bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired chromosome abnormalities: the cytogenetics of cancer
Authors: Gollin Susanne M. 
Published: April 2005

Abstract
Cancer is a disease in which genetic alterations, most frequently chromosomal rearrangements, are acquired in somatic cells resulting in loss of critical cellular checks and balances. This leads to cellular dysregulation, proliferation, and ultimately, malignant transformation. Cancer cytogenetics is the subdiscipline of genetics in which the chromosomal abnormalities present in cancers are identified and investigated. This includes correlation of the cytogenetic abnormalities with clinical diagnosis, prognosis and response to therapy, and may extend to identification of the genes disrupted and/or dysregulated as a result of the chromosomal aberrations. The history of cancer cytogenetics, a description the cytogenetic methodology that has developed and evolved over the past half‐century, clinical applications of cancer cytogenetics, and mechanisms by which cytogenetic abnormalities arise in cancer cells are described in this contribution to the literature.
Comparative genomic hybridization
Authors: Levy Brynn 
Published: April 2005

Abstract
The notion of obtaining a cytogenetic result without actually looking at the patients' chromosomes would have been considered ridiculous more than 12 years ago. The development, in 1992, of comparative genomic hybridization (CGH) has allowed this to become a reality. CGH is a powerful technique that can scan the entire genome in a single step for imbalances in chromosomal material. It can be used as a tool to uncover novel critical cancer causing genes such as tumor suppressors and oncogenes in a variety of solid tumor specimens. CGH can also be used to identify unbalanced chromosomal aberrations of unknown origin in clinical specimens as well as to screen for total aneuploidy in clinical specimens not amenable to analysis by conventional cytogenetic methods. This chapter discusses the technique of CGH and describes its use as both a cancer research tool and a diagnostic technique in clinical cytogenetics.
FISH
Authors: Nagesh Rao P. , Pettenati Mark J. 
Published: April 2005

Abstract
The limitations of classical chromosome studies have been overcome by the introduction of fluorescence in situ hybridization (FISH), which offers a molecular dimension to cytogenetic analyses. It is a very useful technique for detection of targeted chromosomal abnormalities and applicable to many specimen types such as blood, bone marrow, tissue touch preparations, body fluids, and even paraffin‐embedded fixed tissue. Different FISH technologies have emerged, each with their own particular advantages and applications, for example, interphase FISH, whole‐chromosome paints, multicolor‐FISH, conventional comparative genome hybridization, and now array CGH. These techniques are all essentially based upon the annealing of single‐stranded probe DNA to the complementary DNA sequences, present in their natural position on the chromosomes (in situ hybridization). Rapid development of new types of probes such as cosmids, P1, PAC, BAC, YAC, oligos, microdissected chromosome regions, and whole‐chromosome libraries, dramatically increased the possible applications for FISH. Judicious choice from the molecular cytogenetic techniques now available has opened venues to novel applications, and consequently, even more information about cytogenetic abnormalities can now be obtained.
Human sperm–
FISH
for identifying potential paternal risk factors for chromosomally abnormal reproductive outcomes
Authors: Wyrobek Andrew J. , Schmid Thomas E. , Marchetti Francesco 
Published: April 2005

Abstract

Paternally transmitted genetic defects may lead to birth defects and genetic diseases in offspring. In the last decade, a series of sensitive methods has been developed for detecting genetic and chromosomal damage directly in sperm, providing potential biomarkers for paternal risk factors for infertility (
see
Cytogenetics of Infertility
), spontaneous abortions, as well as aneuploidy syndromes (
see
Nondisjunction
), heritable chromosomal rearrangements, and certain genetic diseases in children. Among these, fluorescence in situ hybridization (FISH) has been adapted for the detection of both numerical and structural chromosomal abnormalities in human sperm as well as the sperm of several laboratory and domesticated animal species. Human sperm–FISH has identified several potential risk factors for chromosomally abnormal sperm including certain lifestyles factors and environmental/occupational exposures. Here, we summarize the advantages and challenges of sperm‐FISH for identifying paternal risk factors for abnormal reproductive outcomes.
Concept of complex trait genetics
Authors: Weiss Kenneth M. , Buchanan Anne V. 
Published: April 2005

