The Principles of Clinical Cytogenetics - Extra Materials - Springer

Genomic Imprinting and Uniparental Disomy 515
INTRODUCTION
From: The Principles of Clinical Cytogenetics, Second Edition
Edited by: S. L. Gersen and M. B. Keagle © Humana Press Inc., Totowa, NJ
515
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Genomic Imprinting and Uniparental Disomy
Jin-Chen C. Wang, MD
Genomic imprinting refers to the process of differential modification and expression of parental
alleles. As a result, the same gene can function differently depending on whether it is maternally or
paternally derived. This concept is contrary to that of the traditional Mendelian inheritance in which
genetic information contributed by either parent is assumed to be equivalent.
The term “imprinting” was coined by Crouse (1) to describe the modification and the selective
elimination of paternal X chromosomes from somatic and germline cells of the fly Sciara, in which
the “imprint” a chromosome bears is determined only by the sex of the parent through which the
chromosome has been inherited. It has since been used in many other species, including man (2).
Evidence for the existence of genomic imprinting is manifold. Initial experimental approaches
include studies in mouse embryos using nuclear-transplantation techniques (3–7). These experiments
involve the removal and reintroduction of pronuclei into zygotes, thus creating embryos that have either
only the maternal or paternal genome. In parthenogenetic eggs (i.e., eggs that contain two maternal
pronuclei and no paternal pronucleus), fetal development is relatively good but extraembryonic tissue
development is poor. In contrast, in androgenetic eggs (i.e., eggs containing two paternal pronuclei and
no maternal pronucleus), the development of extraembryonic tissue is good, but fetal development is
poor. In either case, the embryos fail to reach term. Thus, both maternal and paternal genomes are
required for normal development, and it appears that, at least in mice, the maternal genome is essential
for embryogenesis, whereas the paternal genome is essential for placental development.
The human equivalents to these observations in mice are the ovarian teratoma and the complete
hydatidiform mole, and the two types of triploidy, namely digynic triploidy and diandric partial
hydatidiform mole (see Chapter 8). Ovarian teratoma is an embryonal tumor that contains tissues
predominantly derived from ectodermal germ layers, but also mesodermal and endodermal germ
layers. The ovarian teratoma has been shown to be parthenogenetic and contains two sets of the
maternal genome and no paternal genome (8). The complete mole, on the other hand, is androgenetic
and contains two sets of the paternal genome and no maternal genome (9,10). Studies of the parental
origin of the extra haploid set of chromosomes in triploids reveal that this is maternal (digynic triploidy)
when severe intrauterine growth retardation and abnormally small placentas are seen, whereas
it is paternal (diandric triploidy) in partial hydatidiform moles, in which the placenta is abnormally
large (11–13). Intercross experiments in mice between either Robertsonian or reciprocal translocation
carriers further demonstrate that maternal duplication/paternal deficiency or maternal deficiency/
paternal duplication of certain mouse chromosomes or regions of chromosomes results in different
phenotypic abnormalities (14).
Observations of X-chromosome inactivation in different species and different tissues provide further
evidence of imprinting. Although inactivation of the X chromosome in females of placental