Abstract
Genetic variation shapes placental development and function, which has long been known to impact fetal growth and pregnancy outcomes such as miscarriage or maternal pre-eclampsia. Early epidemiology studies provided evidence of a strong heritable component to these conditions with both maternal and fetal-placental genetic factors contributing. Subsequently, cytogenetic studies of the placenta and the advent of prenatal diagnosis to detect chromosomal abnormalities provided direct evidence of the importance of spontaneously arising genetic variation in the placenta, such as trisomy and uniparental disomy, drawing inferences that remain relevant to this day. Candidate gene approaches highlighted the role of genetic variation in genes influencing immune interactions at the maternal-fetal interface and angiogenic factors. More recently, the emergence of molecular techniques and in particular high-throughput technologies such as Single-Nucleotide Polymorphism (SNP) arrays, has facilitated the discovery of copy number variation and study of SNP associations with conditions related to placental insufficiency. This review integrates past and more recent knowledge to provide important insights into the role of placental function on fetal and perinatal health, as well as into the mechanisms leading to genetic variation during development.