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Color Atlas of Genetics
von
Eberhard Passarge
Neuausgabe
Color Atlas of Genetics – Passarge
schnell und portofrei erhältlich bei beck-shop.de DIE FACHBUCHHANDLUNG
Thematische Gliederung:
Humangenetik – Humangenetik
Thieme 2006
Verlag C.H. Beck im Internet:
www.beck.de
ISBN 978 3 13 100363 8
Inhaltsverzeichnis: Color Atlas of Genetics – Passarge
232
Epigenetic Modifications
Genomic Imprinting
In eukaryotes, only one allele of certain genes is
expressed, while the other is permanently repressed. The state of expression depends on
which parent contributes the allele, i.e.,
whether it is of maternal or paternal origin
(parent-specific expression). This is called
genomic imprinting. Genomic imprinting is an
important epigenetic change in mammalian
cells. Imprinting is assumed to have evolved in
mammals in response to intrauterine competition for resources. Natural selection acts differently on genomes of maternal and paternal
origin. A balance between maternal survival
and fetal growth is favorable.
A. The importance of two different
parental genomes
In mice, different developmental results are observed depending on whether the female pronucleus (2) or the male pronucleus (4) is removed from a diploid zygote (1) before they
fuse, instead of leaving both in place (3). If the
female pronucleus is replaced by a male pronucleus, an androgenetic zygote results. In this
case the zygote initially appears normal.
However, if implantation ensues, nearly all
androgenotes will fail to complete preimplantation (2). The rare few that reach postimplantation develop abnormally and do not progress
beyond the 12-somite stage.
In contrast, when a male pronucleus is replaced
by a female pronucleus, a gynogenetic zygote
results (4), which differs markedly from the
androgenote. Although about 85% of gynogenotes develop normally until preimplantation, the extraembryonic membranes are absent or underdeveloped. As a result the embryo
dies at or before the 40-somite stage. (Figure
adapted from Sapienza & Hall, 2001.)
B. Requirement for a maternal and
a paternal genome
A naturally occurring human androgenetic zygote is a hydatidiform mole (1). This is an abnormal placental formation containing two sets of
paternal chromosomes and none from the
mother. An embryo does not develop, although
implantation takes place. The placental tissues
develop many cysts (2). When only maternal
chromosomes are present, an ovarian teratoma
with many different types of fetal tissue
develops (3). No placental tissue is present in
this naturally occurring gynogenetic zygote. In
triploidy, a relatively frequent fatal human
chromosomal disorder (see p. 412), extreme hypoplasia of the placenta and fetus is observed
when the additional chromosomal set is of maternal origin (4). (Photographs kindly provided
by Professor Helga Rehder, Marburg.)
C. Genomic imprinting is established in
early embryonic development
The changes responsible for imprinting occur in
early embryogenesis. The imprint pattern typically present in somatic cells (1), is erased in
primordial germ cells (2). During the formation
of gametes, the imprinting pattern is reset (3).
Imprinted chromosomal regions of paternal
origin receive the paternal pattern; those of maternal origin receive the maternal pattern. As a
result, after fertilization the correct imprint
pattern is present in the zygote (4) and is maintained through all subsequent cell divisions.
Medical relevance
Failure to establish the normal pattern of imprinting due to gene rearrangements causes an
important, heterogenous group of imprinting
diseases (see p. 410).
References
Constância M, Kelsey G, Reik W: Resourceful imprinting. Nature 432: 53–57, 2004.
Horsthemke B, Buiting K: Imprinting defects on
human chromosome 15. Cytogenet Genome Res
113: 292–299, 2006.
Morrison IM, Reeve AE: Catalogue of imprinted genes
and parent-of-origin effects in humans and animals. Hum Mol Genet 7: 1599–1609, 1998.
Reik W, Walter J: Genomic imprinting: parental influence on the genome. Nature Rev Genet 2: 21–32,
2001.
Reik W, Dean W, Walter J: Epigenetic reprogramming in mammalian development. Science 293:
1089–1093, 2001.
Sapienza C, Hall JG: Genetic imprinting in human disease, pp 417–431. In: The Metabolic and Molecular
Bases of Inherited Disease, 8th ed. CR Scriver et al
(eds), McGraw-Hill, New York, 2001.
Wilkins JF, Haig D: What good is genomic imprinting:
the function of parent-specific gene expression.
Nature Rev Genet 4: 359–368, 2003.
Passarge, Color Atlas of Genetics (ISBN 3131003634), 䊚 2007 Georg Thieme Verlag
Genomic Imprinting
233
dies very
early
2
Androgenetic
1
normal
development
Extraembryonic
tissues
3
Diploid zygote
Fetus absent
or stunted
Preimplantation
failure in most
Fetus normal
Preimplantation
Normal
dies
later
4
Gynogenetic
Fetus normal
until 40-somite
stage
Preimplantation normal,
extra-embryonic
tissues underdeveloped
A. The importance of two different parental genomes
Two paternal genomes
1. Hydatidiform mole
Two maternal genomes
3. Ovarian teratoma
2. Hydatidiform mole
4. Triploidy 69,XXX
B. Human embryonic development depends on presence of a maternal and a paternal genome
1.
P
Somatic cells
XX and XY
Male
P
2.
P Paternal
M
Inactive
Active
Active
Inactive
P
M Maternal
Female
M
M
Imprint
erased
Primordial
germ cells
P
M
3.
Imprint
reset
Gametes
P
M
4.
Imprint
established
Zygote
C. Genomic imprinting is established in early embryonic development
Passarge, Color Atlas of Genetics (ISBN 3131003634), 䊚 2007 Georg Thieme Verlag