Analysis of HLA-G long-read genomic sequences in mother-offspring pairs with preeclampsia

Sci Rep. 2020 Nov 18;10(1):20027. doi: 10.1038/s41598-020-77081-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genomics / methods*
  • Genotype
  • Gestational Age
  • HLA-G Antigens / genetics*
  • Humans
  • Infant, Newborn
  • Mothers / statistics & numerical data*
  • Polymorphism, Genetic*
  • Pre-Eclampsia / genetics*
  • Pregnancy

Substances

  • HLA-G Antigens