Genetic Susceptibility to Infectious Diseases

464 Pages·2008·3.02 MB·English

by  R. A. Kaslow, J. McNicholl, A. V. S. Hill

Genetic Susceptibility to Infectious Diseases
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Genetic Susceptibility to Infectious Diseases
Edited by
Richard A. Kaslow
Janet M. McNicholl
Adrian V.S. Hill
1
2008
1
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Library of Congress Cataloging-in-Publication Data
Kaslow, Richard A.
Genetic susceptibility to infectious diseases = Richard Kaslow, Janet
McNicholl, Adrian Hill.
p. cm.
Includes bibliographical references.
ISBN 978-0-19-517490-8
1. Communicable diseases—Genetic aspects. 2. Infection—Genetic aspects.
3. Disease susceptibility—Genetic aspects. I. McNicholl, Janet. II. Hill, Adrian. III. Title.
[DNLM: 1. Communicable Diseases—genetics. 2. Genetic Predisposition
to Disease. 3. Variation (Genetics)—immunology. QZ 50 K19b 2007]
RC112.K27 2007
616.9042—dc22 2007008576
9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper
Preface
The twentieth century was filled with triumph in pose of this volume is to organize existing knowledge of
preventing and controlling infectious diseases. Much those influences into a foundation for future inquiry.
of that success was achieved through a combination of The book was conceived early in 2001 in the
sanitation (simple alterations of the physical environ- ‘‘pregenomic’’ era, a few months before the first draft
ment), antimicrobials (painstaking discovery and test- sequence of the human genome was available and
ing of compounds to inactivate or destroy etiologic before the International HapMap Project was even
agents), and immunization (elegant manipulation of designed. Beyond gathering in one place the infor-
the agents or their products to stimulate protective host mation that a reader would otherwise be forced to ex-
immunity). Of the three approaches, only immuniza- cavate from many sites, this collection is intended to
tion depended on the genetically mediated host im- accomplish a secondary goal: to ‘‘cross-fertilize’’ the
mune responses—and even then only indirectly and work of basic scientists, clinicians, and others who may
often imperceptibly. Numerous vaccines with im- be more familiar with genetics or infection but not
pressive efficacies of 70–90% or higher—the most re- both. It is thus meant to be a blend of the general and
cent example being the remarkable human papillo- the specific—containing aspects of critical review,
mavirus vaccine—were developed with little or no systematic progress report, clinical application, and
attention to the principles of human genetics. In short, prospectus.
throughout decades of progress, our meager knowledge In the gestational period between conception of the
of host genes and genetic variation was largely irrele- text and delivery of the manuscript to the publisher,
vant to the many landmark victories. many new candidate genes with probable influence on
During that same period, numerous assaults on infection and immunity have surfaced, and previously
infectious disease faltered, with grave consequences. quiescent or unrecognized infections of major public
The quarter-century-long explosion of HIV-1 infec- health consequence such as West Nile virus infection
tion, the resurgence of tuberculosis both with and and corona virus–associated severe acute respiratory
without HIV=AIDS, the unshakable persistence of distress syndrome (SARS) have emerged. Meanwhile,
malaria, and biological threats such as anthrax con- revolutionary advances in the knowledge and tech-
tinue to remind us of the inadequacy of previously nology of genetics have continued to sweep through
effective strategies. Those ‘‘failures’’ as much as any- every corner of the biomedical research enterprise. In
thing have refocused attention on the origins of in- the midst of such dynamic changes, we have tried to
fectious diseases in their full complexity. There has maintain as much currency as the constraints of space
been increasing recognition that strategies for con- and time allowed.
