Professional Documents
Culture Documents
1. Understand the glyco-biology of the ABO, Hh and Lewis blood 1. Biochemistry of ABO blood group system
group systems 2. Molecular genetics of the ABO blood group system
2. Understand the molecular basis of the ABO system as an 3. Unusual variants of ABO blood groups
example of the role of SNPs in determining phenotypic 4. Immunology of the ABO blood group system
expression of an oligosaccharide blood group system
5. Biochemistry of the Hh and Lewis blood group system
H/h FUT1 19q13.3 2 40(FUT1) • Phenotypic expression is genetically determined - classical Mendelian
laws
FUT2 38(FUT2)
Lewis FUT3 19p13 1 17
Ii GCNT2 6p24 1 13
1
ABO System
ABO antigens
Antigens Phenotypes Genotypes Antibodies
• Carbohydrate structures present on glycoprotein structures
– band 3(AE1)
– glucose transporter
A A A/A or A/O Anti-B
– RhAg
– aquaphorin
B B B/B or B/O Anti-A
– glycosphingolipid
• A: N-acetyl-D-galactosamine transferase
• B: D-galactose transferase
2
ABO blood group system ABO Gene
• A single gene gives rise to all 3 common phenotypes
• Occurs in several allelic forms – all with 7 exons encoding
Minimal determinant
Antigen Structure
structure glycosyltransferases of 354 aa
• 90% of total coding region in ex6 and 7 and encodes entire catalytic
domain
H
• A and B transferase results from different amino acid sequences
conferring different sugar specificities
B
*: residue could be glucose in case of glycolipids; yellow shade: minimal determinant or core structure; blue arrow: residue added by blood group gene product;
examples of type 1 and 2 core structures are illustrated above but they can vary widely, as they can be assembled on at least six possible types of carbohydrate
chains; they can reside on a variety of protein or lipid glycan structures containing branches, repeats, etc.
3
ABO Gene ABO Gene
• ABO HDN
– IgG anti A,B in group O mothers
– Not common
• A/B not fully expressed on foetal cells
• A/B present on many tissues
4
ABO subgroups ABO subgroups
Phenotype Anti-A Anti-A1 Dolichos
biflorus • A1
A1 +++ ++ +++ • A2
• A3, Aend, Ax, Am, Ay, Ael
A2 ++ - -
• B
• B3, Bx, Bm, Bel
A1B +++ ++ ++
• Show weakened expression of A/B antigen with increased H
antigen due to reduced transferase activity
A2B + - -
ABO subgroups
anti-A Anti-A,B Ab in serum
A3 mf mf Sometimes anti-A1
O AB
anti-B Anti-A,B
B3 mf mf none
5
Cis AB / B(A) phenotypes
AB O
B O
O AB
SNPs leads translation of A
enzymes with both A and B
transferase activity
6
Hh blood group system (FUT1 and FUT2) ABH secretion
Minimal • ABH on red cells – glycoprotein and glycolipid
Phenoty
Structure determinant
pe
structure • ABH in secretions – soluble glycoprotein
– 80% secretors of H (A and/ or B)
– 20% non secretors
H
7
Phenotype Structure Minimal determinant structure
Lea
Leb
Lex
Ley
*: residue could be glucose in case of glycolipids; yellow shade: minimal determinant or core
structure; blue arrow: residue added by blood group gene product;examples of type 1 and 2 core
structures are illustrated above but they can vary widely, as they can be assembled on at least six
possible types of carbohydrate chains; also they can reside on a variety of protein or lipid glycan
structures containing branches, repeats, etc.