown PCR).
Whole‐genome Amplification
Authors: Wells Dagan
Published: September 2006

Whole‐genome amplification (WGA) techniques utilize the principles of the polymerase chain reaction (PCR) to copy enzymatically the deoxyribonucleic acid (DNA) contained within a sample. However, unlike most PCR applications, the amplification is nonspecific and theoretically provides an increase in the copy number of all genomic sequences. WGA is used in areas of research where minute DNA samples are routinely encountered. Applications include preimplantation genetic diagnosis, the creation of probes from microdissected or flow‐sorted chromosomes, forensics and the study of ancient DNA samples.
Yeast Artificial Chromosome (YAC) Clones
Authors: Nagaraja Ramaiah , Schlessinger David
Published: September 2006

Artificial chromosome vector systems have facilitated mapping and sequencing of complex genomes at an increasingly rapid pace. They include cloned DNA fragments ranging from 50 kb to more than 1 million base pairs, as well as sequences that render them capable of growth in yeast or bacteria. Traditional bacterial cloning systems have remained important for the study of relatively short clones, but for the cloning of very large DNA segments artificial chromosomes have completely replaced earlier bacterial systems, including lambda phage‐based cosmids.
Robotics and Automation in Molecular Genetics
Authors: Hawkins Trevor , Elkin Chris , Pollard Martin
Published: September 2006

Robotic platforms and automation can be applied to laboratory molecular biology protocols to achieve high‐throughput sample processing for DNA sequencing, genomics, proteomics and other biological applications.
Genome Mapping
Authors: Dear Paul H
Published: September 2006

Genome maps pinpoint the location of specific features on the chromosomes of an organism. They are essential tools for identifying genes responsible for diseases or traits, for comparing the genomes of different species and for complete genome sequencing.
Genome Map: Resolution
Authors: Dear Paul H
Published: September 2006

The resolution of a genome map is a measure of its accuracy, which is expressed as the minimum distance by which two mapped markers must be separated if their relative order is to be reliably determined.
Expressed‐sequence Tag (EST)
Authors: Dear Paul H
Published: September 2006

An expressed‐sequence tag is a short segment of known deoxyribonucleic acid sequence (typically 50–500 bp long), derived from a gene sequence.
Restriction Fragment Length Polymorphism (RFLP)
Authors: Dear Paul H
Published: September 2006

A restriction fragment length polymorphism is a fragment produced by restriction enzyme digestion of genomic deoxyribonucleic acid, whose length is variable because of a sequence polymorphism that affects the presence or location of a target site for the stated restriction enzyme.
Framework Map
Authors: Dear Paul H
Published: September 2006

A framework map is a genome map giving the positions of selected mapped features at a high degree of confidence. It contrasts with a ‘comprehensive map’, which shows all available mapped markers, even though the local ordering of many of them may be in doubt.
Genetic Linkage Mapping
Authors: Hoh Josephine , Ott Jurg
Published: September 2006

Random occurrences of crossovers along a chromosome permit definition of a genetic distance. Such distances are used to create genetic maps and to localize disease genes on these maps.
Radiation Hybrid Mapping
Authors: Deloukas Panos
Published: September 2006

Radiation hybrid mapping is a method that combines aspects of both genetic and physical mapping and is extensively used in the construction of whole‐genome maps. A panel of radiation hybrid cell lines, each retaining a different portion of the donor genome in the background of a recipient cell, is used to score the presence or absence of sequence tagged sites.
Caenorhabditis elegansGenome Project
Authors: Coulson Alan , Lawson Daniel
Published: September 2006

The sequence of the 100‐Mb genome of the nematodeCaenorhabditis elegans, the first sequence of a multicellular organism, was published in 1998. The methodologies and strategies developed for the worm project, as well as the philosophy of continuous and immediate data release, have carried through to the Human Genome Project (HGP).
Genome Sequencing
Authors: Dunham Ian
Published: September 2006

Genome sequencing determines the order of the DNA bases in an organism. The method of choice for genome sequencing is based on chain termination sequencing and the random shotgun strategy.
Chromosome 22: Sequencing
Authors: Dunham Ian
Published: September 2006

The method of sequencing of human chromosome 22 has implications for sequencing the rest of the human genome.
Sequence Finishing
Authors: Grafham Darren , Willey David
Published: September 2006

