The parent-of-origin effect of 10q22 in pre-eclamptic females coincides with two regions clustered for genes with down-regulated expression in androgenetic placentas

Cees B.M. Oudejans, Joyce Mulders, Augusta M.A. Lachmeijer, Marie van Dijk, Andrea A.M. Könst, Bart A. Westerman, Inge J. van Wijk, Peter A.J. Leegwater, Hidenori D. Kato, Takao Matsuda, Norio Wake, Gustaaf A. Dekker, Gerard Pals, Leo P. ten Kate, Marinus A. Blankenstein

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

By affected sib-pair linkage analysis of 24 families with pre-eclampsia, we confirm a susceptibility locus on chromosome 10q22.1 in Dutch females: a multipoint non-parametric linkage score of 3.6 near marker D10S1432 was obtained. Haplotype analysis showed a parent-of-origin effect: maximal allele sharing in the affected sibs was found for maternally derived alleles in all families, but not for the paternally derived alleles. As matrilineal inheritance suggests the presence of maternally expressed imprinted genes, while imprinting operates predominantly in (extra)embryonic tissues, all genes (n = 132) known on 10q22 between GATA121A08 and D10S580 were screened for seven sequence-related features associated with imprinting and subsequently tested for expression in first trimester placenta. Placental expression of genes selected in this way (n = 55) was compared with expression in androgenetic placentas of identical gestational age. Two regions on 10q22 were identified with developmentally co-repressed genes with non-random chromosomal distribution. Interestingly, these two clusters, near CTNNA3 and KCNMA1 and each containing five genes with down-regulated expression in androgenetic placentas, coincided with the regions with maximal maternal allele sharing seen in the pre-eclamptic sisters. Our linkage and expression data are compatible with the concept that pre-eclampsia involves maternally expressed imprinted genes that operate in the first trimester placenta.

Original languageEnglish
Pages (from-to)589-598
Number of pages10
JournalMolecular Human Reproduction
Volume10
Issue number8
DOIs
Publication statusPublished - 1 Aug 2004

Cite this

Oudejans, Cees B.M. ; Mulders, Joyce ; Lachmeijer, Augusta M.A. ; van Dijk, Marie ; Könst, Andrea A.M. ; Westerman, Bart A. ; van Wijk, Inge J. ; Leegwater, Peter A.J. ; Kato, Hidenori D. ; Matsuda, Takao ; Wake, Norio ; Dekker, Gustaaf A. ; Pals, Gerard ; ten Kate, Leo P. ; Blankenstein, Marinus A. / The parent-of-origin effect of 10q22 in pre-eclamptic females coincides with two regions clustered for genes with down-regulated expression in androgenetic placentas. In: Molecular Human Reproduction. 2004 ; Vol. 10, No. 8. pp. 589-598.
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abstract = "By affected sib-pair linkage analysis of 24 families with pre-eclampsia, we confirm a susceptibility locus on chromosome 10q22.1 in Dutch females: a multipoint non-parametric linkage score of 3.6 near marker D10S1432 was obtained. Haplotype analysis showed a parent-of-origin effect: maximal allele sharing in the affected sibs was found for maternally derived alleles in all families, but not for the paternally derived alleles. As matrilineal inheritance suggests the presence of maternally expressed imprinted genes, while imprinting operates predominantly in (extra)embryonic tissues, all genes (n = 132) known on 10q22 between GATA121A08 and D10S580 were screened for seven sequence-related features associated with imprinting and subsequently tested for expression in first trimester placenta. Placental expression of genes selected in this way (n = 55) was compared with expression in androgenetic placentas of identical gestational age. Two regions on 10q22 were identified with developmentally co-repressed genes with non-random chromosomal distribution. Interestingly, these two clusters, near CTNNA3 and KCNMA1 and each containing five genes with down-regulated expression in androgenetic placentas, coincided with the regions with maximal maternal allele sharing seen in the pre-eclamptic sisters. Our linkage and expression data are compatible with the concept that pre-eclampsia involves maternally expressed imprinted genes that operate in the first trimester placenta.",
keywords = "Chromosome 10, Imprinting, Molar Pregnancy, Pre-eclampsia, Trophoblast",
author = "Oudejans, {Cees B.M.} and Joyce Mulders and Lachmeijer, {Augusta M.A.} and {van Dijk}, Marie and K{\"o}nst, {Andrea A.M.} and Westerman, {Bart A.} and {van Wijk}, {Inge J.} and Leegwater, {Peter A.J.} and Kato, {Hidenori D.} and Takao Matsuda and Norio Wake and Dekker, {Gustaaf A.} and Gerard Pals and {ten Kate}, {Leo P.} and Blankenstein, {Marinus A.}",
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The parent-of-origin effect of 10q22 in pre-eclamptic females coincides with two regions clustered for genes with down-regulated expression in androgenetic placentas. / Oudejans, Cees B.M.; Mulders, Joyce; Lachmeijer, Augusta M.A.; van Dijk, Marie; Könst, Andrea A.M.; Westerman, Bart A.; van Wijk, Inge J.; Leegwater, Peter A.J.; Kato, Hidenori D.; Matsuda, Takao; Wake, Norio; Dekker, Gustaaf A.; Pals, Gerard; ten Kate, Leo P.; Blankenstein, Marinus A.

