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Biochemical Genetics

, Volume 54, Issue 6, pp 816–825 | Cite as

Mass Spectrometry-Based Diagnosis of Hemoglobinopathies: A Potential Tool for the Screening of Genetic Disorder

  • Rajdeep Das
  • Gopa Mitra
  • Boby Mathew
  • Vijay Bhat
  • Cecil Ross
  • Debnath Pal
  • Amit Kumar MandalEmail author
Original Article
  • 346 Downloads

Abstract

Hemoglobinopathies are caused by point mutation in globin gene that results in structural variant of hemoglobin. While 7 % of world populations are carrier of hemoglobinopathies, the prevalence of the disease varies between 3 to 17 % across different population groups in India. In a diagnostic laboratory, alkaline gel electrophoresis and cation exchange-based HPLC (CE-HPLC) are most widely used techniques for characterization of hemoglobin variants. In the above methods, the differential surface charge of hemoglobin molecule in variants is exploited for their characterization. Sometime, co-migration of variants in gel electrophoresis and co-elution or elution with unknown retention time in automated CE-HPLC might lead to ambiguity in the analysis of hemoglobinopathies. Under such circumstances, it is necessary to use other analytical methods that provide unambiguous results. Mass spectrometry-based proteomics approach and DNA sequence analysis are examples of such alternative methods. In the present study, liquid chromatography coupled to mass spectrometry has been used for three commonly observed variants in India, e.g., HbE, HbQ India and HbD Punjab that appeared with inappropriate results in the conventional analysis. A customized hemoglobin variant database has been used in the mass spectrometry-based analysis of those three variants. Mass spectrometry-based proteomics approach was used to analyze above variant sample accurately.

Keywords

Hemoglobinopathy Mass spectrometry HbE HbQ India HbD Punjab 

Notes

Acknowledgments

We acknowledge DST (Government of India) for funding mass spectrometry facility at St. John’s Research Institute. We acknowledge DBT (Government of India) (BT/PR13926/MED/31/97/2010) for partially funding the study. Patients are acknowledged for providing sample. Rajdeep Das was supported with Senior Research Fellowship by ICMR (Government of India).

Compliance with Ethical Standards

Conflict of Interest

There is no conflict of interest among authors.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Rajdeep Das
    • 1
  • Gopa Mitra
    • 1
  • Boby Mathew
    • 1
  • Vijay Bhat
    • 2
  • Cecil Ross
    • 3
  • Debnath Pal
    • 4
  • Amit Kumar Mandal
    • 1
    Email author
  1. 1.Clinical Proteomics Unit, Division of Molecular Medicine, St. John’s Research InstituteSt. John’s National Academy of Health SciencesBangaloreIndia
  2. 2.Manipal HospitalBangaloreIndia
  3. 3.Department of Medicine, St. John’s Medical College and HospitalSt. John’s National Academy of Health SciencesBangaloreIndia
  4. 4.Supercomputer Education and Research CentreIndian Institute of ScienceBangaloreIndia

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