Sequence finishing utilizes a variety of techniques to produce a highly accurate and complete DNA sequence.
Kinship and Inbreeding
Authors: Fernando Rohan L
Published: September 2006

Inbreeding results when makes are genetically related. This principle can be used to calculate degrees of kinship between individuals.
Genetic Distance and Mapping Functions
Authors: Ziegler Andreas , König Inke R
Published: September 2006

While distances between genetic loci are generally measured in four different ways, genetic mapping is specifically based on a distance measure that expresses the probability of observing a recombination in the interval between two marker loci. A map function describes the mathematical relationship between the recombination fraction and the genetic map distance.
Parametric and Nonparametric Linkage Analysis
Authors: Bailey‐Wilson Joan E
Published: September 2006

Parametric or model‐based linkage analysis assumes that models describing both the trait and marker loci are known without error. Nonparametric, model‐free or weakly parametric linkage methods make fewer assumptions about the trait model.
Genetic Maps: Integration
Authors: Collins Andrew
Published: September 2006

Genetic maps describe the order of polymorphisms along a chromosome; however, unlike physical maps, the map distances are related to recombination. The level of recombination varies with position along the chromosome and between the sexes. It is important to integrate genetic and physical or sequence‐based maps to identify regions of elevated or reduced recombination. The presence of recombination hot and cold spots has a bearing on efforts to map disease genes and for the understanding of the biological properties of chromosome location.
Linkage Analysis Software
Authors: Holmans Peter
Published: September 2006

Many methods exist to analyze the linkage of traits to genetic marker data, and various software packages are available to implement these methods.
Quantitative Trait Loci (QTL) Mapping
Authors: Zeng Zhao‐Bang
Published: September 2006

Quantitative trait loci (QTL) mapping is a genome‐wide inference of the relationship between genotype at various genomic locations and phenotype for a set of quantitative traits in terms of the number, genomic positions, effects and interaction of QTLs.
Epistasis
Authors: Wilson Susan R
Published: September 2006

Epistasis is the biological interaction between two or more genes to determine a phenotype. Until relatively recently, there has been confusion in its definition arising from many mathematical and other models not necessarily reflecting biological reality, and underestimation of both its importance in mapping results for complex disease and its potential role in the results of evolutionary genetics.
Twin Methodology
Authors: Snieder Harold , MacGregor Alex J
Published: September 2006

The classic twin study is established as the ideal study design with which to investigate the relative importance of genetic and environmental factors to traits and diseases in human populations. Twin methodology is concerned with analysis techniques that have been developed to estimate and quantify the relative contribution of genes and environment to the disease or trait of interest.
Adoption Studies
Authors: Yates William R
Published: September 2006

Adoption studies are one form of clinical genetic study designed to evaluate genetic and environmental influences on phenotype. In adoption studies the index cases and controls are adoptees.
Population History and Linkage Disequilibrium
Authors: Zöllner Sebastian , von Haeseler Arndt
Published: September 2006

Population history and demographic structure influence the evolution of linkage disequilibrium between loci. Besides recombination and mutation, processes like genetic drift, bottlenecks, admixture, population substructure and population expansion fundamentally influence the amount of linkage disequilibrium.
Disease Associations: Human Leukocyte Antigen (HLA) and Apolipoprotein E (APOE) Gene
Authors: van Duijn Cornelia M
Published: September 2006

The developments of the Human Genome Project have fueled expectations with regard to the potential of associating variations in genes to the risk of common complex diseases. Despite the many problems encountered, the examples of the HLA complex and the apolipoprotein E gene show the usefulness of this approach.
Markov Chain Monte Carlo Methods
Authors: Skaanning Claus
Published: September 2006

Markov chain Monte Carlo methods are used to sample from complicated multivariate distributions that are not computable in practice and from which direct sampling (Monte Carlo) is not feasible. In the field of genetics, they are used in pedigree and linkage analysis to obtain the posterior probabilities of individuals possessing specific genes.
Effective Population Size
Authors: Whitlock Michael C
Published: September 2006

The effective size of a population (
N
e
) is the size of an ideal population that has the same amount of genetic drift, change in heterozygosity or rate of fixation as the population. Thus
N
e
can predict these quantities in a nonideal population.
Nonrandom Mating
Authors: O'Neil Dennis H
Published: September 2006

