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Meiotic Abnormalities in Infertile Males
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Mireia Solé, Francesca Vidal, Joan Blanco, Zaida Sarrate
The use of the three-dimensional fluorescent in situ hybridization (3D-FISH) [52] and the in situ chromosome conformation capture sequencing (Hi-C) techniques (which consist of determine and quantify interactions between loci that are physically close) [53] have demonstrated the functional relevance of genomic architecture. The non-random chromosomal positioning within the nucleus allows a spatiotemporal control of gene transcription and regulation, cell development, and division-fundamental biological processes for cell functionality. In this context, there is a growing idea that chromosomal territoriality could become a potential useful diagnostic tool for different diseases [54] and even infertility [55,56].
Precision medicine for colorectal cancer
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Candan Hızel, Şükrü Tüzmen, Arsalan Amirfallah, Gizem Çalıbaşı Koçal, Duygu Abbasoğlu, Haluk Onat, Yeşim Yıldırım, Yasemin Baskın
Chromatin looping can make it possible for distant regulatory elements to affect the gene expression of their target genes located far away upstream or downstream from where these cis- and transregulatory elements are located. Chromosome conformation capture (3C2)–based methods can be utilized to determine physical interactions between enhancers and promoters (Spilianakis et al., 2005; Simonis et al., 2006; Jäger et al., 2015). GWAS helped determine SNPs that are linked to complex diseases. It has been determined that there may exist many SNPs that are located within regulatory elements and influence through long-range regulation of gene expression (Pomerantz et al., 2009; Ahmadiyeh et al., 2010; Zhang et al., 2012). Consequently, protein–DNA interaction can be facilitated upon dynamic modification of chromatin architecture.
Genetics of Psoriasis and Psoriatic Arthritis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
A third challenge is characterizing the functional relevance of the variants identified thus far. Only a small fraction of psoriasis susceptibility loci identified, including IL23R and CARD14, are located within coding regions, and thus may have rather straightforward causal effects on protein structure or function [93,201,202]. The remaining loci are located outside coding regions, such as in promoters, enhancers, or repressors, where they may function to alter the expression of nearby genes or even genes megabases away. Such expression quantitative trait loci (eQTL) can be identified by correlating SNPs with gene expression data generated from homogeneous and relevant cell types [142]. Bioinformatic tools such as the Encyclopedia of DNA Elements (ENCODE) database may also help to provide clues into the functions of these variants and allow us to generate hypotheses that can be experimentally tested using new techniques, such as chromosome conformation capture to identify interactions between far-apart genes, or CRISPR/Cas9 to confirm the causal nature of variants in cellular or animal models [142].
Analysis of rare thalassemia caused by HS-40 regulatory site deletion
Published in Hematology, 2020
Shiqiang Luo, Xingyuan Chen, Qingyan Zhong, Qiuhua Wang, Zehui Xu, Liuqun Qin, Jingren Wang, Dejian Yuan, Tizhen Yan, Ning Tang
The α-globin gene cluster is located at the 16p13.3 position on chromosome 16, and its arrangement on the gene cluster is 5’-ζ-Ψζ-Ψα2-Ψα1-α2-α1-θ-3’ [8]. In the 40 kb upstream of the ζ-gene, there is an important regulatory site, HS-40, which affects the expression of α-globin gene [9]. Differences in the number, arrangement, type, and even spatial distance between DNA binding sites within enhancers determine differences in spatial and temporal expression of genes. The academic community believes that the chromosome has a spatial structure and is not just linear. Enhancers and promoters interact with each other to form a circular structure through the direct action of specific proteins [10]. The expression of globin genes is highly stage-specific and tissue-specific, and is affected by remote regulatory elements. Coelho et al. applied quantitative chromosome conformation capture (q3C) technology to study the chromatin conformation of α-globin gene clusters, and for the first time confirmed the looping mechanism of long-range enhancer elements [11]. Natural mutations in α-globin gene clusters (mainly large-fragment deletions) can affect gene expression, phenotypic differences, and phenotypic adaptation by disrupting gene activity and altering gene dose, thereby causing disease [12].
Relationship of the Interaction Between Two Quantitative Trait Loci with γ-Globin Expression in β-Thalassemia Intermedia Patients
Published in Hemoglobin, 2018
Shiva NickAria, Sezaneh Haghpanah, Mani Ramzi, Mehran Karimi
There are many strategies in gene activation and repression. Several studies have shown that chromosomes can communicate with each other, and closely align genes in nuclei to regulate expression across the cell cycle [32–35]. They have demonstrated that interchromosomal interactions are mediated by transcriptional mechanisms to preserve true genome architectural features [36,37]. Development in chromosome conformation capture techniques has revealed that interactions are unique for each cell. Furthermore, chromatin localization showed active chromatin domains in the interior of nucleus and inactive domains in peripheral region. This process creates opportunities for different chromosomes to collide with each other during their localization, and DNA bending to facilitate accessibility in cis-acting elements. This mechanism is very significant in erythroid cells for globin expression, along with chromatin looping forming a hub-like structure to reduce the gap between promoters and enhancers with the mediation of transcription factors [38,39]. Our results and the above-mentioned expression mechanisms create a hypothesis that the chromosome 8q12.1 and chromosome 11p15 regions could interact with each other and colocalize to regulate globin gene expression or switching and cell differentiation. It can be argued that polymorphism rs9693712 on the 8q12.1 locus affects the interaction with XmnI on chr11p as well as modifying the expression of the γ-globin gene.
The evolution in our understanding of the genetics of rheumatoid arthritis and the impact on novel drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Filip Machaj, Jakub Rosik, Bartosz Szostak, Andrzej Pawlik
Davison et al. evaluated candidate long-range DNA interactions in the 16p13 region. Gene expression analysis was followed by chromosome conformation capture (3C) experiments. The authors demonstrated that disease-associated SNPs within the CLEC16A gene might influence the expression of the neighboring gene DEXI [96].