China
Africa
Explore chapters and articles related to this topic
Genetics and genomics of exposure to high altitude
Published in Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson, Ward, Milledge and West's High Altitude Medicine and Physiology, 2021
Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson
Numerous studies provide additional support for some of these same genetic adaptations across various locations in Tibet (Bigham et al. 2010; Peng et al. 2011; Xu et al. 2011; Wuren et al. 2014) and among Sherpa (Jeong et al. 2014), with links between another adaptive gene identified in this population (HYOU1) and hemoglobin concentration (Jeong et al. 2014). In addition to EPAS1 and EGLN1 HIF-related genes, several non-HIF pathway targets of selection have been reported in more than one independent study, including CYP17A1, HBB/HBG2, HFE, PKLR, and HMOX2 (Simonson et al. 2010; Yi et al. 2010; Wuren et al. 2014; Simonson 2015). Regulatory variants in HMOX2, which is involved in heme catabolism and oxygen sensing in carotid body chemoreceptors, are further associated with increased gene expression and decreased hemoglobin concentration in 1250 Tibetan men (Yang et al. 2016). Hundreds of distinct putatively adaptive genes have been identified in individual studies to date. These inconsistencies may reflect differences in analytical approaches, population locations/histories, and/or the stage and degree of adaptation.
Oncogene and Tumor Suppressor Gene Involvement in Human Lung Carcinogenesis
Published in George E. Milo, Bruce C. Casto, Charles F. Shuler, Transformation of Human Epithelial Cells: Molecular and Oncogenetic Mechanisms, 2017
Teresa A. Lehman, Curtis C. Harris
We have studied chromosome 11 extensively for loss of alleles because it has been speculated to have at least one, if not more, tumor suppressor gene. Six different loci on this chromosome have been studied. LOH was observed in 45% of the squamous cell carcinomas and adenocarcinomas studied.72 LOH was most frequently observed at the HBG2, insulin, and cHa-ras loci in both types of cancers. From these data, it was possible to establish two commonly deleted regions in lung cancer for this chromsome, namely, 11pter-p15.5 and 11p13-11q13 (see Figure 2). These findings are consistent with observations that describe two separate regions on chromosome 11 that may harbor tumor suppressor genes that correspond to 11p13 in Wilms’ tumor and 11pter-11p15.5 in rhabdomyosarcoma.58,79
Targeting fetal hemoglobin expression to treat β hemoglobinopathies
Published in Expert Opinion on Therapeutic Targets, 2022
Human β-like globin genes are in a cluster on the short arm of chromosome 11 at p15.4. Their expression is controlled by a super-enhancer upstream of the ε-globin gene (HBE) called the locus control region or LCR. (Figure 2) The LCR loops to globin gene promoters, and along with many recruited protein complexes, governs developmental and high-level globin-gene expression. HbF is encoded by two closely linked and structurally similar genes, HBG2 and HBG1 (referred to herein as HBG). A switch from HbF to HbA (α2βA2) expression starts midway through gestation and by age 6 mos. Is complete with HbF constituting <1% of total hemoglobin. Levels of HbF in sickle cell anemia are much higher than those of normal people and take 5 to 10 years to stabilize depending on the HBB haplotype. In β0 thalassemia, even though HbF is the only hemoglobin present except for a small amount of HbA2 its levels are almost always insufficient for normal life.
Association Between Genetic Polymorphisms and Hb F Levels in Heterozygous β-Thalassemia 3.5 kb Deletions
Published in Hemoglobin, 2020
Wanicha Tepakhan, Sataron Kanjanaopas, Korntip Srewaradachpisal
We did not find an association between Hb F levels and three of the SNPs (re4671393 in BCL11A, rs7482144 in HBG2 and rs2072596 in KLF1) in our subjects. This might be due to the low frequencies of rs7482144 in HBG2 (TC 11.0%, CC 0.0%) and rs2072596 in KLF1 (TC 0.9%, CC 0.0%) observed in our subjects. The variability of SNP frequencies was presented in different ethnic backgrounds. BCL11A, a zinc finger protein, plays an important role in silencing the HBG gene by forming a repressor complex to inhibit HBG expression [28]. Recent studies have demonstrated that many SNPs are associated with elevated Hb F levels, such as rs4671393 in healthy adults and sickle cell patients, and rs766432 in heterozygous β-thal individuals [10,19,20,27]. In this study, a high frequency of rs4671393 in BCL11A was observed (GA 27.9% and AA 4.5%). However, we did not find any relationship between rs4671393 and elevated Hb F levels in heterozygous β-thal 3.5 kb deletion cases using multiple regression analysis. The significantly increased Hb F levels in subjects with this SNP when compared with the wild type genotype (Figure 1) might be due to the fact that one subject can carry more than one SNP. We found that some of our subjects had rs9399137 or rs4895441 in HMIP.
Multi-Locus Models to Address Hb F Variability in Portuguese β-Thalassemia Carriers
Published in Hemoglobin, 2020
Licínio Manco, Celeste Bento, Luís Relvas, Elisabete Cunha, Janet Pereira, Valeria Moreira, Manuela Alvarez, Tabita Maia, M. Letícia Ribeiro
The first described polymorphism influencing γ-globin gene expression was the –158 (C>T) (XmnI) variant (rs7482144) in the promoter of the HBG2 gene within the β-globin gene cluster at chromosome 11p15 [4]. Although the increases in Hb F associated with XmnI-HBG2 are minimal or undetectable in healthy adults, association studies have shown that under conditions of stress erythropoiesis, as in β-thal or sickle cell disease, the presence of the XmnI-HBG2 T-allele correlates with higher Hb F levels [2]. Several reports also showed that β-thal carriers with raised Hb F levels have a significantly higher rs7482144 (T) minor allele frequency than patients with low Hb F levels [2]. The functional significance of the XmnI-HBG2 mutation has never been clearly defined and it is possible that it reflects a marker in linkage disequilibrium (LD) with other variant(s) elsewhere on chromosome 11p. In particular, it has been suggested that the role assigned to XmnI could be played by polymorphism rs16912979 A>G in the palindromic region of the 5′ hypersensitive site 4 (5′HS4) β-globin locus control region (LCR) [5].