bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of cognitive disorders
Authors: Abrahams Brett S. , Geschwind Daniel H. 
Published: July 2005

Abstract
Disorders of cognition impair mental processes mediating awareness, perception, reasoning, or judgment, and consequently interfere with thought. Although interindividual differences in human cognition are easily observed, little is known about the genetic factors underlying such phenotypic variation, or the relationship of such variation to disease. Global measures of intelligence, such as Spearman's “g”, are heritable and thus likely to engender new links between genes and cognition. However, the breadth of these measures may limit the extent to which mechanistic insights are obtained. Finding readily measurable and heritable components of disease (endophenotypes) represents one of the most promising avenues for a precise understanding of how individual genes come to modulate brain function. The high heritability of interindividual differences in brain morphology suggests that a more thorough understanding of disease‐associated structural variation may clarify the relationship between individual genes and disorders of cognition. Identification and study of endophenotypes for autism and disorders of spoken and written language will facilitate a deeper understanding of how genetic variation comes to modulate the structure and function of particular neural systems and in turn contributes to specific cognitive deficits.
Hypertension genetics: under pressure
Authors: Charchar Fadi J. , Tomaszewski Maciej , Dominiczak Anna F. 
Published: July 2005

Abstract
Hypertension genetics is now at a critical juncture. The molecular methods used so far have not revealed the numerous genes causing the common familial forms of hypertension. Here we present a brief review of the future directions of hypertension genetics research and what its implication and challenges are.
Current approaches to prenatal screening and diagnosis
Authors: Cosper Paula C. 
Published: July 2005

AbstractPrenatal screening and diagnosis has advanced tremendously since its inception in 1966. We now have various means for screening in the first and second trimesters of pregnancy using noninvasive techniques such as ultrasound and maternal serum screening. For diagnostic testing, invasive procedures are required. The most frequently used procedures are chorionic villus sampling and amniocentesis. The types of testing on these fetal cells and number of abnormalities detectable are changing rapidly. Techniques allowing defects to be detected before pregnancy are also becoming more readily available. The current methods and technologies for prenatal screening and diagnosis are discussed.
Mechanisms of inheritance
Authors: Aylsworth Arthur S. 
Published: July 2005

Abstract
Inheritance patterns depend on genetic factors that can be monogenic or multigenic and deterministic or nondeterministic. Environment, epistasis, and chance are the factors that affect phenotypic expression. Variations on the basic themes of monogenic inheritance commonly involve issues of penetrance and expression. Mendel's concepts of dominance and recessiveness are now blurred by our recognition of phenomena such as heterozygote expression, incomplete penetrance, gene–gene interaction, and gene–environment interaction. While pedigrees with only distant relatives affected are frequently interpreted as representing examples of complex or multifactorial inheritance, it is clear that the same patterns of inheritance can be caused by chromosome rearrangements and mutations in single genes with major effects. The causes of complex phenotypes are heterogeneous and include stochastic combinations of genetic and environmental factors, where the genetic contribution may be determined by one or more genes.
Genetic counseling process
Authors: Schneider Gretchen H. 
Published: July 2005

Abstract
Genetic counseling is a process whose aim is to communicate information about genetic disease to patients or families. This process involves multiple steps that may include, but not be limited to, gathering and assessment of information, establishment of a diagnosis or risk of disease, and discussion of the implications as well as available options to address risk for family members. Support and counseling is also a very important component of this process, which focuses on promoting informed decision‐making for patients who are often in very difficult situations.
Gene therapy I: principles and clinical applications
Authors: Ulm J. Wesley 
Published: July 2005

