title: Mass Spectrometry-Based Diagnosis of Hemoglobinopathies: A Potential Tool for the Screening of Genetic Disorder.
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.
authors.affiliation: Clinical Proteomics Unit, Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, 100ft Road, Koramangala, Bangalore, 560034, India.
authors.forename: Rajdeep
authors.initials: R
authors.lastname: Das
authors.affiliation: Clinical Proteomics Unit, Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, 100ft Road, Koramangala, Bangalore, 560034, India.
authors.forename: Gopa
authors.initials: G
authors.lastname: Mitra
authors.affiliation: Clinical Proteomics Unit, Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, 100ft Road, Koramangala, Bangalore, 560034, India.
authors.forename: Boby
authors.initials: B
authors.lastname: Mathew
authors.affiliation: Manipal Hospital, Old Airport Road, Bangalore, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Bhat
authors.affiliation: Department of Medicine, St. John's Medical College and Hospital, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: Cecil
authors.initials: C
authors.lastname: Ross
authors.affiliation: Supercomputer Education and Research Centre, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Debnath
authors.initials: D
authors.lastname: Pal
authors.affiliation: Clinical Proteomics Unit, Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, 100ft Road, Koramangala, Bangalore, 560034, India. amit@sjri.res.in.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Mandal
mesh_terms: D006453:Hemoglobinopathies / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007194:India; D008403:Mass Screening; D013058:Mass Spectrometry / Q000379:methods*; D017354:Point Mutation; D040901:Proteomics / Q000379:methods
chemical_list: D006454:Hemoglobins
keywords: HbD Punjab; HbE; HbQ India; Hemoglobinopathy; Mass spectrometry