A new imprinted gene cloned by a methylation-sensitive genome scanning method

Hatada, Izuho; Sugama, Takako; Mukai, Tsunehiro

doi:10.1093/nar/21.24.5577

Cited by 101 publications

(80 citation statements)

References 7 publications

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“…This suggests that imprinting of genes on chr 11 modulates the susceptibility to astrocytoma. Imprinted genes have been identified on chr 11 in the mouse, supporting this possibility (29,30). The F 1 data suggest that inheritance of the WT chr 11 from the father increases susceptibility, whereas inheritance of the WT chr 11 from the mother decreases susceptibility.…”

Section: Discussionmentioning

confidence: 82%

Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects

Reilly

Tuskan

Christy

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Astrocytoma is the most common malignant brain tumor in humans. Loss of the p53 signaling pathway and up-regulation of the ras signaling pathway are common during tumor progression. We have shown previously that mice mutant for Trp53 and Nf1 develop astrocytoma, progressing to glioblastoma, on a C57BL͞6J strain background. In contrast, here we present data that mice mutant for Trp53 and Nf1 on a 129S4͞SvJae background are highly resistant to developing astrocytoma. Through analysis of F 1 progeny, we demonstrate that susceptibility to astrocytoma is linked to chromosome 11, and that the modifier gene(s) responsible for differences in susceptibility is closely linked to Nf1 and Trp53. Furthermore, this modifier of astrocytoma susceptibility is itself epigenetically modified. These data demonstrate that epigenetic effects can have a strong effect on whether cancer develops in the context of mutant ras signaling and mutant p53, and that this mouse model of astrocytoma can be used to identify modifier phenotypes with complex inheritance patterns that would be unidentifiable in humans. Because analysis of gene function in the mouse is often performed on a mixed C57BL͞6,129 strain background, these data also provide a powerful example of the potential of these strains to mask interesting gene functions.A strocytoma is a characteristically diffuse tumor of the central nervous system (CNS). Because of its diffuse infiltration, it often cannot be completely resected, leading to a very poor prognosis for patients. Astrocytoma, together with glioblastoma (the highest grade of astrocytoma), accounts for more than three-quarters of all gliomas, making it the most common malignant brain tumor (1). The 5-year survival rate for glioblastoma is Ͻ3%. A better understanding of the genetic risk factors associated with astrocytoma will give insight into the mechanism of astrocytoma initiation and progression and will lead to better screening methods and new targets for therapy.Data from human populations pointing to genetic risk factors for astrocytoma are sparse. Malmer et al. (2) have examined the increased family risk of developing low-vs. high-grade glioma and favor the view that autosomal recessive genes affect astrocytoma risk, although the role of a common environment in familial risk cannot be excluded. Several familial cancer syndromes show an increased risk for astrocytoma, including neurofibromatosis type 1 (NF1) (3, 4) and Li-Fraumeni syndrome (LFS) (5). NF1 patients have a mutation in the NF1 gene (6) (Nf1 in the mouse) and are predisposed to neurofibromas and optic gliomas, with an increased risk for malignant peripheral nerve sheath tumors and diffuse astrocytoma͞glioblastoma (3, 4). Studies of NF1 families have demonstrated a role for modifier genes unlinked to NF1 in the severity of the disease with respect to the numbers of neurofibromas and the presence or absence of optic gliomas (7). Studies of NF1 patients have also shown that patients with optic glioma are more likely to develop CNS tumors such as astrocytoma ...

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Section: Discussionmentioning

confidence: 82%

Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects

Reilly

Tuskan

Christy

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Ndn (MacDonald and Wevrick 1997) and Magel2 (Boccaccio et al 1999) are both expressed in the mouse placenta, whereas the imprinting status was not clear. Rian (Hatada et al 2001), Zim1 (Kim et al 1999), Meg3 (Miyoshi et al 2000), Mirg (Seitz et al 2004), Usp29 (Kim et al 2000), Impact (Hagiwara et al 1997), Nnat (Kagitani et al 1997), Zdbf2 (Kobayashi et al 2009), and Zrsr1 (Hatada et al 1993) were not previously reported to be imprinted in the mouse placenta either. Therefore, we identified 12 candidate genes with novel mouse placenta imprinting status.…”

Section: Detection Of Significant Parent-of-origin Effectsmentioning

confidence: 96%

A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq

2011

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Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F 1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of 23 known imprinted genes in the placenta and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a wellreplicated design using an orthogonal allelic-expression technology, we verified 5 novel imprinted genes that were not previously known to be imprinted in mouse (Pde10, Phf17, Phactr2, Zfp64, and Htra3). Our data suggest that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally expressed imprinted genes, with the addition of our validated set of placenta-imprinted genes, this maternal bias has disappeared.

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“…Iff2, H19, Ins2, Mash2, Snrpn, ZNF127, and another imprinted gene, p57 raP2, are all located on the mouse chromosome 7. With the restriction landmark genome scanning (RLGS) method, the paternally expressed mouse gene, SP2 (U2aJbp-rs), was isolated (Hatada et al, 1993;Hayashizaki et al, 1994), assigned to an imprinting region of chromosome 11, and possibly plays a role in the determination of body size. Another approach, a screening of the genome by means of the subtraction hybridization method made it possible to isolate two novel mouse paternally expressed genes: Pegl (paternally expressed gene 1), which was mapped to chromosome 6 (Kaneko-Ishino et aL, 1995), and the other, Peg3, mapped to the proximal region of chromosome 7 (Kuroiwa et aL, 1996).…”

Section: Identification Of Imprinted Genesmentioning

confidence: 99%

Genomic imprinting and its relevance to genetic diseases

Niikawa

1996

Jap J Human Genet

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SummaryGenomic imprinting is a biological phenomenon determined by an evolutionally acquired, underlying system that may control harmonious development and growth in mammals. It is also relevant to some genetic disorders in man. In this article, lines of biological evidence of imprinting, characteristics of the mouse and human imprinted genes, and findings and mechanisms on the occurrence of several human imprinting disorders are reviewed.

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A new imprinted gene cloned by a methylation-sensitive genome scanning method

Cited by 101 publications

References 7 publications

Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects

Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects

A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq

Genomic imprinting and its relevance to genetic diseases

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