Blood Cell Biochemistry Volume6 Molecular Basis of Human Blood Group Antigens

Blood Cell Biochemistry Series Editor J. R. Harris, Institute of Zoology, University of Mainz, Mainz, Germany

Volume 1

Volume 2

Volume 3

Volume 4

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Volume 6

Erythroid Cells Edited by J. R. Harris

Megakaryocytes, Platelets, Macrophages, and Eoslnophils Edited by J. R. Harris

Lymphocytes and Granulocytes Edited by J. R. Harris

Basophil and Mast Cell Degranulation and Recovery Ann M. Dvorak

Macrophages and Related Cells Edited by Michael A. Horton

Molecular Basis of Human Blood Group Antigens Edited by Jean-Pierre Cartron and Philippe Rouger

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Blood Cell Biochemistry Volume6 Molecular Basis of Human Blood Group Antigens

Edited by Jean-Pierre Cartron and Philippe Rouger National Institute of Blood Transfusion Paris, France

Springer Science+Business Media, LLC

Library of Congress Cataloging-in-Publication Data

On file

This limited facsimile edition has been issued for the purpose of keeping this title available to the scientific community.

ISBN 978-0-306-44853-9 ISBN 978-1-4757-9537-0 (eBook) DOI 10.1007/978-1-4757-9537-0

Originally published by Plenum Press, New York in 1995

1098765432

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Contributors

Peter Agre Departments of Medicine and Cell Biology j Anatomy, Johns Hop-kins University School of Medicine, Baltimore, Maryland 21205, USA

Pascal Bailly Unite de Recherche U76 de l'Institut National de la Sante et de la Recherche Medicale (INSERM), Institut National de Transfusion Sanguine, 75739 Paris Cedex 15, France

Olga 0. Blumenfeld Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA

Jean-Fran~ois Bouhours Unite de Recherche U76 de l'lnstitut National de la Sante et de la Recherche Medicale (INSERM), Institut de Transplantation et de Recherche en Transplantation, Centre Hospitalier Regional, 44035 Nantes Cedex, France.

Jean-Pierre Cartron Unite de Recherche U76 de l'Institut National de la Sante et de la Recherche Medicale (INSERM), Institut National de la Transfusion Sanguine, 75015 Paris, France

Asok Chaudhuri Laboratory of Cell Biology, Lindsley F. Kimball Research Institute, The New York Blood Center, New York, New York 10021, USA

Yves Colin Unite de Recherche U76 de l'Institut National de la Sante et de la Recherche Medicale (INSERM), Institut National de la Transfusion Sanguine, 75015 Paris, France

Geoff Daniels Medical Research Council Blood Group Unit, London NW1 2HE, United Kingdom

Jean Delaunay Unite de Recherche Associee-1171 du Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lyon, 69365 Lyon Cedex 07, France

Sen-itiroh Hakomori The Biomembrane Institute and Department of Patho-biology, University of Washington, Seattle, Washington 98195, USA

Cheng-Han Huang Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021, USA

v

vi Contributors

Soohee Lee Department of Biochemistry. Lindsley F. Kimball Research Insti-tute, The New York Blood Center. New York. New York 10021. USA

Pierre-Yves Le Pennec Centre National de Reference pour les Groupes San-guins, Institut National de Transfusion Sanguine. 75012 Paris. France

Caroline LeVan Kim Unite de Recherche U76 de l'Institut National de Ia Sante et de Ia Recherche Medicale (INSERM). Institut National de Ia Transfusion Sanguine, 75015 Paris, France

Marion Lewis Rh Laboratory, Department of Pediatrics and Child Health, and Department of Human Genetics, Faculty of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada R3E OL8

John B. Lowe Howard Hughes Medical Institute, Department of Pathology. University of Michigan Medical School, Ann Arbor, Michigan 48109-0650, USA

Joann M. Moulds Division of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas 77225, USA

Rafael Oriol Unite de Recherche U 178 de l'Institut National de Ia Sante et de Ia Recherche Medicale (INSERM), 94807 Villejuif Cedex, France

A. Oscar Pogo Laboratory of Cell Biology, Lindsley F. Kimball Research In-stitute, The New York Blood Center, New York, New York 10021, USA

Neeraja Rao Department of Medicine, Division of Hematology /Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA

