Biology:Hemoglobin variants
Hemoglobin is a protein that transports oxygen in the blood. Genetic differences lead to structural variants in the hemoglobin protein structure. Some variants can cause disease while others have little to no effect.
The normal hemoglobin types are Hemoglobin A (HbA), which makes up 95–98% of total hemoglobin in adults, Hemoglobin A2 (HbA2), which constitutes 2–3% of total hemoglobin in adults, and Hemoglobin F (HbF), which is the predominant hemoglobin in the fetus during pregnancy, and may persist in small amounts in adults.[1]
Hemoglobin variants occur when there are mutations in specific genes that code for the protein chains, known as globins, which make up the hemoglobin molecule. This leads to amino acid substitutions in the hemoglobin molecule that could affect the structure, properties, and/or the stability of the hemoglobin molecule. There are over 1,000 naturally occurring structural variants of hemoglobin in humans.[2]
Effects of variants
The physiological effects of these variants can range from minor to severe.[3] Mutations can caused impaired production of hemoglobin (thalassemia) or produce structurally altered hemoglobins. Some hemoglobin variants, such as HbS which causes sickle-cell anemia, are responsible for severe diseases and are considered hemoglobinopathies. Other variants cause no detectable pathology, and are thus considered non-pathological variants.[4][5]
Discovery of variants
Hemoglobin variants can be discovered through examination, routine laboratory testing, or evaluation of patients with severe anemia.[3] In some countries, all newborns are tested for hemoglobinopathies, thalassemias, and HbS. Isoelectric focusing or high-performance liquid chromatography are used to identify structural abnormalities in hemoglobin.
Examples of variants
There are in excess of 1,000 known hemoglobin variants.[2] A research database of hemoglobin variants is maintained by Penn State University.[6] A few of these variants are listed below.
Normal hemoglobins
- Embryonic
- HbE Gower 1 (ζ2ε2)
- HbE Gower 2 (α2ε2)
- HbE Portland I (ζ2γ2)
- HbE Portland II (ζ2β2)
- HbE Portland III (ζ2δ2)
- Fetal
- Adult
Pathologic/abnormal hemoglobins
Relatively common
Source:[7]
Less frequent
- Hb Bassett
- Hb Kansas[8][9]
- Hb D-Punjab
- Hb O-Arab[10][11]
- Hb G-Philadelphia
- Hb Hasharon
- Hb Kirklareli[12]
- Hb Lepore
- Hb M
- Hb Hope
- Hb Pisa
- Hb J
- Hb N-Baltimore
- Hemoglobin Chesapeake
- Hemoglobin Louisville
- Hemoglobin Vanvitelli [13]
References
- ↑ "Hemoglobinopathies". 17 April 2002. http://sickle.bwh.harvard.edu/hemoglobinopathy.html.
- ↑ 2.0 2.1 "Understanding haemoglobinopathies" (in en). 6 July 2018. https://www.gov.uk/government/publications/handbook-for-sickle-cell-and-thalassaemia-screening/understanding-haemoglobinopathies.
- ↑ 3.0 3.1 Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J. (2013-03-01). "Hemoglobin Variants: Biochemical Properties and Clinical Correlates" (in en). Cold Spring Harbor Perspectives in Medicine 3 (3). doi:10.1101/cshperspect.a011858. ISSN 2157-1422. PMID 23388674. PMC 3579210. https://perspectivesinmedicine.cshlp.org/content/3/3/a011858.
- ↑ Huisman THJ (1996). "A Syllabus of Human Hemoglobin Variants". Pennsylvania State University. https://globin.cse.psu.edu/html/huisman/variants/.
- ↑ "Hemoglobin Variants". American Association for Clinical Chemistry. 2007-11-10. https://www.labtestsonline.org/understanding/analytes/hemoglobin_var/glance-3.html.
- ↑ "A Database of Human Hemoglobin Variants and Thalassemia mutations". December 2024. https://globin.bx.psu.edu/hbvar/menu.html.
- ↑ Weatherall, D J; Clegg, J B (2001-10-24). "Inherited haemoglobin disorders: an increasing global health problem" (in en). Bulletin of the World Health Organization 79 (8): 704–712. PMID 11545326.
- ↑ Bonaventura, J; Riggs, A (1968). "Hemoglobin Kansas, a human hemoglobin with a neutral amino acid substitution and an abnormal oxygen equilibrium". The Journal of Biological Chemistry 243 (5): 980–91. doi:10.1016/S0021-9258(18)93612-4. PMID 5640981.
- ↑ "rs33948057". National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/snp/rs33948057.
- ↑ Zimmerman, Sherri A; O'Branski, Erin E; Rosse, Wendell F; Ware, Russell E (1999). "Hemoglobin S/OARAB: Thirteen new cases and review of the literature". American Journal of Hematology 60 (4): 279–84. doi:10.1002/(SICI)1096-8652(199904)60:4<279::AID-AJH5>3.0.CO;2-2. PMID 10203101.
- ↑ "Anemia Associated with Hemoglobin O-Arab | Hematology News". http://www.mdedge.com/hematologynews/dsm/2216/anemia/anemia-associated-hemoglobin-o-arab.
- ↑ "Biological signaling by carbon monoxide and carbon monoxide-releasing molecules". American Journal of Physiology. Cell Physiology 312 (3): C302–C313. March 2017. doi:10.1152/ajpcell.00360.2016. PMID 28077358.
- ↑ Casale, M.; Cozzolino, F.; Scianguetta, S.; Pucci, P.; Monaco, V.; Sanchez, G.; Santoro, C.; Rubino, R. et al. (2019). "Hb Vanvitelli: A new unstable α-globin chain variant causes undiagnosed chronic haemolytic anaemia when co-inherited with deletion - α3.7.". Clinical Biochemistry 74: 80–85. doi:10.1016/j.clinbiochem.2019.09.002. PMID 31493379.
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