bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritability Wars
Authors: Wickham Harvey , Sham Pak
Published: September 2006

The use of statistics to estimate the capability of human behaviors to be genetically transmitted is controversial.
Animal Models of Human Behavior
Authors: Maxson Stephen C
Published: September 2006

Animal models should be viewed only as generating hypotheses about human behavior, because there are differences between animal and human behavior as well as similarities. There are two ways that gene‐based behavioral variants of animals can be used for this: the first way is in identifying and mapping genes with effects on human behavior; and the second is in developing hypotheses about the biological causes of human behavior.
Alzheimer Disease
Authors: Reynolds Chandra A , Crowe Michael
Published: September 2006

Alzheimer disease (AD) is a complex, progressive neurodegenerative disease. Several mutations have been characterized and susceptibility genes implicated as playing a role in the disorder. While a substantial proportion of the liability for AD may be accounted for by genetic factors, environmental factors probably play a significant role.
Human Variation Databases
Authors: Sherry Stephen T
Published: September 2006

Individual variations in genomic sequence are useful reagents in physical mapping, linkage analysis and the functional study of individual genes. Several public databases exist as comprehensive or specialized resources to organize these data for sequence annotation and research.
Protein Databases
Authors: Gerritsen Vivienne Baillie , Bairoch Amos
Published: September 2006

An abundance of protein databases are available, dealing with fields as diverse as protein sequences, protein domains, posttranslational modifications and protein–protein interactions. Such resources are crucial to proteomics research.
Structural Databases of Biological Macromolecules
Authors: Berman Helen M
Published: September 2006

The Protein Data Bank began as an archive of the structural data available about known biological macromolecules. The advances made in all technologies have been mirrored in further development of the Protein Data Bank and in the structural, speciality and structural characteristic databases that have also evolved.
FASTA Algorithm
Authors: Pearson William R
Published: September 2006

The FASTA programs search protein and DNA databases for sequences with statistically significant similarity. The programs compare proteins, DNA and short peptides and oligonucleotides, and run on most popular computers.
Multiple Alignment
Authors: Thompson Julie , Poch Olivier
Published: September 2006

Multiple alignment is a powerful integrative tool that addresses a variety of biological problems, ranging from key functional residue detection to the evolution of a protein family. Traditionally, a multiple alignment was generally constructed as a series of pairwise alignments; however, the recent application of various new computational techniques to the multiple alignment problem has led to a number of interesting new developments.
Profile Searching
Authors: Hofmann Kay
Published: September 2006

A profile is a computational representation of sequence properties derived from a family of related proteins. Analogous to single sequences, profiles can be used for database searches using a dynamic programming algorithm. Because profiles allow position‐specific scoring systems and gap parameters, profile searches offer a greatly increased sensitivity in detecting distant protein relationships.
Sequence Complexity and Composition
Authors: Konopka Andrzej K
Published: September 2006

Local compositional complexity is a numerical measure of repetitiveness of sequences of symbols from a finite alphabet. Highly repetitive sequences are considered simple, whereas highly nonrepetitive sequences are considered complex.
Alignment: Statistical Significance
Authors: Mott Richard
Published: September 2006

Computation of the probability that an observed alignment between two protein or DNA sequences could have arisen by chance is useful for identifying genuinely related sequences.
Hidden Markov Models
Authors: Przytycka Teresa M
Published: September 2006

A hidden Markov model is a statistical tool that is frequently used for modeling biological sequences. In applying it, a sequence is modeled as an output of a discrete stochastic process, which progresses through a series of states that are ‘hidden’ from the observer. At each state, the process outputs a symbol from a finite alphabet according to a given probability distribution.
Repetitive Elements: Detection
Authors: Jurka Jerzy , Kapitonov Vladimir V , Smit Arian FA
Published: September 2006

Multicopy, or repetitive, deoxyribonucleic acid (DNA) is routinely being detected and analyzed by computer‐assisted comparison of genomic DNA with representative reference databases of repeats.
RNA Gene Prediction
Authors: Holbrook Stephen R , Carter Richard J , Meraz Richard F
Published: September 2006

The rapid growth of sequenced genomes and the discovery of numerous novel RNA species has made the development of methods for the computational identification of genes encoding functional RNA a high priority. Recent developments of algorithms for RNA gene prediction are based on diverse criteria, including location of promoters and terminators, sequence conservation among related genomes, RNA base‐pairing and nucleotide composition.
DNA Replication
Authors: Zannis‐Hadjopoulos Maria , Price Gerald B
Published: September 2006

Deoxyribonucleic acid replication is the process leading to the duplication of genetic material in an organism.
DNA Repair
Authors: Reed Simon Huw , Waters Raymond
Published: September 2006

The primary structure of DNA is subject to constant change caused by chemical and physical factors. If unchecked, these changes would quickly erode the genetic information. DNA repair mechanisms have evolved to remove potentially deleterious damage and maintain the integrity of the genome in all organisms.
Transcriptional Regulation: Coordination
Authors: Egly Jean‐Marc , Rochette‐Egly Cécile
Published: September 2006

