Genetics and exercise: an introduction
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
Other types of small DNA variants are variable number of repeat sequences. These are DNA variants where 2, 3 or more nucleotides are repeated multiple times. For instance, there is an abundance of CA dinucleotide repeats in the human genome. Some people may carry as few as 100 copies of the CA repeat at a given chromosomal site, whilst others may carry 10,000 or more copies of the repeat. Such repeat sequences are like a DNA fingerprint of an individual and are commonly used in forensic science to match DNA samples to an individual. One copy number variation occurs in the human AMY1 gene which encodes the starch-digesting enzyme, amylase. Humans have a large variation in the number of copies of the amylase gene, and people of agricultural societies that eat more starch have on average more copies than e.g. hunter-gatherers, who eat less starch (23).
Genetics of gastric cancer
J. K. Cowell in Molecular Genetics of Cancer, 2003
The TP53 gene has been shown to be altered in gastric cancers by a variety of different methods. TP53 mutation is frequently accompanied by loss of heterozygosity (LOH) which provides the second hit needed to inactivate all p53 function in the tumor cells. LOH has been shown in 60% of gastric cancers and mutational analysis reveals 30–50% of tumors carry TP53 mutations. The differences in incidence between studies is likely a consequence of the mutation screening technique employed (single strand chain polymorphism (SSCP) or degenerative gradient gel electrophoresis (DGGE)) and sample sizes of the study (Hollstein et al., 1991; Powell, 1998). The spectrum of mutations in TP53 seen in gastric cancer appears similar to that seen in other tumors with mutations of TP53 clustering at 4 hot spots in highly conserved regions (domains II-V). The mutations found to occur commonly in gastric carcinoma are G:C to A:T transitions at CpG dinucleotide repeats.
Pharmacogenomics of Colorectal Cancer
Jim Cassidy, Patrick Johnston, Eric Van Cutsem in Colorectal Cancer, 2006
TS gene polymorphisms have the potential to predict clinical outcome and toxicity; therefore, it is an important factor to consider when deciding on patient treatment. The TS gene promoter is polymorphic and usually has two (TSER 2) or three (TSER 3) 28-base pair tandem repeat sequences (66). The tandem repeats may affect transcriptional and/or translational efficiency of the TS gene. It has been demonstrated that TSER 3/TSER 3 homozygous patients are less likely to respond to 5-FU than TSER 2/ TSER 2 homozygous, or TSER 2/TSER 3 heterozygous patients (67). This may be due to the fact that TS promoters with the TSER 3 sequence have been reported to generate 3-fold higher mRNA than those with the TSER 2 sequence (68), and therefore patients with this genotype may express higher levels of TS and be less responsive to 5-FU. This relationship is further enhanced by the presence of a single nucleotide protein (SNP) in the tandem repeat region (69). The identification of the polymorphism provides a means of selecting patients who are likely to respond to 5-FU-based chemotherapy and also identifies patients who will experience increased toxicity. Recently, a six base-pair polymorphic deletion in the 3′ UTR of the TS gene has been identified; however, it is unclear at present whether this polymorphic change influences TS gene expression or mRNA stability.
Further Characterization of Hb Bronovo [α103(G10)His→Leu; HBA2: c.311A>T] and First Report of the Homozygous State
Published in Hemoglobin, 2020
Nikita Mehta, J. Martin Johnston, Molly Hein, Benjamin R. Kipp, Lea Coon, Michelle E. Savedra, James D. Hoyer, Rong He, Aruna Rangan, Min Shi, Jennifer L. Oliveira
Uniparental disomy (UPD) analysis of chromosomes 11 and 16 were also performed for the proband and his parents. Uniparental disomy studies were performed by a previously described technique [7,8]. In brief, samples were genotyped using PCR of chromosome-specific microsatellite markers (dinucleotide repeats). The markers used for chromosome 16 were D16S521, D16S418, D16S500, D16S3041, D16S3100, D16S3034, D16S3057, D16S503, D16S515, D16S516, D16S505 and D16S520; the markers used for chromosome 11 were D11S1363, D11S4046, D11S4146, D11S1760, D11S1338, D11S4116, D11S935, D11S987, D11S1314, D11S937, D11S901, D11S898, D11S4151, D11S1320 and D11S968. Diagnosis of UPD required that the proband carries at least two informative markers representing uniparental inheritance of chromosome 16, in addition to all informative markers for chromosome 11 showing biparental inheritance [9].
Microsatellite variation of ESR1, ESR2, and AR in Serbian women with primary ovarian insufficiency
Published in Climacteric, 2018
J. Li, R. Dalgleish, S. Vujovic, S. Dragojevic-Dikic, M. Ivanisevic, M. Ivovic, M. Tancic, J. Thompson, F. Al-Azzawi
Ligand-bound gonadal steroid receptors act as DNA transactivation factors and are thus responsible for mediating the effects of steroids on development, reproduction, proliferation, cellular homeostasis, and gene expression12,13. Estrogen contributes to the regulation of cyclic gonadotropin release via its action on estrogen receptor alpha, encoded by ESR1, in the hypothalamic–hypophyseal axis and to enhancing folliculogenesis through its actions via estrogen receptor beta, encoded by ESR2, in the ovary14. A dinucleotide TA tandem repeat polymorphism is located in the promoter region of ESR1, while a dinucleotide CA tandem repeat is located in intron 5 of ESR2. The functional significance of ESR1 (TA)nand ESR2 (CA)n in POI remains unknown, although previous studies have shown associations between these two microsatellites and POI15,16.
Emerging roles for Interleukin-11 in disease
Published in Growth Factors, 2019
Paul M. Nguyen, Suad M. Abdirahman, Tracy L. Putoczki
Chronic obstructive pulmonary disorder (COPD) and ulcerative colitis (UC) are two inflammatory conditions where IL-11 polymorphisms are implicated in disease pathogenesis. In a population of COPD patients, it was found that a SNP in the promoter region of IL11 (−518 G/A) was strongly linked with a dinucleotide repeat (IL11.A2 (GT)7(CT)6) in the same region, with the repeat observed to be decreased in patients compared to healthy controls (Klein et al. 2004). Similarly, the frequency of another dinucleotide repeat (IL11.A1 (GT)7(CT)8) also in the promoter region was found to be increased in UC patients, although the significance of the allele was not investigated (Klein et al. 2002).
Related Knowledge Centers
- DNA
- Microsatellite
- Microsatellite Instability
- Minisatellite
- Variable Number Tandem Repeat
- Protein Tandem Repeats
- Satellite DNA
- Hereditary NONpolyposis Colorectal Cancer
- Trinucleotide Repeat Disorder
- Macrosatellite