Nonrandom mating occurs when there is discrimination between potential mates and selection or rejection of them based on their phenotypical characteristics. This deviation from random mating results in predictable changes in genotype frequencies in subsequent generations.
Forensic Genetics: Mathematics
Authors: Brenner Charles H
Published: September 2006

DNA identification consists in using DNA polymorphisms in order to link DNA samples, such as a suspect to a crime stain. Probability, population genetic, and statistical issues that arise offer considerable scope for mathematical treatment.
DNA Evidence: Inferring Identity
Authors: Weir Bruce
Published: September 2006

The advent of DNA profiling had greatly enhanced our ability to determine the precise source of a biologic sample. This has found a variety of applications.
Kinship Testing
Authors: Krawczak Michael
Published: September 2006

In kinship testing, the level of genetic similarity between individuals is utilised to assess their degree of familial relationship. Inference is made either by evaluating the available phenotypic information under different hypotheses about kinship, represented by different pedigree structures, or through the direct quantification of kinship coefficients using a statistical approach.
Population Differentiation: Measures
Authors: Bertorelle Giorgio
Published: September 2006

The genetic divergence between populations can be quantified using different measures.
Evolutionary Conflicts
Authors: Cannings Chris
Published: September 2006

Conspecifics compete for resources, and the outcomes impact on reproductive success. The theory of evolutionary conflict addresses the issues of what strategies prevail and coexistence within these competitions under natural selection.
Mutations: Dating
Authors: Colombo Roberto
Published: September 2006

The age of a mutation can be estimated from the decay of linkage disequilibrium with flanking or intragenic polymorphisms because of recombination and mutation and from the frequency of the mutation itself as a consequence of genetic drift. Several methods have been proposed, and the results from their applications can be combined with population data to provide a critical view of the origin and natural history of the mutation.
Evolutionary Networks
Authors: Bandelt Hans‐Jürgen
Published: September 2006

Evolutionary networks are labeled and weighted connected graphs that, in contrast to genetic trees, may contain cycles. A network can accommodate ambiguities concerning evolutionary pathways and thus simultaneously represent alternative estimates of a phylogeny.
Diffusion Theory
Authors: McVean Gil
Published: September 2006

The mathematical description of the process of diffusion has proved a powerful tool for describing how deterministic forces, such as mutation, selection and migration, and the stochastic process of genetic drift interact to influence the fate of mutations in populations.
Beyond the Genome
Authors: Stent Gunther S
Published: September 2006

Beyond the genome lies the phenome, which term denotes the global – partly impressionistic – set of traits according to which biologists categorize an organism as a member of one particular taxonomic entity rather than of another. Although there does exist a causal ontogenetic relation between genome and phenome, it is not the case that an organism's genome can be usefully considered as a one‐dimensional representation of its multidimensional phenome.
Genetic Disorders
Authors: Langenbeck Ulrich
Published: September 2006

Genetic disorders afflict between 1% and 4% of the newborn population, and the contribution of genes to public health problems rises considerably above this level in adults. Mutations are due to disruption of, or interference with, functional/structural networks of genes, ribonucleic acids and proteins. The identification of disease genes and pathogenetic mechanisms in genetic diseases is a goal of genetic medicine.
Dominance and Recessivity
Authors: Wilkie Andrew OM
Published: September 2006

Dominance and recessivity are not intrinsic properties of genes or alleles but describe, in diploid organisms, the pattern of occurrence of a phenotypic trait with respect to the possible combinations of two alleles. If the trait is present in the heterozygote, it is said to be dominant or semidominant, and if it is present only in one of the homozygotes, it is recessive.
Mosaicism
Authors: Hall Judith G
Published: September 2006

Mosaicism refers to the presence of genetically different cells in a multicellular organism that have been derived from a single fertilized egg. The genetic change can take many forms and occur through many mechanisms. The clinical manifestations of mosaicism may be reflected in patchy or streaky pigment, overgrowth or undergrowth, and asymmetric growth or anomalies. When considering mosaicism, it is important to study other tissues in addition to blood.
X‐chromosome Inactivation and Disease
Authors: Lyon Mary F
Published: September 2006

X‐chromosome inactivation is the phenomenon in which one of the two X chromosomes in every somatic cell of female mammals becomes transcriptionally inactive early in embryonic development. This has the result of equalizing the effective gene dosage of X‐linked genes in chromosomally XX females and XY males, and is hence known as a dosage compensation mechanism. In humans, X‐chromosome inactivation has implications for the effects seen in diseases due either to X‐linked genes or to numerical or structural anomalies of the X chromosome.
Ethnicity and Disease
Authors: Peltonen Leena
Published: September 2006