In higher eukaryotes, gene expression is tightly coordinated at multiple stages with other events that orchestrate the life of the cell. Prompted by an initial signal, regulatory transcription factors are activated, assemble at specific enhancer sequences and trigger a cascade of reactions, resulting in an appropriately remodeled chromatin template, with functional transcription machinery on the promoter. Phosphorylation, acetylation and methylation orchestrate the interconnection of the different steps.
Tissue‐specific Locus Control: Structure and Function
Authors: Bonifer Constanze
Published: September 2006

All developmental processes involve decisions in which the developmental fate of precursor cells is restricted to a single lineage by establishing a unique gene expression pattern. The activation at each of these gene loci involves restructuring chromatin as a necessary prerequisite for the assembly of the transcription apparatus. Tissue‐specific locus activation is controlled by the interplay between sequence‐specific transcription factors, chromatin‐modifying activities and basic chromatin components.
Homologous, Orthologous and Paralogous Genes
Authors: Li Wen‐Hsiung
Published: September 2006

Orthology and paralogy are two different types of homology, depending on whether the genes in question derive from a duplication event or a speciation event.
Hominids
Authors: Wood Bernard
Published: September 2006

‘Hominid’ is the term traditionally used to refer to the human clade, that is, all the extinct taxa that are more closely related to modern humans than they are to any other living animal. Given the molecular and other evidence for the close relationship between modern humans and the other higher primates (chimps, gorilla and the orang), there is an emerging consensus that the latter should be included in the Hominidae.
Gene Structure: Evolution
Authors: Ohta Tomoko
Published: September 2006

Two fundamental processes in the evolution of gene structure in populations are the production of variations by mutations and the natural selection that filters these variations. Mutations occur randomly in genomes of germ cell lineages and are rejected or selected for, so that genes perform needed functions. As a result of minute effects of most mutations, both genetic drift and natural selection influence their fate in a population.
Mammalian Phylogeny
Authors: Penny David , Phillips Matthew
Published: September 2006

The evolutionary tree of mammals is being resolved rapidly by the increased availability of DNA sequences. Highlights include the placement of humans within the African apes (chimpanzees and gorillas), and the uniting of primates as a whole with flying lemurs and tree shrews to form paraprimates. These join with rodents and rabbits to form the group Supraprimates.
Kimura, Motoo
Authors: Ohta Tomoko
Published: September 2006

Motoo Kimura (1924–1994) was a Japanese population geneticist who proposed the neutral theory of molecular evolution.
Zuckerkandl, Emile
Authors: Morgan Gregory J
Published: September 2006

Emile Zuckerkandl (1922–) discovered the molecular evolutionary clock and founded the
Journal of Molecular Evolution
.
Bioinformatics: Technical Aspects
Authors: Jongeneel C Victor
Published: September 2006

The genome projects have depended heavily on powerful computers and high‐speed networks. Much software was written specifically for them to cover technical requirements from data handling to the presentation of genome data to the scientific community. The projects also spurred the development of new types of computer hardware, which are designed specifically for the needs of genome scientists.
Genetic Databases: Mining
Authors: Risler Jean‐Loup , Louis Alexandra
Published: September 2006

The exhausting pace at which new genomic sequences are deposited with the databanks makes it essential to put efficient retrieval systems at the scientific community's disposal. Entrez and SRS are two such programs, freely accessible from the Web, that enable powerful simple and Boolean queries.
Sequence Similarity
Authors: Heringa Jaap
Published: September 2006

Sequence similarity is a measure of an empirical relationship between sequences. A common objective of sequence similarity calculations is establishing the likelihood for sequence homology: the chance that sequences have evolved from a common ancestor. A similarity score is therefore aimed to approximate the evolutionary distance between a pair of nucleotide or protein sequences. Many implementations for measuring sequence similarity exist.
Sequence Alignment
Authors: Thompson Julie D , Poch Olivier
Published: September 2006

Definition sequence comparison or alignment is the cornerstone of bioinformatics, providing the basis for sequence database searching, three‐dimensional structure modeling and evolutionary studies. A sequence alignment shows how a set of sequences may be related by identifying and arranging in columns the structurally and functionally equivalent residues common to all the sequences.
Kilobase Pair (kbp)
Authors: Dear Paul H
Published: September 2006

A kilobase pair (kbp) is a unit of length of nucleic acids, equal to 1000 base pairs.
Nucleic Acid Hybridization
Authors: Chan Sarah WL , Choo Andy KH
Published: September 2006

Nucleic acid hybridization allows the identification of homologous DNA and RNA sequences. This technique is used for gene mapping, gene expression studies and analysis of genomic organization.
Ancient DNA: Recovery and Analysis
Authors: Hummel Susanne
Published: September 2006

Ancient DNA can be recovered from any preserved organic remains of both dead and living organisms and is characterized by degradation down to a few hundred base pairs. The analysis requires especially adapted parameters for DNA extraction, PCR‐based amplification and specific strategies for data validation.
Neanderthal DNA
Authors: Goodwin William , Ovchinnikov Igor
Published: September 2006

