Abstract
Preeclampsia is a pregnancy-induced disorder that is characterized by hypertension and is a leading cause of perinatal and maternal–fetal morbidity and mortality. HLA-G is thought to play important roles in maternal–fetal immune tolerance, and the associations between HLA-G gene polymorphisms and the onset of pregnancy-related diseases have been explored extensively. Because contiguous genomic sequencing is difficult, the association between the HLA-G genotype and preeclampsia onset is controversial. In this study, genomic sequences of the HLA-G region (5.2 kb) from 31 pairs of mother–offspring genomic DNA samples (18 pairs from normal pregnancies/births and 13 from preeclampsia births) were obtained by single-molecule real-time sequencing using the PacBio RS II platform. The HLA-G alleles identified in our cohort matched seven known HLA-G alleles, but we also identified two new HLA-G alleles at the fourth-field resolution and compared them with nucleotide sequences from a public database that consisted of coding sequences that cover the 3.1-kb HLA-G gene span. Intriguingly, a potential association between preeclampsia onset and the poly T stretch within the downstream region of the HLA-G*01:01:01:01 allele was found. Our study suggests that long-read sequencing of HLA-G will provide clues for characterizing HLA-G variants that are involved in the pathophysiology of preeclampsia.
Highlights
Preeclampsia (PE) is a pregnancy-induced condition that is characterized by hypertension and is a leading cause of perinatal and maternal–fetal morbidity and mortality
HLA-G, which is expressed in the extravillous trophoblasts of the placenta, is believed to play an important role in the establishment of maternal–fetal immune tolerance, and associations between HLA-G gene polymorphisms and PE have been suggested[9]
Using single-molecule real-time sequencing on the PacBio RS II instrument, we obtained full‐length consensus sequences of HLA-G loci in 18 PE and 13 healthy mother–offspring pairs
Summary
Preeclampsia is a pregnancy-induced disorder that is characterized by hypertension and is a leading cause of perinatal and maternal–fetal morbidity and mortality. HLA-G is thought to play important roles in maternal–fetal immune tolerance, and the associations between HLA-G gene polymorphisms and the onset of pregnancy-related diseases have been explored extensively. Preeclampsia (PE) is a pregnancy-induced condition that is characterized by hypertension and is a leading cause of perinatal and maternal–fetal morbidity and mortality. HLA-G, which is expressed in the extravillous trophoblasts of the placenta, is believed to play an important role in the establishment of maternal–fetal immune tolerance, and associations between HLA-G gene polymorphisms and PE have been suggested[9]. Decreased in PE patients compared with healthy c ontrols[12] These studies suggest that soluble HLA-G plays a critical role in the induction of immune tolerance in the fetus.
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