Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the ...Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the genetic bases of adaption to high-altitude environments （Bigham et al., 2010; Simonson et al., 2010）. The domestic dog （Canisfamiliaris） is the first animal that developed an intimate relationship with human beings. Dogs migrated with human beings and have adapted to variety of ecological niches （Savolainen et al., 2002）. Our previous research revealed parallel evolution and convergent evolution in the adaptation of dogs and humans to the high-altitude environment of the Tibetan plateau （Wang et al., 2013, 2014）, suggesting that exploring the adaption of domestic dogs to high-altitude hypoxia is an interesting and important question.展开更多
Single nucleotide polymorphism is an interesting problem that can alter gene expression,recode amino acids and affect protein function.Protein structural changes have generally been attributed to amino acid replacemen...Single nucleotide polymorphism is an interesting problem that can alter gene expression,recode amino acids and affect protein function.Protein structural changes have generally been attributed to amino acid replacements,and only a few research efforts have examined the effects of mRNA structural changes to the conformation of the corresponding protein coded by the mRNA.In the present study,the human β-globin HBB gene and four variants were examined.The mRNA secondary structures were constructed using the dynamic extended folding method and the encoded protein secondary structures were obtained from related databases.Comparisons were performed between these structures before and after mutations were introduced into the mature mRNAs and the proteins.We focused on the structural changes from mRNA to protein and found that regular protein conformations tend to match stable mRNA regions,whereas irregular protein conformations,such as β/γ turns and random coils,often match unstable mRNA regions.Mutations within unstable regions can alter the mRNA secondary structure and leave footprints in the protein structure.Comparison of the mRNA-protein secondary structure relationships represents a potential strategy to explore protein functional changes.展开更多
Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB);however of this fact, the...Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB);however of this fact, there is extreme variability in occurrence and clinical presentation of sickle cell disease which may be explained by some other genetic changes associated with the gene. In the present study we examined the association between HBB gene polymorphism rs33949930 T>C in the occurrence of sickle cell disease in Saudi Arabia population. Materials and Methods: A case control study of 100 sickle cell disease patients and 100 healthy controls from Tabuk, Saudi Arabia. HBB gene rs33949930 T>C polymorphism was analyzed using Allele specific polymerase chain reaction technique. Results: It was observed that the genotype percentages TT, TC and CC among the patients with sickle cell disease were 63.0%, 35.0% and 2.0% and healthy controls were 68.0%, 27.0% and 5.0% respectively. Allele frequency for T allele was observed to be fT = 0.20 and fT = 0.19, where as for C allele was fC = 0.80 and fC = 0.81 among cases and controls respectively (p = 0.29). Compared to the TT genotype, the odds ratio of 1.4 (95% CI 0.76 - 2.57), risk ratio of 1.2 (95% CI 0.86 - 1.65) and risk difference of 8.4 (-6.66 - 23.38) for heterozygous genotype of HBB rs33949930 T>C was observed in relation to sickle cell disease. In addition, some difference in the laboratory values was observed among sickle cell disease patients with the different variants of HBB gene rs33949930 T>C polymorphism, especially the carriers of heterozygous TC genotype;however, the difference doesn’t reach to statically significant number. Conclusion: Present study suggested that there was not any significant association between HBB gene rs33949930 T>C polymorphism and occurrence of sickle cell disease. However, the heterozygous TC genotype of the polymorphism showed some higher ratios among cases as compared to healthy control group.展开更多
基金supported by the National Natural Science Foundation of China(No.91231108)the Breakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences(No.XDB13000000)+1 种基金the Key Research Program of the Chinese Academy of Sciencesthe Youth Innovation Promotion Association,Chinese Academy of Sciences(to GDW)
文摘Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the genetic bases of adaption to high-altitude environments （Bigham et al., 2010; Simonson et al., 2010）. The domestic dog （Canisfamiliaris） is the first animal that developed an intimate relationship with human beings. Dogs migrated with human beings and have adapted to variety of ecological niches （Savolainen et al., 2002）. Our previous research revealed parallel evolution and convergent evolution in the adaptation of dogs and humans to the high-altitude environment of the Tibetan plateau （Wang et al., 2013, 2014）, suggesting that exploring the adaption of domestic dogs to high-altitude hypoxia is an interesting and important question.
基金supported by the National Natural Science Foundation of China (30971454 and 90208018)
文摘Single nucleotide polymorphism is an interesting problem that can alter gene expression,recode amino acids and affect protein function.Protein structural changes have generally been attributed to amino acid replacements,and only a few research efforts have examined the effects of mRNA structural changes to the conformation of the corresponding protein coded by the mRNA.In the present study,the human β-globin HBB gene and four variants were examined.The mRNA secondary structures were constructed using the dynamic extended folding method and the encoded protein secondary structures were obtained from related databases.Comparisons were performed between these structures before and after mutations were introduced into the mature mRNAs and the proteins.We focused on the structural changes from mRNA to protein and found that regular protein conformations tend to match stable mRNA regions,whereas irregular protein conformations,such as β/γ turns and random coils,often match unstable mRNA regions.Mutations within unstable regions can alter the mRNA secondary structure and leave footprints in the protein structure.Comparison of the mRNA-protein secondary structure relationships represents a potential strategy to explore protein functional changes.
文摘Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB);however of this fact, there is extreme variability in occurrence and clinical presentation of sickle cell disease which may be explained by some other genetic changes associated with the gene. In the present study we examined the association between HBB gene polymorphism rs33949930 T>C in the occurrence of sickle cell disease in Saudi Arabia population. Materials and Methods: A case control study of 100 sickle cell disease patients and 100 healthy controls from Tabuk, Saudi Arabia. HBB gene rs33949930 T>C polymorphism was analyzed using Allele specific polymerase chain reaction technique. Results: It was observed that the genotype percentages TT, TC and CC among the patients with sickle cell disease were 63.0%, 35.0% and 2.0% and healthy controls were 68.0%, 27.0% and 5.0% respectively. Allele frequency for T allele was observed to be fT = 0.20 and fT = 0.19, where as for C allele was fC = 0.80 and fC = 0.81 among cases and controls respectively (p = 0.29). Compared to the TT genotype, the odds ratio of 1.4 (95% CI 0.76 - 2.57), risk ratio of 1.2 (95% CI 0.86 - 1.65) and risk difference of 8.4 (-6.66 - 23.38) for heterozygous genotype of HBB rs33949930 T>C was observed in relation to sickle cell disease. In addition, some difference in the laboratory values was observed among sickle cell disease patients with the different variants of HBB gene rs33949930 T>C polymorphism, especially the carriers of heterozygous TC genotype;however, the difference doesn’t reach to statically significant number. Conclusion: Present study suggested that there was not any significant association between HBB gene rs33949930 T>C polymorphism and occurrence of sickle cell disease. However, the heterozygous TC genotype of the polymorphism showed some higher ratios among cases as compared to healthy control group.