Mitochondrial deoxyribonucleic acid (mtDNA) has been successfully extracted and analyzed from three Neanderthal specimens recovered from the Feldhofer Cave in Germany, the Mezmaiskaya Cave in the Caucasus Mountains and the Vindija Cave in Croatia. The Neanderthals' mtDNA pool is distinct from modern human mtDNA and forms a separate phylogenetic clade. Using mtDNA as a molecular clock, the split between the mtDNA of modern humans and Neanderthals has been dated at approximately 600000 years. Like modern humans, the Neanderthals of 30000–40000 years ago display a low level of sequence diversity.
DNA Cloning
Authors: Quail Michael Andrew
Published: September 2006

Deoxyribonucleic acid (DNA) cloning is the art of creating recombinant DNA molecules that can be introduced into living cells, replicated and stably inherited, such that multiple ‘clonal’ copies of that DNA are produced. Techniques for cloning and the various vectors that can be used are described.
Genome Map
Authors: Dear Paul H
Published: September 2006

A genome map is a diagram, chart, table or database that shows the location in a genome of a number of identifiable features. Many methods are available for making genome maps, differing in their accuracy and in the types of feature that can be mapped.
Restriction Mapping
Authors: Tümmler Burkhard , Mekus Frauke
Published: September 2006

Deoxyribonucleic acid is partially or completely digested with one or more restriction endonucleases. The generated fragments are separated by size, and then ordered by combinatorial analysis to generate a physical map.
Optical Mapping
Authors: Mishra Bud
Published: September 2006

Optical mapping generates an ordered restriction map of a DNA molecule, that is, an ordered enumeration of the restriction sites along with the estimated lengths of the restriction fragments between consecutive restriction sites and various statistics, which model the errors in estimating the restriction fragment lengths and due to unrepresented and misrepresented restriction sites in the map. They have applications in improving the accuracy and algorithmic efficiency of sequence assembly, validating assembled sequences, characterizing gaps in the assembly and identifying candidates for finishing steps in a sequencing project, etc.
Contig Assembly
Authors: Gregory Simon G
Published: September 2006

The generation of a contig, by overlapping consensus segments within a region of deoxyribonucleic acid, can facilitate the identification of genes and provide the basis for structural and functional analyses. Contigs can be constructed in a directed approach using region‐specific markers or by whole‐genome analysis.
Gene Mapping and Positional Cloning
Authors: Little Peter FR
Published: September 2006

Gene mapping and positional cloning are used to identify a gene or genes that, when variant or mutated, contribute to the causation of a genetically defined disorder or condition.
Cystic Fibrosis Gene: Identification
Authors: Rommens Johanna M
Published: September 2006

Genetic and physical mapping studies of chromosome 7 led to the identification of the CF gene before the Human Genome Project.
Insulin‐dependent Diabetes Mellitus (IDDM): Identifying the Disease‐causing Gene at the
IDDM11
Locus
Authors: Zollo Massimo , Dear Paul , Pociot Flemming
Published: September 2006

In complex diseases, genome linkage analysis, fine mapping and association studies are used to identify disease‐causing genes. With the completion of the human genome sequence and its annotation, positional candidate gene studies have become an attractive method to identify genes involved in complex disorders by screening for selected chromosomal interval regions.
Primer Walking
Authors: Sverdlov Eugene , Azhikina Tatyana
Published: September 2006

Primer walking is a step‐by‐step approach to sequencing long DNA templates from end to end that overcomes the inability of the Sanger chain termination method to read more than a few hundred bases in a single reaction. After an initial round of sequencing from a known sequence at one end of the template, each subsequent round is initiated from a new primer, which is based on the end of the sequence obtained from the previous reaction.
Sequence Accuracy and Verification
Authors: Beck Stephan
Published: September 2006

Analyses involving deoxyribonucleic acid sequences have to consider three main parameters concerning accuracy: sequence quality, sequence contiguity and sequence fidelity. Here, sequence quality defines the probability of error for any base‐call, contiguity defines the completeness and correctness of the assembly of subsequences and fidelity defines the correctness of the genomic representation of the assembly.
Single Nucleotide Polymorphisms (
SNPs
): Identification and Scoring
Authors: Kwok Pui‐Yan
Published: September 2006

Single nucleotide polymorphisms (SNPs) are the most abundant DNA sequence variations in the human genome. Numerous methods have been developed to identify and score them. A large set of human SNPs have been identified and mapped to the reference human genome sequence. The SNP markers are useful for the study of the genetic basis of many human diseases.
Human Genome: Draft Sequence
Authors: Hubbard Tim JP
Published: September 2006

Researchers have been allowed free, early access to a nearly complete, human genome sequence. The draft contained many gaps and ambiguities; however, a continuous process of finishing over the last few years has resolved most of them.
Linkage Analysis
Authors: Meerman GJ te
Published: September 2006

Linkage analysis is the study of the association of inheritance of chromosome parts with phenotype in pedigrees.
Lod Score
Authors: Thompson Elizabeth A
Published: September 2006

Lod scores are test statistics based on likelihood ratios. They are used to detect genetic linkage.
Model‐based Linkage Analysis
Authors: Teare Marion Dawn
Published: September 2006

Model‐based linkage analysis is the analysis of the cosegregation of genetic loci in pedigrees. The most common form of linkage analysis uses pedigrees selected due to the presence of individuals affected by a disease that is assumed or known to have a major genetic component. Genetic markers are then examined to identify loci that appear to be cotransmitted with the predisposing disease locus.
Multilocus Linkage Analysis
Authors: Strauch Konstantin
Published: September 2006