Abstract
Complex traits are those for which there is no single main‐effect cause with high predictive power. These traits generally involve multifactorial causation, including gene–gene and/or gene–environment interaction, although generally an exhaustive set of causal factors has not been possible to enumerate. Common complex chronic diseases in humans illustrate this heterogeneous category of traits and possible reasons for the difficulty human genetics and epidemiology have had in parsing them. It may be that a history of success with “simpler” diseases, those caused by strong environmental risk factors or single genes with strong effect, predisposes investigators to assume a similar model for complex disease. However, there are numerous reasons that complex diseases do not conform to the same model.
Advances in newborn screening for biochemical genetic disorders
Authors: Sahai Inderneel , Levy Harvey L. 
Published: April 2005

AbstractNewborn screening (NBS) has evolved significantly since its introduction in 1962 for determining one biochemical genetic disorder, phenylketonuria (PKU), to now include endocrinopathies, hemoglobinopathies, congenital infections, cystic fibrosis, and congenital deafness as well as many biochemical genetic disorders. The wide coverage of biochemical genetic disorders has been facilitated by the recent addition of tandem mass spectrometry (MS/MS) to the technology for newborn screening. MS/MS enables measurement of amino acids and acylcarnitine conjugates of organic and fatty acids in the Guthrie blood specimen from newborns in one assay, thus allowing for screening for multiple disorders with abnormalities in these analytes simultaneously. The newly detectable biochemical genetic disorders can be broadly classified into amino acid, organic acid, and fatty acid oxidation disorders. This article briefly reviews the MS/MS technology, the disorders identifiable by this technology, and the distinguishing analytes during newborn screening. Though newborn screening has now been expanded to include many biochemical genetic disorders, most of these disorders remain undetectable by newborn screening. Even in disorders detectable by screening, the biochemical abnormalities may not be present during the newborn period. Thus, individuals suspected of having a biochemical genetic disorder should undergo specific testing. Newborn screening continues to be modified with advances in molecular, enzymatic, and other technologies and continues to include a greater number of disorders.
Carrier screening: a tutorial
Authors: Grody Wayne W. , Amos Jean A. 
Published: April 2005

Abstract

Population carrier screening for cystic fibrosis mutations was launched in the United States in 2001. Despite three years of accrued experience on large numbers of tested couples, many aspects of the testing protocol and the genetic counseling remain problematic, owing to the complexity of the causative
CFTR
gene, the large number of possible mutations within it, the uncertain genotype–phenotype correlation, and the varying residual risks of a negative test in those with or without a positive family history of the disorder. The clinical vignette presented in this tutorial illustrates many of these issues and the appropriate approach for addressing them.
The physical examination in clinical genetics
Authors: Falk Marni J. , Robin Nathaniel H. 
Published: April 2005

AbstractThe genetics physical examination provides an objective tool that supplements medical and familial historical information in an effort to identify a unifying etiology for a child, fetus, or adult with multiple birth defects, developmental problems, or other abnormal findings present. The genetics examination, while similar to any general medical examination, has several facets that distinguish it. First, it is necessary to understand the art and science of “dysmorphology”, the study of abnormal form. Precise observation and accurate description, followed by careful collation, interpretation, and categorization of any physical differences present are required to reach an accurate genetic diagnosis. Here, we review the general principles and specific components of the genetic physical exam, as well as how to integrate the physical exam findings into the overall medical genetic evaluation.
Cancer genetics
Authors: Schneider Katherine A. , Branda Kelly J. , Chittenden Anu B. , Shannon Kristen M. 
Published: April 2005

