Aneuploidy in health and disease

254 Pages·2012·16.018 MB·English

by  Zuzana Storchova

ANEUPLOIDY IN HEALTH
AND DISEASE
Edited by Zuzana Storchova
ANEUPLOIDY IN HEALTH
AND DISEASE

Edited by Zuzana Storchova
Aneuploidy in Health and Disease
Edited by Zuzana Storchova

Published by InTech
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Copyright © 2012 InTech
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First published May, 2012
Printed in Croatia

A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]

Aneuploidy in Health and Disease, Edited by Zuzana Storchova
p. cm.
ISBN 978-953-51-0608-1

Contents

Preface IX
Section 1 Causes and Consequences of Aneuploidy 1
Chapter 1 The Causes and Consequences
of Aneuploidy in Eukaryotic Cells 3
Zuzana Storchova
Chapter 2 Uncover Cancer Genomics by Jointly
Analysing Aneuploidy and Gene Expression 23
Lingling Zheng and Joseph Lucas
Chapter 3 Sister Chromatid Cohesion and Aneuploidy 41
Erwan Watrin and Claude Prigent
Chapter 4 Mouse Models for Chromosomal Instability 59
Floris Foijer
Section 2 The Impact of Aneuploidy on Human Health 79
Chapter 5 Aneuploidy and Epithelial Cancers: The Impact
of Aneuploidy on the Genesis, Progression and
Prognosis of Colorectal and Breast Carcinomas 81
Jens K. Habermann, Gert Auer, Madhvi Upender, Timo Gemoll,
Hans-Peter Bruch, Hans Jörnvall, Uwe J. Roblick and Thomas Ried
Chapter 6 Aneuploidy and Intellectual Disability 107
Daisuke Fukushi, Seiji Mizuno, Kenichiro Yamada, Reiko Kimura,
Yasukazu Yamada, Toshiyuki Kumagai and Nobuaki Wakamatsu
Chapter 7 Sex Chromosome Aneuploidies 123
Eliona Demaliaj, Albana Cerekja and Juan Piazze
Chapter 8 Human Male Meiosis and Sperm Aneuploidies 141
María Vera, Vanessa Peinado, Nasser Al-Asmar, Jennifer Gruhn,
Lorena Rodrigo, Terry Hassold and Carmen Rubio
VI Contents

Chapter 9 Morphology and Aneuploidy of
in vitro Matured (IVM) Human Oocytes 163
Lidija Križančić Bombek, Borut Kovačič and Veljko Vlaisavljević
Chapter 10 Comparing Pig and Amphibian Oocytes: Methodologies
for Aneuploidy Detection and Complementary Lessons for
MAPK Involvement in Meiotic Spindle Morphogenesis 193
Michal Ješeta and Jean-François L. Bodart
Chapter 11 The Role of Aneuploidy Screening in
Human Preimplantation Embryos 217
Christian S. Ottolini, Darren K. Griffin and Alan R. Thornhill

Preface

Genetic information is physically carried on large DNA strings that are organized into
chromosomes. Each species is characterized by a chromosome set that carry the
information necessary and sufficient for its development and survival. Eukaryotic
organisms are mostly diploid, containing two sets of chromosomes with each pair
carrying nearly identical genetic information. Occasionally, exceptions to this rule are
found, such as haploid yeast (with only one set of chromosomes) or polyploid ferns
and frogs (with multiple sets). Nevertheless, the composition of chromosome set
remains identical within a species.
Aneuploidy describes exceptions from this rule. Some organisms or individual cells
might contain an extra chromosome or two, some might have lost a chromosome arm.
These alterations might be rare in normal, healthy organisms, but are often found
under pathological conditions. Years of research uncovered a multitude of
mechanisms and defects in cellular pathways that can lead to aneuploidy, and the list
is still growing. Recent analysis shed first light on the effects that aneuploidy instigates
upon cells. Only slowly we start to untangle the intricate relationship between
chromosome numbers and structure and cell physiology.
Part of the urge to study aneuploidy is triggered by the clear association of aneuploidy
with various pathologies. In humans, aneuploidy is the most frequent cause of
spontaneous abortions as it severely impairs embryo development. A handful of
aneuploidies compatible with survival leads to newborns with variable handicaps and
a limited life span. The majority of malignant tumors consists of cells with an
aneuploid karyotype. The relationship of tumorigenesis and aneuploidy remains
enigmatic despite growing scientific interest. Recently, novel observations suggest that
aging and, in particular, neurodegeneration might be associated with aneuploidy as
well.
Aneuploidy means anything that is not euploid, anything that stands outside the
norm. Thus, aneuploidy takes numerous variable features and is remarkably
demanding to study. Two particular characteristics make the studies of aneuploidy
challenging. First, it is often hard to distinguish what is a cause and what is a
consequence. Was aneuploidy first and then the pathological conditions came? Or is
aneuploidy itself a consequence of a gene mutation or other cellular changes? The
X Preface

progress in long term imaging techniques as well as the techniques enabling to
generate artificially aneuploid cells expand our experimental tools to address these
questions. Secondly, aneuploidy is often associated with chromosomal instability, a
persistent defect of the cellular ability to equally distribute genetic information into
daughter cells. Thus, working with aneuploid, chromosomally unstable cells means to
analyze an ever changing creature and capture the features that persist. The hopes are
high that new genome-wide systems biology approaches will help to identify the
patterns shared among aneuploid cells and organisms.
This book attempts to map our current knowledge on aneuploidy from the basic
research view on the causes and consequences of aneuploidy, covered in Part I, to the
medical relevance of aneuploidy in cancer research, reproductive biology and stem
cell research, which is addressed in Part II. The multitude of covered topics reflects the
variability of aneuploid cells as well as the broad extent of methods applied in
aneuploidy research. I would like to thank the authors for the broad and at the same
time deep review of their topics, and the editors for the support that enabled to
produce the book in your hands.

Dr. Zuzana Storchová
Max Planck Institute of Biochemistry
Martinsried, Germany