With multilocus linkage analysis, more than two loci are simultaneously considered for linkage. When mapping a disease gene relative to a group of markers with known intermarker recombination fractions, it is possible to perform parametric (lod score) as well as nonparametric analysis.
Quantitative Genetics
Authors: Neale Michael C
Published: September 2006

Quantitative genetics is the assessment of variation due to genetic and environmental factors. It can be used to identify the sources of similarity between relatives.
Heritability
Authors: Schonemann Peter H
Published: September 2006

Heritability coefficients (‘heritabilities’) are variance ratios intended to measure the relative contribution of genetic versus environmental factors to physical and psychological individual differences.
Quantitative Trait Loci (QTL) Mapping Methods
Authors: Mott Richard
Published: September 2006

Quantitative trait loci mapping methods are statistical methods for identifying loci associated with a quantitative phenotype.
Genetic Epidemiology of Complex Traits
Authors: Rana Brinda K , Schork Nicholas J
Published: September 2006

Genetic epidemiology evaluates the contribution of genetic factors to disease incidence, prevalence, diagnosis, prevention and treatment in the population at large. Since most traits and diseases are influenced by a number of genetic and nongenetic factors, the identification and characterization of such factors using population‐based studies is extremely difficult, although ‘assays’ that investigate aspects of genetic population structure make meaningful analysis possible.
Gene–Environment Interaction
Authors: Kardia Sharon LR
Published: September 2006

Gene–environmental interactions are likely to play a key role in the development, prevention and treatment of common diseases.
Linkage and Association Studies: Replication
Authors: Fallin M Daniele , Pulver Ann E
Published: September 2006

Conclusions regarding identification of disease genes are currently limited by the failure to replicate linkage and association findings across studies. Issues such as heterogeneity, limited power and inadequate marker information should be considered carefully to guide design strategies most likely to provide interpretable results across studies.
Psychiatric Disorders: The Search for Genes
Authors: Craddock Nick
Published: September 2006

Psychiatric disorders are a set of common complex genetic disorders in which the core features include pathological disturbances of mood, cognition and behavior. Genes have already been identified for some psychiatric disorders such as Alzheimer disease, and large‐scale positional and candidate gene studies are ongoing for several others including schizophrenia, bipolar disorder, depression, alcohol abuse, autism and attention deficit hyperactivity disorder.
Segregation Analysis Software
Authors: Stricker Christian , Fernando Rohan L
Published: September 2006

Segregation analysis software is used to test modes of inheritance and to provide parameter estimates for genetic models.
Twin Studies: Software and Algorithms
Authors: Neale Michael C
Published: September 2006

The implementation and advantages of likelihood‐based model fitting approaches to the analysis of data collected from MZ and DZ twins. Estimation of heritability and environmental components of variance that contribute to individual differences.
Epidemiological Tools
Authors: Gwinn Marta , Khoury Muin J
Published: September 2006

Epidemiological studies are useful for investigating the prevalence of genetic traits, gene–disease associations, and gene–gene and gene–environment interactions. Epidemiological tools are used to select study samples, estimate risk and evaluate associations.
Sample Size Requirements
Authors: Knapp Michael
Published: September 2006

Sample size requirements in the context of linkage analysis between a trait and genetic markers refer to the calculation of the sample size required for a linkage study to guarantee a certain power of the study against an assumed inheritance model. The power against an assumed inheritance model is the probability of correctly declaring a linkage when in fact the assumed inheritance model is true and the trait and marker loci are linked.
Path Analysis in Genetic Epidemiology
Authors: Rao DC , Rice Treva
Published: September 2006

The method of path analysis evaluates the importance of genetic and familial environmental effects for explaining the variability in a trait. The method may be applied to data on simple families, twins and other extended families.
Mutation Rate
Authors: Müller‐Myhsok Bertram
Published: September 2006

Mutation rate is the probability that a mutation occurs on a defined piece of genetic material over a given time frame.
Inbreeding
Authors: Charlesworth Deborah
Published: September 2006

The mating of related individuals (inbreeding) is important in plant and animal breeding and in human populations, as well as in zoo populations and conservation efforts. The homozygosity due to inbreeding often causes reduced fitness (inbreeding depression), and this is also important in the evolution of systems evolved by organisms to avoid inbreeding.
Fitness and Selection
Authors: Charlesworth Brian
Published: September 2006

When genotypes differ in their fitnesses, selection will affect the genetic composition of a population. Precise mathematical definitions of fitness have been developed and can be applied to the estimation of genotypic fitnesses in human populations.
Genetics of Large Populations and Association Studies
Authors: Chikhi Lounès , Garnier‐Géré Pauline Hélène
Published: September 2006

Association studies aim to discover the genetic basis of genetic diseases or drug responses through the comparison of genotypes at marker loci with phenotypes of affected and nonaffected individuals in large populations assumed to be at Hardy–Weinberg equilibrium.
Polymorphisms: Origins and Maintenance
Authors: Weiss Kenneth M
Published: September 2006