Abstract
Hereditary cancer syndrome account for about 5–10% of cancer cases. The three classes of genes that are highly important in the development of cancer are termed tumor suppressor genes, DNA repair genes, and proto‐oncogenes. Germline mutations in any of these genes can lead to increased susceptibility to cancer. Over 200 cancer syndromes have been identified, but most are rare. Features of 12 hereditary cancer syndromes are listed in this article, and two syndromes – hereditary breast/ovarian cancer syndrome and hereditary nonpolyposis colon cancer syndrome (HNPCC) – are described in detail. Cancer genetic counseling is a communication process concerning an individual's risks of developing specific inherited forms of cancer. Cancer genetic counseling sessions include collecting detailed family histories, providing risk assessments, discussing follow‐up medical options, and arranging genetic testing, if appropriate.
Prenatal aneuploidy screening
Authors: Wenstrom Katharine D. 
Published: April 2005

Abstract

Prenatal screening for birth defects gives the pregnant woman autonomy by providing her with information that she can use to decide either to continue the pregnancy or to terminate it. The most widely used prenatal screening tests are designed to detect fetal Down syndrome and trisomy 18. The basis of most of these screening protocols is the woman's age‐related risk, which is modified by the results of a blood test and/or an ultrasound exam. Ultrasound can also be used to screen for major malformations and minor dysmorphisms that independently indicate increased aneuploidy risk. The woman is then counseled regarding the composite estimated risk of fetal aneuploidy determined by her
screening test
s, and offered a definitive
diagnostic test.
Currently, diagnostic testing can only be performed on fetal cells obtained by an invasive procedure such as amniocentesis or chorionic villous sampling, which each entail a finite risk of post‐procedure pregnancy loss. Ultimately, the decision to undergo prenatal serum or ultrasound screening and then to undergo invasive testing must be made by the woman, on the basis of information provided during counseling and her own beliefs and values.
Gene transfer to the skin
Authors: Gagnoux‐Palacios Laurent , Spirito Flavia , Meneguzzi Guerrino 
Published: April 2005

Abstract
The transplantation of autologous artificial epithelia expressing recombinant genes, and direct transfer of DNA to the skin represent potential therapeutic approaches for a local or systemic delivery of active molecules. Successful cutaneous gene therapy trials require development of protocols for efficient gene transfer to epidermal stem cells, and information about the host immune response to the recombinant polypeptides produced by the delivered genes.
LinkingDNAto production: the mapping of quantitative trait loci in livestock
Authors: Moore Stephen S. , Hansen Christiane , Li Changxi 
Published: April 2005

AbstractThe concept that quantitative variation is controlled by an infinite number of genes was a widely accepted hypothesis until the 1980s. The more recent concept of a few genes of moderate to large effect underlying quantitative variation is integral to our ability to detect genes affecting quantitative trait loci (QTL). This latter hypothesis has gained credence owing to the success of QTL mapping studies in multiple livestock species including cattle, sheep, swine, and chickens. A large number of QTL have been mapped for a variety of traits in livestock species. Only very few genes underlying QTL have, however, been identified to date. Methodologies are being developed that will increase our ability to identify the genes underlying QTL. This chapter gives an overview of the work that has been done to map QTL in cattle, swine, sheep, and chickens.
Segmental duplications and the human genome
Authors: Vallente Rhea U. , Eichler Evan E. 
Published: April 2005

AbstractSegmental duplications are a newly identified class of repetitive elements that consist of physically interspersed blocks of duplicated material in a genome. Initial sequence analysis of the human genome has shown that ∼5–6% of the genome is highly homologous sequences, ranging in size from a few to hundreds of kilobases. Closely located segmental duplications are one of the factors predisposing to the occurrence of genomic disorders and are one of the major driving forces in primate genome evolution, by acting as highly unstable hotspots for chromosomal rearrangements. A combination of computational, molecular, sequence, and cytogenetic methods has facilitated the detection and characterization of segmental duplications. Understanding the origin and propagation of segmental duplications will provide fundamental insight into how genes and genomes change during the course of time.
Pseudogenes
Authors: Torrents David 
Published: April 2005

