# Presentation: 469003

## Slide 1

## Phenotypes in the World of Blood Group Antigens

- Olga O. Blumenfeld & Santosh K. Patnaik
- Departments of Biochemistry (OOB) & Cell Biology (SKP)
- Albert Einstein College of Medicine, New York
- www.bioc.aecom.yu.edu/bgmut/index.htm

**Phenotypes in the World of Blood Group Antigens**

- documented in the
- Database of DNA Variation in Genes Encoding Blood Group Antigens

## Blood Group Antigens

**Blood Group Antigens**

**proteins, glycans or glycolipids**
**variety of functions **
**expressed at the surface of red cells **
**polymorphic in the population**

**Y**

**Y**

**Y**

## Blood Group System

**A set of variant antigens **
**resulting from alleles of a single locus, **
**each defining a common serological phenotype.**

## Summary: 29 blood group systems, 40 genes, 707 alleles

**Summary: 29 blood group systems, 40 genes, 707 alleles**
- Also detailed: non-human counterparts for H/h, MN, Rh

**System****	****	****Locus****	****Funcion****	****Alleles**
- ABO		ABO        enzyme	115
- Chido- Rodgers 	C4A,        factor	7+
- 		C4B
- Colton		AQP1	channel	7
- Cromer		DAF       	receptor	13
- Diego		SLC4A1	exchanger  78
- Dombrock	DO	unknown	9
- Duffy		FY	receptor	7
- Gerbich (Ge)	GYPC	structure	9
- GIL		AQP3	channel	2
- H/h		FUT1,	enzymes	57
- 		FUT2
- I		GCN2	enzyme	8
- 		(IGnT)
- Indian (IN)	CD44	adhesion	2
- JMH                         SEMA7A 	signaling   0
- Kell (with Kx)	KEL,	enzyme	67
- 		XK
- Kidd		SLC14A1	transport	8
- Knops		CR1	receptor	24+

**System****	****	****Locus****	****Function****	****Alleles**
- Landsteiner-	ICAM4	adhesion	3
- Weiner		(LW)
- Lewis		FUT3,	enzymes	36
- 		FUT6,
- 		FUT7
- Lutheran		LU	adhesion	16
- MNS		GYPA,	unknown	43
- 		GYPB,
- 		GYPE
- OK		BSG	adhesion	5
- P-related		A4GALT,	enzymes	27
- 		B3GALT3
- RAPH-MER2           CD151                     3
- Rh		RHCE,	transport	126
- 		RHD, RHCG
- 		RHAG, RHBG
- Scianna		ERMAP	adhesion	4
- Xg		XG,	adhesion	0
- 		CD99 (MIC2)
- YT		ACHE	enzyme	4

## Summary of DNA alterations

**Summary of DNA alterations**

## Phenotype vs genotype

**Phenotype vs genotype**

**A number of alleles give rise to the same blood group phenotype **
- 		Silencing mutations
- 		nonsense, deletions, insertions, splicing, regulatory regions 		rearrangements, gross deletions (null phenotype in nearly all 		systems) Kell, Rh, Diego, ABO, others
- 		Gene rearrangements
- 		GYPA, Rh ex. Sta - 7 genotypes; RH neg - 17 genotypes
**A single allele gives rise to a unique blood group phenotype**
- 		Missense mutations
- 		Kell, Diego, RH, Duffy, ABO and others
- 		Gene rearrangements
- 		GYPA, Miltenberger series; Rh, weak D(Du), DAU & others

## Same Blood Group Phenotype, Multiple Genotypes

**Same Blood Group Phenotype, Multiple Genotypes**
**	****Kell null **
- 	1 phenotype
- 	11 genotypes
- 		7 nonsense
- 		3 splicing
- 		1 deletion

## Same Blood Group Phenotype, Multiple Genotypes 

**O gene-null**
- Same deletion in many alleles (261delG  in 38 of 43 O null alleles)

**19 variants**

*Popov et al. JBC.1997,272,18325*

**Band 3 Glycoprotein**

- del

- del

- 19 blood group phenotypes
- 54 other phenotypes (spherocytosis, etc.)

- anion exchanger

- anion ex.

- Binds torbc cytoskeleton

** **

## Diego

**Diego**
- 19 of 19 alleles

**Multiple Blood**
**Group **
**Phenotypes,**
**Multiple **
**Genotypes**

## Sites and distribution of alterations vs location of epitopes:

**Sites and distribution of alterations vs location of epitopes:**
**Kell (KEL)**

- Each polymorphic site can be assigned to a different Kell antigen
**	**24 missense mutations at positions in extracellular domains
- 	7 nonsense; 3 splicing ;1 del
- Sets of polymorphic residues
- 	Each expressed in different individuals at different frequencies.
- Common phenotype
- 	K-1, 2*; -3, -21, 4*; -6, 7*; 11*, -17; 14*, -24; 10, 5, 12, 13, 16, 18, 20, 		22, -23
- Known antithetical partners
- 	K2/K1; K4/K3/K21; K7/K6; K11/K17

## The Kell Glycoprotein

**The Kell Glycoprotein**

## Single Blood Group Phenotype, Single Genotype

**Single Blood Group Phenotype, Single Genotype**

**Kell       **22 of 24 alleles

**note**

**note**

**note**

## Same Blood Group Phenotype, Multiple Genotypes:

**Same Blood Group Phenotype, Multiple Genotypes:**
**Examples in the KEL blood group system**

## Single Blood Group Phenotype, Single Genotype

**Single Blood Group Phenotype, Single Genotype**

**Rh**

## Examples of genotypes vs phenotypes due to DNA rearrangements in GYPA family

**Examples of genotypes vs phenotypes due to DNA rearrangements in GYPA family**

**Gene       ****	****	****	****Sequence             ****	****	****Phenotype**
- GYPA 			ex3 EET ex4 GER**V**QL	wild type
- GYPB 			ex2 QTN ex4 GETGQL	wild type s
- GYPB 			ex2 QTN ex4 GEMGQL 	wild type S
- hyb.A-Bs  Recombination	ex3 EET ex4 GETGQL 	HIL
- hyb.A-BS Recombination  	ex3 EET ex4 GEMGQL 	SJLhyb.BAB  Gene conversion  	ex3 EET ex4 GETGQL   	HIL
- hyb.B-A	 Recombination  	ex2 QTN ex4 GER**V**QL 	Sta
- Johe,Vengelen-Tyler,Leger,Blumenfeld Blood 1991,78:2456

## Examples were provided showing that, on the red cell surface, single amino acid or carbohydrate alterations, resulting from missense  mutations or other DNA changes are recognized, as one might expect, as foreign by the immune system and, remarkably, can be detected by serological approaches .

## Acknowledgements

**Acknowledgements**

- Contributors to the database
- Departments of Biochemistry and Cell Biology,
- Albert Einstein College of Medicine
**Thank you!**