Abstract
Copy number variations (CNVs) can cause many genetic disorders and the structure analysis of unknown CNVs is important for clinical diagnosis. The human α-globin gene cluster lies close to the telomere of the short arm on chromosome 16. Copy number variations of this region produce excessive or insufficient α-globin chains which imbalances the β-globin chains, resulting in thalassemia. However, these CNVs usually cannot be precisely defined by traditional methods. Here, we designed a technique strategy and applied it to identify two CNVs involving the α-globin gene cluster causing thalassemia in two Chinese families. A novel 282 kb duplication (αααα282) was identified in family A and a novel 235 kb deletion (--235) in family B. Proband A is a coinheritance of βCD41–42 and αααα282 and showed severe β-thalassemia intermedia phenotype. Proband B is a compound heterozygote of --235/αCSα genotype and was diagnosed with hemoglobin H disease. The clinical phenotypic features of the CNVs carriers were described, together with a complete picture of molecular structure of these rearrangements. Two CNVs are novel rearrangements in α-globin clusters and the αααα282 is the first to identify the exact insert position of a duplication region from the telomere on chromosome 16. In a conclusion, successful identification and characterization of these two novel CNVs not only demonstrates the precision and effectiveness of our strategy in analyzing the structure of unknown CNVs, but also extended the spectrum of thalassemia and provide new examples for studying genomic recombination.
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Acknowledgments
This study was supported by grants from the National Natural Science Foundation of China (81200403, 81360091 and U1401221), Science and Technology Program of Guangzhou (201300000095) and the Special Project on the Integration of Industry, Education and Research of Guangdong Province (2012B091000148).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Communicated by Q. Wang.
L. Hu and X. Shang contributed equally to this work.
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Hu, L., Shang, X., Yi, S. et al. Two novel copy number variations involving the α-globin gene cluster on chromosome 16 cause thalassemia in two Chinese families. Mol Genet Genomics 291, 1443–1450 (2016). https://doi.org/10.1007/s00438-016-1193-0
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DOI: https://doi.org/10.1007/s00438-016-1193-0