Abstract
Gene therapy encompasses a recently developed group of pharmaceuticals in which the therapeutic agent consists of nucleic acid sequences – DNA, RNA, or some modification thereof – rather than a small molecule. The field arose in the 1980s in the wake of improvements in recombinant DNA technology, and in the midst of better comprehension of gene regulation and modulation processes that could be exploited to construct practical gene therapy systems. Most gene therapy vectors are viral in nature, with retroviruses, adenoviruses, and AAVs (adeno‐associated viruses) dominating most protocols, and they have been applied to treat a wide variety of disease subtypes: inherited genetic disorders, cancer, protein aggregation diseases, cardiovascular diseases, and infectious diseases have all been considered in proposed modalities. Gene therapy offers the potential to treat disease with an unprecedented selectivity and therapeutic index, and to allow the flexible design of new pharmaceutical agents on a much more rapid scale than in most traditional schemes. However, technical obstacles related to vector delivery, adequate expression levels, and persistence of viral transgenic sequences continue to pose difficult challenges for clinical application. This article reviews the basic gene therapy principles, common vectors and disease targets, and clinical approaches to convey the current state of the field and its future directions.
Adeno‐associated viral vectors: depend(o)ble stability
Authors: Snyder Richard O. 
Published: July 2005

Abstract
Recombinant adeno‐associated viral (rAAV) vectors can mediate the safe and long‐term correction of genetic diseases in animal models following a single administration, and have been shown to persist and are safe in humans following delivery to lung, sinus, skeletal muscle, brain, and liver. The physiochemical properties of rAAV vector virions are amenable to industry‐accepted manufacturing methodologies, long‐term storage, and direct in vivo administration.
Gene transfer to skeletal muscle
Authors: Chamberlain Jeffrey S. 
Published: July 2005

Abstract
Muscle tissue is an important target for gene therapy applications due to the large number of disorders of skeletal and cardiac muscle. These include inherited disorders such as Duchenne muscular dystrophy (DMD) and acquired disorders such as heart failure and age‐associated muscle weakness (sarcopenia). A potentially powerful approach to treating these various conditions involves delivery of a gene or genes to the affected muscles. In the case of a genetic disorder, the goal may be to deliver a normal version of the defective gene. In other cases, benefit might result from delivery of a gene that could augment normal muscle function, such as a growth factor gene. Other applications include delivery of DNA fragments that could modulate gene expression or lead to correction of a genetic mutation. Since muscle tissue represents nearly 40% of the total body mass, gene transfer to muscle is an enormously challenging proposition. Consequently, numerous types of gene or DNA vectors and delivery strategies are being explored for gene therapy of muscle disorders. No single gene vector or delivery method is likely to be universally applicable for all conditions, but some have been developed to greater degrees than others. This article briefly reviews the major vectors and delivery methods currently being developed for gene therapy of muscle diseases.
Gene transfer to the liver
Authors: Ponder Katherine Parker 
Published: July 2005

Abstract
The liver is an important organ for gene therapy. There are a large number of genes that are expressed in the liver whose deficiency results in a genetic disorder that might be treated by expressing the deficient protein in the liver. In addition, hepatitis B and C are very common, and might be treated with vectors that express small interfering RNAs that downregulate viral gene expression. Hepatocytes are readily accessible to viral or plasmid vectors that are injected systemically owing to the fenestrations in the blood vessels in the liver, which makes in vivo delivery feasible. Gene therapy has had considerable success in the liver in animal models. Both retroviral and AAV vectors have been delivered to animals with no obvious toxicity and have resulted in long‐term expression in both small‐ and large‐animal models. Although adenoviral vectors have achieved very high levels of expression in rodents, they have evoked substantial inflammation, and have not resulted in stable expression in most large‐animal studies. Plasmid vectors have been effective, although efficient delivery to the hepatocyte remains a problem. One or more of these gene therapy approaches will likely translate into an effective therapy for patients in the near future.
Hierarchical, ordered mapped large insert clone shotgun sequencing
Authors: Roe Bruce A. 
Published: July 2005

