The medical literature does not support the utility of the above tests for screening, diagnosis, or management of CHD. Homocysteine Testing Aetna considers homocysteine testing experimental and investigational for assessing CHD or stroke risk and for evaluating women with recurrent pregnancy loss see CPB - Recurrent Pregnancy Loss. Homocysteine testing may be medically necessary for the following indications: Measurement of Carotid Intima-media thickness Aetna considers measurement of carotid intima-media thickness experimental and investigational for assessing CHD risk because its effectiveness has not been established.
A Received Sep 6; Accepted Aug 1. Abstract There is increasing information on the importance of genetic polymorphisms in human genes. Polymorphisms occur on average once every — base pairs in the human genome and are useful in the identification of genes involved in human disease.
Some genetic polymorphisms have functionally significant effects on the gene product and are the most useful type of polymorphism in disease association studies while others are simply useful markers. There are two main approaches using polymorphisms in the identification of genes involved in polygenic diseases.
The first involves examining inheritance patterns for genetic polymorphisms in family studies and the second case-control studies which compare genotype frequencies for candidate disease genes in unrelated individuals with the disease and healthy controls. Use of family studies is generally the preferred approach but this is only feasible if the genetic component of the disease is relatively strong, DNA samples are available from other family members and the disease is relatively easy to diagnose and is not stigmatized.
Population case-control studies are useful both as an alternative and an adjunct to family studies. When performing case-control studies factors such as study design, methods for recruitment of cases and controls, functional significance of polymorphisms chosen for study and statistical analysis of data require close attention to ensure that only genuine associations are detected.
The normal definition of a genetic polymorphism is a variation in DNA sequence that occurs at least once in every copies [ 1 ]. Except in the case of genes on sex chromosomes, each individual will have two copies of every gene so the variation needs to occur at least once in every 50 individuals to be classed as a polymorphism.
Rarer sequence variation will also occur but these rare variants are usually referred to as isolated mutations rather than genetic polymorphisms.
The normal DNA sequence for a particular gene is usually referred to as the wild-type allele and the rarer sequence referred to as a variant allele with the term allele defined as an alternative form of a gene.
It is not uncommon for several different variant alleles to occur for a single gene. Different polymorphisms that occur close together are often linked, that is they are found on the same chromosome more frequently than would be expected by chance.
The arrangement of genetic polymorphisms within a single chromosome in an individual is known as a haplotype.
Frequently certain haplotypes are more common as a result of linkage than would be expected if each polymorphism was inherited randomly.
In this case, the polymorphisms are said to be in linkage disequilibrium. Genetic polymorphisms can be of several types. The most common type is a single nucleotide polymorphism or SNP where a base is simply replaced by another.
Insertions of additional sequences or deletions can also occur and these range in size from one to several thousand base pairs.
Many genetic polymorphisms are silent with no effect on gene products but may still be useful genetic markers in studies on disease association. In general, functionally significant effects associated with genetic polymorphisms are most likely when they are associated with an amino acid substitution in the gene product, when a deletion or insertion results in a frameshift in the coding region, when a gene is completely deleted or when the polymorphism directly affects gene transcription, RNA splicing, mRNA stability or mRNA translation.
Since SNPs and other polymorphisms are useful markers for a variety of genetic studies including those on susceptibility to polygenic diseases and adverse drug reactions, it is suggested that the SNP map will facilitate more accurate drug prescribing and also the development of new drugs due to a better understanding of disease causation [ 2 ].
However, there is controversy as to the exact number of SNPs required for disease gene mapping and whether this will be feasible using random SNPs to map disease associations through linkage disequilibrium or whether only SNPs giving rise to functionally significant polymorphisms will provide meaningful information on complex diseases [ 34 ].
There is already substantial information on SNPs and other polymorphisms available for many genes, especially those encoding enzymes important in drug metabolism and those affecting immunity and inflammation. A number of these are attractive candidates for disease susceptibility genes and this has already prompted a large number of case-control studies on associations between particular polymorphisms and diseases.
