Human Molecular Genetics, Vol 7, 1149-1159, Copyright © 1998 by Oxford University Press
M Paulsen, KR Davies, LM Bowden, AJ Villar, O Franck, M Fuermann, WL Dean, TF Moore, N Rodrigues, KE Davies, RJ Hu, AP Feinberg, ER Maher, W Reik and J Walter
In human and mouse, most imprinted genes are arranged in chromosomal
clusters. Their linked organization suggests co-ordinated mechanisms
controlling imprinting and gene expression. The identification of local and
regional elements responsible for the epigenetic control of imprinted gene
expression will be important in understanding the molecular basis of
diseases associated with imprinting such as Beckwith- Wiedemann syndrome.
We have established a complete contig of clones along the murine imprinting
cluster on distal chromosome 7 syntenic with the human imprinting region at
11p15.5 associated with Beckwith- Wiedemann syndrome. The cluster comprises
approximately 1 Mb of DNA, contains at least eight imprinted genes and is
demarcated by the two maternally expressed genes Tssc3 (Ipl) and H19 which
are directly flanked by the non-imprinted genes Nap1l4 (Nap2) and Rpl23l
(L23mrp), respectively. We also localized Kcnq1 (Kvlqt1) and Cd81 (Tapa-1)
between Cdkn1c (p57(Kip2)) and Mash2. The mouse Kcnq1 gene is maternally
expressed in most fetal but biallelically transcribed in most neonatal
tissues, suggesting relaxation of imprinting during development. Our
findings indicate conserved control mechanisms between mouse and human, but
also reveal some structural and functional differences. Our study opens the
way for a systematic analysis of the cluster by genetic manipulation in the
mouse which will lead to animal models of Beckwith-Wiedemann syndrome and
childhood tumours.
ARTICLES
Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK.
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