Features such as migration waves, regional founder effects, several bottlenecks (caused by wars, famine, catastrophes of nature) and expansion periods in the global populations, along with sometimes dramatic isolation (caused by geographical, linguistic or cultural factors) of different populations, have molded the human gene pool and resulted in genetic differences between world populations. Also the prevalence of various diseases and disease mutations greatly varies within different populations, and a substantial amount of our understanding of the history of various population‐specific differences has actually emerged from the studies of genetic diseases in different populations.
Haploinsufficiency
Authors: Read Andrew P
Published: September 2006

Diploid organisms like humans have two copies of each autosomal gene, and usually loss of one copy has no effect. Haploinsufficiency describes the situation where having only a single functioning copy of a gene is not enough for normal function, so that loss‐of‐function mutations cause a dominant phenotype.
Mutations: Penetrance
Authors: Houlston Richard
Published: September 2006

A given genotype does not necessarily lead to the same phenotype. Individuals with a specific genotype will display a range of phenotypes. The relationship between genotype and a specific phenotype is referred to as penetrance.
RNA Processing and Human Disorders
Authors: Lejeune Fabrice , Maquat Lynne E
Published: September 2006

Errors in messenger ribonucleic acid biogenesis at any one of a number of steps often result in human disease because of the failure to synthesize functional protein.
Protein Aggregation and Human Disorders
Authors: Moir Robert D , Tanzi Rudolph E
Published: September 2006

The deposition of insoluble proteinaceous material is a distinct pathological process associated with a broad range of disparate diseases. Modulating the self‐aggregation of the proteins that form these deposits has emerged as a major therapeutic strategy for disease treatment.
Posttranslational Modification and Human Disorders
Authors: Wisdom G Brian
Published: September 2006

Most proteins undergo modification involving specific cleavage of the polypeptide backbone and/or changes to the side chains. Some of these modifications result in disease or disorder; others may be used diagnostically.
G‐protein‐mediated Signal Transduction and Human Disorders
Authors: Spiegel Allen M
Published: September 2006

Heterotrimeric G proteins couple to seven‐transmembrane receptors, producing diverse signals to effectors that generate intracellular signals. Loss‐ and gain‐of‐function mutations in genes encoding G‐protein‐coupled receptors and the α subunit of heterotrimeric G proteins have been increasingly recognized as causes of human disease.
Intersex Disorders
Authors: Sarafoglou Kyriakie
Published: September 2006

Human intersex conditions arise during the complex developmental processes of sexual determination and differentiation resulting in discordance between genetic sex, gonadal sex and sexual phenotype. In humans and other mammals, a regulatory cascade of sex‐linked and autosomal genes determines sex. Contingent on the gene mutation, a remarkable range of possible phenotypes are seen, including sex‐reversed females and sex‐reversed males.
Craniofacial Abnormalities: Molecular Basis
Authors: Müller Ulrich
Published: September 2006

Monogenic abnormalities of skull differentiation can be grouped into three categories: disorders of cranial ossification (craniosynostosis, foramina parietalia), of midface development (holoprosencephaly, cleft lip and palate) and of differentiation of the first and second branchial arches (branchio‐oto‐renal dysplasia and Treacher–Collins). Many of the genes identified in these groups code for transcription factors and signaling proteins.
Intellectual Disability: Genetics
Authors: Flint Jonathan
Published: September 2006

Genetic effects on intellectual disability, or mental retardation, are well established and are particularly important for moderate to severe disability. Cloning of abnormal genes gives some clues about the biology of cognition.
Pulmonary Disorders: Hereditary
Authors: Lomas David A
Published: September 2006

Hereditary lung disease can present in neonates, children and adults. Greater understanding of the genetic basis of these conditions has provided new insights into the underlying pathophysiology and important information for counseling affected families.
Gastrointestinal Tract: Molecular Genetics of Hirschsprung Disease
Authors: Passarge Eberhard
Published: September 2006

