An imprinted locus associated with transient neonatal diabetes mellitus
An imprinted locus associated with transient neonatal diabetes mellitus
Recently, we reported the localization of a gene for transient neonatal diabetes mellitus (TNDM), a rare form of childhood diabetes, to an approximately 5.4 Mb region of chromosome 6q24. We have also shown that TNDM is associated with both paternal uniparental disomy (UPD) of chromosome 6 and paternal duplications of the critical region. The sequencing of P1-derived artificial chromosome clones from within the region of interest has allowed us to further localize the gene and to investigate the methylation status of the region. The gene is now known to reside in a 300-400 kb region of 6q24 which contains several CpG islands. At one island we have demonstrated differential DNA methylation between patients with paternal UPD of chromosome 6 and normal controls. In addition, two patients with TNDM, in whom neither paternal UPD of chromosome 6 nor duplication of 6q24 have been found, show a DNA methylation pattern identical to that of patients with paternal UPD of chromosome 6. Control individuals show a hemizygous methylation pattern. These results show that TNDM can be associated with a methylation change and identify a novel methylation imprint on chromosome 6 associated with TNDM.
Blotting, Southern, Chromosomes, Human, Pair 6, CpG Islands, DNA Methylation, Diabetes Mellitus, Expressed Sequence Tags, Fathers, Female, Gene Dosage, Gene Duplication, Genomic Imprinting, Humans, Infant, Newborn, Male, Mothers, Polymerase Chain Reaction, Restriction Mapping, Sequence Tagged Sites, Journal Article, Research Support, Non-U.S. Gov't
589-96
Mackay, D.J.
588a653e-9785-4a00-be71-4e547850ee4a
Mungall, A.J.
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Polychronakos, C
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Siebert, R
4297324b-08e2-4ed7-8f63-43a4b18eae1b
Shield, J.P.
87978770-3a64-4fc2-aedc-535657d2be5f
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Robinson, D.O.
dcef4b3b-ac9b-4c1b-b8b2-1bee4b81a8cc
1 March 2000
Mackay, D.J.
588a653e-9785-4a00-be71-4e547850ee4a
Mungall, A.J.
f0483516-ee99-4fe8-9e3e-0e76893018d6
Polychronakos, C
6e93c69c-7640-4f2a-8f39-6119f4400cf0
Siebert, R
4297324b-08e2-4ed7-8f63-43a4b18eae1b
Shield, J.P.
87978770-3a64-4fc2-aedc-535657d2be5f
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Robinson, D.O.
dcef4b3b-ac9b-4c1b-b8b2-1bee4b81a8cc
Mackay, D.J., Mungall, A.J., Polychronakos, C, Siebert, R, Shield, J.P., Temple, I.K. and Robinson, D.O.
(2000)
An imprinted locus associated with transient neonatal diabetes mellitus.
Human Molecular Genetics, 9 (4), .
Abstract
Recently, we reported the localization of a gene for transient neonatal diabetes mellitus (TNDM), a rare form of childhood diabetes, to an approximately 5.4 Mb region of chromosome 6q24. We have also shown that TNDM is associated with both paternal uniparental disomy (UPD) of chromosome 6 and paternal duplications of the critical region. The sequencing of P1-derived artificial chromosome clones from within the region of interest has allowed us to further localize the gene and to investigate the methylation status of the region. The gene is now known to reside in a 300-400 kb region of 6q24 which contains several CpG islands. At one island we have demonstrated differential DNA methylation between patients with paternal UPD of chromosome 6 and normal controls. In addition, two patients with TNDM, in whom neither paternal UPD of chromosome 6 nor duplication of 6q24 have been found, show a DNA methylation pattern identical to that of patients with paternal UPD of chromosome 6. Control individuals show a hemizygous methylation pattern. These results show that TNDM can be associated with a methylation change and identify a novel methylation imprint on chromosome 6 associated with TNDM.
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Published date: 1 March 2000
Keywords:
Blotting, Southern, Chromosomes, Human, Pair 6, CpG Islands, DNA Methylation, Diabetes Mellitus, Expressed Sequence Tags, Fathers, Female, Gene Dosage, Gene Duplication, Genomic Imprinting, Humans, Infant, Newborn, Male, Mothers, Polymerase Chain Reaction, Restriction Mapping, Sequence Tagged Sites, Journal Article, Research Support, Non-U.S. Gov't
Identifiers
Local EPrints ID: 418399
URI: http://eprints.soton.ac.uk/id/eprint/418399
ISSN: 0964-6906
PURE UUID: 3effdfd5-8cf2-4561-b7bf-0e269c0d951f
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Date deposited: 06 Mar 2018 17:30
Last modified: 19 Jan 2024 02:36
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Contributors
Author:
A.J. Mungall
Author:
C Polychronakos
Author:
R Siebert
Author:
J.P. Shield
Author:
D.O. Robinson
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