Evidence that insulin is imprinted in the human yolk sac

Allelic variation in the size of the insulin (INS) variable number tandem r epeat (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, polycyst ic 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 gen omic imprinting in these phenotypes. In mice, Ins2 is imprinted and paterna lly expressed in the yolk sec. In humans, evidence for the imprinting of IN S is circumstantial, with occasional monoallelic expression in the thymus. In the present study, we found evidence for the imprinted paternal expressi on of INS in the human yolk sec. Two other imprinted genes from the same cl uster are also expressed monoallelically in the human yolk sac. IGF2 was ex pressed solely from the paternal allele, and H19 was expressed solely from the maternal allele. These data suggest not only further functional roles f or the human yolk sac in early fetal growth, but also evidence for a potent ial causal link between the control of insulin expression during developmen t and insulin/growth-related diseases in later life.