The gastrointestinal (GI) tract is involved in numerous genetic disorders, either isolated or as part of a multisystemic disease. Relatively few genes have been identified that play a role in the development and function of the GI tract, but the molecular basis of Hirschsprung disease, a complex, heterogeneous disorder, resulting from absence of the intramural intestinal ganglion cells due to failure of migration from the neural crest during embryonic development, has been elucidated.
Hemophilia and Other Bleeding Disorders: Genetics
Authors: McVey John H , Tuddenham Edward GD
Published: September 2006

Hemophilia is the term applied to a group of hereditary disorders characterized by excessive bleeding and which are due to lack or defective function of one or more blood coagulation factors.
Cystic Fibrosis (CF)
Authors: Tsui Lap‐Chee
Published: September 2006

Cystic fibrosis is an inherited disorder of serious medical consequence and is the most common such disorder among Caucasians.
Prader–Willi Syndrome and Angelman Syndrome
Authors: Horsthemke Bernhard
Published: September 2006

The Prader–Willi and Angelman syndromes are distinct neurogenetic syndromes that are caused by the loss of function of imprinted genes on human chromosome 15. Genetic defects include deletions, uniparental disomy, imprinting defects and single‐gene mutations.
Neurofibromatosis: Type I
Authors: Viskochil David
Published: September 2006

Neurofibromatosis type I (NF1) is a common, autosomal dominant condition that manifests as multiple café‐au‐lait spots, peripheral nerve sheath tumors, optic nerve pathway tumors, orthopedic abnormalities and learning disabilities. The gene for NF1 encodes neurofibromin, a large protein that downregulates intracellular Ras signaling.
Paroxysmal Nocturnal Hemoglobinuria
Authors: Kinoshita Taroh
Published: September 2006

Paroxysmal nocturnal hemoglobinuria is a peculiar acquired clonal genetic disease caused by somatic mutation of the X‐linked
PIGA
gene in a hematopoietic stem cell.
Mitochondrial Disorders: Nuclear Gene Mutations
Authors: Zeviani Massimo
Published: September 2006

In addition to mutations of mitochondrial DNA, many mitochondrial syndromes are due to abnormalities in nuclear genes related to oxidative phosphorylation (OXPHOS). Nuclear genes encode hundreds of proteins involved in mitochondrial OXPHOS. Nevertheless, the identification of these genes has proceeded at a much slower pace, compared with the discovery and characterization of mitochondrial DNA mutations. This scenario is rapidly changing because of the discovery of several OXPHOS‐related human genes and the identification of mutations responsible for different clinical syndromes.
Fusion Proteins and Diseases
Authors: Saha Vaskar , Jones Louise Kathleen
Published: September 2006

Fusion proteins occur as a result of chromosomal translocations in cancerous cells. The proteins targeted are either transcription factors or tyrosine kinases. The fusion proteins are associated with developmental malignancies and thyroid carcinomas.
Monosomies
Authors: Fryns Jean‐Pierre , Lukusa Tshilobo Prosper
Published: September 2006

Errors in meiosis result in gametes with abnormal numbers of chromosomes and production, after fertilization, of an aneuploid conceptus. The genetic imbalance resulting from the loss of an entire chromosome in individuals with deletion‐type aneuploidy is generally lethal, except for the full X chromosome monosomy. Most survivable partial monosomies are associated with significant dysmorphism and mental retardation.
Cancer: Chromosomal Abnormalities
Authors: Mitelman Felix
Published: September 2006

Cancer cells are characterized by acquired, specific chromosome abnormalities, often balanced structural aberrations. At the molecular level, the balanced rearrangements exert their action through one of two alternative mechanisms: deregulation of one gene by relocation to an immunoglobulin gene or T‐cell receptor gene, or the creation of a hybrid gene by fusion of parts of two genes. The genetic abnormalities have important diagnostic and prognostic implications.
Environmental Mutagenesis
Authors: Parry James M , Parry Elizabeth M
Published: September 2006

Environmental mutagenesis is the study of induced mutation above the background or spontaneous rate (characteristic of any particular organism) produced by exposure to mutagens identified in materials ranging from foods to pharmaceutical drugs. Environmental mutagenesis involves the study of the mechanisms by which chemicals induce mutation and the development of test methods and regulatory procedures to identify and control environmental mutagens since such agents may be of major concern to public health.
Digenic Inheritance
Authors: Vockley Jerry
Published: September 2006