Polymorphism is variation in specific locations in the deoxyribonucleic acid (DNA) sequence. Some authors use the term only for variant alleles with at least 1% frequency in a population. This shows the population dependence of the concept itself. Variation arises initially by some form of mutation in a single individual but, because DNA is transmitted from parent to offspring, over time the frequency and geographical distribution of a genetic variant is essentially a population concept that depends on history.
DNA Fingerprinting in Ecology
Authors: Harley Eric Hugh
Published: September 2006

DNA fingerprinting involves the use of individual, population or species‐specific DNA patterns for providing quantitative or qualitative information for population genetic, forensic and conservation management purposes.
Fixation Probabilities and Times
Authors: Otto Sarah P , Whitlock Michael C
Published: September 2006

The fixation probability of an allele is the probability that it will eventually be the ancestor of all the alleles within a population at that locus. The time to fixation is the number of generations that it takes for the allele to progress from its initial frequency to fixation.
Stationary Allele Frequency Distributions
Authors: Rannala Bruce
Published: September 2006

Forces that determine the allele frequencies in natural populations include genetic drift, natural selection, migration and mutation. A balance of opposing forces can, in some cases, cause allele frequencies to approach a stationary distribution over time. The form of this distribution is not influenced by initial allele frequencies, but instead is determined by the relative magnitudes of different evolutionary forces.
Mutations in Human Genetic Disease
Authors: Antonarakis Stylianos E , Cooper David N
Published: September 2006

Mutations in human genetic disease include single base‐pair substitutions in coding, regulatory and splicing‐relevant regions of human genes. Other kinds of pathogenic mutations are micro‐deletions, micro‐insertions, duplications, repeat expansions, combined micro‐insertions/deflections (‘indels’), inversions, gross deletions and insertions, and complex rearrangements.
Imprinting Disorders
Authors: Feinberg Andrew P , Niemitz Emily L
Published: September 2006

Genomic imprinting is an example of epigenetic inheritance in which differences in gene function depend on whether the allele was inherited from the mother or father. Many disorders now appear to involve epigenetic alterations, and the mechanism of normal imprinting as well as its perturbation in disease is becoming understood and amenable to experimentation.
Linkage and Association Studies
Authors: Borecki Ingrid B
Published: September 2006

Identification of genetic factors underlying predisposition to complex human diseases has relied on linkage studies to map the relevant loci and on association studies to evaluate the putative role of specific genetic variants on the risk for disease or on levels of quantitative risk factors. While both approaches seek an association between a genetic sequence and a phenotype of interest, their respective utility and power depend on the specific problem.
Disease‐related Genes: Functional Analysis
Authors: Rugarli Elena I , Ballabio Andrea
Published: September 2006

Functional analysis of genes involved in human diseases is a critical step in understanding disease pathogenesis. The function of a given gene can be determined either at the cellular level or at the level of a whole organism in both normal and pathological conditions. Functional analysis is achieved through integration of information derived from various experimental strategies, for example, determination of gene‐expression pattern, exploitation of bioinformatic resources, and biochemical and cellular studies.
Cp
G
Dinucleotides and Human Disorders
Authors: Antonarakis Stylianos E
Published: September 2006

Analysis of the mutation spectra of single nucleotide substitutions associated with monogenic disorders strongly suggests that CG to TG mutations are among the most frequent causes of human genetic disease phenotypes. This is probably due to the mechanism of methylation–deamination of cytosine. In addition, this substitution mechanism results in a substantial fraction of the polymorphic variability of the human genome.
Nonsense‐mediated
m
RNA
Decay
Authors: Mendell Joshua T , Dietz Harry C
Published: September 2006

Nonsense‐mediated mRNA decay is the recognition and selective decay of transcripts containing premature termination codons, which occurs in all studied eukaryotic organisms.
3′
UTR
Mutations and Human Disorders
Authors: Conne Béatrice , Stutz André , Vassalli Jean‐Dominique
Published: September 2006

The 3′ untranslated region (3′ UTR) of a number of messenger ribonucleic acids (mRNAs) is involved in the regulation of the processing, localization, translation or degradation of the transcript. Perturbations in such 3′ UTR‐mediated functions are implicated in a variety of human diseases.
Development: Disorders
Authors: Carrozzo Romeo , Boncinelli Edoardo
Published: September 2006

Development is the process leading to completely differentiated tissues an organs derived from a single fertilized egg. Many advances have been made toward understanding the molecular and biological basis of the cellular events involved in normal development, which allow us to foresee the classification of genetic and acquired disorders of development.
Eye Disorders: Hereditary
Authors: Kaplan Josseline , Rozet Jean‐Michel
Published: September 2006

Hereditary visual deficiencies can result from isolated or associated alterations of any structure of the eye. The identification of the molecular bases of ophthalmological disorders has revived interest in several conditions forgotten since their original description and allowed the development of specific therapeutic projects.
Deafness: Hereditary
Authors: Hardelin Jean‐Pierre , Levilliers Jacqueline , Petit Christine
Published: September 2006

There are 35 genes known to cause nonsyndromic hearing loss, and many more are expected to come out in the next few years. However, difficulties inherent in genetic linkage analysis, coupled with the possible involvement of environmental causes, have prevented the characterization of the main genes causative or predisposing to the late‐onset forms of deafness.
Metabolism: Hereditary Errors
Authors: Groop Leif
Published: September 2006

