A phased SNP-based classification of sickle cell anemia HBB haplotypes

A phased SNP-based classification of sickle cell anemia HBB haplotypes

Author Shaikho, Elmutaz M. Google Scholar
Farrell, John J. Google Scholar
Alsultan, Abdulrahman Google Scholar
Qutub, Hatem Google Scholar
Al-Ali, Amein K. Google Scholar
Figueiredo, Maria Stella Autor UNIFESP Google Scholar
Chui, David H. K. Google Scholar
Farrer, Lindsay A. Google Scholar
Murphy, George J. Google Scholar
Mostoslavsky, Gustavo Google Scholar
Sebastiani, Paola Google Scholar
Steinberg, Martin H. Google Scholar
Abstract Background: Sickle cell anemia causes severe complications and premature death. Five common beta-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful. The first method of haplotype classification used restriction fragment length polymorphisms (RFLPs) to detect single nucleotide polymorphisms (SNPs) in the beta-globin gene cluster. This is labor intensive, and error prone. Methods: We used genome-wide SNP data imputed to the 1000 Genomes reference panel to obtain phased data distinguishing parental alleles. Results: We successfully haplotyped 813 sickle cell anemia patients previously classified by RFLPs with a concordance >98%. Four SNPs (rs3834466, rs28440105, rs10128556, and rs968857) marking four different restriction enzyme sites unequivocally defined most haplotypes. We were able to assign a haplotype to 86% of samples that were either partially or misclassified using RFLPs. Conclusion: Phased data using only four SNPs allowed unequivocal assignment of a haplotype that was not always possible using a larger number of RFLPs. Given the availability of genome-wide SNP data, our method is rapid and does not require high computational resources.
Keywords SNPs
Sickle cell
Haplotype classification
Language English
Sponsor NIH Bethesda, MD
Grant number NIH: R01 HL 068970
NIH: RC2 HL 101212
NIH: R01 87681
NIH: T32 HL007501
Date 2017
Published in Bmc Genomics. London, v. 18, p. -, 2017.
ISSN 1471-2164 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Origin http://dx.doi.org/10.1186/s12864-017-4013-y
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000408035900004
URI http://repositorio.unifesp.br/handle/11600/51394

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