Monogenic inheritance refers to genetic control of a phenotype or trait by a single gene. Many traits are not determined so simply, and either involve the interaction of many genes with (multifactorial inheritance) or without (polygenic inheritance) environmental effects. Less commonly, the interaction of only two genes is required for expression of a phenotype, a mechanism referred to as digenic inheritance.
Diabetes: Genetics
Authors: Zimmet Paul , Walder Ken , Collier Greg R
Published: September 2006

Diabetes, a syndrome characterized by hyperglycemia (high blood sugar), has reached epidemic proportions in both developed and developing nations. The two forms of the disease both have a genetic basis, but are influenced by different genetic and environmental factors.
Rheumatoid Arthritis: Genetics
Authors: Gregersen Peter K
Published: September 2006

Rheumatoid arthritis is a heterogeneous inflammatory disorder of unknown cause with features suggestive of autoimmunity. The genetic components are complex and appear to overlap with other autoimmune diseases.
Epilepsy: Genetics
Authors: Gardiner Mark
Published: September 2006

Some forms of epilepsy have a simple Mendelian mode of inheritance, but these are very rare. The more usual forms have a complex genetic background, but new DNA‐based diagnostic techniques bring hope of elucidating these.
Fetal Diagnosis
Authors: Holzgreve Wolfgang , Hahn Sinuhe
Published: September 2006

Fetal diagnosis is the examination of the fetal genetic status during pregnancy.
Preimplantation Diagnosis
Authors: Anver Kuliev , Yury Verlinsky
Published: September 2006

Preimplantation diagnosis is testing for a causative gene before pregnancy, allowing the preselection of unaffected embryos before implantation into the uterus. It has currently become an alternative to prenatal diagnosis, providing an option for at‐risk couples to have unaffected children of their own without facing the risk of a pregnancy termination after prenatal diagnosis.
Neonatal Screening
Authors: Holtzman Neil A
Published: September 2006

In many countries, all newborns are screened for several diseases, most of which are inherited.
Clinical Molecular Cytogenetics
Authors: Romana Serge P , Vekemans Michel
Published: September 2006

Molecular cytogenetics is an important tool for the diagnosis and characterization of chromosome aberrations in clinical and cancer cytogenetics.
Mouse as a Model for Human Diseases
Authors: David Steve , Brown Macleod
Published: September 2006

The mouse is a key organism for the study of mammalian development, physiology and biochemistry and therefore an important model for the study of human disease. Mouse strains and mutants are important tools for dissecting the genetic pathways involved with human genetic disease.
Drosophila
as a Model for Human Diseases
Authors: Reiter Lawrence T
Published: September 2006

The fruit fly
Drosophila melanogaster
is a powerful genetic model organism that can be easily manipulated. Advanced tools have been constructed in
Drosophila
for disruption of genes (both somatic and germ line) as well as misexpression of endogenous and foreign transgenes. A high degree of similarity between these two proteomes suggests that as many as 74% of human disease‐causing genes could be studied in a
Drosophila
model.
Zebrafish as a Model for Human Diseases
Authors: Fraenkel Paula Goodman , Zon Leonard I
Published: September 2006

Zebrafish (Danio rerio) are small freshwater fish, the only vertebrate model in which a large‐scale mutagenesis strategy has been undertaken as an approach to the study of the development of blood and vital organs. The development of techniques for gene mapping in zebra fish and the anticipated completion of the zebra fish genome sequencing project in 2002 will enhance the use of zebra fish as models for human diseases.
Mammalian Artificial Chromosomes (MACs)
Authors: Farr Christine J , Spence Jennifer M
Published: September 2006

By analogy with yeast artificial chromosomes, a mammalian artificial chromosome (MAC) would be a molecule of defined structure comprising combinations of various cloned or synthesized chromosomal elements that had been individually manipulated, tested and optimized as part of a controlled construction process.
De novo
human chromosomes have been produced through cell‐mediated assembly processes and these, together with minichromosomes generated by manipulating existing chromosomes, are providing the basis for developing the first MAC‐based vectors for use in vertebrate cells.
In Vitro
Mutagenesis
Authors: Bowen Derrick John
Published: September 2006

In vitro
mutagenesis allows a nucleic acid sequence (and hence an encoded protein sequence) to be altered either randomly or in a predefined way. Its principal applications are the investigation of nucleic acid or protein structure/function, the investigation of cellular pathways (for example, biochemical or signaling) and gene therapy.
Expression Analysis
In Vivo
: Cell Systems
Authors: Dirks Roeland W , Molenaar Chris , Tanke Hans J
Published: September 2006