Colvin M. Redman Department of Biochemistry, Lindsley F. Kimball Research Institute, The New York Blood Center, New York, New York 10021, USA

Dieter Roelcke Institute for Immunology, University of Heidelberg, 6900 Hei-delberg, Germany

Philippe Rouger 15, France

Institut National de Ia Transfusion Sanguine, 75739 Paris Cedex

Marilyn J, Telen Department of Medicine, Division of Hematology /Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA

Patricia Tippett Medical Research Council Blood Group Unit, London NW1 2HE, United Kingdom

Winifred M. Watkins Department of Haematology, Royal Postgraduate Med-ical School, Hammersmith Hospital, London W12 ONN, United Kingdom

Teresa Zelinski Rh Laboratory, Department of Pediatrics and Child Health, and Department of Human Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E OL8

Preface

The science of blood groups was born at the beginning of this century, when the field of immunology married that of genetics. Most of the subsequent progress in immunogenetics was achieved by British investigators. The six consecutive editions of the unequaled Blood Groups in Man have long been considered as the bible of blood groupers. It is quite unfortunate that this book has not been revisited since 1975.

Although one cannot do without immunogenetics, which remains useful for the identification of new blood groups and genetic studies, the focus of interest has moved somewhat today. After several decades, the molecular basis of blood groups can be investigated by biochemists. From 1950 to 1980, the ABO, Hh, and Lewis blood groups served as models and their chemical basis came to be established. The red cell membrane glycophorins carrying the MN and Ss antigens and the glycolipids with P blood group specificities were also identified and characterized. The chemical basis of the other groups, however, remained largely unknown.

As had happened in many fields of biology, the interest with respect to molec­ular genetics, namely for genes, grew. Glycophorins A/B, which carry the MN/Ss blood groups, and glycophorins C/D, which carry the Gerbich blood groups, were first cloned in 1986. This was followed between 1990 and 1992 by the cloning of the ABO, Hh, Lewis, and RH blood group systems, and later by the cloning of Kell, Duffy, L W, and Lutheran. In addition, a number of blood groups were localized on known molecules, some with important biological functions. For instance, Cromer blood groups, McCoy /Knops and Indian antigens were found to reside on the decay­accelerating factor (OAF, CD55), the complement C3b/C4b receptor (CR1), and the adhesive CD44 molecule acting as a homing receptor, respectively. These find­ings, and others, like the potential role of Kidd antigens in urea transport and the recognition of Duffy as a receptor for P. vivax and some interleukins, clearly indicate that blood groups are markers of a large series of molecules with diverse unrelated functions. A future challenge will be to gain more insight into the relationship be­tween these blood groups and biological functions. This will be the next approach for the field of cell biology.

vii

viii Preface

At present, most of the major blood groups have been cloned or have found a molecular basis, and the large amount of knowledge accumulated has brought the need for a comprehensive review of these findings. This book represents the first thorough compilation of the most recent findings. All contributors are strongly in­volved experts and leading authorities in their field. The reports of their respective experiences add a still more attractive interest to this new '""state of the art," as they drive us into the very heart of their personal research.

At present, the rapid development in the molecular biology of blood groups is impressively explosive. Scientists, especially those involved in blood group reference laboratories, urge taking into account this prodigious new basis of knowledge, which will probably lead in the near future to the revision of methods for the detection, identification, and characterization of antigens. In addition, invaluable information on gene diversity and polymorphism, useful for genetic analysis, will be provided. Moreover, early and safe antenatal diagnosis of some genes (like Rh or Kell) in a fetus at risk of hemolytic disease will be available for a better management and follow-up of pregnancy, where alloimmunization is present or may occur.

It is increasingly clear that blood groups and other markers of the red cell mem­brane could be of greatest interest to pathology as they are already to transfusion medicine. Malaria is the red cell disease of the most worldwide importance. Duffy antigens and glycophorins are involved in the invasion of red cells. In addition, red cell membrane properties are affected in several cases such as the Leach phenotype, Rhnun or McLeod conditions, and clarification of these defects may provide new insight into the physiology of the red cell membrane.

I am very enthusiastic about this book and appreciate its new approaches to the ever-fascinating blood groups. You must read it!

