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Preimplantation Genetic Testing of Aneuploidies (PGT-A)
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Daniela N. Bakalova, Darren K. Griffin, Maria E. Póo, Alan R. Thornhill
Single nucleotide polymorphisms (SNPs) are variations in DNA sequence found in various regions of the genome that are highly variable within the human population. As for aCGH, SNP microarray methodology requires DNA hybridization and fluorescence microscopy. However, SNP arrays interrogate specific polymorphisms of the 300 million present across the human genome (with microarray densities typically ranging from 100K to 1M); this provides a genotype for the test sample which is then compared to known maternal and paternal SNP patterns to identify a ploidy status based on predicted heterozygous patterns at specific loci [50]. When compared to classic microarray technologies for PGT-A analysis that can only detect gains and losses at specific chromosomal regions, SNP arrays can simultaneously identify the ploidy status of samples, the parental origin of chromosomal abnormalities, uniparental disomy (UPD), and specific artefactual errors such as allele dropout (ADO).
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Various SNP-screening projects underway have the goal of associating gene variations with specific diseases such as asthma, diabetes, arteriosclerosis, psychiatric disorders, and a predisposition to cancer. The other important application of SNP analysis is the prediction of drug safety and efficacy for individual patients. One of the first applications to be explored was evaluation of the status of drug-metabolizing enzymes such as cytochrome P450 to attempt to predict exposure and dose. Warfarin, still the most widely used anticoagulant drug worldwide, is often quoted as proof-of-concept for this approach in Precision Medicine. Although the activity of warfarin is closely related to its concentration in blood, patients’ responses to the drug are highly variable. Therefore, they must be monitored closely during the first few days of treatment so that the dose can be optimized according to the International Normalized Ratio (INR) for prothrombin. In fact, the blood concentration of warfarin is a balance between intake, metabolism, and elimination. It is metabolized in the liver by the enzyme CYP2C9, whose activity varies genetically in 35% of the white population. Therefore, testing for CYP2C9 genetic variants can provide clinical support for dose adjustment and can reduce the risk of life-threatening bleeding particularly when initiating patients on warfarin.
The Meta-Analysis of Genetic Studies
Published in Christopher H. Schmid, Theo Stijnen, Ian R. White, Handbook of Meta-Analysis, 2020
Cosetta Minelli, John Thompson
The range of options open to the meta-analyst is dictated by the quality of the reporting of the primary studies. The typical candidate-gene study reports on the genotypic effects of biallelic single nucleotide polymorphisms (SNPs), where the genetic variant can take only two possible forms (alleles) and the variation consists of a replacement of a single base with another (Attia et al., 2009). If a SNP can take two forms, A and a, then a participant who inherits a separate copy of their DNA from each parent can have one of three genotypes AA, Aa, or aa. When the outcome under study is binary, such as disease status, then the data from the study can be summarized as counts of participants in a 2 × 3 table and when this information is available, the meta-analysis is equivalent to an analysis of individual participant data (IPD), as discussed in Chapter 8. For a continuous outcome, such as the measurement of a biomarker, the number, mean, and standard deviation of the measurements in each cell of the 2 × 3 table, would, under a Gaussian model, be equivalent to having IPD (see Chapter 5).
Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab
Published in Modern Rheumatology, 2021
Yoshie Gon, Hajime Yoshifuji, Toshiki Nakajima, Kosaku Murakami, Ran Nakashima, Koichiro Ohmura, Tsuneyo Mimori, Chikashi Terao
We compared the efficacy of IS and biologics for the treatment of TAK, using a single-centre cohort of 163 patients. In the IS and biologics groups, the proportions of patients with HLA-B*52 and the risk-type alleles of the SNP in the IL12B gene region were similar (Table 1). We previously reported that the risk allele of the SNP was found to be associated with disease activity [9]. Note that in the present study, all the patients in the biologics group (11/11) had the risk allele; this suggests that patients with the risk allele develop more severe disease and require stronger treatment. Both the IS and biologics groups showed significant GC-sparing effects at 12 months from the initiation of treatment (Figure 2). All patients in biologics group had been previously treated with one to three types of IS (Supplementary Table 1). Therefore, biologics seemed to have GC-sparing effects in TAK patients with an insufficient response to IS. ESR and CRP levels were significantly decreased at 12 months in the biologics group, whereas only CRP levels were significantly decreased in the IS group (Figure 2). Moreover, the absolute ΔESR was significantly larger in the biologics group than in the IS group (Figure 3), implying the superiority of biologics. These results were similar to the findings previously reported by Mekinian et al. [7].
What’s new in chronic pain pathophysiology
Published in Canadian Journal of Pain, 2020
Numerous mutation sites may cause a similar end phenotype or disease state. For example, cystic fibrosis is a disease that may result from any one mutation of more than 1000 described variants in the CFTR gene. These mutations can be as small as a single nucleotide polymorphism (SNP) in which a single base-pair substitution occurs in the genetic code at a specific point in the genome. This base pair can then have a downstream effect on the gene expression, including qualitative and quantitative defects of the resulting protein complexes. SNPs that occur together with high frequency are often referred to as a given haplotype. Haplotypes help identify other polymorphic sites on the same chromosome and are implicated in the pathogenesis of certain genetically linked disorders. There are more than 400 genes that encode human ion channels, and an almost endless number of permutations of mutations can occur.
Role of CD226 Rs763361 Polymorphism in Susceptibility to Multiple Autoimmune Diseases
Published in Immunological Investigations, 2020
Linfu Bai, Jinyue Jiang, He Li, Rui Zhang
Investigating candidate genes is a useful measure for checking the gene–disease association, but the shortcomings are indeed unavoidable. The exact relationship between the SNP and disease susceptibility may be missed if multiple SNPs are responsible for it. Nie et al. found that the combination of polymorphisms in the CD226 (rs763361) and CD40 (rs4810485) gene was related to a genetic predisposition to SLE (Nie et al. 2016). Additionally, three-variant haplotype of CD226 gene together contributed to the susceptibility of SSc-related pulmonary fibrosis (Bossini-Castillo et al. 2012). Owing to a lack of the same haplotype data in the original studies, it was impossible for us to evaluate the haplotype association by meta-analysis. Also, exploring the gene–disease association should take other clinical parameters such as age, gender, and severity into account. More investigations are required to check the effect of CD226 haplotypes on ADs susceptibility, which could provide the data basis for meta-analysis of haplotype.