Pedigree Analysis of Nonhomologous Sequence Recombination of HBA1 and HBA2 Genes

Abstract

The aim of this study was to investigate a family with nonhomologous sequence recombination of HBA1 and HBA2 genes and provide a favorable basis for genetic counseling and eugenics. Peripheral blood of family members was collected. Hematological parameters were determined by an automated cell counter and hemoglobin (Hb) analysis was performed using high performance liquid chromatography (HPLC). Villus samples were taken for prenatal diagnosis (PND). Gap-polymerase chain reaction (gap-PCR) and reverse dot-blot were used for thalassemia genotyping. DNA sequencing was used to analyze the gene sequence of HBA1 (α1-globin) and HBA2 (α2-globin). The nonhomologous sequence recombination allelic variant of HBA1 and HBA2 genes were identified, namely, a gene conversion on the HBA2 gene called α12 (HBA12). The α12 allele consists primarily of the HBA2 gene sequence except for a segment of the IVS-II in which HBA2-specific sequences have been replaced by HBA1-specific sequences. The following genotypes were observed: – –^SEA/αα12 (Southeast Asian deletion), αα/αα12 and α^QSα/αα12 (Hb Quong Sze or Hb QS; HBA2: c.377T>C), and all manifested as small cell hypochromic anemia. To find the α12 allele in the Chinese population and clarify the influence of the α12 allele and its common inheritance with abnormal Hb and α-thalassemia (α-thal) on α-globin gene expression can help guide clinical diagnosis and genetic counseling.

Keywords:

• α-Globin gene
• α12 allele
• gene conversion
• thalassemia

Author contributions

S-Q. Luo and X-Y. Chen designed the study, performed the experiments, drafted the manuscript, compiled the data and contributed to writing the article. N. Tang and J. Huang performed the analyses and helped in drafting the manuscript. Q-Y. Zhong reviewed the manuscript and helped to shape the manuscript. R. Cai and T-Z. Yan provided valuable suggestions and clinical output. All the authors read and approved the final manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [Grant No. 81360091], Liuzhou Science and Technology Innovation Capability and Conditions Construction Project [Grant No. 2018AF10501 and No. 2014G010404] and Scientific Research Fund of the Health and Family Planning Commission of the Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China [Grant No. Z20170528 and No. Z20170531].