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Epigenetics in Sperm, Epigenetic Diagnostics, and Transgenerational Inheritance
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Jennifer L. M. Thorson, Millissia Ben Maamar, Michael K. Skinner
Molecular diagnostics are shifting the evaluation and treatment of human diseases. In reproductive health, male factors are involved in the couple's infertility in 50% of cases (73). The diagnosis to establish a male infertility is currently primarily through semen analysis, which evaluates sperm concentration, motility, and morphology using light microscopy (74). However, semen analysis is a poor predictor of a male fertility except in cases of oligospermia, azoospermia, or oligozoospermia (75,76).
Phenylketonuria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Restriction enzyme polymorphism permitted heterozygote detection and prenatal diagnosis in the approximately 75 percent of families in which relevant polymorphism was identified [18]. Affected fetuses have been diagnosed prenatally in this way. Restriction fragment length polymorphism (RFLP) exists in or near the phenylalanine hydroxylase gene that permits assessment of the transmission of alleles within a family. A composite family of RFLPs on an allele is referred to as an “RFLP haplotype”. Some 50 haplotypes have been described for the phenylalanine hydroxylase locus. Once the mutation in the phenylalanine hydroxylase gene is known, mutational analysis may be used for prenatal diagnosis and for heterozygote detection. This provides a practical argument for seeking the precise molecular diagnosis. In the best studied Northern European population, eight mutations have resulted in 64 percent of the mutant phenylalanine hydroxylase chromosomes [4, 5]. Two mutations, in each of which there was zero enzyme activity and cross-reacting material (CRM), accounted for 46 percent; these were an arginine to tryptophan change in amino acid residue 408 (R408W) of exon 12 and a splicing mutation of intron 12. A number of the abnormal alleles identified have involved cytosine-phosphate-guanine (CpG) dinucleotides, which are known to be highly mutable.
TAILORx: Rationale for the Study Design
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
TAILORx represents a major step forward into the era of personalized medicine for breast cancer. By integrating a molecular diagnostic test into clinical decision making, patients and clinicians will be able to make more informed decisions regarding the most appropriate treatment options for a subset of patients for whom the test results in a clear treatment path and refine the utility of the assay for those for whom the result may be uninformative. This trial will also serve as an important resource for evaluating new molecular signatures and other technologies, such as proteomics, epigenomics, and pharmacogenomics, as these technologies evolve.
Molecular detections of coronavirus: current and emerging methodologies
Published in Expert Review of Anti-infective Therapy, 2022
Mingkun Diao, Lang Lang, Juan Feng, Rongsong Li
Nucleic acid sequence based analysis allows precise detection of pathogens. The coronavirus genome is composed of single-stranded RNA. Hence, most of its molecular diagnostic methods are based on detecting its RNA sequences (Figure 1). Amplification-based detections, such as RT-PCR and LAMP, are commonly used molecular diagnostic methods. There are also amplification independent methods, for example, biosensor-based methods that convert the interactions of biological molecules into physical, chemical, or optical signals [7,8]. The Clustered Regularly Interspaced Short Palindromic Repeats/Clustered Regularly Interspaced Short Palindromic Repeats-associated protein (CRISPR/Cas) based methods combine amplification and the cleavage of fluorescence probe containing viral specific sequence. Whole genome sequencing can also be used for the detection of coronaviruses, but it is mostly for research purpose rather than clinic diagnostics.
Molecular diagnosis of toxoplasmosis: recent advances and a look to the future
Published in Expert Review of Anti-infective Therapy, 2021
Marie Gladys Robert, Marie-Pierre Brenier-Pinchart, Cécile Garnaud, Hélène Fricker-Hidalgo, Hervé Pelloux
Immunocompromised patients are particularly at risk of severe and potentially fatal toxoplasmosis, which results mainly from the reactivation of a chronic infection and more rarely from a primary infection or, in the case of solid organ transplant, from the transmission of T. gondii encysted in the graft from a seropositive donor to a seronegative recipient. Various clinical presentations may be encountered, with the most frequent being cerebral, pulmonary or disseminated toxoplasmosis [9]. These urgent situations require immediate treatment and therefore a quick diagnosis. However, serological tests may lack sensitivity in this population. Direct diagnostic techniques are of great interest. Among them, molecular diagnosis is an essential option as it is sensitive and fast. Its effectiveness is, however, relatively difficult to evaluate in the particular context of toxoplasmosis in an immunocompromised patient, because the definitive diagnosis is often based on a combination of clinical and paraclinical arguments [47]. Nevertheless, in a recent review of the practice in 11 European countries regarding toxoplasmosis in transplant recipients, PCR has been shown to be the most useful diagnostic tool, surpassing imaging and serology [48]. The use of PCR in the diagnosis of cerebral, pulmonary and disseminated toxoplasmosis is discussed in the following paragraphs. Ocular toxoplasmosis is treated separately below as it also concerns immunocompetent patients.
Clinical genomics and contextualizing genome variation in the diagnostic laboratory
Published in Expert Review of Molecular Diagnostics, 2020
James R. Lupski, Pengfei Liu, Pawel Stankiewicz, Claudia M. B. Carvalho, Jennifer E. Posey
Clinical genomics may perhaps best be defined, from a retrospective historical and operational standpoint [1,2], as utilizing the variation inherent to the personal genome of an individual patient to formulate a molecular diagnosis that may be potentially clinically impactful. A molecular diagnosis is not a clinical diagnosis, but rather variation of a gene or genome that may potentially have contributory consequences for the patient’s disease process, either at present, or in the future. The predictive advantage of molecular diagnoses is particularly poignant in cases for which there is no family history of the clinical diagnosis or clinically observed phenotype to otherwise impart clinical suspicion. Like other clinical laboratory testing, the derived molecular diagnosis needs to be contextualized with the clinical observations. When the molecular and the clinical diagnoses are consistent with the patient’s assessment, i.e. clinical history and physical examination, and the emerging clinical picture for a given gene or variant allele matches the clinical synopsis of an online Mendelian Inheritance in Man (OMIM: https://www.omim.org/) defined phenotype, it may be clinically informative. Molecular diagnosis can sometimes help resolve clinical diagnostic ambiguities and be used to explore a differential diagnosis for a known rare disease [3], but should we begin to utilize it to assist in the formulation of a differential diagnosis? Moreover, how can we further elevate the individual clinical case ‘solved rate’ for molecular diagnoses achieved through genomics?