Great strides in precision medicine: Personalized oncology and molecular diagnostics
Priya Hays in Advancing Healthcare Through Personalized Medicine, 2017
HNPCC is the most common form of hereditary colon cancer and accounts for about 2%–3% of CRCs. HNPCC is characterized by a few polyps that have a potential rapid transformation to carcinoma (one to two years). HNPCC individuals have a lifetime risk of 70%–80% of developing CRC. Ninety percent of HNPCC mutations are observed in genes MLH1 and MSH2. The mutations are located throughout these genes and are diverse. Almost all errors made during replication are proofread by DNA polymerase; the remaining uncorrected mismatched bases will be repaired by the MMR system before cell division. Microsatellites (short tandem repeats) are sensitive to errors during DNA replication. Some targeted genes with repetitive sequences in their coding region that are affected in individuals with MSI include TGFβ receptor, IGF receptor, BAX, MSH6, and MSH3. Eighty-five to ninety percent of HNPCC tumors have MSI. MSI is the production of new alleles from unrepaired replication errors, as shown in Figure 5.3.
An Overview of Parasite Diversity
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2015
First we introduce several terms that are applied to variant forms within a species. The term isolate describes a sample of a parasite species derived from a particular host at a particular time. Strain refers to an intraspecific group of parasites that differs from other such groups in one or more traits, including traits that might be relevant to control or treatment. Subspecies is used to identify a distinctive group of organisms within a species that may occupy a particular region and that can interbreed with other subspecies. In this case, however, the organisms typically do not interbreed because of their isolation or another reason. Subspecies are given a formal name, such as Trypanosoma brucei rhodesiense, with rhodesiense being the subspecies name. Also, whereas studies to discriminate among species rely on less variable genetic markers such as SSU rDNA or cytochrome oxidase (see Section 2.3), studies of intraspecific diversity rely on more variable markers, such as other genes or sequences associated with the mitochondrial genome, or microsatellite markers. Microsatellite markers are short repeat sequences (usually 2 to 6 nucleotides long) that undergo rapid change in the number of times they are duplicated, providing a good way to discriminate among individual parasites.
Colon cancer: pathology and natural history
A. R. Genazzani in Hormone Replacement Therapy and Cancer, 2020
Recognition of the role of defective MMR in HNPCC has been gready facilitated by recognition that tumors defective in MMR demonstrate the associated phenotype of instability of micro-satellite (MSI) DNA sequences. DNA microsatellites are regions of repetitive DNA sequences in which the repeated unit is from one to three DNA bases long. The most common class of such microsatellites is of the form (CA)n. Such microsatellite repeats are scattered throughout the human genome. DNA polymerases are prone to slip while copying long stretches of these repetitive DNA sequences; thus, in the absence of effective DNA MMR, the resulting insertion or deletion errors are undetected and unrepaired. Tumors that demonstrate such MSI are alternatively referred to as tumors that demonstrate replication errors (RER+).
Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature
Published in Acta Clinica Belgica, 2021
Anke Delie, Anke Verlinden, Karolien Beel, Dries Deeren, Dominiek Mazure, Frédéric Baron, Dimitri Breems, Ann De Becker, Carlos Graux, Philippe Lewalle, Johan Maertens, Xavier Poire, Helene Schoemans, Dominik Selleslag, Florence Van Obbergh, Tessa Kerre
Short tandem repeats are units of 2 to 6 base pairs in length repeated multiple times within a given DNA fragment. These DNA fragments have a highly polymorphic nature between individuals, with a variable number of repeats at each tested locus. By using PCR-based amplification of these loci, patient and donor DNA can be identified based on the length of the resulting PCR products [2,9–12]. There are several commercial kits available with up to 16 STR markers, originally designed for use in forensic identification, which cover multiple ethnic backgrounds [2,9,12]. Short tandem repeat based chimerism analysis has a reported sensitivity of 1-5% [1,10,11,13] with a high reproducibility and an applicability (or informativity, i.e. the number of donor/recipient couples that can be evaluated using this technique) of nearly 100% [14]. (Table 2)
Ethical considerations for DNA testing as a proxy for nationality
Published in Global Bioethics, 2021
Valedie Oray, Sara H. Katsanis
Different DNA tests can provide different kinds of evidence for biological relationships. Short tandem repeat (STR) DNA analyses examine a set of certain locations in DNA that tend to be highly variable from one person to the next. By looking at a specific set of such markers, the numbers of copies found at each STR location comprise a unique genetic profile for an individual. This type of STR analysis is commonly used for kinship analysis (e.g. paternity testing) and can indicate the likelihoods of biological relationships of immediate family members, including siblings (Wenk, 2004). Autosomal STR tests for kinship are fairly accurate for determining the likelihood of a parent and child being related, and X- and Y-STRs can supplement these data (Diegoli, 2015). Male heredity can be traced through Y-chromosome STRs since the Y-chromosome is inherited from a father to his son (Kayser, 2017), whereas X-chromosomes are in both males and females. Y-chromosome DNA also has high conservation between the father and male offspring, so Y-STR testing is also considered reliable in terms of accurate detection of the variants at each marker (Kayser, 2017). Determining full siblings and grandparents using STRs is also fairly reliable, but half-siblings and avuncular relationships have less reliability since they only shared 25% of their genetic makeup between one another (Katsanis & Kim, 2014; Zhang et al., 2020).
Genetic diversity of 23 STR loci of the Guizhou Tujia ethnic minority and the phylogenetic relationships with 22 other populations
Published in Annals of Human Biology, 2023
Shuhua Li, Siyu Chai, Limei Yu, Tao Zhang, Zulin Liu, Yinlei Lei, Kaiqin Chen, Hao Zhang, YanFei Liu, Pengyu Chen
Short tandem repeats (STRs) are repetitive nucleotide sequences ranging from 2 to 6 base pairs widely distributed throughout the human genome (Edwards et al. 1991; Ellegren 2004; Jobling and Gill 2004; Chen et al. 2018). Due to their high level of polymorphic information, STR markers have become the gold standard in forensic DNA analysis, especially in human identification and paternity testing, surpassing other DNA markers such as single nucleotide polymorphisms (SNPs) (Zhang 2015; Yao and Wang 2016; He et al. 2018; Wu et al. 2020). In recent years, new commercial multiple STR detection systems containing more autosomal STRs have been developed to further improve their discriminating ability with the increasing growth of forensic DNA databases. Additionally, STRs are frequently used in human population genetics to predict the population genetic structure of geographically and ethno-linguistically diverse subpopulations via genetic affinity analysis (Gao et al. 2021; Kumar et al. 2021; Tran et al. 2021; Wang et al. 2021; Chandra et al. 2022).
Related Knowledge Centers
- DNA
- DNA Profiling
- Genome
- Minisatellite
- Mutation
- Variable Number Tandem Repeat
- Sequence Motif
- Base Pair
- Genetic Diversity
- Genetic Genealogy