Genomic Disorders: The Genomic Basis of Disease

419 Pages·2006·5.73 MB·English

by  James R. Lupski MD

G D
ENOMIC ISORDERS
G
ENOMIC
D
ISORDERS
The Genomic Basis of Disease
Edited by
J R. L , ,
AMES UPSKI MD PhD
P S , ,
AWEL TANKIEWICZ MD PhD
/
Department of Molecular and Human Genetics
Baylor College of Medicine, Houston, TX
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Library of Congress Cataloging-in-Publication Data
Genomic disorders : the genomic basis of disease / edited by James R. Lupski, Pawe Stankiewicz.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58829-559-1 (alk. paper)
1. Genetic disorders--Molecular aspects.
[DNLM: 1. Genetic Diseases, Inborn. 2. Chromosome Aberrations. 3. Genome Components. 4. Genome.
5. Genomics--methods. QZ 50 G3354 2006] I. Lupski, James R., 1957- II. Stankiewicz, Pawe .
RB155.5.G465 2006
616'.042--dc22
2005020461
Dedication
To our many mentors who have nurtured our intellectual curiosity and to our
dedicated families for their love and support.
—J. R. L. and P. S.
v
In Memorium
In memory of Carlos A. Garcia (1935–2005) and his passion for medicine, science,
and the patients and families for whom he cared.
vii
Preface
Uncovering Recurrent Submicroscopic Rearrangements As a Cause of Disease
For five decades since Fred Sanger's (1) seminal discovery that proteins have a specific
structure, since Linus Pauling's (2) discovery that hemoglobin from patients with sickle
cell anemia is molecularly distinct, and since Watson and Crick's (3) elucidation of the
chemical basis of heredity, the molecular basis of disease has been addressed in the
context of how mutations affect the structure, function, or regulation of a gene or its
proteinproduct. Molecular medicine has functioned in the context of a genocentric world.
During the last decade it became apparent, however, that many disease traits are best
explained not by how the information content of a single gene is changed, but rather on
the basis of genomic alterations. Furthermore, it has become abundantly clear that architec-
tural features of the human genome can result in susceptibility to DNA rearrangements that
cause disease traits. Such conditions have been referred to as genomic disorders (4,5).
It remains to be determined to what extent genomic changes are responsible for disease
traits, common traits (including behavioral traits), or perhaps sometimes represent benign
polymorphic variation. The widespread structural variation of the human genome, alter-
natively referred to as large-copy number polymorphisms, large-scale copy number varia-
tions, or copy number variants has begun only recently to be appreciated (6–9).
High-resolution analysis of the human genome has enabled detection of genome changes
heretofore not observed because of technology limitations. Whereas agarose gel electro-
phoresis enables detection of changes of the genome up to 25–30 kb in size, and cytoge-
netic banding techniques can resolve deletion rearrangements only greater than 2–5 Mb
in size, alterations of the genome between more than 30 kb and less than 5 Mb defied
detection until pulsed-field gel electrophoresis and fluorescence in situ hybridization
became available to resolve changes in the human genome of such magnitude (10–12).
Those methods were limited to detection of specific genomic regions of interest and could
not evaluate genomic rearrangements in a global way.
The availability of a “finished” human genome sequence (13) and genomic microarrays
(14) have enabled approaches to resolve changes in the genome heretofore impossible to
assess on a global genome scale (i.e., simultaneously examining the entire genome rather
than discreet segments). Array comparative genome hybridization (aCGH) is one powerful
approach to high-resolution analysis of the human genome. The CGH determines differ-
ences by comparisons to a reference “normal genome,” whereas the array enables detec-
tion of such changes at essentially any resolution that is desired, limited only by
imagination and cost. Furthermore, the application of bioinformatic analyses to the
finished human genome sequence and comparative genomic analysis enable information
technology approaches to identify key architectural features throughout the entire
genome that are associated with known recurrent rearrangements causing genomic
disorders.
An increasing number of human diseases are recognized to result from recurrent DNA
rearrangements involving unstable genomic regions. A combination of high-resolution
ix
x Preface
genome analysis with informatics capabilities to examine individuals with well-
characterized phenotypic traits is a powerful approach to address the question: To what extent
are constitutional DNA rearrangements in the human genome responsible for human traits?
Such approaches may also yield insights into recurrent somatic rearrangements (15).
Genomic Disorders: The Genomic Basis of Disease attempts to survey the subject area of
genomic disorders in the beginning of the postgenomic era. After a short historical
presentation (Part I) describing the trials and tribulations involved in uncovering the recurrent
submicroscopic duplication associated with Charcot-Marie-Tooth disease type 1A, the book
is organized into parts on genome structure (II), genome evolution (III), genomic rearrange-
ments and disease traits (IV), functional aspects of genome structure (V), and modeling and
assays for genomic disorders (VI). Finally, Part VII includes appendices that delineate
disease traits and genomic features (listed in tabular form) for well-characterized genomic
disorders as well as clinical phenotypes for which chromosome microarray analysis may be
used to detect the responsible rearrangement mutation. We believe that the topics chosen for
individual chapters illustrate the genomic basis of disease.
James R. Lupski, MD,PhD
Pawe/l Stankiewicz, MD,PhD
REFERENCES
1. Sanger F. The terminal peptides of insulin. Biochem J 1949;45:563–574.
2. Pauling L, Itamo HA, Singer SJ, Wells IC. Sickle cell anemia, a molecular disease. Science
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3. Watson DA, Crick FHC. Molecular structure of nucleic acids. A structure for deoxyribose nucleic