Emeritus Director lnstitut National de La Transfusion Sanguine Paris

Charles Salmon

Contents

Chapter 1 Red Cell Membrane: Structure and Function Jean Delaunay

1 . General Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. 1 . The Red Cell Membrane as a Whole . . . . . . . . . . . . . . . . . . . . . . 1 1.2. The Parts of the Red Cell Membrane . . . . . . . . . . . . . . . . . . . . . . 2

2. The Lipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.1. Lipid Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.2. Lipid Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.3. Lipid Movements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3. Transporters and Pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3. 1. Anion Exchanger . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3.2. Stomatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.3. CHIP28 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.4. Glucose Transporter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.5. Ca2+ -ATPase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

4. GPI-Linked Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 5. Glycophorins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 6. Skeletal Main Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

6.1. Spectrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 6.2. Actin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 6.3. Protein4.1 ... .. . . . .... .. . .. .. . . .. ... . . . ... ....... .. . . . 15

7. Skeletal Accessory Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 7. 1 . Adducin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 7 .2. Dematin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 7.3. Myosin, Tropomyosin, and Tropomodulin . . . . . . . . . . . . . . . . . . 17

8. Proteins Involved in Linking the Skeleton to Transbilayer Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 8. 1. Ankyrin (Protein 2. 1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

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8.2. Protein 4.2 (Pallidin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IS 8.3. Protein p55 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IS

9. Hereditary Spherocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 8 9. I. Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 8 9. 2. Mutations of Ankyrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 9 9.3. Mutations of the Anion Exchanger . . . . . . . . . . . . . . . . . . . . . . . . I 9

10. 4.2 (-) Hemolytic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 I I . Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis . . . . . . . . 20

I I .1. Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 I 1.2. Mutations of Spectrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 I 1.3. 4. I (-) Hereditary Elliptocytosis . . . . . . . . . . . . . . . . . . . . . . . . . 22 I 1.4. GPC (-) Hereditary Elliptocytosis . . . . . . . . . . . . . . . . . . . . . . . 23

12. Southeast Asian Ovalocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 13. Hereditary Stomatocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 I4. Congenital Dyserythropoietic Anemia Type II . . . . . . . . . . . . . . . . . . . 24 I5. Paroxysmal Nocturnal Hemoglobinuria . . . . . . . . . . . . . . . . . . . . . . . . . 24 16. Red Cell Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 17. Concluding Remarks and Future Directions . . . . . . . . . . . . . . . . . . . . . 25 18. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Chapter 2 ABO, Hh, Lewis, and Secretion: Serology, Genetics, and Tissue Distribution Rafael Oriol

I. Definition and Structure of ABH and Lewis Antigens . . . . . . . . . . . . . 37 I. I. Precursor Chains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 1.2. Polymorphisms at Three Levels of the Molecule . . . . . . . . . . . . . 40 1.3. Epistatic Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

2. Serology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 2. I. The Anti-A, Anti-B, and Anti-A, B Monoclonal

Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 2.2. The Anti-Lewis Monoclonal Antibodies . . . . . . . . . . . . . . . . . . . . 45 2.3. The Anti-H Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

3. Formal Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 3. I. ABO on Chromosome 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 3.2. A1, A2 , and Other Weak Phenotypes . . . . . . . . . . . . . . . . . . . . . . . 50 3.3. H-h and the Bombay and Reunion Phenotypes . . . . . . . . . . . . . . . 51 3.4. The First Three-Gene Model for H, Se, and Z Loci . . . . . . . . . . 51 3.5. The Two-Structural-Gene Model for Hand Se Loci . . . . . . . . . . 52 3.6. Le-le on Chromosome 19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 3.7. Other Fucosyltransferase Genes on Chromosomes 19 and II . . . 54

4. Tissue Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 4. I. Embryo-Fetal Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 4.2. Adult Expression and Cell Differentiation . . . . . . . . . . . . . . . . . . 58

5. Other Vertebrate Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

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6. Functions of Histo-Blood Group Antigens . . . . . . . . . . . . . . . . . . . . . . . 64 6.1. Polymorphic Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 6.2. Monomorphic Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

7. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Chapter 3 Biochemistry and Biosynthesis of ABH and Lewis Antigens: Characterization of Blood Group-Specific Glycosyltransferases John B. Lowe

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 2. Structure and Biosynthesis of the ABH Blood Group

