Abstract

Abnormal haemoglobin (Hb) variants result in the most commonly inherited disorders in humans worldwide. In this study, we investigated the molecular epidemiology characteristics of Hb variants, along with associated structural and functional predictions in the Yunnan province population of Southwestern China. A total of 41,933 subjects who sought haemoglobinopathy screening were included. Based on bioinformatics and structural analysis, as well as protein modeling, the pathogenesis and type of Hb genetic mutations were characterized. Among all individuals studied, 328 cases (0.78%) were confirmed as carriers of Hb variants, with 13 cases (0.03%) presenting α-globin variants, 313 (0.75%) β-globin variants, and two δ-globin variants. A total of 19 different mutations were identified, including three novel mutations. In addition, 48 cases of ααCS mutations and 14 cases of Hb H or Hb Bart’s were found. The isoelectric point, evolutionary conservation, and genotype-phenotype correlation for these mutations were predicted. Additionally, secondary and tertiary protein structure modeling were performed for three selected mutations. In conclusion, the prevalence of Hb variants in the Yunnan population is much higher than other regions of China. Complete characterization of these Hb variants is essential for generating a rational strategy to control the haemoglobinopathies in this region.

Details

Title
Molecular epidemiology, pathogenicity, and structural analysis of haemoglobin variants in the Yunnan province population of Southwestern China
Author
Zhang, Jie 1 ; Li, Peng 2 ; Yang, Yang 2 ; Yan Yuanlong 3 ; Zeng Xiaohong 3 ; Li, Dongmei 3 ; Chen, Hong 3 ; Su, Jie 3 ; Zhu Baosheng 1   VIAFID ORCID Logo 

1  Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, The First People’s Hospital of Yunnan Province, Genetic Diagnosis Center, Yunnan Province, China (GRID:grid.414918.1); The First People’s Hospital of Yunnan Province, Department of Hematology, Yunnan Province, China (GRID:grid.414918.1); The Affiliated Hospital of Kunming University of Science and Technology, Department of Pediatrics, Kunming, China (GRID:grid.218292.2) (ISNI:0000 0000 8571 108X) 
2  Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, The First People’s Hospital of Yunnan Province, Genetic Diagnosis Center, Yunnan Province, China (GRID:grid.414918.1); The Affiliated Hospital of Kunming University of Science and Technology, Department of Pediatrics, Kunming, China (GRID:grid.218292.2) (ISNI:0000 0000 8571 108X) 
3  Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, The First People’s Hospital of Yunnan Province, Genetic Diagnosis Center, Yunnan Province, China (GRID:grid.414918.1) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-44793-0
ProQuest document ID
2235044503
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.