Abstract
DNA sequencing has become a powerful tool to deepen our understanding of the genetic basis for living systems. Although the basic principles of the Sanger dideoxynucleotide chain extension approach have changed little since it was developed over 30 years ago, the detailed methodology and technology to implement it have resulted in an approximate doubling of the amount of DNA sequence data annually since then. From its initial labor‐intensive implementation by which only fairly short DNA segments could be sequenced, present day DNA sequencing now entails a shotgun‐based approach that can yield the complete sequence of target regions that are in the megabase pair range. However, when the shotgun approach is coupled with a hierarchical approach in which megabase to gigabase genomes are dissected into ordered maps of large insert clones that are tractable to highly automated shotgun sequencing, that the complete, highly accurate reference genomes for several organisms, including humans, have been determined. But science and technology do not stand still, as new and exciting approaches to obtain DNA sequence data hundreds to thousands of times faster and less expensive than presently available loom on the horizon, giving us the ability to gain an even deeper understanding of the genomes of hundreds of diverse organisms, from animals to plants, as well as the readily available sequence of our individual hereditary material and the prediction of our individual predisposition to genetic‐based diseases and physical traits.
Genome mapping overview
Authors: Warren Wesley C. , Lovett Michael 
Published: July 2005

Abstract
Genome mapping has had a central and fundamental influence on both genomic sequencing and positional cloning over the past 20 years. The technologies underlying this field fall into three broad categories: (1) true physical maps based upon ordered genomic clones or the cytogenetic map; (2) inferred physical maps based upon a statistical analysis of map order, for example, radiation hybrid (RH) maps; (3) genetic maps that deliver a relative order of polymorphic markers based upon statistical analysis of meiotic recombination crossovers. All three types of reference mapping resources have caveats and limitations. The first is the assumption that the reference map truly reflects the underlying genome. Genomic duplications, inversions, and other complex rearrangements (which may vary between individuals) can complicate the interpretation of these maps. Sex‐specific differences can complicate genetic maps. Any type of statistically based map (whether RH or genetic linkage) should be carefully scrutinized for the likely odds of marker order. There are also gaps in many of the available maps and these can also present problems. Here we present a brief overview of the various genome mapping methods.
Linkage mapping
Authors: Samuels Mark E. , Dubé Marie‐Pierre 
Published: July 2005

AbstractLinkage mapping refers to the specification of a particular chromosomal segment or segments within the genome that carry a causal DNA variant or mutation leading to a biological phenotype of interest. The appropriate chromosomal segment is determined through the use of anonymous polymorphic DNA markers as tags in different individuals who share the phenotype. Statistical analysis of data is usually critical in the determination. For whole‐genome linkage analysis, the most commonly used polymorphic markers are short tandem repeats, known as microsatellites or STRs. The experimental use of these markers has many subtleties and pitfalls, which are reviewed. Successful linkage mapping for a phenotypic trait is followed by the process of positional cloning, whereby the true underlying genetic variant is discovered. The final step from anonymous chromosomal segment to sequence variant detection can be relatively straightforward or highly demanding, depending on the complexity of the phenotype, the severity of the mutation in affecting gene function, and the extent to which carriers of the mutation are predisposed to the phenotype.
Microarray comparative genome hybridization
Authors: Holt Robert A. , Krzywinski Martin 
Published: July 2005

Abstract
Microarray comparative genome hybridization (maCGH) is a highly parallel assay for detecting DNA copy number changes. The method has been used to detect copy number alterations associated with cancer, congenital anomalies, and developmental disorders. CGH extends the diagnostic power of G‐banding and FISH imaging, but is limited to the detection of only those aberrations that are accompanied by changes in the copy number of genomic segments. Over the past decade, different CGH formats have been explored (chromosome spreads, clone microarrays, and oligonucleotide microarrays) in efforts to increase both resolution and sensitivity, and thereby improve the utility of the approach for both research and clinical applications.
The
H
appy mapping approach
Authors: Galibert Francis 
Published: July 2005

Abstract
“Happy mapping” is an in vitro genome mapping method for type 1 and 2 markers that offers several advantages over the RH method. However, it is highly dependent on a whole‐genome amplification step that till now has been difficult to realize given the very small amount of starting DNA. In this article, advantages and possible future developments are discussed in light of the difficulties inherent in the method.
The distribution of genes in human genome
Authors: Bernardi Giorgio 
Published: July 2005