Determinants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 3. The Molecular Cloning of the Human ABO Blood Group Locus . . . . 83 4. Subgroups of A and B Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5. The Human Hand Secretor Blood Group Loci . . . . . . . . . . . . . . . . . . 93 6. Molecular Cloning of the H Blood Group Locus . . . . . . . . . . . . . . . . . 96 7. Molecular Analysis of the H Blood Group Gene in Bombay

and Para-Bombay Individuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 8. The Human Lewis Blood Group Locus . . . . . . . . . . . . . . . . . . . . . . . . . 100 9. Molecular Cloning of the Lewis Blood Group Fucosyltransferase

eDNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 10. Shared, and Distinct, Functions and Structures in a Human

a(I ,3)Fucosyltransferase Gene Family . . . . . . . . . . . . . . . . . . . . . . . . . . 107 11. A Subset of the Lewis Blood Group Family of Oligosaccharide

Molecules Represents Ligands for Cell Adhesion Receptors . . . . . . . . 108 12. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 09

Chapter 4 Serology, Biochemistry, and Pathology of Antigens Defined by Cold Agglutinins Dieter Roelcke

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 1.1. Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 1.2. Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

2. Definition of Cold Agglutinin Specificities . . . . . . . . . . . . . . . . . . . . . . 118 3. Ii Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

3.1. Serologic Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 3.2. Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 3.3. Biologic Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

4. Sia-ll,-b1,-lb1Antigens .................................. 132 4.1. Technical Note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.2. Serologic Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.3. Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

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4.4. Biologic Implication ................................... . 5. Pr, Sa Antigens ........................................... .

5. I. Serologic Characterization .............................. . 5.2. Biochemistry ......................................... . 5. 3. Biologic Implication ................................... .

6. Antigens not Yet Attributed to Antigen Complexes .............. . 6.1. Li Antigen ........................................... . 6.2. Lud Antigen ......................................... . 6.3. IgMWoo Antigen ....................................... . 6.4. Further Examples ..................................... .

7. Final Remark ............................................. . 8. References

Chapter 5 MNSs Blood Groups and Major Glycophorins: Molecular Basis for Allelic Variation Cheng-Han Huang and Olga 0. Blumenfeld

137 138 138 138 143 143 143 143 144 144 144 145

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 2. Antigenic and Biochemical Properties of GPA and GPB:

Their Function, Variation, and Interaction with Pathogens as Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

3. The Glycophorin Gene Family: Structure and Organization . . . . . . . . . 157 4. Glycophorin Variant Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158

4. I. Variant Genes Generated via Combinatorial DNA Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 60

4.2. The Gene Deletion Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 5. Glycophorin Homologues in Nonhuman Primates: An Evolutionary

Relationship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 77 6. Molecular Basis for Allelic Diversity of the Glycophorin Family . . . . I 78

6. I. Recombinational Hotspots in the MNSs Locus . . . . . . . . . . . . . . . I 78 6.2. Modulation of Sequence Exchange and Expression by Coupling

Recombination and Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 6.3. Association of Untemplated Variations with Gene

Conversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 6.4. Aberrant Splicing Caused by Splice Site Mutations . . . . . . . . . . . 180

7. A Paradigm of Allelic Diversification: Similarity between the MNSs and MHC Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

8. Summary and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 9. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I 83

Chapter 6 RH Blood Groups and Rh-Deficiency Syndrome Jean-Pierre Cartron and Peter Agre

I . Immunogenetic Basis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 1. 1. Historical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

Contents xiii

1.2. Common Rh Gene Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 I . 3. Other Rh Gene Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 1.4. Rh Deficiency Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

2. Properties of Rh and Rh-Associated Polypeptides . . . . . . . . . . . . . . . . . 194 2.1. Sulfhydryl and Lipid Requirements . . . . . . . . . . . . . . . . . . . . . . . . 194 2.2. Membrane Skeleton Linkage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 2.3. Molecular Characterization of Rh and Rh-Associated

Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 2.4. Relationship between Rh and LW . . . . . . . . . . . . . . . . . . . . . . . . . 197 2.5. Tissue-Specific Expression of Rh Proteins . . . . . . . . . . . . . . . . . . 198

3. Molecular Cloning of Rh and Rh-Associated Polypeptides . . . . . . . . . 198 3 .1. Cloning of the RhCE mRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 3.2. Cloning of the RhO mRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 3. 3. Cloning of Other Proteins Deficient in Rhnull Cells . . . . . . . . . . . 199 3.4. Cloning of the LW mRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200

