A Phased SNP-based Classification of Sickle Cell Anemia HBB Haplotypes

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2017 Aug 13

PMID 28800727

Citations 20

Authors

Elmutaz M Shaikho

John J Farrell

Abdulrahman Alsultan

Hatem Qutub

Amein K Al-Ali

Maria Stella Figueiredo

David H K Chui

Lindsay A Farrer

George J Murphy

Gustavo Mostoslavsky

Paola Sebastiani

Martin H Steinberg

Affiliations

Soon will be listed here.

Abstract

Background: Sickle cell anemia causes severe complications and premature death. Five common β-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 β-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.

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