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Genetic Imprinting
No parthenogenesis in mammals
Genomic imprinting and the strange case of the insulin-like growth
factor II receptor.
Haig D, Graham C. Cell. 64:1045-6 (1991)
Maternal-Paternal Conflict Theory
The sins of the fathers and mothers: genomic imprinting
in mammalian development.
Tilghman SM. Cell;96:185-93 (1999).
A growth-deficiency phenotype in heterozygous mice carrying an
insulin-like growth factor II gene disrupted by targeting.
DeChiara TM, Efstratiadis A, Robertson EJ.
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Nature. 1990, 345,78-80.
Loss of the imprinted IGF2/cation-independent
mannose 6-phosphate receptor results in fetal overgrowth
and perinatal lethality.
Lau MM… Stewart CL.
Genes Dev. 1994 ;8, 2953-63.
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Rescue of the T-associated maternal effect in mice carrying
null mutations in Igf-2 and Igf2r,
two reciprocally imprinted genes.
Filson AJ, Louvi A, Efstratiadis A, Robertson EJ
Development. 1993, 118 :731-6.
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Holmes: “When you have eliminated the impossible, whatever remains, however
improbable, must be the truth”
“Perhaps,” said Watson, skeptically, “You may have convinced me as to the
motive, but you are yet to explain how it is done.”
Tilghman SM. Cell 1999 ;96:185-93
A maternal-offspring coadaptation theory for the evolution of genomic imprinting.
Wolf JB, Hager R. PLoS Biol. 2006 Nov;4(12):e380.
Imprinted genes are expressed either from the maternally or paternally inherited
copy only, and they play a key role in regulating complex biological processes,
including offspring development and mother-offspring interactions. There are
several competing theories attempting to explain the evolutionary origin of this
monoallelic pattern of gene expression, but a prevailing view has emerged that
holds that genomic imprinting is a consequence of conflict between maternal and
paternal gene copies over maternal investment. However, many imprinting patterns
and the apparent overabundance of maternally expressed genes remain unexplained
and may be incompatible with current theory. Here we demonstrate that sole
expression of maternal gene copies is favored by natural selection because it
increases the adaptive integration of offspring and maternal genomes, leading to
higher offspring fitness. This novel coadaptation theory for the evolution of
genomic imprinting is consistent with results of recent studies on epigenetic
effects, and it provides a testable hypothesis for the origin of previously
unexplained major imprinting patterns across different taxa. In conjunction with
existing hypotheses, our results suggest that imprinting may have evolved due to
different selective pressures at different loci.
Distinct physiological and behavioural functions for parental
alleles of imprinted Grb10.
Garfield AS…Ward A. Nature. 469(7331):534-8 (2011)
Imprinted genes, defined by their preferential expression of a single parental
allele, represent a subset of the mammalian genome and often have key roles in
embryonic development, but also postnatal functions including energy homeostasis
and behaviour. When the two parental alleles are unequally represented within a
social group (when there is sex bias in dispersal and/or variance in reproductive
success), imprinted genes may evolve to modulate social behaviour, although so
far no such instance is known. Predominantly expressed from the maternal allele
during embryogenesis, Grb10 encodes an intracellular adaptor protein that can
interact with several receptor tyrosine kinases and downstream signalling
molecules. Here we demonstrate that within the brain Grb10 is expressed from the
paternal allele from fetal life into adulthood and that ablation of this
expression engenders increased social dominance specifically among other aspects
of social behaviour, a finding supported by the observed increase in allogrooming
by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an
imprinted gene that regulates social behaviour. It is also currently alone in
exhibiting imprinted expression from each of the parental alleles in a
tissue-specific manner, as loss of the peripherally expressed maternal allele
leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a
unique imprinted gene, able to influence distinct physiological processes, fetal
growth and adult behaviour, owing to actions of the two parental alleles in
different tissues.
High-frequency generation of viable mice from engineered bi-maternal embryos
Manabu Kawahara….& Tomohiro Kono. Nat Biotechnol. 25:1045-50 (2007)
Mammalian development to adulthood typically requires both maternal and paternal genomes,
because genomic imprinting places stringent limitations on mammalian development, strictly
precluding parthenogenesis. Here we report the generation of bi-maternal embryos that develop
at a high success rate equivalent to the rate obtained with in vitro fertilization of normal embryos.
These bi-maternal mice developed into viable and fertile female adults. The bi-maternal embryos,
distinct from parthenogenetic or gynogenetic conceptuses, were produced by the construction of
oocytes from fully grown oocytes and nongrowing oocytes that contain double deletions in the H19
differentially methylated region (DMR) and the Dlk1-Dio3 intergenic germline–derived DMR. The
results provide conclusive evidence that imprinted genes regulated by these two paternally
methylated imprinting-control regions are the only paternal barrier that prevents the normal
development of bi-maternal mouse fetuses to term.
Early mammalian development
Amniotes
Biology (Kampbell & reece)
Amniotic development- reptiles and mammals
Oviparous versus viviparous
http://universe-review.ca/R10-33-anatomy.htm
Monozygotic twins
Dizygotic twins
(identical twins)
(fraternal or non-identical twins)
< 5 days
5-9 days
> 9 days
Blood group chimerism in human multiple births is not rare.
van Dijk BA, Boomsma DI, de Man AJ. Am J Med Genet. 61:264-8. (1996).
Twin blood group chimerism seems to be very rare in humans. The 30-40 previously reported
cases usually were found by mere coincidence during routine blood grouping in hospitals or
blood banks. Usually in these cases frank blood group mixtures of, for example, 50/50%,
25/75%, or 5/95% at most were seen. Smaller percentages are very difficult to notice during
routine work-up. Using a sensitive fluorescence technique (sensitivity > 0.01%) we detected
blood group chimerism in 32/415 (8%) twin pairs and 12/57 (21%) triplet pairs, respectively,
which is a higher incidence than reported previously.
Do monochorionic dizygotic twins increase after pregnancy
by assisted reproductive technology?
Miura K, Niikawa N. J Hum Genet.;50:1-6 (2005).
‫העץ הפילוגנטי המשוער של היונקים‬
‫‪Marsupials‬‬‫יונקי הכיס‬
‫‪Eutherians‬‬
‫יונקי השליה‬
‫יונקי ביב‬
‫‪Monotremata‬‬
Monotreme
‫קיפודן‬
‫ברווזן‬
"Monotremes oviparous, ovum meroblastic" (Caldwell, September 2, 1884)
Biology (Solomon, Berg & Martin)
Life
Marsupials- ‫יונקי הכיס‬
Koala
Tasmanian wolf/tiger
Biology (Solomon, Berg & Martin)
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From: Manipulating the Mouse
Embryo. Hogan et al., Cold
Spring Harbor Laboratory Press,
2nd Edition, 1994.
The first developmental decision: ICM or trophoblast
The first developmental decision: ICM or trophoblast
Dev Biol 9th Ed. (2010)
The first developmental decision: ICM or trophoblast
Trophoblast
ICM
Dev Biol 9th Ed. (2010)
From: Manipulating the Mouse Embryo. Hogan et al., Cold
Spring Harbor Laboratory Press, 2nd Edition, 1994.
Fazleabas and Kim (2003). What Makes an Embryo Stick ? Science 299:355-6.
‫ליאונרדו דה וינצ'י‬
‫עובר ברחם‬
‫‪~1510‬‬