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Molecular Basis of ABO Blood Group Markers

Molecular Basis of ABO Blood Group Markers. September 17, 2019 Arnold Martin Ruste Kamel Lezzaik Christopher Hu Michael Lee. PHM142 Fall 2019 Instructor : Chesa Dojo Soeandy Coordinator: Jeffrey Henderson. Discovery of the ABO Blood Groups.

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Molecular Basis of ABO Blood Group Markers

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  1. Molecular Basis of ABO Blood Group Markers September 17, 2019 Arnold Martin Ruste Kamel Lezzaik Christopher Hu Michael Lee PHM142 Fall 2019 Instructor: Chesa Dojo Soeandy • Coordinator: Jeffrey Henderson

  2. Discovery of the ABO Blood Groups • Karl Landsteiner classified three different blood groups in 1901 • He noticed blood samples from his colleagues only agglutinated with the blood of particular colleagues • He received a Nobel Prize for his description of ABO blood groups in 1930 Wiener klinische Wochenschrift, 1901, 14: 1132 https://www.nobelprize.org/images/landsteiner-12970-content-portrait-mobile-tiny.jpg

  3. What are the ABO Blood Groups? • System used to specify the particular type of antigen found on the surface of an individual’s erythrocytes • An individual typically belongs to one of 4 blood groups: A,B,AB, or O https://i.pinimg.com/originals/9e/34/62/9e34629b6687c29b3d6ba7aa6bc165d5.jpg

  4. Subgroups of Blood Group A (A1 and A2) • Different A blood groups react differently to a specific antibody (lectin) • Called Anti-A1 • A1 reacts with anti-A1 • 80% of blood group A • A2 does not react with anti-A1 • 20% of blood group A

  5. Red Blood Cell Exterior Surface • The external surface of RBCs are packed with glycoproteins and glycolipids • This is where ABO markers can be found https://www.mdpi.com/2077-0375/7/4/56

  6. Additional Antigen: The Rh Factor • Short for “Rhesus” Factor • 49 different antigens documented • Most common: Rh D antigen • Presence of Rh D is Rh positive • Absence of Rh D is Rh negative https://genetics.thetech.org/ask-a-geneticist/rhesus-factor-evolution

  7. Determining Different Blood Groups • Blood groups are determined through the presence or absence of antigens A, B or Rh • Blood samples are run through a dextran serum containing antibodies to determine the presence of antigens • Agglutination (clumping) of the blood sample confirms the type of antigen https://www.apsubiology.org/anatomy/2020/2020_Exam_Reviews/Exam_1/CH17_Blood_Typing.htm

  8. Mendelian Pattern of Inheritance • Blood groups are determined through the Mendelian pattern of inheritance • Each parent passes on a single allele of the ABO gene to their offspring • The O allele is recessive to both the A allele and B allele • Receiving an A allele and a B allele results in co-dominance and expression of both the A and B alleles as blood group AB https://genetics.emory.edu/documents/resources/factsheet43.pdf

  9. Biosynthesis: Precursor Substance • ABO blood group antigens originate from the Precursor Substance (PS) • Oligosaccharide chains consisting of N-Acetyl-Galactosamine, N-Acetyl-Glucosamine and Galactose • There are two main types of precursors • Type 1 Chains have a Beta (1-3) Linkage • Type 2 Chains have Beta (1-4) Linkage http://medlabsc.blogspot.com/2008/10/chemical-characteristics-of-blood-group.html

  10. Biosynthesis: The O Antigen • The H allele codes for fucosyl transferase • Fucosyl transferase catalyzes the addition of fucose to the precursor • This reaction forms the O antigen Precursor O antigen Chase and Morgan, 1991; Painter et al, 1963; Watkins, 1966

  11. Biosynthesis: The A Antigen • The A allele of the ABO gene codes for N-acetylgalactosaminetransferase • This enzyme catalyzes the addition of N-acetylgalactosamine to the O antigen • This reaction forms the A antigen O antigen A antigen Chase and Morgan, 1991; Painter et al, 1963; Watkins, 1966

  12. Biosynthesis: The B Antigen • The B allele of the ABO gene codes for galactosyltransferase • This enzyme catalyzes the addition of D-galactose to the O antigen • This reaction forms the B antigen O antigen B Antigen Chase and Morgan, 1991; Painter et al, 1963; Watkins, 1966