trolling these diseases will likely require insights at the To assist the diverse audience, we have divided the
deeper level of human and microbial genetics—a book into three parts that mirror that diversity in ori-
thorough understanding of the influences of host ge- entation and knowledge base. Part I describes the
netic variation on infection and immunity. The pur- current methods for generating information about
vi PREFACE
genetic variation in populations of humans and ani- Part III reveals notable unevenness in current
mals. Part II highlights families of genes whose varia- knowledge among the diseases of interest. Chapter 18
tion is known or likely to contribute to susceptibility to encompasses uncommon immune deficiencies due to
human infectious disease, and part III covers the major derangements of immunoglobulin genes and others
infectious diseases on which the influences of host showing classic Mendelian inheritance. Subsequent
genetic variation are stronger or better established. chapters cover some diseases of major public health
Sections of individual chapters in parts II and III importance. Some other conditions of comparable
conform roughly to a general outline. General topic impact on populations, such as dengue fever and hu-
headings and the structure of certain tables correspond man papillomavirus infection, are mentioned in the
more closely across chapters; however, the inherent appropriate places in part II but not covered explicitly
disparity in knowledge of each individual gene or in their own right. For most of the disorders included,
disease limited further standardization. investigation of susceptibility due to genetic polymor-
We have made no attempt to catalogue every tech- phism has yielded relatively convincing evidence, but
nique, gene, or disease with some connection to the the diseases and the genes examined vary considerably
title theme; that encyclopedic approach was beyond in that regard. Malaria, HIV=AIDS, and tuberculosis
the scope of the endeavor. At the risk of diluting or show definitive relationships with variable gene con-
omitting, we have tried to be rather more selective, to tent or allelic polymorphisms in numerous chromo-
create an anthology with accessibility to readers in a somal regions. The work on malaria has been thorough
broad set of disciplines. Chapters in part I provide enough to devote a separate chapter in part II to the
more perspective than specifics. Including sections on profound impact of red blood cell genes and a chapter
such topics as bioinformatics tools and applications, in part III to the disease itself.
the latest strategies for genomewide association studies, Interest and information on genetic determinants
whole-genome sequencing or expression microarray of variable response to vaccines for preventing infec-
analysis, proteomics, and alternative animal models tions and to drugs for treating them are expanding.
might have added more specialized material of interest Aside from space limits, a simple reason explains our
to some but are well reviewed elsewhere. deliberate decision to include a chapter on the former
Part II covers 14 families of genes whose variation is but not the latter. Vaccines are biological products—in
known to contribute to differential susceptibility. The some cases actually replicating organisms—to which
relevant polymorphisms of those selected range widely genetically mediated responses may well parallel re-
in the degree of certainty of their involvement and in sponses to the naturally occurring pathogen. Accord-
their importance in terms of population frequency. ingly, observations about variable vaccine response are
For some gene families (e.g., those encoding certain quite likely to inform studies of infection and vice
complement components or immunoglobulin recep- versa. On the other hand, anti-infective pharmaceuti-
tors), clinically significant variation is well established cals are transported and metabolized along pathways
but relatively uncommon. Different chapters reflect whose regulation, for the most part, involves a very
varying perspectives among authors in accepting the different set of genes with more tenuous involvement
validity or relevance of polymorphisms reported to in immunity or susceptibility.
alter immune function or disease susceptibility. For Although we could not continue beyond a point
example, although experimental or epidemiologic to update the text with every new gene family, disease,
studies of various inflammatory diseases have impli- or genotype–phenotype relationship to susceptibility
cated the genes encoding MHC class I polypeptide– whenever potentially relevant information appeared,
related sequence (MICA and MICB) and the Toll-like two efforts have been made to maintain its currency
receptors (TLRs), the chapters on those gene clusters during production. One effort resulted in an appendix
reflect considerable skepticism that published associ- containing a list of particularly informative Web sites
ations of infectious diseases with specific alleles rep- among the many devoted to ‘‘postgenomic’’ activities.
resent effects that are functionally significant and in- Compiling such a compendium was a challenge—one
dependent of alleles in close linkage disequilibrium that is likely to grow as Web sites proliferate even
with unknown variants. Other chapters are more lib- further, but an exercise worth the effort because it will
eral in including reported relationships. not be long before these and subsequent electronic
PREFACE v i i
sources will be providing rich and continuously timely this coevolutionary contest between human and mi-
information beyond the scope of this volume. crobial life have forged remarkable patterns of poly-
The other updating effort followed our decision morphism that remain with us—many probably per-
to use current nomenclature and conventions of the sisting long after the pathogens responsible for driving
U.S. National Center for Biotechnology Information the particular variation have ceased to colonize our
(NCBI) as universally as possible. Names of genes are species. However, the patterns in our DNA do not
intended to follow official NCBI designations uni- constitute mere ‘‘fossil record’’ of these encounters.
formly. Wherever possible, and with a few exceptions Our genetic legacy continues to exert its force and, as
for those likely to be confusing in context, the NCBI in the past, will inevitably shape reemergent and newly
gene symbol has been systematically substituted for the recognized transmissible microorganisms into agents
historical or more common abbreviation, often with a of future epidemics. The difference between the past
parenthetic reference to the older, familiar one. By and the future is that we have recently crossed a thresh-
convention, symbols that refer to a human gene rather old into the promise of a postgenomic world. There we
than to its product or to its specific alleles are meant to can envision far more powerful observational and ex-
be capitalized and italicized; a symbol for a human perimental research that will accelerate the translation
gene accompanied by one or more of its alleles is also of discovery about human genetic susceptibility into
usually capitalized but not italicized. Although the effective measures of disease control. We hope that in
latter convention has not been widely adopted, we some small way this text will equip each reader to
have tried for the most part to conform to it. For HLA contribute to that goal.
genes and alleles, the more exacting nomenclature is
explained in the text. Genes of nonhuman species may
or may not be capitalized but are italicized.