The molecular diagnosis of inherited metabolic disorders has provided not only an accurate diagnostic tool, but also molecular explanations for inherited metabolic diseases.
Skeletal Dysplasias: Genetics
Authors: Superti‐Furga Andrea , Unger Sheila
Published: September 2006

The skeletal dysplasias and dysostoses are a group of genetic disorders that manifest as disproportionate short stature, deformity and various medical complications. Dysplasias may result from genetic mutations that affect structural components, metabolic pathways, signal transduction mechanisms or gene expression patterns involved in skeletal growth and development.
Kidney: Hereditary Disorders
Authors: Esquivel Ernie L , Somlo Stefan
Published: September 2006

Hereditary disorders of the kidney consist of a heterogeneous group of diseases characterized by abnormalities in the ability of the kidneys to filter waste products and/or maintain acid–base and fluid homeostasis. Elucidation of the underlying genetic lesions has enhanced our basic understanding of renal physiology, as well as of normal kidney development and cellular differentiation.
Infertility: Genetic Disorders
Authors: Vogt Peter H
Published: September 2006

Identification of genetic disorders causing human male or female infertility is of paramount importance in each infertility clinic that has to consider the possible risk of transfer of a specified genetic abnormality (i.e. a distinct chromosomal aberration and/or a specific gene mutation) to the offspring created by the applied artificial fertilization protocol. This is useful especially for those men and women where no obstructions of the germ line can be observed and who are therefore diagnosed in the clinic as having idiopathic infertility.
Fetal Wastage: Molecular Basis
Authors: Fryns Jean‐Pierre , Witters Ingrid
Published: September 2006

Fetal wastage has a chromosomal and molecular basis.
Endocrine Disorders: Hereditary
Authors: Phillips John A
Published: September 2006

Many genes that comprise endocrine pathways have been discovered. A variety of endocrine disorders caused by variations in these genes are now well understood in terms of their molecular basis and mode of inheritance.
Immunological Disorders: Hereditary
Authors: Puck Jennifer M
Published: September 2006

Inherited immunological disorders include a diverse range of diseases characterized by susceptibility to one or more classes of infections, immune dysregulation (autoimmunity) or both.
Skin: Hereditary Disorders
Authors: Corden Laura D , McLean WH Irwin , Irvine Alan D
Published: September 2006

There are many disorders with skin phenotypes for which the underlying molecular defect is now known. These include blistering diseases, pigmentary disorders, disorders of cornification and those with tumor predisposition.
Aging: Genetics
Authors: Zwaan Bastiaan Johannes
Published: September 2006

Aging is under genetic control and the genes, which ensure organism integrity and life span for successful reproduction, appear to have been highly conserved in evolution. These genes regulate the balance between survival and reproduction.
Trinucleotide Repeat Expansions: Disorders
Authors: Nelson David , Zoghbi Huda
Published: September 2006

Trinucleotide repeat mutations, also known as dynamic mutations, were discovered only in the early 1990s, but are responsible for many important neurological disorders, such as Huntington disease, fragile X mental retardation and myotonic dystrophy.
Hemochromatosis
Authors: Beutler Ernest
Published: September 2006

Essentially a clinical diagnosis, classically the term
hemochromatosis
has denoted iron storage disease of varying etiology accompanied by tissue damage. Common pathologic manifestations are cirrhosis of the liver, diabetes, darkening of the skin and cardiac arrhythmias and failure. The cause can be hereditary, as in the HLA‐linked form most common in Europeans, or acquired, as the result of transfusions and/or disordered erythropoiesis as in thalassemia. With the positional cloning of the
HFE
gene, the term hemochromatosis has been increasingly taken to represent an
HFE
genotype, with or without pathologic changes.
Mitochondrial Disorders
Authors: Hofmann Sabine , Bauer Matthias F
Published: September 2006

Mitochondria are double‐membrane organelles which play a pivotal role in cellular metabolism and are responsible for creating free energy, in the form of ATP, essential for the normal function and maintenance of all human organ systems. Genetic defects of mitochondrial functions cause human diseases associated with a wide spectrum of clinical phenotypes.
Fragile Sites
Authors: Sutherland Grant R
Published: September 2006

Fragile sites are specific points on chromosomes that show nonrandom gaps or breaks when the cells from which the chromosomes have been prepared have been exposed to a specific chemical agent or condition of tissue culture. Hence a fragile site is an area of chromatin which is not compacted when viewed in mitosis.
Microdeletion Syndromes
Authors: Schinzel Albert , Riegel Mariluce , Baumer Alessandra
Published: September 2006

A microdeletion syndrome is the clinical consequence of a submicroscopic chromosome deletion leading to the monosomic state of a small chromosomal segment. Clinical pictures of well‐known microdeletion syndromes are mostly specific, and cytogenetic confirmation is done by either fluorescent
in situ
hybridization or microsatellite marker analysis.
Colorectal Cancer: Genetics
Authors: Frayling Ian M
Published: September 2006

The genetic changes in bowel cancers are particularly well defined, partly because the genetic syndromes that predispose to it are well understood.
Polygenic Disorders
Authors: Comings David E
Published: September 2006