AbstractPseudogenes are nonfunctional genomic regions that arise mostly from the duplication of functional genes. Two types of pseudogenes are generally formed by independent mechanisms that are believed to have different implications in gene evolution.Nonprocessedpseudogenes arise after partial or complete segmental duplication of genes and subsequent loss of function by mutations.Processedpseudogenes, in contrast, are formed through the reverse transcription of mature RNAs and their integration back in the genome (retrotransposition). As pseudogenes share many sequence characteristic with functional genes, the identification and differentiation of pseudogenes is often difficult and prone to controversy. Nevertheless, a few sequence features that suggest the absence of functionality have been exploited to obtain pseudogene collections from different available genomes. In human and rodents, nearly 20 000 pseudogenes have been identified, most of which were found to have a retrotranspositional origin. In contrast, a much lower number of pseudogenes could be identified in other organisms, such as chicken and nonvertebrates. Despite the recent identification of large collections of pseudogenes, improvements in the distinction between functional and pseudogenic regions are still required in order to determine what the actual impact of these regions is in the evolution of the genomes.
Endogenous retroviruses
Authors: Mayer Jens 
Published: April 2005

Abstract
Endogenous retroviruses (ERVs) are an integral part of vertebrate genomes. ERVs became inherited genomic components by formation of proviruses of exogenous retroviruses in germ cell genomes. Repeated endogenization of diverse exogenous retroviruses and subsequent increase of provirus numbers resulted in a considerable retroviral load in host genomes. For instance, the human and the mouse genome hold 8 and 10%, respectively, of sequences of retroviral origin. Most ERV sequences accumulated numerous nonsense mutations over time, rendering them defective. Nevertheless, ERVs can affect the host genome in various ways. Long terminal repeats influence transcription of nearby cellular genes. ERV proteins protect from exogenous retrovirus infection. Human ERV sequences may be involved in placenta development and in the formation of germ cell tumors. ERVs are therefore important genome components that contributed significantly to the evolution of host genomes.
Mouse models
Authors: Goldsworthy Michelle E. , Cox Roger D. 
Published: April 2005

Abstract
The mouse has a proven track record as a model organism that has made a significant contribution to the understanding of disease and biology relevant to the human. It is not the only model organism by any means but for the study of human disease it is perhaps one of the most widely used. We have tried to illustrate in this review the multiple approaches that have been utilized using as examples the study of type 2 diabetes and obesity in the mouse. Spontaneous mutations and knockouts have given insight into the relative contributions of differing genes in the regulation of glucose homeostasis, insulin resistance, β‐cell function, and adiposity. Tissue‐specific knockouts have gone some way in dissecting the relative contributions of multiple tissues and organs to disease progression. Combinations of different mutants, which individually would not produce disease, have provided polygenic models of type 2 diabetes. Sensitized ENU mutagenesis screens may yield additional novel diabetes genes. The mouse has only been one of the approaches available to us to investigate human disease but together with studies in human populations, other model organisms, and in vitro systems, it has opened unprecedented opportunities in this new century to tackle the problem of common human disease.
Mouse mutagenesis and gene function
Authors: Kühn Ralf , Wurst Wolfgang 
Published: April 2005

AbstractWith the completion of the mouse and human genome sequences, a major challenge is the functional characterization of every gene within the mammalian genome. The mouse offers many advantages for the use of genetics to the study of human biology and disease. A variety of mouse mutagenesis technologies, either gene‐ or phenotype‐driven, are used as systematic approaches. The availability of the mouse genome supports gene‐driven approaches such as gene‐trap and targeted mutagenesis in embryonic stem (ES) cells, allowing an efficiency and precision of gene disruption unmatched among other mammals. Furthermore, chemical and transposon mutagenesis of the mouse genome allows to perform phenotype‐driven screens for the unbiased identification of phenotype–genotype correlations. These technologies already resulted in a collection of several thousand mutants. In this article on mouse mutagenesis and gene function, we present a comprehensive review of gene‐ and phenotype‐driven mouse mutagenesis strategies. Besides a summary of the basic principles of each approach, we emphasize on the latest and future developments of mouse mutagenesis.
Functional genomics in

S
accharomyces cerevisiae
Authors: Dolinski Kara , Troyanskaya Olga 
Published: April 2005