Acknowledgments
As the mining of the human genome for suscepti-
bility genes gathers pace, with greatly improved tech- Every text is ultimately more than the sum of its pub-
nologies and larger study populations, the relevance of lished parts. This one represents the collective, orga-
this work to public health will expand. The number of nized wisdom of the authors and the product of con-
susceptibility gene discoveries that have so far gener- tinuous editorial exchange about content and form.
ated new intervention strategies is still small but likely However, other contributions were essential. At the
to grow rapidly, particularly for the major killers that earliest conceptual stages, three individuals with dif-
have proved most refractory to more traditional ap- ferent orientations understood the theme of genetic
proaches. New susceptibility profiles will have appli- susceptibility to infection and were of common mind
cation to risk assessment, to prioritization of individu- as they envisioned something like this text. Jeffrey
als for prophylaxis, and to selection of alternative House, the Oxford University Press representative for
treatments. Equally important, pathways identified many years; Emil Skamene, the eminent McGill
through the recognition of novel susceptibility genes University immunobiologist and physician; and Muin
have already suggested unexpected mechanisms with Khoury, the Centers for Disease Control and Preven-
candidate molecular targets. tion genetic epidemiologist and public health expo-
Research on genetic susceptibility to infectious nent, deserve our special gratitude for encouraging us
diseases has often taken place at the interface between to convert our shared vision into reality. Throughout
the science of evolutionary biology and the real world the process that followed, we have relied on others be-
of treatment and prevention. The text summarizes the hind the scenes to inspire, encourage, facilitate, tol-
scientific discoveries of more than half a century in a erate, restrain, revive, and (still) love us for what we
series of stories about an ancient, ongoing struggle were trying to do. To them—our families, friends,
between host and pathogen. Victories on both sides of colleagues—we owe our profound gratitude.
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Contents
Contributors xi 8. Red Blood Cell Genes and Malaria 107
David Weatherall
I METHODS AND TOOLS
9. Immunoglobulin (Fc) and Related
1. Genetic Epidemiology of Infectious Disease 3 Receptor Genes 120
Priya Duggal & Terri H. Beaty Jennifer A. Croker & Robert P. Kimberly
2. Laboratory Analysis of Genetic Variation 18 10. Mannose-Binding Lectin Genes 137
Meredith Yeager, Robert A. Welch, Richard Bellamy
& Stephen J. Chanock
11. Complement Genes 151
3. Mouse Models for Genetic Susceptibility Keith D. Crawford & Chester A. Alper
to Infection in Humans 32
Anny Fortin, Ellen Buschman, & Emil Skamene 12. Toll-Like Receptor Genes 165
Bruce Beutler
II IMMUNE RESPONSE GENES
AND INFECTION 13. Metal Transport Genes 175
Jean-Franc¸ois Marquis, John R. Forbes,
4. MHC Class I and Related Genes 47 Franc¸ois Canonne-Hergaux, Cynthia Horth,
Henry A. F. Stephens & Philippe Gros
5. MHC Class II and Related Genes 62 14. Tumor Necrosis Factor and
Janet M. McNicholl, Peter E. Jensen, Related Genes 190
& Jeremy M. Boss Grant Gallagher, Milton O. Moraes,
& Juan-Manuel Anaya
6. MHC Class I Polypeptide–Related
Sequence A and B (MICA and MICB) 15. Cytokine Genes I: IL10, IL6, IL4, and the
Genes 83 IL1 Family 208
Seiamak Bahram Milton O. Moraes, Janet M. McNicholl,
Tom W. J. Huizinga, & Tom H. M. Ottenhoff
7. Killer Immunoglobulin-Like Receptor
and Related Genes 89 16. Cytokine Genes II: IL12, IFNG, and Their
Maureen P. Martin, M. Tevfik Dorak, Receptor Genes 227
& Mary Carrington Margje H. Haverkamp & Stephen M. Holland