An Approach to Inherited Pulmonary Disease
Stephen D. Litwin in Genetic Determinants of Pulmonary Disease, 2020
The term phenotype can be applied to any property observable in an organism or in specimens obtained from an organism. By genetic analysis phenotypes can be attributed to the action of certain genes whose presence in an individual organism is inferred from the phenotype and the pedigree. The complement of genes present in an organism is called the genotype. In diploid organisms such as humans there are two complete sets of the genes carried on the autosomes, those chromosomes other than the X and Y. A pair of genes occupies a specific place in the genome called a locus. Commonly the term genotype is used in reference to only the two genes at the one locus relevant to a specific phenotype. Alternative forms of a gene which can occupy the same locus are called alleles. An individual who has two different genes at one locus is said to be heterozygous at that locus, or a heterozygote. An individual who has two copies of the same gene at one locus is said to be homozygous at that locus, or a homozygote.
HLA-DR and -DQ Typing by DNA-RFLP Analysis
M. Kam, Jeffrey L. Bidwell in Handbook of HLA TYPING TECHNIQUES, 2020
For each probe used, a series of reference HLA-DR/DQ/Dw homozygous and/or heterozygous cell DNAs should be included (examples are shown in Figures 4 to 6). Interpretation of test samples is by visual comparison with the reference cell patterns. Reference RFLP patterns of homozygous typing cells (HTCs) are shown schematically in Figures 8 to 10. Heterozygous specificities are identified by simple deduction from combinations of HTC patterns. Correlation between phenotypic and RFLP specificities is detailed in Figures 8 to 10. Discrimination between similar or identical TaqI DRB RFLP patterns for the DR3/DR6 and DR7/DR9 group (see Figure 8) is based upon identification of DRB-DQB-DQA RFLP associations due to linkage disequilibrium (Figure 7).7,8 Under the standard electrophoresis conditions described in the Methods section, five TaqI DQA1 locus-specific RFLP patterns are observed (la, lb, lc, 2 and 3; Figures 6 and 10). In addition, two alleles of the DQA2 locus (DQA2U and DQA2L, formerly DX aU and DX a L) may be identified. Under these standard conditions, the patterns lb and 4 cannot be resolved. Similarly, the patterns 3b and 2 cannot be resolved (Figure 10). If required, these bands may be resolved by long-run electrophoresis (52 h at 30 V18,19), though for routine identification purposes we have found that this is seldom necessary.
Patterns of Inheritance: Mendelian and Non-Mendelian
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Mendelian diseases are grouped into autosomal if they are encoded by genes on one of the 22 pairs of autosomes, or nonsex chromosomes, and X-linked if encoded by a mutant gene on the X chromosome, one of the two sex chromosomes. As Mendel described with garden peas, there are two types: dominant and recessive. Dominant refers to those conditions that are expressed in heterozygotes or individuals having one copy of a mutant allele and one copy of a normal, or wild-type allele. Recessive refers to those conditions that clinically manifest only in individuals homozygous for the mutant allele and carry a double dose or two copies of the abnormal gene. Most dominant genes code for structural proteins while recessive genes code for enzymes or regulatory proteins. Of the 8000 human phenotypes that are known to be inherited in a Mendelian fashion, more than one-half are classified as autosomal dominant, about one-third are autosomal recessive, and about one-tenth are X-linked.
Quantile-specific heritability of serum growth factor concentrations
Published in Growth Factors, 2021
Schuler et al. (2018) reported that the effects of increasing dietary fat on serum VEGF concentrations were significantly affected by rs9472159 (in linkage disequilibrium with rs6921438 (Stathopoulou et al. 2013) and postulated to regulate VEGF expression (Schüler et al. 2018)). Specifically, they reported that serum VEGF concentrations increased significantly more when switching from 30% to a 45% fat diet in rs9472159 CC homozygotes than in CA heterozygotes (P = 0.01) or AA homozygotes (P = 0.02, Figure 3(F) histogram). However, VEGF concentrations were significantly higher at the end of high-fat than low-fat diet (292.8 ± 20.1 versus 271.5 ± 18.0 pg/ml, P = 0.002), and we estimate from their figures that the difference between homozygotes was greater at the higher mean concentration of the high fat diet than at the lower mean concentration of the low-fat diet (CC minus AA: 443 versus 365 pg/ml).
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.
Important pharmacogenomic aspects in the management of HIV/AIDS
Published in South African Family Practice, 2019
A Marais, E Osuch, V Steenkamp, L Ledwaba
Approximately 80% of all drugs are metabolized by the hepatic cytochrome P450 enzyme system, of which the phase 1 metabolism iso-forms CYP1A2 (8.9%), CYP2C9 (12.8%), CYP2C19 (6.8%), CYP2D6 (20%), and CYP3A4/CYP3A5 (30.2%) are the most important.6 Each CYP450 enzyme is encoded for by a specific gene, which in turn is determined by inherited alleles – one from each parent. These alleles contribute to the phenotype (observable characteristics) of the individual, and may either be dominant or recessive.7 When heterozygous alleles are present, the dominant allele will determine the phenotype. Alleles occurring most commonly in the general population are known as “wild type” (or normal), whereas “variant” (or mutation) recessive alleles will only determine the phenotype if a homozygous combination is present. Sequence variations (or Single Nucleotide Polymorphisms/variations – SNPs or SNVs) may occur when a variant allele replaces one or both wild-type alleles. Every individual SNV is allocated a unique reference SNP ID number (rs#) by the HUGO Gene Nomenclature Committee (HGNC) – established by the US National Human Genome Research institute and the Wellcome Trust, to ensure unambiguous reference to genes in scientific communications.8 Variant alleles usually encode an enzyme or protein that has reduced (or no) activity, resulting in phenotypical changes which may have an altered effect on drug metabolism or response.9
Related Knowledge Centers
- Allele
- Eukaryote
- Homologous Chromosome
- Ploidy
- Genotype
- Zygote
- Chromosome
- Gene
- Locus
- Genetic Disorder