Gene expression involves RNA synthesis and processing, RNA transport, and protein synthesis and localization, which are dynamic processes in time and space. With the advent of nucleic acid probe and green fluorescent protein technologies, and developments in real‐time microscopy, it is possible now to study these processes at real time in single cells, meaning that information concerning transcription, protein localization and protein–protein interactions can be obtained from genes whose functions might be known or unknown.
Animal Models
Authors: Beier David R
Published: September 2006

There is a long‐standing tradition of using a variety of animal models for genetic and functional studies relevant to human biology. Recent technical developments and the ongoing acquisition of genomic sequence have markedly enhanced the usefulness of such models.
Mouse Genetics as a Research Tool
Authors: Moen Corina , Hofker Marten
Published: September 2006

Mouse genetics elaborates on the genetic variation between genetically homogeneous inbred strains. Because the genetic variation can be controlled, crosses between such inbred strains allow unraveling of the genetic basis of multigenic disorders such as cancer and atherosclerosis.
Minigenes
Authors: Warner Laura E , Chamberlain Jeffrey S
Published: September 2006

A minigene is a compact version of a gene in which regions have been removed without affecting protein function. Understanding the structure and function of the protein produced from the gene of interest is critical in determining which portions of the gene can be deleted. The compact size of minigenes makes them easier to isolate and insert into cloning and viral vectors.
Fusion Proteins as Research Tools
Authors: Dorsman Josephine C
Published: September 2006

Fusion proteins encompass a protein or small peptide moiety which is used as a tag, fused to another protein of interest. Fusion proteins are used in biochemical and in genetic (high‐throughput) applications and are especially suited to study protein–protein interactions, even on a genome‐wide scale, and for the generation of antibodies.
Genomic Imprinting at the Transcriptional Level
Authors: Constância Miguel , Murrell Adele , Reik Wolf
Published: September 2006

Genomic imprinting is an epigenetic mechanism of gene regulation that results in the expression of only one allele at a locus, dependent on the parental origin of the allele. These parent‐of‐origin effects are exerted largely at the level of transcription and are brought about by epigenetic imprints laid down in the parental germ cells. Gene regulation by genomic imprinting affects (a minority of) mammalian loci that have crucial developmental roles. Aberrant imprinted gene regulation is the cause of various disease syndromes.
Proteomics: A Molecular Scanner in Medicine
Authors: Steen Hanno , Pandey Akhilesh
Published: September 2006

Proteomics is the large‐scale identification and characterization of proteins and posttranslational modifications. Several proteomic methodologies, especially microarrays and mass spectrometry, offer the promise of use in a variety of clinical settings.
Protein Isoforms and Isozymes
Authors: Gunning Peter William
Published: September 2006

Isoforms are highly related gene products that perform essentially the same biological function. Isozymes are isoforms of an enzyme. Isoforms can differ in their biological activity, regulatory properties, temporal and spatial expression, intracellular location or any combination thereof. Isoforms are almost always either the products of one gene or of multiple genes that evolved from a single ancestor gene.
Protein Folding and Chaperones
Authors: Ellis R John , Hartl F‐Ulrich
Published: September 2006

The specific conformation characteristic of each protein is determined by the amino acid sequence of that protein by the process of protein folding. Molecular chaperones use two distinct mechanisms to prevent premature folding and aggregation by a subset of newly synthesized proteins.
Protein Degradation and Turnover
Authors: Saric Tomo , Goldberg Alfred L
Published: September 2006

The protein constituents of an organism and its cells are continuously being synthesized and degraded (turned over). Protein degradation is essential for recycling of amino acids, removal of damaged or misfolded proteins and controlling a variety of fundamental biological processes.
Protein Characterization: Analytical Approaches and Applications to Proteomics
Authors: Gevaert Kris , Vandekerckhove Joël
Published: September 2006

Edman chemical sequencing and biological mass spectrometry are used routinely to identify and to characterize proteins. Two‐dimensional polyacrylamide gel electrophoresis, highly sensitive mass spectrometry and sequence database searching algorithms have merged to form proteomics – the analysis of the protein complement of the genome.
Array‐based Proteomics
Authors: Walter Gerald , Büssow Konrad , Konthur Zoltan , Lueking Angelika , Glökler Jörn , Schneider Ulrich
Published: September 2006

