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of the human genome sequence in 2000 provided more precise estimates of the position of genes and has largely superseded the use of karyotype analysis (i.e. chromosome banding).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.
Patterns of Inheritance: Mendelian and Non-Mendelian
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
To understand the principles by which diseases are inherited, we need to define and clarify several specific terms. For example, a genetic locus is a specific position or location on a chromosome frequently referred to as a gene which is a unique DNA sequence encoding the message for a protein. Alleles are alternative forms of a gene or segment of DNA at a specific locus. When both alleles at a locus are identical, the individual is homozygous at that locus. If the alleles are different, he or she is heterozygous. Such individuals are homozygotes or heterozygotes, respectively. An individual with two different mutant alleles at a given locus is referred to as a compound heterozygote, while an individual with one mutant allele at each of two different loci is referred to as a double heterozygote. The genotype is the genetic make-up of a single individual, while the phenotype is the observed result or outcome of the interaction of the genotype with the environment.
Genomics and Hearing Loss: Toward a New Standard of Care?
Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm in Advances in Audiology and Hearing Science, 2020
The genotype of an individual is determined by alleles (variant form of a gene) that are received from the individual’s parents. The alleles contribute to the organism’s phenotype, which is the combination of an individual’s observable characteristics or traits, such as its morphology, development, physiological properties, and behavior. The phenotype is the result of the expression of an individual’s genotype, but also of the influence of environmental factors and the interactions between the two. The alleles of an individual control if a trait is dominant or recessive. Traits are dominant if only one copy of the allele is required for expression of the trait. Traits are recessive if two copies of an allele are required for expression of the trait. X-linked traits are those controlled by an allele that is carried on the X chromosome, while autosomal characteristics are controlled by alleles located on any “nonsexual” chromosome, that is, excluding the chromosomes X or Y. For any given phenotypical characteristic, an individual inherits one gene from each parent so that the individual has a pairing of two genes. If the two alleles that form the pair for a trait are identical, then the individual is said to be homozygous for that characteristic and if not, the individual is then heterozygous.
Fat mass and obesity-associated (FTO) and leptin receptor (LEPR) gene polymorphisms in Egyptian obese subjects
Published in Archives of Physiology and Biochemistry, 2021
Ehab M. M. Ali, Thoria Diab, Afaf Elsaid, Hamada A. Abd El Daim, Rami M. Elshazli, Ahmad Settin
The data processing and analysis were done using the IBM Statistical Package of Social Science (SPSS, version 25.0, Thousand Oaks, CA). The continuous variables were analysed and compared as means ± standard deviation (M±SD) using Student’s t test, while the categorical variables were processed as numbers with percentage (n, %) using Fisher’s exact test with odds ratio (OR) and the 95% confidence interval (95% CI). The frequencies of the genotypes and alleles of FTO T>A (rs9939609) and LEPR Q223R (rs1137101) variants among obese subjects compared with healthy controls were calculated using Fisher’s exact test with two-tailed p values. The models designed for evaluating genetic inheritance of FTO T>A (rs9939609) and LEPR Q223R (rs1137101) variants include allelic, dominant, recessive, heterozygote, and homozygote. In the allelic model, the rare allele was emulated with the common allele in obese subjects and healthy control groups. In the dominant model, the rare allele carriage was compared vs. the common genotype, while in the recessive model, the rare genotype was compared vs. the other genotypes. Moreover, in the heterozygote and homozygote models, the heterozygote and homozygote genotypes were compared with the common genotype (Elsaid et al.2018). The equilibrium and disequilibrium between obese subjects vs. healthy controls were estimated using the Hardy–Weinberg equation. The p values achieved a statistically significant with a level below to .05.
CYP2C19 genotype and adverse cardiovascular outcomes after stent implantation in clopidogrel-treated Asian populations: A systematic review and meta-analysis
Published in Platelets, 2019
Ziwei Xi, Fang Fang, Jiayang Wang, Jumana AlHelal, Yujie Zhou, Wei Liu
The relative association between heterozygotes and homozygotes could be evaluated in 10 studies. Homozygotes (carriers of two CYP2C19 LOF alleles) were a higher risk of MACE than heterozygotes (carriers of only one CYP2C19 LOF alleles) (OR for homozygotes: 3.08, 95% CI: 1.85 to 5.13, and OR for heterozygotes: 1.92, 95% CI: 1.34 to 2.76) (Figure 4). The subgroup analysis according to nationality showed that the increased risk of MACE remained more significant in Chinese (OR: 2.28 95% CI: 1.91 to 2.73, p < .001) and Japanese (OR: 1.97, 95% CI: 1.47 to 2.63, p < .001), and was less significant in Korean (OR: 1.35, 95% CI: 1.08 to 1.69, p < .001) (Figure 5). Moreover, in the subgroup analysis according to different loading dose of clopidogrel (600mg vs. 300mg), we found that carriers of CYP2C19 LOF alleles in both group were at a significantly higher risk of MACE compared with non-carriers (high dose: OR 1.72, 95% CI: 1.37 to 2.16, and routine dose: OR 2.22, 95% CI: 1.68 to 2.94, p for subgroup heterogeneity = 0.16). (Figure 6).
Mipomersen and its use in familial hypercholesterolemia
Published in Expert Opinion on Pharmacotherapy, 2019
Johnathon Seth Parham, Anne Carol Goldberg
FH homozygotes have the same mutation in both alleles of the same gene. Compound heterozygotes have different mutations in each allele of the same gene and, double heterozygotes have mutations in two different genes affecting LDL receptor function. Patients who are homozygotes (or compound heterozygotes) have much higher LDL-C levels and earlier clinical atherosclerosis than heterozygotes [4]. Historically, the prevalence of homozygous FH (HoFH) has been estimated at 1 in 1,000,000, but recent data from the Netherlands suggest that this number could be as low as 1 in 160,000 and is likely to be about 1 in 250,000 [6]. Studies based on the Dutch Lipid Clinic Network criteria suggest the prevalence of heterozygous FH (HeFH) may be as high as 1 in approximately 250 patients [4]. Because of its prevalence and impact on cardiovascular events, the CDC Office of Public Health Genomics recommends Tier 1 genomic application of cascade screening for FH [7].
Related Knowledge Centers
- Allele
- Eukaryote
- Homologous Chromosome
- Ploidy
- Genotype
- Zygote
- Chromosome
- Gene
- Locus
- Genetic Disorder