4. Membrane Organization of Rh and Rh-Associated Polypeptides . . . . . 201 4.1. Primary Sequences of Rh Proteins . . . . . . . . . . . . . . . . . . . . . . . . . 201 4.2. Predicted Topology of Rh Proteins . . . . . . . . . . . . . . . . . . . . . . . . 201 4.3. Primary Sequence and Predicted Topology of Rh-Associated

Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 5. Structure of the RH Locus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

5.1. RH Locus Structure and RhO+ /RhO- Polymorphism . . . . . . . . 205 5.2. CE Gene and Transcripts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 5. 3. D Gene and Transcripts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 5.4. Prenatal Determination of RhO Gene Status in Fetuses . . . . . . . . 207 5.5. Evolutionary Pathway of the RH Locus . . . . . . . . . . . . . . . . . . . . 210

6. Molecular Basis of Rh Blood Group Specificities . . . . . . . . . . . . . . . . . 210 6.1. RhO Epitopes and Molecular Variants . . . . . . . . . . . . . . . . . . . . . 210 6.2. Molecular Basis of Rh C, c, E, and e Specificities . . . . . . . . . . . 211 6.3. D-- and De- Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214

7. Membrane Assembly of Rh Polypeptides . . . . . . . . . . . . . . . . . . . . . . . 214 7.1. The Rh Membrane Complex Hypothesis . . . . . . . . . . . . . . . . . . . . 214 7. 2. Expression of Rh Proteins in Rh Glycoproteins . . . . . . . . . . . . . . 217

8. Molecular Analysis of RH Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . 218 9. Potential Physiologic Function of Rh Proteins . . . . . . . . . . . . . . . . . . . 219

1 0. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220

Chapter 7 Kell Blood Group System and the McLeod Syndrome Colvin M. Redman and Soohee Lee

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 2. Keii Blood Group Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228

2.1. Early Biochemical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 2.2. Possible Interaction with Cytoskeletal and Other Membrane

Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

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2.3. Primary Structure of Kell Protein Derived from Its eDNA . . . . . 229 2.4. Sequence and Structural Homology with Zinc Neutral

Endopeptidases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 3. The Kell Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234

3.1. General Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 3.2. KEL Gene is Localized on 7q33 . . . . . . . . . . . . . . . . . . . . . . . . . . 234 3.3. Expression of Kell Is Restricted to Erythroid Tissues . . . . . . . . . 236 3.4. Transfected Cells Express Defined Kell Antigens . . . . . . . . . . . . 236

4. Variant Kell Phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 4.1. Ko(null) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 4.2. Weak Kell Phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 4.3. The McLeod Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238

5. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

Chapter 8 The Duffy Blood Group System and Malaria Asok Chaudhuri and A. Oscar Pogo

I. 2.

3.

4.

5. 6. 7.

Background .............................................. . Duffy Antigenic Determinants ............................... . 2.1. Fy" and Fl Antigens .................................. . 2.2. Fy3 Antigen .......................................... . 2.3. Fy4 Antigen .......................................... . 2.4. Fy5 Antigen .......................................... . 2.5. Fy6 Antigen .......................................... . 2.6. Fy', a Variant of Fl .................................. . Biochemistry ............................................. . 3.1. Isolation and Characterization of the Duffy Complex ........ . 3.2. Subunit Composition ................................... . 3.3. Amino Acid and Carbohydrate Composition of the Major

Subunit of the Duffy Complex ........................... . 3.4. Biochemical Properties of pD Protein ..................... . Duffy Blood Group Antigens and Malaria ...................... . 4.1. Duffy Antigen, Plasmodium vivax (Human Malaria) and

Plasmodium knowlesi (Monkey Malaria) Invasion ........... . 4.2. Plasmodium vivax and Plasmodium knowlesi Erythrocyte-

Binding Proteins ...................................... . Summary ................................................ . Addendum ............................................... . References

Chapter 9 The Kidd Blood Group and Urea Transport Joann M. Moulds

243 244 244 245 245 245 246 246 246 246 247

248 254 256

256

260 261 261 262

I. Genetics of the Kidd Blood Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 I. I. Inheritance Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

