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Detection Techniques for Single Nucleotide Polymorphisms
Published in Attila Lorincz, Nucleic Acid Testing for Human Disease, 2016
W. Mathias Howell, Johan Stenberg, Chatarina Larsson, Mats Nilsson, Ulf Landegren
The demands on SNP genotyping techniques vary greatly, depending on intended applications, for example, studies designed to seek the genetic determinants of disease where hereditary components are implicated. A classic approach is to perform an association study (reviewed in Reference 45). In this design, a group of individuals affected with a disease of interest (cases), and a group of people from the general population (controls) are selected. The cases and controls are chosen to be as closely matched as possible to avoid stratification due to genetic and environmental differences that are irrelevant for the investigated trait.
Preimplantation Genetic Testing for Monogenic Disorders
Published in Darren K. Griffin, Gary L. Harton, Preimplantation Genetic Testing, 2020
Martine De Rycke, Pieter Verdyck
Following WGA, either an approach of STR-based haplotyping via targeted PCR is applied, or WGA products are analyzed via a generic platform, SNP array, or NGS-based technology. SNP arrays are high-density oligo arrays containing up to several million probes, which allow genotyping of hundreds of thousands of selected SNPs across all chromosomes in a single reaction. SNPs are mostly biallelic, alleles are indicated as A and B, and genotypes are homozygous AA or BB, or heterozygous AB. The commercially available SNP arrays use different methods for SNP genotyping: hybridization to SNP allele−specific probes or single-base extension reactions are often applied [26]. The arrays are scanned, and SNP genotypes are called based on the total fluorescence and the ratio of hybridization intensities for A and B (allele frequencies) (e.g., AB is called in case of similar intensities of an intermediate level). Targeted multiplex PCR and SNP array share the same principle of linkage-based testing, but the SNP array workflow is much more standardized and uniform, without the need for a locus-specific preclinical workup. This reduces the laboratory workload and the waiting time for the couples substantially. Only a short family-specific workup with analysis of genomic DNA samples of the couple and a suitable reference (child or grandparent with known genetic status) is recommended to determine the number of informative SNPs in the region of interest and to establish phasing. The SNP array platform is especially powerful for double indications (for instance, two monogenic disorders or a monogenic disorder with HLA matching): following a minimal workup, whole-genome haplotyping is accomplished from a single data set. Haplotyping via SNP array can also be applied for balanced translocations or inversions: analysis reaches a high resolution and allows us to distinguish normal from balanced translocation carriers. The major requirements for SNP array application are that the chromosomal or monogenic aberration(s) are inherited, and relevant family samples are available for haplotyping. An example of a SNP array−based preclinical workup and clinical results for PGT-M are shown in Figure 5.2.
Genome-wide analysis of runs of homozygosity in Pakistani controls with no history of speech or language-related developmental phenotypes
Published in Annals of Human Biology, 2023
Tahira Yasmin, Erin M. Andres, Komal Ashraf, Muhammad Asim Raza Basra, Muhammad Hashim Raza
We used DNA samples of 100 controls and performed SNP genotyping using the Illumina Infinium QC Array-24. The SNP genotyping was outsourced to the Johns Hopkins University School of Medicine, Genetic Resources Core Facility (https://grcf.jhmi.edu/genotyping/). The Illumina Infinium QC Array-24 array is a cost-effective, low-density SNP array, proven to be efficient in detecting sample-specific variant calls, consanguinity in samples, sex, and ethnicity (Ponomarenko et al. 2017). It has been widely used in association studies and proved efficient enough to find genetic linkage and associations (Ponomarenko et al. 2017; Andres et al. 2019; 2020; Pinese et al. 2020). This array contains 15,949 SNPs evenly distributed throughout the genome with an average density of 0.5 megabases (Mbs). There are 11,994 SNPs spread across autosomal chromosomes, and the rest are dispersed across sex chromosomes and mitochondrial chromosomes. The SNP genotyping data of 97 control individuals was available, and 4 CEPH samples were used as positive controls during genotyping. The SNP genotyping was unsuccessful for the three controls, one belonged to the related individuals, and the other two were unrelated. In the current study, we excluded the genotyping data of related individuals from the analysis and only the data of 86 unrelated individuals (39 males, 47 females) were used in the ROH analysis.
Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant
Published in The American Journal of Drug and Alcohol Abuse, 2020
Daryl I. Shorter, Xuefeng Zhang, Coreen B. Domingo, Ellen M. Nielsen, Thomas R. Kosten, David A. Nielsen
A total of 201 individuals from the greater Houston area who were seeking treatment for cocaine dependence (DSM-IV criteria, equivalent to CUD in DSM-5) (29) were screened between October 2009 and September 2013 at the Outpatient Clinical Trials Research Clinic at Michael E. DeBakey Veterans Administration Medical Center. Among them, 16 participants were excluded because they did not meet the inclusion criteria, and 89 participants were lost to follow up before randomization into this study. Thus, 96 individuals entered into the study, and were randomly assigned into the doxazosin or the placebo groups. SNP genotyping was performed in all participants after randomization, as described in detail below. Following randomization, seven participants were lost to follow up. Further, of the remaining 89 randomized participants, a total of 13 participants opted out of the pharmacogenetic testing, an optional component within the approved Informed Consent Form, which precluded their inclusion in the pharmacogenetic data analysis. In summary, a total of 76 CUD patients participated in this pharmacogenetic trial and the generated data were analyzed in this 12-week, double-blind, randomized, and placebo-controlled pharmacogenetic study (Figure 1).
Integrating transcriptome-wide association study and mRNA expression profiling identified candidate genes and pathways associated with osteomyelitis
Published in Scandinavian Journal of Rheumatology, 2020
L Zhang, Y Du, Y Wen, M Ma, S Cheng, B Cheng, P Li, X Qi, C Liang, L Liu, X Liang, X Guo, F Zhang
The GWAS summary data of OM were taken from the UK Biobank (http://geneatlas.roslin.ed.ac.uk/) (5). In brief, this GWAS sample consists of over 452 264 individuals, including 698 OM patients. The study subjects were from the UK, and aged between 40 and 69 years. SNP genotyping was performed using the UK Biobank Axiom array, which was specifically designed by an expert group for the purpose of genotyping the UK Biobank participants. The array also consisted of coding variants across a range of minor allele frequencies and markers which could provide good genome-wide coverage for imputation in European populations. Principal component analysis was used to evaluate the potential impact of population structure. Genotype imputation was performed using IMPUTE4 (https://jmarchini.org/software/). In total, after quality control, the GWAS summary data of 35 971 522 SNPs were used in this study. A detailed description of study subjects, genotyping, imputation, association analysis, and quality control can be found in a previously published study (5).