  13. Summary of Antigen Structures • O antigens contain no additional sugar linked to the peripheral galactose due to the absence of the A and B alleles • The specific transferases encoded by the A and B alleles can only add their respective sugar after the fucose has been added • Type AB erythrocytes contain a mixture of both A and B antigens on their cell surface https://qph.fs.quoracdn.net/main-qimg-4105c9f94c3ade55bc00c19dfc7d3555.webp

  14. Antigenic Specificity is based on Sugar Composition • The sugar composition of RBC surface molecules determine their antigenic specificity https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-3148.2001.00321.x

  15. The Bombay or hh Blood Group • The H gene has 2 alleles: H and h • A small number of individuals are homozygous recessive for the h allele of gene and are unable to synthesize the O antigen • Since both the A andB antigens are synthesized from the O antigen, Bombay individuals don’t belong to any of the traditional ABO blood groups https://www.researchgate.net/figure/Biochemical-basis-of-ABO-groups_fig1_233799814

  16. ABO Genes and Gene Products • There are only a few critical single nucleotide polymorphisms (SNPs) associated between Antigen A and B • Antigen O does not code for functional transferases due to critical deletions causing a frameshift https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2004.05065.x?sid=nlm%3Apubmed

  17. Blood Groups and Blood Transfusions • Successful transfusions require compatible blood types between donor and recipient • O(-) = Universal Donor • AB(+) = Universal Recipient • Use of the wrong blood type results in hemolytic reaction https://www.sciencebuddies.org/blog/students-explore-blood-type-chemistry

  18. The Hemolytic Reaction DONOR = A | RECIPIENT = A • Hemolysis is when red blood cells are rejected and destroyed by the body • Occurs when non-compatible blood mix (i.e. Transfusion) • Antibodies within the hosts blood cells target foreign blood • Acute Haemolytic Transfusion Reactions (AHTR) • Delayed Hemolytic Transfusion Reactions (DHTR) DONOR = B | RECIPIENT = A http://www.biosciencenotes.com/wp-content/uploads/2018/05/agglutination1.png

  19. Summary • The ABO Blood Groups is a system used to signify which antigens are present on the cell surface of an individual’s erythrocytes • An individual’s blood type is determined by the alleles of the ABO gene they inherit from their parents • The different antigens are not direct products of the genes, they are synthesized from the precursor substance • Different alleles of the ABO gene encode specific transferases which catalyze the addition of a sugar onto the O antigen • Mixing blood from different groups induces agglutination and hemolysis which causes complications during blood transfusions

  20. References • Landsteiner K. On Agglutination of Normal Human Blood. Transfusion. 1961;1(1):5–8. • Giriyan SS, Agrawal A, Bajpai R, Nirala NK. A1 and A2 sub-types of blood group ‘A’: A reflection of their prevalence in north Karnataka Region. J Clin Diagnostic Res. 2017 May 1;11(5):EC40–2. • Hayden O, Mann KJ, Krassnig S, Dickert FL. Biomimetic ABO blood-group typing. Angew Chemie - Int Ed. 2006 Apr 10;45(16):2626–9. • Dean L. Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2005. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2261/ • Dungern E, Hirschfeld L. Über Vererbung gruppenspezifischer Strukturen des Blutes. Z Indukt Abstamm Vererbungsl. 1911 Dec;5(1):196–7. • Aoki T. A comprehensive review of our current understanding of red blood cell (RBC) glycoproteins. Membranes (Basel). 2017 Dec 1;7(4). • Rege VP, Painter TJ, Watkins WM, Morgan WTJ. Three new trisaccharides obtained from human blood-group A, B, H and lea substances: Possible sugar sequences in the carbohydrate chains. Nature. 1963;200(4906):532–4. • Watkins WM. Blood-group substances. Science (80- ). 1966;152(3719):172–81. • Watkins WM. The ABO blood group system: Historical background. Vol. 11, Transfusion Medicine. 2001. p. 243–65. • Starry JR, Olsson ML. Genetic basis of blood group diversity. Vol. 126, British Journal of Haematology. 2004. p. 759–71. • Yamamoto FI, Clausen H, White T, Marken J, Hakomori SI. Molecular genetic basis of the histo-blood group ABO system. Nature. 1990;345(6272):229–33. • Yahalom V, Zelig O. Handling a transfusion haemolytic reaction. ISBT Sci Ser. 2015 Apr;10(S1):12–9.

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