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Hemoglobin variants

{{Short description|Forms of hemoglobin caused by variations in genetics}}File:Red Blood Cell abnormalities.pngHemoglobin 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.{{cite web |date=17 April 2002 |title=Hemoglobinopathies |url=http://sickle.bwh.harvard.edu/hemoglobinopathy.html |access-date=2009-02-06 |website=Brigham and Women's Hospital}}

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.

Effects of variants

The physiological effects of these variants can range from minor to severe.{{Cite journal |last=Thom |first=Christopher S. |last2=Dickson |first2=Claire F. |last3=Gell |first3=David A. |last4=Weiss |first4=Mitchell J. |date=2013-03-01 |title=Hemoglobin Variants: Biochemical Properties and Clinical Correlates |url=https://perspectivesinmedicine.cshlp.org/content/3/3/a011858 |journal=Cold Spring Harbor Perspectives in Medicine |language=en |volume=3 |issue=3 |pages=a011858 |doi=10.1101/cshperspect.a011858 |issn=2157-1422 |pmc=3579210 |pmid=23388674}} 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.{{cite web | url = https://globin.cse.psu.edu/html/huisman/variants/ | title = A Syllabus of Human Hemoglobin Variants | author = Huisman THJ | year = 1996 | website = Globin Gene Server | publisher = Pennsylvania State University | access-date = 2008-10-12 | archive-url = https://web.archive.org/web/20081211113441/https://globin.cse.psu.edu/html/huisman/variants/ | archive-date = 2008-12-11 | url-status = live }}{{cite web | url = https://www.labtestsonline.org/understanding/analytes/hemoglobin_var/glance-3.html | title = Hemoglobin Variants | date = 2007-11-10 | website = Lab Tests Online | publisher = American Association for Clinical Chemistry | access-date = 2008-10-12 | archive-url = https://web.archive.org/web/20080920042335/https://www.labtestsonline.org/understanding/analytes/hemoglobin_var/glance-3.html | archive-date = 2008-09-20 | url-status = live }}

Discovery of variants

Hemoglobin variants can be discovered through examination, routine laboratory testing, or evaluation of patients with severe anemia. 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.{{Cite web |date=6 July 2018 |title=Understanding haemoglobinopathies |url=https://www.gov.uk/government/publications/handbook-for-sickle-cell-and-thalassaemia-screening/understanding-haemoglobinopathies |access-date=2024-12-28 |website=Public Health England |language=en}} A research database of hemoglobin variants is maintained by Penn State University.{{Cite web |date=December 2024 |title=A Database of Human Hemoglobin Variants and Thalassemia mutations |url=https://globin.bx.psu.edu/hbvar/menu.html |website=Penn State University}} A few of these variants are listed below.

= Normal hemoglobins =

;Embryonic

;Fetal

;Adult

= Pathologic/abnormal hemoglobins =

== Relatively common ==

Source:{{Cite journal |last=Weatherall |first=D J |last2=Clegg |first2=J B |date=2001-10-24 |title=Inherited haemoglobin disorders: an increasing global health problem |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC2566499/ |journal=Bulletin of the World Health Organization |language=en |volume=79 |issue=8 |archive-url=http://web.archive.org/web/20241220092717/https://pmc.ncbi.nlm.nih.gov/articles/PMC2566499/ |archive-date=2024-12-20}}

== Less frequent ==

  • Hb Bassett
  • Hb Kansas{{cite journal |pmid=5640981 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=5640981 |year=1968 |last1=Bonaventura |first1=J |title=Hemoglobin Kansas, a human hemoglobin with a neutral amino acid substitution and an abnormal oxygen equilibrium |journal=The Journal of Biological Chemistry |volume=243 |issue=5 |pages=980–91 |last2=Riggs |first2=A | doi=10.1016/S0021-9258(18)93612-4 | doi-access=free }}{{cite web |url = https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=33948057 |title = rs33948057 |author= |publisher = National Center for Biotechnology Information |accessdate = 7 February 2014 |website = dbSNP }}
  • Hb D-Punjab
  • Hb O-Arab{{cite journal |doi=10.1002/(SICI)1096-8652(199904)60:4<279::AID-AJH5>3.0.CO;2-2 |pmid=10203101 |title=Hemoglobin S/OARAB: Thirteen new cases and review of the literature |journal=American Journal of Hematology |volume=60 |issue=4 |pages=279–84 |year=1999 |last1=Zimmerman |first1=Sherri A |last2=O'Branski |first2=Erin E |last3=Rosse |first3=Wendell F |last4=Ware |first4=Russell E |s2cid=71251127 |doi-access= }}{{Cite web |url=http://www.mdedge.com/hematologynews/dsm/2216/anemia/anemia-associated-hemoglobin-o-arab |title=Anemia Associated with Hemoglobin O-Arab | Hematology News |access-date=2017-11-13 |archive-date=2017-11-14 |archive-url=https://web.archive.org/web/20171114040255/http://www.mdedge.com/hematologynews/dsm/2216/anemia/anemia-associated-hemoglobin-o-arab |url-status=dead }}{{full citation needed|date=November 2017}}
  • Hb G-Philadelphia
  • Hb Hasharon
  • Hb Kirklareli{{cite journal | vauthors = Motterlini R, Foresti R | title = Biological signaling by carbon monoxide and carbon monoxide-releasing molecules | journal = American Journal of Physiology. Cell Physiology | volume = 312 | issue = 3 | pages = C302–C313 | date = March 2017 | pmid = 28077358 | doi = 10.1152/ajpcell.00360.2016 | doi-access = free }}
  • Hb Lepore
  • Hb M
  • Hb Hope
  • Hb Pisa
  • Hb J
  • Hb N-Baltimore
  • Hemoglobin Chesapeake
  • Hemoglobin Louisville
  • Hemoglobin Vanvitelli {{Cite journal |pmid = 31493379|year = 2019|last1 = Casale|first1 = M.|last2 = Cozzolino|first2 = F.|last3 = Scianguetta|first3 = S.|last4 = Pucci|first4 = P.|last5 = Monaco|first5 = V.|last6 = Sanchez|first6 = G.|last7 = Santoro|first7 = C.|last8 = Rubino|first8 = R.|last9 = Cannata|first9 = M.|last10 = Perrotta|first10 = S.|title = Hb Vanvitelli: A new unstable α-globin chain variant causes undiagnosed chronic haemolytic anaemia when co-inherited with deletion - α3.7.|journal = Clinical Biochemistry|volume = 74|pages = 80–85|doi = 10.1016/j.clinbiochem.2019.09.002| s2cid=202003706 }}

References

{{reflist}}

External links

  • [http://globin.cse.psu.edu/html/huisman/variants/ A syllabus of hemoglobin variants]

{{Hemeproteins}}

Category:Red blood cell disorders

Category:Genetic disorders with no OMIM

Category:Hemoglobins

Category:Respiratory physiology