General Biology of Cancer and Metastasis
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Patients with HNPCC have tumors in which there are a large number of microsatellites in the genome of the tumor. Microsatellites are short (two to four nucleotides; e.g., CACA on one strand and GTGT on the other), noncoding, tandem repeats of DNA, which are found throughout the genome and which show pronounced polymorphism. Abnormalities in microsatellites have been found in Huntington’s chorea, the fragile X syndrome, and spinobulbar atrophy, in which, over several generations, there is a progressive expansion of the nucleotide repeats in the genes of interest. This leads to disease, but it is found that with each succeeding generation there is an increased severity of the disease because the microsatellites become longer. This phenomenon is called genetic anticipation. In HNPCC, microsatellite instability is thought to be the result of failure to correct replication errors that occur during cell division. This failure is caused by hereditary defects in the enzymes responsible for the repair of these replication mismatch errors. These enzymes include MSH2, MLH1, GTBP, and PMS1.
Impact of Integrated Omics Technologies for Identification of Key Genes and Enhanced Artemisinin Production in Artemisia annua L.
Tariq Aftab, M. Naeem, M. Masroor, A. Khan in Artemisia annua, 2017
It was also revealed that predicted SSR–ESTs have potential for various molecular functions: regulation of transcription (mRNA synthesis), transport regulation, signaling, defense response, stress, and tRNA processing. Computational approaches help to provide an attractive alternative to conventional laboratory methods for the rapid and economical development of SSR markers by using freely available genomic sequences in public databases for A. annua. Microsatellite distributions are helpful in understanding mutational processes and evolutionary selection constraints as well as development in DNA repair mechanisms. In order to effectively use the studied information related to EST and to extend the utility of SSRs in A. annua, future work should be focused on both computational and molecular biology. Further sequence information can be used for the development of DNA chips with DNA sequences for the identification and screening of high-AN-producing lines (Harvey et al. 2015). DNA chip technology can provide a rapid, high-throughput screening and information-rich tool for genotyping, quality assurance, and species confirmation.
Expression Profile Analysis of Brain Aging
David R. Riddle in Brain Aging, 2007
Another successful method to delineate potential causal/susceptibility genes is linkage analysis using a genome-scan approach. A current strategy is to employ markers termed “microsatellite markers” comprised of polymorphisms that likely represent random genetic variations [84]. Microsatellite maps have been generated that span the entire genome [86], and several studies have used linkage-based approaches to find candidate genes in age-related paradigms, including AD and Parkinson’s disease (PD) [87–89]. Genome-wide linkage studies of aging cohorts have also been performed for macular degeneration of the eye [90–92]. Comparative studies across phyla have also been utilized to identify genetic changes associated with the aging process [93, 94]. Moreover, employing animal models to study senescence avoids some of the aforementioned confounds of evaluating genes associated with aging in humans.
Combining inhibition of immune checkpoints and PARP: rationale and perspectives in cancer treatment
Published in Expert Opinion on Therapeutic Targets, 2022
Martina Catalano, Luigi Francesco Iannone, Federica Cosso, Daniele Generali, Enrico Mini, Giandomenico Roviello
Microsatellites are distributed throughout the human genome, arranged in tandem and particularly prone to accumulate errors during the DNA replication. The state of microsatellite instability can be defined through two main methods: molecular tests of MSI analysis carried out on DNA extracted from neoplastic cells and evaluation of the immunohistochemical expression of the proteins of the MMR system on neoplastic tissue sections. Among the most used panels for MSI detection, Pentaplex analyzes 5 loci and defines MSI when at least three loci are unstable, whereas tumors with none or an unstable locus are considered microsatellite stable (MSS). Using larger panels, the tumor is considered MSS when no locus (0%) results unstable, MSI-low with unstable loci less than 30% and MSI-high if greater than 30% [12].
Challenges managing women with suspected Lynch Syndrome in Zimbabwe: a case report
Published in Southern African Journal of Gynaecological Oncology, 2021
Kotti-Emily Mukucha, Marshall T Manase, Charles Muronda, Judy Whittaker, Bothwell T Guzha
LS is an autosomal dominant, highly penetrant, germline mutation disorder that predisposes women to colorectal, endometrial and other extracolonic malignancies.1,4 Mutations in MMR genes are responsible for this syndrome. MMR genes code for MMR proteins, which recruit repair enzymes to correct damaged DNA by excising the incorrect DNA sequence to allow correct resynthesis of the sequence by DNA polymerase. A mutation in the MMR genes results in their inactivation, causing MSI. Microsatellites are short-tandem DNA repeats that occur in coding and non-coding genes and when unstable are prone to expansion or contraction – the instability which can cause an abnormal gene expression. MSI is characteristic of DNA replication errors and is the hallmark of a number of LS-associated tumours.
Clinicopathological and molecular features of colorectal cancer with synchronous adenoma
Published in Scandinavian Journal of Gastroenterology, 2020
Xizhen Sun, Dongyan Zhao, Sidan Long, Shuo Chen, Qian Cai, Shukun Yao
First, all tissues’ genomic DNA was successfully extracted by phenol-chloroform method. Second, the microsatellite genomic DNA was analyzed. The MSI test was performed using a PCR-based assay by amplifying MONO-27, BAT-25, NR-21, BAT-26, and NR-24. After the gene-specific primers were synthesized, five microsatellite loci were amplified with the corresponding specific primers by polymerase chain reaction (PCR) (American ALT Company, model: UV Stratalinker 2400), and PCR products were obtained. Finally, the PCR products were sequenced by a genetic analyzer (American ABI Company, model: ABI 3730XL) to confirm the sequence and variation of DNA. The presence of 2 or more positive sites among the 5 loci indicated MSI-H, one positive site indicated MSI-L, and no positive sites indicated MSS.
Related Knowledge Centers
- DNA
- DNA Profiling
- Genome
- Minisatellite
- Mutation
- Variable Number Tandem Repeat
- Sequence Motif
- Base Pair
- Genetic Diversity
- Genetic Genealogy