In: Molecular Human Reproduction, Vol. 10, No. 8, 01.08.2004, p. 589-598.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The parent-of-origin effect of 10q22 in pre-eclamptic females coincides with two regions clustered for genes with down-regulated expression in androgenetic placentas

AU - Oudejans, Cees B.M.

AU - Mulders, Joyce

AU - Lachmeijer, Augusta M.A.

AU - van Dijk, Marie

AU - Könst, Andrea A.M.

AU - Westerman, Bart A.

AU - van Wijk, Inge J.

AU - Leegwater, Peter A.J.

AU - Kato, Hidenori D.

AU - Matsuda, Takao

AU - Wake, Norio

AU - Dekker, Gustaaf A.

AU - Pals, Gerard

AU - ten Kate, Leo P.

AU - Blankenstein, Marinus A.

PY - 2004/8/1

Y1 - 2004/8/1

N2 - By affected sib-pair linkage analysis of 24 families with pre-eclampsia, we confirm a susceptibility locus on chromosome 10q22.1 in Dutch females: a multipoint non-parametric linkage score of 3.6 near marker D10S1432 was obtained. Haplotype analysis showed a parent-of-origin effect: maximal allele sharing in the affected sibs was found for maternally derived alleles in all families, but not for the paternally derived alleles. As matrilineal inheritance suggests the presence of maternally expressed imprinted genes, while imprinting operates predominantly in (extra)embryonic tissues, all genes (n = 132) known on 10q22 between GATA121A08 and D10S580 were screened for seven sequence-related features associated with imprinting and subsequently tested for expression in first trimester placenta. Placental expression of genes selected in this way (n = 55) was compared with expression in androgenetic placentas of identical gestational age. Two regions on 10q22 were identified with developmentally co-repressed genes with non-random chromosomal distribution. Interestingly, these two clusters, near CTNNA3 and KCNMA1 and each containing five genes with down-regulated expression in androgenetic placentas, coincided with the regions with maximal maternal allele sharing seen in the pre-eclamptic sisters. Our linkage and expression data are compatible with the concept that pre-eclampsia involves maternally expressed imprinted genes that operate in the first trimester placenta.

AB - By affected sib-pair linkage analysis of 24 families with pre-eclampsia, we confirm a susceptibility locus on chromosome 10q22.1 in Dutch females: a multipoint non-parametric linkage score of 3.6 near marker D10S1432 was obtained. Haplotype analysis showed a parent-of-origin effect: maximal allele sharing in the affected sibs was found for maternally derived alleles in all families, but not for the paternally derived alleles. As matrilineal inheritance suggests the presence of maternally expressed imprinted genes, while imprinting operates predominantly in (extra)embryonic tissues, all genes (n = 132) known on 10q22 between GATA121A08 and D10S580 were screened for seven sequence-related features associated with imprinting and subsequently tested for expression in first trimester placenta. Placental expression of genes selected in this way (n = 55) was compared with expression in androgenetic placentas of identical gestational age. Two regions on 10q22 were identified with developmentally co-repressed genes with non-random chromosomal distribution. Interestingly, these two clusters, near CTNNA3 and KCNMA1 and each containing five genes with down-regulated expression in androgenetic placentas, coincided with the regions with maximal maternal allele sharing seen in the pre-eclamptic sisters. Our linkage and expression data are compatible with the concept that pre-eclampsia involves maternally expressed imprinted genes that operate in the first trimester placenta.

KW - Chromosome 10

KW - Imprinting

KW - Molar Pregnancy

KW - Pre-eclampsia

KW - Trophoblast

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U2 - 10.1093/molehr/gah080

DO - 10.1093/molehr/gah080

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JO - Molecular Human Reproduction

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