These studies are easy to perform—needing only a stored DNA sample and access to a relevant clinical data set—but there are many potential pitfalls to performing candidate gene association studies which have resulted in substantial criticism of this kind of study. This report contains the collective views of international groups of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization, or the World Health Organization. Genetics Clinical Genetics Population Genetics Genome Biology Biostatistics Epidemiology Bias & Confounding HLA MHC Glossary Homepage. GENETIC EPIDEMIOLOGY GLOSSARY. Mehmet Tevfik DORAK. Accompanying Genetic Epidemiology Lecture Note & Presentation (see also Genome Biology for Genetic Epidemiologists) ACCE project (analytic validity, clinical validity, clinical utility, associated .
Since improved understanding of the specific genes involved in disease causation is likely to lead to the development of new drug treatments, candidate gene association studies are very relevant to the area of clinical pharmacology. As information on candidate genes and candidate SNPs increases, it is important that study design and data analysis in disease-association studies utilizing them should receive careful attention to ensure that a large number of spurious associations are not reported and that genuine disease genes are identified.
Design and interpretation of disease association studies Family studies and studies based on linkage-disequilibrium mapping Almost all human diseases have some genetic component determining who will be affected though the extent of this component varies widely.
The clearest example of a genetic disease is where there is a single defective gene which affects all individuals with the particular genotype. The normal approach to identifying the gene responsible for such disorders is to carry out linkage studies using large affected kindreds.
Linkage studies differ in a number of ways from association studies as summarized in Table 1 though there is some overlap between the two types of study. In linkage studies, polymorphic genetic markers from different chromosomes either microsatellite where a sequence of a few bp is repeated a variable number of times or SNP are used to pinpoint the chromosomal location of the disease gene on the basis that markers close to the gene will cosegregate with the disease within the family.
Table 1 Linkage studies Used mainly up to the present in the study of single gene disorders Use genetic markers situated throughout genome.
I was stepping out of an American political cave that shrouded the beauty of Cuba and stepping candidate gene case control association studies advantages and potential pitfalls another, after my candidate gene case control association studies advantages and potential pitfalls . Genetic association studies are used to find candidate genes or genome regions that contribute to a specific disease by testing for a correlation between disease status and genetic variation. focusing on case–control studies in candidate genes or regions. Candidate gene association studies most commonly test for a difference in allele. Genetics Clinical Genetics Population Genetics Genome Biology Biostatistics Epidemiology Bias & Confounding HLA MHC Glossary Homepage. GENETIC EPIDEMIOLOGY GLOSSARY. Mehmet Tevfik DORAK. Accompanying Genetic Epidemiology Lecture Note & Presentation (see also Genome Biology for Genetic Epidemiologists) ACCE project (analytic validity, clinical validity, clinical utility, associated .
In contrast to single gene disorders, in polygenic diseases possession of a particular variant of a gene associated with the disease does not mean that an individual will necessarily develop the disease, simply that they have an increased risk of disease development.
Family based linkage studies can also be used in the identification of this type of gene but in this case, it is more usual to use large sets of different families [ 5 ].Read "Candidate gene case‐control association studies: advantages and potential pitfalls, British Journal of Clinical Pharmacology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
An examination of the blood smear (or film) may be requested by physicians or initiated by laboratory staff. With the development of sophisticated automated blood-cell analyzers, the proportion of blood-count samples that require a blood smear has steadily diminished and .
Footnotes for Framingham point scoring ** Note: Framingham risk scoring for men and women is presented in the Appendix below..
Aetna considers hs-CRP testing experimental and investigational for all other indications, including use as a screening test for the general population and for monitoring response to therapy, because its clinical value for these uses has not been established.
Candidate gene case-control association studies: advantages and potential pitfalls. There are clear potential pitfalls in both the design and interpretation of candidate gene association studies but the availability of more comprehensive information about genetic polymorphisms and the increasing availability of better systems for studying.
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I was stepping out of an American political cave that shrouded the beauty of Cuba and stepping candidate gene case control association studies advantages and potential pitfalls another, after my candidate gene case control association studies advantages and potential pitfalls .