Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

Masayo Kagami; Yoichi Sekita; Gen Nishimura; Masahito Irie; Fumiko Kato; Michiyo Okada; Shunji Yamamori; Hiroshi Kishimoto; Masahiro Nakayama; Yukichi Tanaka; Kentarou Matsuoka; Tsutomu Takahashi; Mika Noguchi; Yoko Tanaka; Kouji Masumoto; Takeshi Utsunomiya; Hiroko Kouzan; Yumiko Komatsu; Hirofumi Ohashi; Kenji Kurosawa; Kenjirou Kosaki; Anne C. Ferguson-Smith; Fumitoshi Ishino; Tsutomu Ogata

doi:10.1038/ng.2007.56

Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

Masayo Kagami, Yoichi Sekita, Gen Nishimura, Masahito Irie, Fumiko Kato, Michiyo Okada, Shunji Yamamori, Hiroshi Kishimoto, Masahiro Nakayama, Yukichi Tanaka, Kentarou Matsuoka, Tsutomu Takahashi, Mika Noguchi, Yoko Tanaka, Kouji Masumoto, Takeshi Utsunomiya, Hiroko Kouzan, Yumiko Komatsu, Hirofumi Ohashi, Kenji KurosawaKenjirou Kosaki, Anne C. Ferguson-Smith, Fumitoshi Ishino, Tsutomu Ogata

Center for Medical Genetics

Research output: Contribution to journal › Article › peer-review

245 Citations (Scopus)

Abstract

Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.

Original language	English
Pages (from-to)	237-242
Number of pages	6
Journal	Nature genetics
Volume	40
Issue number	2
DOIs	https://doi.org/10.1038/ng.2007.56
Publication status	Published - 2008 Feb

ASJC Scopus subject areas

Genetics

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Kagami, M., Sekita, Y., Nishimura, G., Irie, M., Kato, F., Okada, M., Yamamori, S., Kishimoto, H., Nakayama, M., Tanaka, Y., Matsuoka, K., Takahashi, T., Noguchi, M., Tanaka, Y., Masumoto, K., Utsunomiya, T., Kouzan, H., Komatsu, Y., Ohashi, H., ... Ogata, T. (2008). Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes. Nature genetics, 40(2), 237-242. https://doi.org/10.1038/ng.2007.56

Kagami, M, Sekita, Y, Nishimura, G, Irie, M, Kato, F, Okada, M, Yamamori, S, Kishimoto, H, Nakayama, M, Tanaka, Y, Matsuoka, K, Takahashi, T, Noguchi, M, Tanaka, Y, Masumoto, K, Utsunomiya, T, Kouzan, H, Komatsu, Y, Ohashi, H, Kurosawa, K, Kosaki, K, Ferguson-Smith, AC, Ishino, F & Ogata, T 2008, 'Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes', Nature genetics, vol. 40, no. 2, pp. 237-242. https://doi.org/10.1038/ng.2007.56

@article{0c9880b8985b41fa895996de57bfd987,

title = "Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes",

abstract = "Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.",

author = "Masayo Kagami and Yoichi Sekita and Gen Nishimura and Masahito Irie and Fumiko Kato and Michiyo Okada and Shunji Yamamori and Hiroshi Kishimoto and Masahiro Nakayama and Yukichi Tanaka and Kentarou Matsuoka and Tsutomu Takahashi and Mika Noguchi and Yoko Tanaka and Kouji Masumoto and Takeshi Utsunomiya and Hiroko Kouzan and Yumiko Komatsu and Hirofumi Ohashi and Kenji Kurosawa and Kenjirou Kosaki and Ferguson-Smith, {Anne C.} and Fumitoshi Ishino and Tsutomu Ogata",

note = "Funding Information: We would like to thank all the affected individuals and their family members who participated in this study. This work was supported by Grants for Child Health and Development (17C-2) and for Research on Children and Families (H18-005) from the Ministry of Health, Labor, and Welfare, and by Grants-in-Aid for Scientific Research (priority areas: 16086215 and 1508023; category B: 19390290) from the Ministry of Education, Culture, Sports, Science and Technology.",

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doi = "10.1038/ng.2007.56",

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volume = "40",

pages = "237--242",

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T1 - Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

AU - Kagami, Masayo

AU - Sekita, Yoichi

AU - Nishimura, Gen

AU - Irie, Masahito

AU - Kato, Fumiko

AU - Okada, Michiyo

AU - Yamamori, Shunji

AU - Kishimoto, Hiroshi

AU - Nakayama, Masahiro

AU - Tanaka, Yukichi

AU - Matsuoka, Kentarou

AU - Takahashi, Tsutomu

AU - Noguchi, Mika

AU - Tanaka, Yoko

AU - Masumoto, Kouji

AU - Utsunomiya, Takeshi

AU - Kouzan, Hiroko

AU - Komatsu, Yumiko

AU - Ohashi, Hirofumi

AU - Kurosawa, Kenji

AU - Kosaki, Kenjirou

AU - Ferguson-Smith, Anne C.

AU - Ishino, Fumitoshi

AU - Ogata, Tsutomu

N1 - Funding Information: We would like to thank all the affected individuals and their family members who participated in this study. This work was supported by Grants for Child Health and Development (17C-2) and for Research on Children and Families (H18-005) from the Ministry of Health, Labor, and Welfare, and by Grants-in-Aid for Scientific Research (priority areas: 16086215 and 1508023; category B: 19390290) from the Ministry of Education, Culture, Sports, Science and Technology.

PY - 2008/2

Y1 - 2008/2

N2 - Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.

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Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

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