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Pharmacogenomics encompasses several major areas: the study of polymorphic variations to drug response and disease susceptibility, identification of the effects of drugs/xenobiotics at the genomic level, and genotype/phenotype associations. The most common type of human genetic variations is single-nucleotide polymorphisms (SNPs). Several novel approaches to detection of SNPs are currently available. The range of new methods includes modifications of several conventional techniques such as PCR, mass spectrometry, and sequencing as well as more innovative technologies such as fluorescence resonance energy transfer and microarrays. The application of each of these techniques is largely dependent on the number of SNPs to be screened and sample size. The current chapter presents an overview of the general concepts of a variety of genotyping technologies with an emphasis on the recently developed methodologies, including a comparison of the advantages, applicability, cost efficiency, and limitations of these methods. [ABSTRACT FROM AUTHOR]

Breast cancer incidence varies considerably between Western and non-Western countries. Breast cancer incidence and mortality rates are highest in North America and Northern Europe, intermediate in Southern Europe and Latin America, and lowest in Asia and Africa. In recent years, however, a dramatic increase in breast cancer incidence has been reported in several Asian countries, including Korea. Immigrant studies have suggested that environmental rather than genetic factors are primarily responsible for the international variability and secular trend of breast cancer rates. This chapter presents current findings on environmental risk factors for breast cancer, specifically in terms of gene–environment interactions. The scope of environmental factors encompasses obesity, hormonal factors, including menstrual and reproductive history, and dietary factors, including alcohol, folate, fruits, vegetables, antioxidant vitamins, and meats and their metabolic mutagens. For each environmental factor, we reviewed articles that assessed genetic polymorphisms that have a plausible biological mechanism for breast cancer risk modification. [ABSTRACT FROM AUTHOR]

CYP2C9 is one of the major cytochrome P450 enzymes that play a crucial role in metabolic clearance of several drugs in the current clinical used. CYP2C9 has several allelic variant forms each of which arises from single amino acid substitution and could reduce/increase enzyme activities and affect drug metabolism. Mutant alleles may cause serious toxicity in some narrow therapeutic index drugs. CYP2C9*13, one of the CYP2C9 variant forms that is commonly found in Asian population, has a Leu90Pro amino acid substitution that leads to defective drug metabolism in individuals who carry this allele. It has been reported that metabolic activity of CYP2C9*13 was reduced towards some CYP2C9 substrates compared to wildtype. In this study, X-ray crystal structure of human cytochrome P450 2C9 complexed with flurbiprofen (PDB code: 1R9O) was represented to wildtype and the structure of CYP2C9*13 was constructed based on the X-ray crystal structure of CYP2C9-flurbiprofen complex. Herein, molecular docking of CYP2C9*1 and CYP2C9*13 with flurbiprofen was performed in search for flurbiprofen orientation that corresponds to its binding state before undergoing monooxygenation. Subsequently, molecular dynamics simulation was operated to compare binding of flurbiprofen in catalytic cavity of these 2 variants. Substrate access channel of CYP2C9*13 has a dramatic effect on an interaction between the drug and the enzyme. Consequently, this study can lead to an understanding of structural pathology caused by single amino acid change in CYP2C9*13 variant. [ABSTRACT FROM AUTHOR]

There is currently no consensus on the effectiveness of preprocessing methods used in pooled DNA (Deoxyribonucleic Acid) microarray analysis of SNP (Single Nucleotide Polymorphism) data. We investigated two normalization methods, cyclic loess and quantile, before identifying susceptibility genes of type 2 diabetes mellitus (T2DM). The probe data set is filtered by discrimination score and range of estimate allele frequency to remove unreliable probe intensities. The results show that both normalizations can reduce variation; however, there is no significant difference in identifying significant SNPs. The probe data set that uses only perfect match intensity is preferred. The mismatch probe intensities are used to exclude unreliable SNPs in the step of filtering. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) are the most frequently occurring genetic variations. Biologists use identified SNPs to investigate genetic diseases; current heredity markers, as well as to prevent side effects of medication. Thus, SNPs play an important role in personalized medicine. However, many association studies provide only the relationship between SNPs, diseases and cancers, without giving an SNP ID. In order to identify SNPs in a sequence, this research built dbSNP, SNP fasta and SNP flanking marker databases for the rat, mouse and human genome from the NCBI database. It utilizes SNP flanking markers that are extracted from a SNP fasta sequence and the combines them with a Boyer-Moore algorithm with a dynamic programming method to match unknown sequences with data from the NCBI SNP fasta sequence database to retrieve SNP IDs. The experimental results show that this method is indeed able to determine the exact SNP IDs from sequence. It constitutes a novel application to identify SNP IDs from the literature and can be used systematic association studies. [ABSTRACT FROM AUTHOR]

An encyclopedia entry for the term "metabolic polymorphisms and cancer susceptibility" is presented. It refers to the genetic basis for inter-individual differences in cancer susceptibility. The genetic factors that determine individuality in response to drugs and other therapeutic agents is encompassed by the term pharmacogenetics. Therapeutic response is elicited through introduction in the body circulation. The biological half-life of a drug is determined by the rate of metabolism.