The vast majority of common disorders affecting humans are polygenic, due to the additive and interactive effect of multiple genes, each with a small effect, interacting with the environment. Because of their importance and frequency, polygenic disorders have a great economic impact. The identification of the genes involved promises to be significantly more difficult than the identification of the genes involved in single gene disorders.
Susceptibility Genes: Detection
Authors: White Nicola J , Riley John H
Published: September 2006

Complex disorders result from the interaction of multiple susceptibility genes with diverse environmental factors. Identification of susceptibility genes is a challenging process; however, the publication of the human genome sequence and a wealth of data on Single nucleotide polymorphisms will greatly facilitate this process.
Multiple Sclerosis (
MS
): Genetics
Authors: Dyment D A , Ebers G C
Published: September 2006

Multiple sclerosis is a complex trait and highlights the interplay between nature, nurture and chance. Genetic–epidemiological and prevalence studies demonstrate the importance of genes and that environmental factors operate on a population‐based level. There is an association with HLA polymorphisms located at 6p21; genome searches have not yet identified a novel susceptibility locus.
Asthma: Genetics
Authors: Cookson William OCM
Published: September 2006

Asthma is an inflammatory disease of the small airways of the lung. It is strongly influenced by genetic factors. Specific genes have been shown to predispose to the disease by a variety of mechanisms. Positional cloning of other genes takes place from several chromosomal regions.
Obesity: Genetics
Authors: Coe Natalie , Naggert Jürgen
Published: September 2006

Obesity can be defined as a state of excessive body fat accumulation that is associated with negative health consequences. Once simply thought to be an unhealthy side effect of inactivity coupled with overeating, obesity is now accepted as a serious disorder with a strong genetic component.
Databases in Genetics Clinics
Authors: Pagon Roberta A , Tarczy‐Hornoch Peter , Beahler Christine
Published: September 2006

Medical geneticists, genetics counselors and nurses in genetics who staff medical genetics clinics rely upon internet‐accessible and stand‐alone databases for access to the medical literature, for disease recognition, for current information on genetic test availability and use, for patient‐support materials, and for locating other genetics professionals.
Yeast as a Model for Human Diseases
Authors: Fridovich‐Keil Judith L
Published: September 2006

Yeasts are single‐celled eukaryotes that provide a genetically and biochemically amenable model system for biomedical research. Over the past decades, studies in yeast have established a foundation for much of our current knowledge on such fundamental processes as eukaryotic cell cycle control, genetic instability and colon cancer, metabolism and metabolic disease and even aging. Through basic science and pharmaceutical applications, studies in yeast hold promise for even greater contributions in the future.
Transgenic Mice
Authors: Babinet Charles
Published: September 2006

Transgenic mice carry exogenous genetic material introduced by the experimenter. Homologous recombination is used to introduce programmed modifications of the mouse genome.
Olfactory Receptors
Authors: Giorgi Dominique , Gaillard Isabelle , Rouquier Sylvie
Published: September 2006

The sense of smell is mediated by olfactory receptors belonging to the seven‐transmembrane G‐protein‐coupled receptor superfamily. They are expressed at the surface of the cilia of olfactory sensory neurons that emerge in the olfactory epithelium of the nasal cavity. The specific binding of odorant ligands initiates signals transmitted to the central nervous system through different relays, allowing an individual to identify precisely a particular odor.
Cytochrome P450 (
CYP
) Gene Superfamily
Authors: Nebert Daniel W , Nelson David R
Published: September 2006

Cytochrome P450, which was first named a ‘pigment in the cell’ and thought to be a single enzyme in the early 1960s, was correlated with drug and steroid metabolism by the late 1960s and recognized eventually to comprise an ancient gene superfamily encoding numerous ubiquitous enzymes that participate in countless essential life processes. Defects in many of the 57 human functional
CYP
genes are involved in some inborn errors of metabolism and other clinical diseases.
Immunoglobulin Genes
Authors: Fanning Liam J
Published: September 2006

Through a process of random gene segment rearrangements and mutation, the immune system is uniquely positioned to generate an apparently inexhaustible array of responses to foreign antigenic challenges.
Potassium Channels
Authors: Coetzee William A , Rudy Bernardo
Published: September 2006

Potassium channels constitute a highly diverse class of ion channel and thus participate in multiple modulatory functions. There are several functional types of K
+
channel, including voltage‐gated K
+
channels, Ca
2+
‐activated K
+
channels, inward rectifiers, leak K
+
channels and Na
+
‐activated K
+
channels. Principal or pore‐forming subunits of at least the first four types have been identified and are classified into three groups of proteins on the basis of their structural properties.
Mutation Detection
Authors: Cotton RGH
Published: September 2006

Mutation detection is essential for the practice of modern biology. Because sequencing deoxyribonucleic acid (DNA) to detect changes in DNA (mutations) is not cost‐effective, a range of methods have been developed to detect mutations for the first time and a different set of methods to look for previously defined mutations.
Expression Studies
Authors: Datson Nicole , Vreugdenhil Erno
Published: September 2006

Changes in gene expression underlie almost every biological process. Highly sensitive methods to monitor changes in expression of individual or complex groups of genes are now available.
DNA Chip Revolution
Authors: Lockhart David J
Published: September 2006