Abstract
The human genome is a mosaic of isochores, long (>300 kb) DNA regions, each one of which is characterized by a low compositional heterogeneity. Isochores belong, however, to a small number of families that cover a very broad GC range (GC is the molar percentage of guanine + cytosine in DNA). An isochore pattern is very widespread in eukaryotes. This pattern (the “genome phenotype”) is stable over geological times, but is different in different vertebrate and plant classes. In all vertebrates, there are good correlations between the GC levels of coding and contiguous noncoding sequences, as well as among the GC levels of different codon positions. Such correlations amount to a “genomic code”.
Gene distribution is bimodal in vertebrates, gene density being very high in the small “genome core” (corresponding in the human genome to the GC‐richest isochore families H2 + H3) and very low in the vast “genome desert” (formed by the other isochore families L1, L2, and H1). The gene distribution of vertebrates is correlated with important structural, functional, and evolutionary features.
Functional analysis of genes
Authors: Woychik Rick , Bult Carol 
Published: July 2005

Abstract
Studying the function of genes is a multidimensional process that involves many organisms and a large variety of experimental approaches. No single organism is best suited for all experiments, and no single experimental strategy is appropriate for all genes. In the end, integrated electronic resources with data collected from all genes in yeast, flies, worms, mice, zebra fish, rats, and human will best serve the needs of the biomedical research community to study gene function.
The rat as a model physiological system
Authors: Gauguier Dominique 
Published: July 2005

AbstractThe laboratory rat is a major experimental animal in all fields of biomedical research. It provides a broad range of models for accurately characterizing the effects of naturally occurring gene variants on the regulation of complex phenotypes underlying the pathogenesis of common and prevalent human genetic disorders. The completion of the rat genome sequence and progress in comparative genomics provide key resources that facilitate the characterization of disease genes at quantitative trait loci (QTLs). Genetic, physiological, and functional genomics investigations in existing inbred rat strains and emerging congenic and consomic panels are now contributing, in combination with studies in mouse models, to the functional annotation of mammalian genomes, and the identification of candidate genes for human multifactorial diseases.
The Fugu and
Z
ebrafish genomes
Authors: Elgar Greg 
Published: July 2005

Abstract

Ray‐finned fish comprise the most abundant class of vertebrates with over 20 000 different species covering almost every aquatic habitat on Earth. They represent a tremendously diverse evolutionary range, having evolved from a common ancestor as far back as 450 million years ago, at around the same time they split from the lobe‐finned lineage that led to the tetrapods, including amphibians, birds, reptiles, and mammals. While there is a considerable amount of genomic and genetic data for a number of fish species, two have been particularly well studied at the genome level, the zebrafish,
Danio rerio
, and the Pufferfish,

Fugu rubripes

(Fugu). Interestingly, these two fish are only distantly related, each having its own unique characteristics, and this has resulted in them being exploited in quite different ways by molecular biologists.
The staphylococci
Authors: Gill Steven R. 
Published: July 2005

AbstractThe staphylococci are opportunistic pathogens and a major cause of hospital‐ and community‐acquired infections ranging in severity from minor skin infections to widespread life‐threatening infections. The occurrence of highly virulent community‐acquiredStaphylococcus aureus(CASA) and continued progression of resistance to multiple antimicrobials, including vancomycin, marks a re‐emergence of the staphylococci as serious health care threat. Multiple genomes of the two major staphylococcal pathogens,S. aureusandStaphylococcus epidermidis, have been sequenced (genomes of sevenS. aureusisolates and twoS. epidermidisisolates). Comparative analysis of these genomes has shown that they are syntenic along their length and share a core set of genes with roles in metabolism and general housekeeping functions. Nonsyntenic regions contain species‐specific genes and pathogenicity genomic islands, including bacteriophages, which are the primary source of variations in pathogenicity and resistance. Overall differences in pathogenicity between the two species can be attributed to genome islands inS. aureus, which encode exotoxins, leukocidins, and leukotoxins not found inS. epidermidis. Gene transfer among staphylococci and with other low GC gram‐positive bacteria has contributed to the evolution of resistance and virulence and is likely playing a role in the emergence of increasingly virulent members of the staphylococcal family.
Spirochete genomes
Authors: Weinstock George 
Published: July 2005