Array technology enables genome‐wide screening for protein expression and interactions at high throughput. Protein microarrays are emerging as a major technology platform for functional genomics.
Structural Predictions and Modeling
Authors: Norin Martin
Published: September 2006

Computer models form the basis for the predictions of the molecular three‐dimensional structures of polypeptides – the proteins. The different models all use the polypeptide amino acid sequence as the starting point for the prediction.
Adenoviral Vectors in Gene Therapy
Authors: Graham FL
Published: September 2006

Adenovirus vectors are widely used for delivery of foreign deoxyribonucleic acid to mammalian cells. They are important tools in research and for use in gene therapy and vaccines.
Retroviral Vectors in Gene Therapy
Authors: Miller A Dusty
Published: September 2006

Retroviruses have a positive‐strand nonsegmented RNA genome that undergoes reverse transcription to a double‐stranded DNA form prior to random integration into the genome of a target cell in a form called the provirus. The provirus is transcribed into mRNAs that encode the viral proteins, and these proteins package the full‐length genomic mRNA into virions to complete the virus life cycle. Retroviral vectors are retroviruses engineered to transfer and integrate specific DNA sequences into the genomes of target cells, and are often designed to be replication‐defective to avoid further spread after the initial transfer event. Gene transfer and expression by a replication‐defective retroviral vector is referred to as transduction to differentiate this process from infection by a typical virus that leads to virus production and spread.
Lentiviral Vectors in Gene Therapy
Authors: Lever AML
Published: September 2006

Lentiviruses are a family of retroviruses capable of inserting their genome into the genetic material of dividing and nondividing cells. Retroviral vectors based on lentiviruses retain these properties, and have been developed as candidate therapeutic agents for gene delivery to cells of the central nervous system, muscle and hepatocytes as well as antigen‐presenting cells in the immune system.
RNA Viral Vectors in Gene Therapy
Authors: Russell Stephen J
Published: September 2006

Genes can be delivered into mammalian cells using synthetic nonviral vectors or recombinant viral vectors derived from DNA virsuses, retroviruses and, more recently, RNA viruses.
Delivery Targeting in Gene Therapy
Authors: Glasgow Joel N , Curiel David T
Published: September 2006

Delivery targeting is a novel approach for the design and administration of therapeutic agents wherein the agent is rationally designed to localize to the site of disease in a self‐directed manner, usually via exploitation of unique biophysical properties of the diseased tissue.
Cystic Fibrosis: Gene Therapy
Authors: Flotte Terence R , Virella‐Lowell Isabel
Published: September 2006

Cystic fibrosis is an autosomal recessive disease caused by mutations of the CFTR protein, a member of the ATP‐binding cassette superfamily of transmembrane proteins. CFTR can act as a cAMP‐activated chloride channel and as a regulator of other ion channels in exocrine glands and other ductular structures.
Cardiovascular Disease: Gene Therapy
Authors: Morishita Ryuichi
Published: September 2006

Gene therapy at the somatic level has the potential to become an effective treatment for cardiovascular disease. However, early clinical trials have had some setbacks, and issues of control of gene expression need to be resolved.
Gene Transfer in Transplantation
Authors: Anegon Ignacio
Published: September 2006

The introduction of genetic information into tissues or organs to be transplanted aims to confer new biological properties on the grafts. Gene transfer has already shed light on the basic mechanisms of graft rejection and tolerance, and has the potential to be applied in the clinic.
Infectious Diseases: Gene Therapy
Authors: Fidler S , Weber J
Published: September 2006

Human gene therapy is defined as the introduction of new genetic material into the cells of an individual with the intention of producing a therapeutic benefit for that individual. Gene therapy may be applied to any infectious disease whereby the infecting organism inserts its own genetic material into the genome of the host cell genome.
Chimera‐directed Gene Repair
Authors: Kmiec Eric B
Published: September 2006

The information gained from the Human Genome Project must be formulated such that the function of newly discovered genes can be elucidated. A tool to aid in defining gene function is targeted gene repair, a technique that may also be valuable in human gene therapy.
Hematopoietic Stem Cells
Authors: Kohn Donald B , Nolta Jan A , Crooks Gay M
Published: September 2006

Hematopoietic stem cells are the common ancestor to every type of blood cell. They undergo massive proliferation and differentiation to produce billions of red blood cells, white blood cells and platelets.