IMPRINTED GENES IN NORMAL AND ABNORMAL PLACENTAL/FETAL FUNCTION

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Intrauterine growth retardation (IUGR) is a significant cause of infant mortality and morbidity, affecting over 8% of all pregnancies. lUGR-related complications include intrauterine death, intrapartum fetal distress, and perinatal asphyxia. This is in addition to both prenatal difficulties and increased adult predisposition to ailments such as coronary heart diseases, hypertension and diabetes. While the causes of IUGR are varied, in a significant proportion of cases it is associated with placenta! dysfunction. The placenta is a complex organ that performs many functions including nutrient and waste transfer, in addition to serving as an active endocrine organ. Imprinted genes play a major role in placenta!, fetal and neural development. Of the over 75 imprinted genes presently known, 21 are implicated in either placental-specific imprinting patterns or disruption of placental function when expressed abnormally, indicating their critical role in placental function. In order to elucidate the role of imprinted genes in IUGR we propose to undertake a detailed analysis of known imprinted gene expression in normal and IUGR placentas. In addition, we have developed a model for identifying novel imprinted genes involved in placental transport functions. The expression of these novel genes will also be studied in normal and IUGR placentas. We propose to compare gene expression profiles of uni- and bi-parental tissues, and IUGR and normal placentas. The information generated will be compiled, and candidate genes selected for further analysis. Gene expression level and SNPs association analysis will be carried out in placentas from IUGR and normal pregnancies