Abstract
Spirochetes are a group of bacteria with a common threadlike morphology. Nevertheless, these organisms show great genomic diversity, ranging in size from 1 to over 4 Mb and in chromosome structure from the simple bacterial circular chromosome to complex collections of linear and circular chromosomes. The gene content of pathogenic spirochetes often shows few of the virulence factors found in the more extensively studied Proteobacteria or gram‐positive bacteria. This may reflect the significant evolutionary distance from spirochetes to these other microbes as well as different strategies of infection.
SNPsand human history
Authors: Wall Jeffrey D. 
Published: July 2005

AbstractEvolutionary geneticists have shown great interest in using patterns of single‐nucleotide polymorphism (SNP) variation to make inferences about models of human evolution. Although there is a large amount of variability in the patterns across regions, a couple of trends have emerged: overall levels of variability are low, indicative of a small historical effective population size, and there are systematic differences in the patterns of SNP variation both across different regions of the genome and across human populations. The connections between these broad patterns and models of human evolution are unclear, in part because of the difficulty in quantifying the verbal models of physical anthropology. This will change soon with the development of new analytical methods and the gathering of more human SNP data.
The role of nonsense‐mediated decay in physiological and pathological processes
Authors: Holbrook Jill A. , Neu‐Yilik Gabriele , Hentze Matthias W. , Kulozik Andreas E. 
Published: July 2005

AbstractIn eukaryotes, a conserved surveillance pathway known as nonsense‐mediated decay (NMD) regulates the abundance of mRNAs containing premature termination codons (PTCs), defined as in‐frame stop codons located upstream of the physiological (i.e., normal) stop codon. PTCs often arise as the result of mutations but can also occur in normal transcripts as a result of physiological processes. NMD appears to have evolved as a means of both controlling expression of physiological (i.e., nonmutated) transcripts containing PTCs and of limiting production of protein from abnormal PTC‐containing transcripts. The mechanism of NMD is described and its roles in normal cellular function and in some forms of genetic disease are discussed.
Microarrays: an overview
Authors: Hoheisel Jörg D. 
Published: July 2005

Abstract
Microarrays have become a tool that is synonymous to modern molecular biology. From beginnings that were aimed at the high‐throughput sequencing of the human genome, a wide variety of different technology platforms emerged, on which an even larger number of assay formats are performed. Currently, the technology is in a state of transition. The initial developmental phase is finished, with part of the technology established to a degree that processes are on the brink of routine application. Simultaneously, however, new applications and technical advances emerge continuously, which require further development and evaluation, also moving into fields other than the analysis of nucleic acids.
Genomic analysis of host pathogen interactions
Authors: Kellam Paul , Gale Catherine V. 
Published: July 2005

AbstractInfection of multicellular organisms by microbes occurs throughout, and can shape, the evolutionary history of both the host and the pathogen. Following exposure, transcriptional remodeling of infected cells and cells of the innate and adaptive arms of the immune system results in both disease symptoms and eventually in pathogen clearance. Failure of this integrated system results in host death. More sophisticated microbes are able to dramatically blunt cellular defense mechanisms, and in some cases, reprogram cellular gene networks to allow persistence within the host. This is sometimes a beneficial, symbiotic relationship, but often results in life‐long host infection, occasionally with delayed pathogenesis. Transcriptional profiling studies have started to uncover the coordinated host response to microbial encounter that should ultimately produce a greater understanding of microbial pathogenesis.