Abstract

The availability of the
Saccharomyces cerevisiae
genome has fueled an explosion of high‐throughput methods aimed at the functional characterization of all proteins in yeast. These diverse methods include expression and protein microarray experiments, protein–protein and protein–DNA interaction studies, proteomics data, and phenotype analyses. Integrated bioinformatics analysis is necessary to utilize the full potential of these data. Such analysis can be facilitated by public distribution of these data sets in standardized form and by development of accurate and efficient analysis algorithms. In this chapter, we outline available data sources and their distribution, data sharing standards, and data integration methods.
The

D
rosophila

genome(s)
Authors: Russell Steven , Bergman Casey M. 
Published: April 2005

Abstract

Since its introduction as a research tool in the early twentieth century,

Drosophila melanogaster

has occupied center stage in genetics as an experimentally tractable model for understanding the structure of genomes. It was used to prove the chromosomal theory of heredity (Bridges,

) and to first localize particular genes to cytologically defined regions of the chromosome (Bridges,

). With the virtual completion of the genome sequence, the fly continues to hold sway. We briefly assess the status of the current sequence, describe how other
Drosophila
sequences are being used to provide an evolutionary perspective to the genome and highlight how the sequence is enabling large‐scale functional analysis of conserved aspects of eukaryotic biology. Finally, we consider how the polytene chromosomes may provide a system to move from the linear DNA sequence to the challenging area of chromatin organization and chromosome structure.
Genomics of the

M
ycobacterium tuberculosis

complex and

M
ycobacterium leprae
Authors: Gordon Stephen V. , Brosch Roland 
Published: April 2005

Abstract

Diseases caused by mycobacteria continue to exact a terrible burden across the globe, with an urgent need for new treatments and control strategies. Elucidation of the genome sequences of these pathogens therefore offers a cost‐effective approach to catalyze research and accelerates our understanding of them. The genome sequence of the hallmark strain,
Mycobacterium tuberculosis
H37Rv, has been available since 1997 and this serves as the lynchpin for comparative genomics across the complex. Our review will use comparative genomics to explore the wealth of sequence data available for the pathogenic mycobacteria and highlight similarities and parallels that impact upon important biological characteristics. Such analyses are providing novel insights into how pathogenic mycobacteria exploit the in vivo niche, and in so doing expose targets for drug development and diagnostic reagents.
Genomics of enterobacteriaceae
Authors: Glasner Jeremy D. , Perna Nicole T. 
Published: April 2005

Abstract

Enterobacteria were among the earliest targets for genome sequencing and are still the most densely sampled clade of bacteria in the genomics arena. Twenty complete genome sequences are available for members of the family as of September 2004, and the NCBI list of genomes in progress includes another 20 enterobacteria. This is undoubtedly an underestimate of the sequences that will be available for enterobacteria in the coming two years. Among the complete genomes are representatives of nine genera, including
Escherichia
,
Shigella
,
Salmonella
,
Yersinia
,
Erwinia
,
Buchnera
,
Photorhabdus
,
Wigglesworthia,
and
Candidatus Blochmannia
. Genomes in progress will add additional strains and species of these, as well as additional genera such as
Klebsiella
,
Proteus
,
Citrobacter
,
Enterobacter
,
Dickeya
, and
Pantoea
. Among these are standard laboratory research strains, human pathogens, livestock pathogens, plant pathogens, and insect endosymbionts. Each genome sequence aids in understanding the biology of the individual organism, but some of the greatest insights come from comparisons between the genomes. For many of these genera, sequences are available for multiple species or strains, providing unique perspectives on genome‐wide polymorphism. Enterobacteria are also very experimentally tractable, and we are beginning to see a boom in downstream research making use of the sequences.
The organelles of apicomplexan parasites
Authors: Ajioka James W. , Brooke‐Powell Elizabeth T. , Wan Kiew‐Lian 
Published: April 2005

Abstract
The apicomplexa are a highly diverse phylum of parasitic protists that are descended from a secondary endosymbiosis of a photosynthetic algae and single eukaryotic cell. Throughout the evolution of the phylum, most species have maintained a single mitochondrion and a plastid‐like organelle called the apicoplast. The genomes associated with these organelles are vastly reduced compared to counterparts in other eukaryotic lineages and this probably reflects a concomitant reduction in function.