acids. Nature 1953;171:737–738.
4. Lupski JR. Genomic disorders: structural features of the genome can lead to DNA rearrangements and
human disease traits. Trends Genet 1998;14:417–422.
5. Stankiewicz P, Lupski JR. Genome architecture, rearrangements and genomic disorders. Trends
Genet 2002;18:74–82.
6. Shaw-Smith C, Redon R, Rickman L, et al. Microarray based comparative genomic hybridisation
(array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with
learning disability/mental retardation and dysmorphic features. J Med Genet 2004;41:241–248.
7. Iafrate AJ, Feuk L, Rivera MN, et al. Detection of large-scale variation in the human genome. Nat
Genet 2004;36:949–951.
8. Sebat J, Lakshmi B, Troge J, et al. Large-scale copy number polymorphism in the human genome.
Science 2004;305:525–528.
9. Tuzun E, Sharp AJ, Bailey JA, et al. Fine-scale structural variation of the human genome. Nat Genet
2005;37:727–732.
10. Schwartz DC, Cantor CR. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel
electrophoresis. Cell 1984;37:67–75.
11. Pinkel D, Straume T, Gray JW. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence
hybridization. Proc Natl Acad Sci USA 1986;83:2934–2938.
12. Lupski JR. 2002 Curt Stern Award Address. Genomic disorders: recombination-based disease resulting
from genomic architecture. Am J Hum Genet 2003;72:246–252.
13. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the
human genome. Nature 2004;431:931–945.
14. Carter NP, Vetrie D. Applications of genomic microarrays to explore human chromosome structure
and function. Hum Mol Genet 2004;13:R297–R302.
15. Barbouti, A., Stankiewicz, P., Birren, B., et al. The breakpoint region of the most common isochro
mosome, i(17q), in human neoplasia is characterized by a complex genome architecture with large
palindromic low-copy repeats. Am J Hum Genet 2004;74:1–10.
Contents
Dedication ......................................................................................................................v
In Memorium .............................................................................................................. vii
Preface...........................................................................................................................ix
Contributors..................................................................................................................xv
P I I
ART NTRODUCTION
1 The CMT1A Duplication: A Historical Perspective Viewed
From Two Sides of an Ocean.......................................................3
James R. Lupski and Vincent Timmerman
P II G S
ART ENOMIC TRUCTURE
2 Alu Elements ...................................................................................21
Prescott Deininger
3 The Impact of LINE-1 Retrotransposition on the Human
Genome.......................................................................................35
Amy E. Hulme, Deanna A. Kulpa, José Luis Garcia Perez,
and John V. Moran
4 Ancient Transposable Elements, Processed Pseudogenes,
and Endogenous Retroviruses....................................................57
Adam Pavlicek and Jerzy Jurka
5 Segmental Duplications..................................................................73
Andrew J. Sharp and Evan E. Eichler
6 Non-B DNA and Chromosomal Rearrangements..........................89
Albino Bacolla and Robert D. Wells
7 Genetic Basis of Olfactory Deficits..............................................101
Idan Menashe, Ester Feldmesser, and Doron Lancet
8 Genomic Organization and Function of Human
Centromeres..............................................................................115
Huntington F. Willard and M. Katharine Rudd
P III G E
ART ENOME VOLUTION
9 Primate Chromosome Evolution ..................................................133
Stefan Müller
10 Genome Plasticity in Evolution: The Centromere Repositioning ....153
Mariano Rocchi and Nicoletta Archidiacono
xi
xii Contents
P IV G R D T
ART ENOMIC EARRANGEMENTS AND ISEASE RAITS
11 The CMT1A Duplication and HNPP Deletion ............................169
Vincent Timmerman and James R. Lupski
12 Smith-Magenis Syndrome Deletion, Reciprocal Duplication
dup(17)(p11.2p11.2), and Other Proximal
17p Rearrangements.................................................................179
Pawe/l Stankiewicz, Weimin Bi, and James R. Lupski
13 Chromosome 22q11.2 Rearrangement Disorders........................193
Bernice E. Morrow
14 Neurofibromatosis 1 .....................................................................207
Karen Stephens
15 Williams-Beuren Syndrome .........................................................221
Stephen W. Scherer and Lucy R. Osborne
16 Sotos Syndrome ............................................................................237
Naohiro Kurotaki and Naomichi Matsumoto
17 X Chromosome Rearrangements..................................................247
Pauline H. Yen
18 Pelizaeus-Merzbacher Disease and Spastic Paraplegia Type 2........263
Ken Inoue
19 Y-Chromosomal Rearrangements and Azoospermia...................273
Matthew E. Hurles and Chris Tyler-Smith
20 Inversion Chromosomes...............................................................289
Orsetta Zuffardi, Roberto Ciccone, Sabrina Giglio,
and Tiziano Pramparo
21 Monosomy 1p36 As a Model for the Molecular Basis
of Terminal Deletions...............................................................301
Blake C. Ballif and Lisa G. Shaffer
22 inv dup(15) and inv dup(22).........................................................315
Heather E. McDermid and Rachel Wevrick
23 Mechanisms Underlying Neoplasia-Associated Genomic
Rearrangements ........................................................................327
Thoas Fioretos
P V F A G S
ART UNCTIONAL SPECTS OF ENOME TRUCTURE
24 Recombination Hotspots in Nonallelic Homologous
Recombination..........................................................................341
Matthew E. Hurles and James R. Lupski
25 Position Effects.............................................................................357
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PawelStankiewicz