Evidence That Insulin is Imprinted in the Human Yolk Sac
- Gudrun E. Moore,
- Sayeda N. Abu-Amero,
- Gill Bell,
- Emma L. Wakeling,
- Amanda Kingsnorth,
- Philip Stanier,
- Eric Jauniaux and
- Simon T. Bennett
- From the Molecular Biology Laboratory for Fetal Development (G.E.M., S.N.A.-A., G.B., E.L.W., P.S.), Division of Paediatrics, Obstetrics and Gynaecology, Queen Charlotte's and Chelsea Hospital, Imperial College of Science, Technology and Medicine; the Academic Division of Obstetrics and Gynaecology (E.J.), Royal Free and University College Medical School, University College, London; the Department of Medical Genetics (A.K.), Wellcome Trust Centre of Molecular Mechanisms in Disease, CIMR, University of Cambridge, Cambridge; and the Oxagen Limited (S.T.B.), Abingdon, Oxon, U.K.
- Address correspondence and reprint requests to Dr. Gudrun Moore, Molecular Biology Laboratory for Fetal Development, Division of Paediatrics, Obstetrics and Gynaecology, Queen Charlotte's and Chelsea Hospital, Imperial College of Science, Technology and Medicine, Goldhawk Rd., London W6 OXG, U.K. E-mail: gemoore{at}ic.ac.uk .
Abstract
Allelic variation in the size of the insulin (INS) variable number tandem repeat (VNTR) correlates with the expression of both INS in the pancreas and thymus and IGF2 (the gene downstream of INS) in the placenta. In addition, the shorter, class I alleles are associated with type 1 diabetes, whereas the longer, class III alleles are associated with type 2 diabetes, polycystic ovary syndrome (PCOS), and size at birth. Parent-of-origin effects have been reported for type 2 diabetes and PCOS, thus implicating a role for genomic imprinting in these phenotypes. In mice, Ins2 is imprinted and paternally expressed in the yolk sac. In humans, evidence for the imprinting of INS is circumstantial, with occasional monoallelic expression in the thymus. In the present study, we found evidence for the imprinted paternal expression of INS in the human yolk sac. Two other imprinted genes from the same cluster are also expressed monoallelically in the human yolk sac. IGF2 was expressed solely from the paternal allele, and H19 was expressed solely from the maternal allele. These data suggest not only further functional roles for the human yolk sac in early fetal growth, but also evidence for a potential causal link between the control of insulin expression during development and insulin/growth-related diseases in later life.
Footnotes
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PCOS, polycystic ovary syndrome; PCR, polymerase chain reaction; RT, reverse transcriptase; VNTR, variable number tandem repeat.
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- Accepted September 25, 2000.
- Received April 19, 2000.
- by the American Diabetes Association, Inc.