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1.2. The Kidd Null Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268 1.3. Chromosomal Location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270

2. Biochemistry of the Kidd Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270 2.1. Location and Structure of the Kidd Protein . . . . . . . . . . . . . . . . . 270 2.2. Resistance to Urea Lysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271 2.3. The Urea Transporter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272 2.4. Water Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 2.5. Cloning the Kidd Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275

3. Possible Disease Associations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 3.1. Hematological Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 3.2. Kidney Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 3.3. New Areas of Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276

4. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276

Chapter 10 Lutheran Antigens, Lutheran Regulatory Genes, and Lutheran Regulatory Gene Targets Neeraja Rao and Marilyn J. Telen

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 2. Development of the Lutheran Blood Group into a Multiantigen

System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 3. Biochemistry of Lutheran Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 4. The Lu( a-b-) Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 5. Lutheran Regulatory Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286

5.1. The ln(Lu) Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286 5.2. The XS2 Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288

6. Molecules Affected by the ln(Lu) Gene . . . . . . . . . . . . . . . . . . . . . . . . . 288 6.1. CD44 [ln(Lu)-Related p80] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288 6.2. AnWj Antigen: The Hemophilus influenzae Receptor . . . . . . . . . 290

7. Future Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 8. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292

Chapter 11 P Blood Group and Related Antigens Pascal Bailly and Jean-Fram;ois Bouhours

I. Antigens and Phenotypes of the Blood Group P System . . . . . . . . . . . 300 1.1. Antigens of the P System Are Glycosphingolipids . . . . . . . . . . . . 300 1.2. Red Blood Cell Phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302

2. Extensions of the Blood Group P System . . . . . . . . . . . . . . . . . . . . . . . 309 2.1. Blood Group Antigens of the Neolactoseries . . . . . . . . . . . . . . . . 309 2.2. Blood Group Antigens of the Globoseries . . . . . . . . . . . . . . . . . . 310 2.3. Relationships with Other Blood Group Systems . . . . . . . . . . . . . . 312

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3. Antibodies and Detection of Blood Group P Antigens . . . . . . . . . . . . . 312 3.1. Accessibility of Blood Group P Antigens at the Red

Cell Surface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 3.2. Alloantibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 3.3. Monoclonal Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313

4. Disorders Linked to the Existence of Blood Group P Antigens . . . . . . 313 4.1. Alloantibodies and Blood Transfusion . . . . . . . . . . . . . . . . . . . . . . 313 4.2. Abortion in p and P" Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 4.3. Expression of Blood Group P Antigens during Development

and Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 4.4. Paroxysmal Cold Hemoglobinuria . . . . . . . . . . . . . . . . . . . . . . . . . 315 4.5. Anti-P 1 Antibodies Raised by Infectious Agents

or Environmental Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315 4.6. Auto-anti-PP1pk in Western Australian Women . . . . . . . . . . . . . . 316 4. 7. Binding of Bacterial Proteins to Globoseries Glycolipids . . . . . . 316 4.8. Parvovirus Binding to Globoside . . . . . . . . . . . . . . . . . . . . . . . . . . 317

5. Biosynthesis and Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 5 .1. Synthesis of pk and P Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 5.2. Synthesis of P-Like and Forssman Antigens . . . . . . . . . . . . . . . . . 319 5.3. Synthesis of P1 Antigen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319

6. Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 7. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321

Chapter 12 Gerbich Blood Groups and Minor Glycophorins Yves Colin and Caroline Le Van Kim

l. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 2. Organization of the Gerbich or GYPC Locus . . . . . . . . . . . . . . . . . . . . 333

2.1. Primary Sequence of GPC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 2.2. Structural Organization of the GYPC Gene . . . . . . . . . . . . . . . . . 333 2.3. Primary Structure of GPO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334

3. Gerbich Antigens and Glycophorins C and D . . . . . . . . . . . . . . . . . . . . 336 3.1. Nomenclature of Gerbich Antigens . . . . . . . . . . . . . . . . . . . . . . . . 336 3.2. GPC and GPD Are the Carriers of Gerbich Antigens . . . . . . . . . 337

4. GYPC Gene Structure of GE Variants . . . . . . . . . . . . . . . . . . . . . . . . . . 339 4.1. Leach-Type(Ge:-2,-3,-4) ............................. 339 4.2. Yus-Type (Ge:-2,3,4) and Ge-Type (Ge:-2, -3,4) . . . . . . . . . . 341 4.3. Ls• Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 4.4. Webb Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 4.5. Dh" Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 4.6. An• Variant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343