Amyloid-β peptide, derived from the amyloid precursor protein, plays a crucial role in the pathogenesis of Alzheimer's disease. Processing of amyloid precursor protein by β-secretase generates C99, which is further cleaved by γ-secretase, yielding two major species of β-amyloid, β-amyloid40 and β-amyloid42, differing in length of the amino acid chain. β-amyloid is normally secreted; however are produced, remaining inside the cells. In the present study, we investigated the intracellular metabolism of AAP using a truncated γ-secretase-specific β-amyloid precursor, C99. We have selected two point mutations close to the β-amyloid42/40 ratio of β-amyloid secreted, and examined their effects on the formation of β-amyloidi. Analysis of SH-SY5Y cells stably expressing these constructs led to the unexpected result, that the β-amyloid42/40 ratios of β-amyloidI and β-amyloid secreted were differently influenced by the introduced point mutations. [ABSTRACT FROM PUBLISHER]

Genetic linkage studies have identified two genetic polymorphisms that seem to operate as risk factors in late-onset Alzheimer's disease and three causative genes that are directly involved in the development of early on-set Alzheimer's disease. The precise sequence of events underlying Alzheimer's disease-associated neurodegeneration still remains unknown. In the present study we have used a genetic approach to assess the mechanism by which cholesterol regulates β-amyloid generation. Specifically, we have used Chinese hamster ovary cells with a defect in the molecular pathway that regulates the expression of the genes involved with the uptake and biosynthesis of cholesterol. Here, we have identified a novel link between intracellular cholesterol compartmentation, FAD- associated forms of APP and cell death. [ABSTRACT FROM PUBLISHER]

A key factor in the prevention of diabetic complications is represented by the early identification of the subset of patients who are prone to develop end-stage renal failure. Molecular biology techniques that allow us to address candidate gene polymorphisms in diabetic nephropathy are increasingly available, and the number of reports in this area is growing exponentially. In the process of understanding the nature of renal susceptibility genes, two major strategies can be followed. The functional cloning requires that a biological abnormality (intermediate phenotype) of nephropathy can be explained by genetic polymorphism. Positional cloning techniques will eventually provide a clue to the chromosomal region(s) which include candidate loci, and there is some evidence that this may be the case for chromosome 3q. It is to be hoped that novel risk markers for diabetic nephropathy may be developed soon, and help understanding of the pathogenesis of this complication. [ABSTRACT FROM PUBLISHER]

The article offers information on pharmacogenomics. It discusses the genetic variation within the human genome and its forms. The clinical significance of genetic polymorphisms is also tackled, along with outcomes which can be associated with polymorphisms. An overview of how to incorporate pharmacogenetic information into clinical practice is offered.

The article presents an encyclopedia entry for cytokine polymorphisms and its immunotoxicology. it mentions the several types of polymorphisms in the genome. It describes the characteristics of single nucleotide polymorphisms. It explains the use of single nucleotide polymorphisms as a method for examining the genetic etiology of human diseases and in gene-environment interactions. It discusses its relevance to clinical trials of drugs.

A definition of the term "polymorphism" is presented. It refers to any variation of a character or gene within a population. It is the existence of a character in two or more variant forms in a population, where the least common form is present in more than one percent of individuals.

A definition of the term "variable region" is presented. It refers to segments of immunoglobulin heavy or light chains. They vary in sequence in chains of similar allotype and isotype.

A definition of the term "non-obese diabetic mouse" is presented. It refers to the murine model for insulin-dependent diabetes mellitus. Information on how the role of gene polymorphisms is elucidated in disease susceptibility is provided.

A definition of the term "genetic polymorphism" is presented. It refers to the phenomenon of multiple forms of the same gene. This can be detected at the level of the DNA sequence, which may or may not change the amino acid sequence of the protein for which the gene codes.

This article offers information about allotypic epitopes. A response of allotypic epitopes may be induced when immunoglobulins which are isolated from one strain of a species are injected into another strain.

A list of commonly used genetic terms is presented. Candidate genes are genes with perceived relevance to trait in question, which can be used to compare allele frequencies. In addition, heritability is the proportion of phenotypic variance that attributes to additive genetic variance. Lastly, polymorphism is the occurrence of something in several forms with regards to genes.

A definition of the term "UDP-glucuronyl transferase" (UGT) is presented. It refers to a group of enzymes which catalyze the transfer of uridine diphosphate-glucuronyl moieties into different small lipophilic agents, like xenobiotics. Since the genes responsible for the encoding of UGT are cloned, at least 15 UGT can be found in the mammalian system. Genetic polymorphisms of UGT is responsible for differences in drug metabolism.

A definition of the term "genetic polymorphism" is presented. It refers to a difference in DNA sequence that has a frequency of at least 1% in a population. Some DNA sequence differences have the capacity to change the expression or function of drug metabolizing enzymes, drug transporters or drug target proteins.

The article presents a definition of the term "allele," which refers to a form in which a polymorphism exists.

A definition of the term "single nucleotide polymorphism" is presented. It refers to the most common type of genetic variation, which consists of a single base change within a DNA molecule.

An encyclopedia entry for restriction fragment length polymorphism (RFLP) is presented. It refers to the inherited differences in sites for restriction enzymes in DNA. An example is given to describe RFLP. RFLP is used for genetic mapping in order to link the genome directly to a conventional genetic marker.

A definition of the term "pharmacogenetics" is presented. It refers to the clinically important hereditary variation in drug response, such as cancer susceptibility and metabolic polymorphisms.

A definition of the term "metabolic polymorphisms" is presented. It refers to polymorphisms of genes encoding enzymes involved in the metabolism of carcinogens or anticarcinogens. These predisposing gene variations have relatively low penetrance which may result in a moderate increase in the risk of certain cancers.

A definition of the term "Haplotype" is presented. The term refers to a linked set of alleles associated with one parental genome. Basically, it is the particular combination of alleles in a defined region of some chromosome, in effect the genotype in miniature. The term was originally used to describe combinations of major histocompatibility complex alleles. Now, it is used to describe particular combinations of restriction fragment length polymorphisms or microsatellite alleles.

A definition of the term "genetic polymorphism" is presented. The term refers to the presence of multiple inheritable characteristics of a gene within the population. Genetic polymorphism is also a genetic trait where the least common allele is found in approximately at least one percent of the population