Molecular Markers Ppt Download
Melony Holden
Molecular markers have the potential to serve not only as prognostic factors but may be targets for new therapeutic strategies and predictors of response in a range of cancers. Prostate cancer development and progression is predicated on a series of genetic and epigenetic events within the prostate cell and its milieu. Within this review, we identify candidate molecules involved in diverse processes such as cell proliferation, death and apoptosis, signal transduction, androgen receptor (AR) signalling, cellular adhesion and angiogenesis that are linked to outcome in prostate cancer. Current markers with potential prognostic value include p53, Bcl-2, p16INK4A, p27Kip1, c-Myc, AR, E-cadherin and vascular endothelial growth factor. Evolving technology permits the identification of an increasing number of molecular markers with prognosis and predictive potential. We also review the use of gene microarray analysis in gene discovery as a means of identifying and cosegregating novel markers of prostate cancer outcome. By integrating selected markers into prospective clinical trials, there is potential for us to provide specific targeted therapy tailored for an increasing number of patients.
A molecular marker is a molecule, sampled from some source, that gives information about its source. For example, DNA is a molecular marker that gives information about the organism from which it was taken. For another example, some proteins can be molecular markers of Alzheimer's disease in a person from which they are taken.[1] Molecular markers may be non-biological. Non-biological markers are often used in environmental studies.[2]
In genetics, a molecular marker (identified as genetic marker) is a fragment of DNA that is associated with a certain location within the genome. Molecular markers are used in molecular biology and biotechnology to identify a particular sequence of DNA in a pool of unknown DNA.
There are many types of genetic markers, each with particular limitations and strengths. Within genetic markers there are three different categories: "First Generation Markers", "Second Generation Markers", and "New Generation Markers".[3] These types of markers may also identify dominance and co-dominance within the genome.[4] Identifying dominance and co-dominance with a marker may help identify heterozygotes from homozygotes within the organism. Co-dominant markers are more beneficial because they identify more than one allele thus enabling someone to follow a particular trait through mapping techniques. These markers allow for the amplification of particular sequence within the genome for comparison and analysis.
Molecular markers are effective because they identify an abundance of genetic linkage between identifiable locations within a chromosome and are able to be repeated for verification. They can identify small changes within the mapping population enabling distinction between a mapping species, allowing for segregation of traits and identity. They identify particular locations on a chromosome, allowing for physical maps to be created. Lastly they can identify how many alleles an organism has for a particular trait (bi allelic or poly allelic).[5]
Genomic markers as mentioned, have particular strengths and weakness, so, consideration and knowledge of the markers is necessary before use. For instance, a RAPD marker is dominant (identifying only one band of distinction) and it may be sensitive to reproducible results. This is typically due to the conditions in which it was produced. RAPD's are used also under the assumption that two samples share a same locus when a sample is produced.[4] Different markers may also require different amounts of DNA. RAPD's may only need 0.02 ug of DNA while an RFLP marker may require 10 ug of DNA extracted from it to produce identifiable results.[6] currently, SNP markers have turned out to be a potential tool in breeding programs in several crops.[7]
Molecular mapping aids in identifying the location of particular markers within the genome. There are two types of maps that may be created for analysis of genetic material. First, is a physical map, that helps identify the location of where you are on a chromosome as well as which chromosome you are on. Secondly there is a linkage map that identifies how particular genes are linked to other genes on a chromosome. This linkage map may identify distances from other genes using (cM) centiMorgans as a unit of measurement. Co-dominant markers can be used in mapping, to identify particular locations within a genome and can represent differences in phenotype.[8] Linkage of markers can help identify particular polymorphisms within the genome. These polymorphisms indicate slight changes within the genome that may present nucleotide substitutions or rearrangement of sequence.[9] When developing a map it is beneficial to identify several polymorphic distinctions between two species as well as identify similar sequences between two species.
When using molecular markers to study the genetics of a particular crop, it must be remembered that markers have restrictions. It should first be assessed what the genetic variability is within the organism being studied. Analyze how identifiable particular genomic sequence, near or in candidate genes. Maps can be created to determine distances between genes and differentiation between species.[10]
Genetic markers can aid in the development of new novel traits that can be put into mass production. These novel traits can be identified using molecular markers and maps. Particular traits such as color, may be controlled by just a few genes. Qualitative traits (requires less than 2 genes) such as color, can be identified using MAS (marker assisted selection). Once a desired marker is found, it is able to be followed within different filial generations. An identifiable marker may help follow particular traits of interest when crossing between different genus or species, with the hopes of transferring particular traits to offspring.
One example of using molecular markers in identifying a particular trait within a plant is, Fusarium head blight in wheat. Fusarium head blight can be a devastating disease in cereal crops but certain varieties or offspring or varieties may be resistant to the disease. This resistance is inferred by a particular gene that can be followed using MAS (Marker Assisted Selection) and QTL (Quantitative Trait Loci).[11] QTLs identify particular variants within phenotypes or traits and typically identify where the GOI (Gene of Interest) is located. Once the cross has been made, sampling of offspring may be taken and evaluated to determine which offspring inherited the traits and which offspring did not. This type of selection is becoming more beneficial to breeders and farmers because it is reducing the amount of herbicides, fungicides and insecticides needed to be used on crops.[11] Another way to insert a GOI is through mechanical or bacterial transmission. This is more difficult but may save time and money.
Biochemical markers are generally the protein marker. These are based on the change in the sequence of amino acids in a protein molecule. The most important protein marker is alloenzyme. Alloenzymes are variant forms of an enzyme that are coded by different alleles at the same locus and this alloenzymes differs from species to species. So for detecting the variation alloenzymes are used. These markers are type-i markers.
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
Results: Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded, such that most thyroid cancers now have known gene driver events. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer and for the introduction of new entities such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The progress with molecular tests for thyroid nodules started in the 1990s from demonstrating feasibility of detecting various molecular alterations in fine-needle aspiration (FNA) material collected from thyroid nodules. It was followed by the introduction of the first single-gene mutational markers, such as BRAF, and a small mutational panel into clinical practice in the mid 2000s. Currently, several more advanced molecular tests are available for clinical use. They are based on multiple molecular markers and have increasing impact on the clinical management of patients with thyroid nodules.
Conclusion: The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA samples to inform more individualized management of these patients.
TC subtypes derived from follicular cells can be histologically divided into differentiated (DTC), poorly differentiated (PDTC), and anaplastic thyroid cancer (ATC) [18]. However, since the discovery of the oncogenic role of the BRAFV600E mutation in 2003, various molecular and genetic markers in TC have been identified, and added an additional layer to the classification of TC [19,20,21]. Although the total mutational burden (TMB) is lower than in most other cancer entities, the increasing importance of molecular alterations was underlined by The Cancer Genome Atlas (TCGA), which identified genetic alterations in 97% of the studied tumours [20,22]. While the TCGA analysis only included papillary thyroid cancer (PTC), subsequent studies have shown several markers and their combination play a significant role in the development of other TC subtypes as well as the progression and dedifferentiation to more advanced cancer subtypes [23,24,25]. An example of evolving biomarkers for diagnosis and prognosis in TC are MicroRNAs (miRNA). By regulating target genes of various signalling pathways including gene expression of known oncogenes and tumour suppressor genes, they play a crucial role for cell differentiation, migration, invasion and even epithelial-to-mesenchymal transition (EMT) [26,27,28]. Furthermore, different and distinct miRNA profiles were identified in different TC subtypes [28,29,30,31,32,33].
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