5. Expression and Tissue Specificity of Glycophorins C and D . . . . . . . . 343 5.1. Cell Surface Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 5.2. Differential Expression of the GYPC Gene in Erythroid

and Nonerythroid Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343

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6. Function of GPC and GPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344 7. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 7

Chapter 13 Sd• and Cad Antigens Winifred M. Watkins

1. Sid and Cad Blood Group Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 1. 1. Discovery and Inheritance of Sd" Antigen . . . . . . . . . . . . . . . . . . 351 1.2. Development of Sd• Antigen on Erythrocytes . . . . . . . . . . . . . . . . 352 1.3. Human Anti-Sd" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352 1.4. Distribution of Sd" Antigen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352 1.5. Discovery and Inheritance of Cad Antigen . . . . . . . . . . . . . . . . . . 354 1.6. Serological Relationship between Sd• and Cad Antigens . . . . . . . 354

2. Chemistry of Sd" and Cad Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 2.1. The Sd• Determinant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 2.2. The Cad Determinant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359

3. Enzymatic Basis of Sd" and Cad Phenotypes . . . . . . . . . . . . . . . . . . . . 361 3.1. 13-1 ,4-NHTAcetylgalactosaminyltransferases in Animal

Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 3.2. 13-1 ,4-NH2-Acetylgalactosaminyltransferases in Human

Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 4. Development of Sd" Antigenic, and 13-1 ,4-NH2-Acetylgalactos-

aminyltransferase, Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 5. Changes in Sd" Antigenic, and 13-1 ,4-N-Acetylgalactos-

aminyltransferase, Expression in Malignancy . . . . . . . . . . . . . . . . . . . . 367 6. Essential Features of the Sd• Determinant . . . . . . . . . . . . . . . . . . . . . . . 367 7. Genetic Basis of the Sid and Cad Blood Group Systems . . . . . . . . . . . 370

7 .1. The Sid System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370 7.2. The Cad System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370

8. Biological Role of the Sd• and Cad Antigens . . . . . . . . . . . . . . . . . . . . 371 9. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372

Chapter 14 Overview of Other Blood Group Systems Patricia Tippett

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 2. XG Blood Group System and 12E7 Antigen . . . . . . . . . . . . . . . . . . . . . 377

2.1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . 377 2.2. Inactivation of X Chromosome . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 2.3. Relationship of 12E7 Antigen to Xg . . . . . . . . . . . . . . . . . . . . . . . 379 2.4. Model for Regulation of M1C2 and XG Loci . . . . . . . . . . . . . . . . 379 2.5. Biochemical Nature of Xg" and 12E7 Antigens . . . . . . . . . . . . . . 381

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2.6. Cloning of MIC2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382 2.7. Cloning of XG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383

3. Diego Blood Group System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 3.1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 3.2. Distribution of Di" Antigen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 3.3. Relationship to Band 3 and Molecular Basis of DI

Polymorphism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 4. Cartwright (Yt) Blood Group System . . . . . . . . . . . . . . . . . . . . . . . . . . 384

4.1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . 384 4.2. Biochemical Nature and Red Cell Membrane Component . . . . . . 385 4.3. Molecular Basis of YT Polymorphism . . . . . . . . . . . . . . . . . . . . . 386

5. Scianna Blood Group System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386 5.1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . 386 5.2. Relationship to Rd Antigen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 5.3. Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387

6. Dombrock Blood Group System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 6.1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 6.2. Expansion of Dombrock System . . . . . . . . . . . . . . . . . . . . . . . . . . 388 6.3. Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 388

7. Colton Blood Group System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 388 7 .1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . 388 7.2. Null Phenotype, Co(a-b-), in Monosomy 7 . . . . . . . . . . . . . . . . 389 7 .3. Biochemical Nature and Molecular Basis of Colton

Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389 8. Landsteiner-Wiener Blood Group System . . . . . . . . . . . . . . . . . . . . . . . 389

8.1. Basic Serology and Inheritance . . . . . . . . . . . . . . . . . . . . . . . . . . . 389 8.2. Variation of Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390 8.3. Structure of LW Glycoprotein . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390

9. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391

Chapter 15 Blood Group Antigens as Markers of Complement and Complement Regulatory Molecules Geoff Daniels

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397 2. Chido and Rodgers: Blood Group Determinants on C4 . . . . . . . . . . . . 398

2.1. Basic Chido/Rodgers (Ch/Rg) Serology . . . . . . . . . . . . . . . . . . . 398 2.2. C4 Polymorphism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399 2.3. Molecular Genetics of C4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399 2.4. Ch/Rg Antigens Are Located on C4 . . . . . . . . . . . . . . . . . . . . . . . 401 2.5. Ch and Rg-Further Complexities . . . . . . . . . . . . . . . . . . . . . . . . 402 2.6. An Alternative Notation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404

3. Knops: Blood Group Determinants on CRL the C3b/C4b Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404

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3.1. Knops System Antigens and Antibodies . . . . . . . . . . . . . . . . . . . . 404 3.2. Complement Receptor I (CRI. CD35) . . . . . . . . . . . . . . . . . . . . . 405 3.3. Knops System Antigens Are Located on CRI . . . . . . . . . . . . . . . 406 3.4. Cs" and Csb . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408

4. Cromer: Blood Group Determinants on Decay-Accelerating Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408 4.1. Cromer System Antibodies and Antigens . . . . . . . . . . . . . . . . . . . 408 4.2. Decay-Accelerating Factor (DAF, CD55) . . . . . . . . . . . . . . . . . . . 409 4.3. Cromer System Antigens Are Located on DAF . . . . . . . . . . . . . . 410 4.4. Paroxysmal Nocturnal Hemoglobinuria and the Inab

Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410 4.5. Molecular Genetics of Cromer System Variants . . . . . . . . . . . . . . 413

5. Other Glycosyl-phosphatidylinositol-Linked Glycoproteins . . . . . . . . . 414 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415 7. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415

Chapter 16 Histo-Biood Group Antigens as Tumor-Associated Carbohydrate Antigens and Ligands for Cell Adhesion Sen-itiroh Hakomori

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 2. Histo-Blood Group ABH Antigens in Human Cancer . . . . . . . . . . . . . 422 3. Molecular Genetic Basis of Changes of ABH Antigens

in Human Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425 4. Histo-Blood Group Lewis Antigens in Human Cancer . . . . . . . . . . . . . 425 5. Histo-Blood Group I/i Antigens in Human Cancer . . . . . . . . . . . . . . . 428 6. Histo-Blood Group P System in Human Cancer . . . . . . . . . . . . . . . . . . 432 7. Blood Group Tn/Sialosyl-Tn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433 8. Diagnostic and Prognostic Significance of Aberrant Expression

of Histo-Blood Group Antigens in Human Tumors . . . . . . . . . . . . . . . 434 9. Clinical Utilization of Histo-Blood Group Antigen Modifications

in Human Tumors: Proposal for "Antiadhesion" Therapy . . . . . . . . . . 435 10. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437

Chapter 17 Linkage Relationships and Gene Mapping of Human Blood Group Loci Marion Lewis and Teresa Zelinski

I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 2. Methodology in Gene Mapping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446

2.1. Linkage Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446 2.2. Cytogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449 2.3. Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

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2.4. Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452 3. Mapping of Blood Group Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455

3.1. Blood Group Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455 3.2. Blood Group Collections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460 3.3. ISBTWP 700 Series . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460 3.4. ISBTWP 901 Series . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461

4. The Linkage Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 4.1. Sex Difference in Genetic Lengths . . . . . . . . . . . . . . . . . . . . . . . . 462 4.2. Localization and Orientation of Genes . . . . . . . . . . . . . . . . . . . . . 462 4.3. Specific Linkage Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463

5. The Physical Map of Blood Group Genes . . . . . . . . . . . . . . . . . . . . . . . 467 6. Summation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467 7. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468

Chapter 18 Nomenclature of Blood Group Antigens Pierre-Yves Le Pennec and Philippe Rouger

I. Toward an International Terminology for Red Cell Surface Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477 1.1. Blood Group Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478 1.2. Other Antigens and Specificities; Series and Collections . . . . . . . 479

2. Evolution and Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480 2.1. The Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480 2.2. The Evolution of the ISBT Nomenclature . . . . . . . . . . . . . . . . . . . 483

3. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487