Genetics of chronic pain: crucial concepts in genetics and research tools to understand the molecular biology of pain and analgesia
Peter R Wilson, Paul J Watson, Jennifer A Haythornthwaite, Troels S Jensen in Clinical Pain Management, 2008
DNA molecules are wound around histone protein complexes that provide structural support and regulatory functions. This structure permits a remarkable amount of compaction, which results in condensed superstructures called chromosomes. Nucleated cells of humans have 23 pairs of morphologically distinct chromosomes, with one chromosome of a pair inherited from each parent. There are 22 autosomes and a pair of sex chromosomes. The chromosomes that form each pair are termed homologs, and with the exception of a set of genes harbored in the sex chromosomes, each chromosome pair provides two copies of each gene. The two copies of the gene are called alleles. The two alleles are referred to as homozygous if their sequence is the same and heterozygous if each allele’s sequence is different. Chromosomes can be isolated from cells, stained and visualized by microscopy with the total chromosomal set of a cell termed a karyotype (Figure 4.2). Publication of the human genome sequence in 2000 provided more precise estimates of the position of genes and has largely superseded the use of karyotype analysis (i.e. chromosome banding). However, gross chromosomal abnormalities such as extra, missing, or broken chromosomes are still commonly identified by examining the karyotype.
Genetic disorders, skeletal dysplasias and malformations
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Chromosomes can be identified and numbered by microscopic examination of suitably prepared blood cells or tissue samples; the cell karyotype defines its chromosomal complement. Somatic (diploid) cells should have 46 chromosomes: 44 (numbers 1–22), called autosomes, are disposed in 22 homologous pairs – one of each pair being derived from the mother and one from the father, both carrying the same type of genetic information; the remaining 2 chromosomes are the sex chromosomes, females having two X chromosomes (one from each parent) and males having one X chromosome from the mother and one Y chromosome from the father. Germ-line cells (eggs and sperm) have a haploid number of chromosomes (22 plus either an X or a Y). This is the euploidic situation; abnormalities of chromosome number would lead to an aneuploidic state.
Clinical Cytogenetics and Testing for Developmental Disabilities
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Chromosome anomalies identified by karyotyping are described using a nomenclature which is designed to communicate the specifics of the abnormality to other cytogeneticists and those interested in knowing about the chromosome findings. The International System for Cytogenetic Nomenclature (ISCN), first introduced in 1975, has undergone several revisions with the 1995 version in current usage around the world (9). Table 2 summarizes forms of nomenclature used to describe common chromosome anomalies. The ISCN also provides a reference for chromosome band resolution. When treated with trypsin and stained with Giemsa stain, each chromosome has a characteristic banded pattern that uniquely identifies that chromosome. Chromosomes captured at different times of the cell cycle, i.e., metaphase vs. prometaphase, results in chromosomes with more or fewer visible bands. The ISCN defines three different levels of band resolution by the number of visible bands: 400, 550, and 850 bands per haploid karyotype. A typical high-resolution cytogenetic study will have a band resolution of at least 550 bands. In addition to karyotyping, special stains and methods, e.g., C-bands and FISH, are utilized by the laboratory to investigate chromosome anomalies to best define chromosomal losses, gains, and rearrangements that impact patient management and genetic counseling.
Abnormal chromosomes identification using chromosomal microarray
Published in Journal of Obstetrics and Gynaecology, 2022
Yunfang Shi, Xiaozhou Li, Duan Ju, Yan Li, Xiuling Zhang, Ying Zhang
In the past decades, G banding based karyotype analysis has been considered as the gold standard for detection of chromosome abnormalities in prenatal diagnosis. It can detect not only numerical abnormalities, but also structural abnormalities such as translocation, inversion, large deletions or large duplications (Levy and Burnside 2019). Typical karyotype analysis using G banding could delineate chromosomal abnormalities with a length of up to 5–10 Mb (Shaffer and Bejjani 2004). Chromosomal abnormalities of less than 5–10 Mb are usually considered to be beyond the detection limit of routine cytogenetic analysis (Hay et al. 2018). Given the variation in banding resolution from one prenatal preparation to the next or atypical bands, a length of 10–20 Mb or more is a more realistic threshold of detection for conventional karyotype analysis (Levy and Wapner 2018; Qian et al. 2018).
Complex chromosomal aberrations in a fetus originating from oocytes with smooth endoplasmic reticulum (SER) aggregates
Published in Systems Biology in Reproductive Medicine, 2018
Ioannis A. Sfontouris, George T. Lainas, Tryfon G. Lainas, Efthimios Faros, Maria Banti, Katerina Kardara, Katerina Anagnostopoulou, Harris Kontos, George K. Petsas, Efstratios M. Kolibianakis
Array-CGH was performed on uncultured amniocytes using the CytoChip Focus Constitutional BAC array (v1.1) (BlueGnome Ltd, Cambridge, UK) with a resolution of 1Mb. Arrays were analyzed using InnoScan 700 scanner (Arrayit Corporation, Sunnyvale, USA) and BlueFuse Multi software (v3.1) (BlueGnome Ltd, Cambridge, UK). The chromosome positions were given according to the human genome assembly GRCh 37 (hg19). Array-CGH revealed a 7632-Mb deletion at chromosome band 2q31.1q32.1 (175,428,717–183,060,453 bp) (Figure 2). The most distal normal probes were at chromosome position 173,542,101 and 184,711,524 upstream and downstream, respectively. There are 36 OMIM genes mapped in the deleted segment, including the homeobox D (HOXD) cluster that plays a key role in embryonic limb development (Goodman 2002). No aneuploidies were detected.
Advances in genetic testing and optimization of clinical management in children and adults with epilepsy
Published in Expert Review of Neurotherapeutics, 2020
Marcello Scala, Amedeo Bianchi, Francesca Bisulli, Antonietta Coppola, Maurizio Elia, Marina Trivisano, Dario Pruna, Tommaso Pippucci, Laura Canafoglia, Simona Lattanzi, Silvana Franceschetti, Carlo Nobile, Antonio Gambardella, Roberto Michelucci, Federico Zara, Pasquale Striano
As a second step, karyotype may be helpful to identify possible chromosome rearrangements that are not detectable by array CGH, such as translocations. FISH is only indicated in selected cases to search for known deletions or duplications in specific syndromes (e.g., 22q11.2 deletion in suspected Di George syndrome) or to better define chromosome abnormalities identified with other techniques (e.g., the complex rearrangements in the duplication/inversion 15q11 or isodicentric 15 chromosome syndrome). Eventually, multiplex ligation-dependent probe amplification (MLPA) allows to detect deletions and duplications of several exonic sequences and can be used for the screening of entire genes in the same experimental session. Furthermore, MLPA plays a pivotal role in the identification of intragenic deletions in cases where Sanger sequencing and array CGH result negative (e.g., epilepsy due to SCN1A or CDKL5 intragenic deletions).
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