The deoxyribonucleic acid (DNA) chips, arrays or microarrays are powerful new tools, designed and built based on genomic sequence information, that are changing the face of biological and biomedical research. The arrays enable massively parallel measurements of gene expression and genetic variation, and are dramatically increasing our understanding of biology and disease, and promise to have a great impact on drug development and the practice of medicine.
Expression Analysis
In Vitro
Authors: Colosimo Alfredo
Published: September 2006

Expression analysis
in vitro
is a rapidly growing and constantly evolving field, based upon the use of a template of RNA, for a translation reaction, or of DNA, in a coupled transcription–translation system.
Rett Syndrome
Authors: Hoffman Eric P , Moses Linda , Scacheri Cheryl AG , Hoffbuhr Kristen C
Published: September 2006

Rett syndrome is a neurological disease of early postnatal brain growth found almost exclusively in girls. Typically girls with Rett syndrome show developmental regression including loss of communication and motor skills, stereotypic hand movements and a deceleration of head growth. The defective gene, methyl CpG binding protein 2 (Rett syndrome) (
MECP2
) is normally involved in the transcription silencing of genes (turning genes ‘off’): in Rett syndrome, the MECP2 protein does not work properly in approximately half of the patient's cells (heterozygous), leading to the aberrant expression of a cascade of other genes, normally regulated by MECP2.
Turner Syndrome
Authors: Hall Laura L
Published: September 2006

Turner syndrome (TS) results from the absence of some or all of the X chromosome, with a karyotype of 45,X in the fully developed syndrome. Because not all genes on the X chromosome are inactivated normally, the diminished expression of these genes presumably leads to the TS phenotype, including short stature, incomplete sexual development and reproductive function, and other structural and cognitive abnormalities. Research has begun to identify genes that are potentially linked to TS, including the short stature homeobox (
SHOX
) gene and
DFRX
, the human homolog of a fruitfly gene involved in oogenesis.
Megabase Pair (Mbp)
Authors: Dear Paul H
Published: September 2006

A megabase pair (Mbp) is a unit of length of nucleic acids, equal to one million base pairs or to one thousand kilobase pairs.
Down Syndrome
Authors: Villar Angela J , Epstein Charles J
Published: September 2006

Down syndrome, first described by Langdon Down in 1866, is caused by an extra copy of chromosome 21. It is the most commonly recognized genetic cause of mental retardation and is characterized by a number of dysmorphic features and congenital malformations.
Protein Structure
Authors: Pastore Annalisa , Lesk Arthur M
Published: September 2006

The great variety of structures and functions of proteins found in humans and other organisms conceals an underlying unity in chemical structure. All proteins share a common repetitive main chain, while differences in the sequences of side chains give proteins their differences in structure and function.
Protein Transport
Authors: Yoneda Yoshihiro
Published: September 2006

In order for cells to function, proteins are selectively sorted and precisely transported to their destinations after synthesis on ribosomes in the cytoplasm. Proteins contain signals for targeting and cells contain the appropriate machinery to allow the recognition of the signals and the targeting of each protein to its destination.
Protein Secretory Pathways
Authors: Blázquez Mercedes , Shennan Kathleen IJ
Published: September 2006

In many cells proteins can be secreted from particular sites of the membrane or in response to specific stimuli. The eukaryotic cell has developed mechanisms to ensure that proteins are targeted to the correct secretory pathway.
Mass Spectrometry in Protein Characterization
Authors: Steen Hanno , Pandey Akhilesh
Published: September 2006

The complete complement of proteins in a cell, the proteome, is highly complex because a single protein can exist in several different forms. Mass spectrometry has emerged as the tool of choice for protein identification as well as for characterization of posttranslational modifications.
DNA Viral Vectors in Gene Therapy
Authors: Van Craenenbroeck Kathleen , Vanhoenacker Peter , Haegeman Guy
Published: September 2006

DNA viral vectors are gene‐delivery vehicles based on viral sequences.
Naked DNA in Gene Therapy
Authors: Liu Dexi , Satoh Etsuko , Knapp Joseph E
Published: September 2006

‘Naked DNA’ is DNA without an association with any synthetic or naturally occurring compounds. Significant progress has been made in the use of naked DNA for gene delivery.
Regulatable Gene Expression in Gene Therapy
Authors: Rossi Fabio
Published: September 2006

The regulation of exogenous gene expression may soon be a requirement for gene therapy approaches. Several systems promise to fulfill requirements for clinical applications.
Hemophilias: Gene Therapy
Authors: Kaufman Randal J
Published: September 2006

Hemophilia A and B are two bleeding genetic disorders that are corrected by infusion of a single protein. Recent studies in animal models and humans demonstrate feasibility to correct these diseases by gene therapy.
Familial Hypercholesterolemia: Gene Therapy
Authors: Cuchel Marina , Rader Daniel J
Published: September 2006

Familial hypercholesterolemia is a monogenic disease characterized by high levels of plasma cholesterol and premature cardiovascular disease. In its homozygous form, conventional pharmacological therapy is not effective and gene therapy could become a viable treatment.
Muscle Disease: Gene Therapy
Authors: Partridge Terence
Published: September 2006

Muscular dystrophies have been an area of special interest for genetic therapies. The abundance of skeletal muscle tissue in the body presents particular problems for this form of treatment.