A strategy using SNP linkage analysis for monogenic diseases PGD combined with HLA typing

Abstract

Preimplantation genetic diagnosis (PGD) of genetic diseases, combined with human leukocyte antigen (HLA) typing (PGD-HLA), is a useful technique to have healthy offspring that are compatible with a sibling for hematopoietic stem cells transplantation (HSCT) to treat their genetic diseases. Here, we report a new strategy using single nucleotide polymorphism (SNP) linkage analysis for monogenic disease PGD combined with HLA typing, to simultaneously obtain the information of chromosomal aneuploidy, target mutations and HLA typing through a single low-depth next generation sequencing (NGS) procedure. In this study, five couples with probands underwent SNP linkage analysis for PGD-HLA typing were recruited. Within these five couples, two couples fortunately harvested four unaffected and HLA matched embryos with their siblings. After embryo transfer, two healthy neonates were born successfully. Subsequently, cord blood hematopoietic stem cells obtained from these two neonates were collected and frozen for treating their sick siblings. This novel strategy could provide abundant and specific SNPs for each family, therefore linkage information adjacent and even within HLA clusters were apparent. This study offers a highly flexible and precise method which could eliminate misdiagnosis caused by chromosomal recombination of the HLA gene, thus potentially benefit the success rate of HSCT.

Keywords: HLA typing; PGD; SNP; linkage analysis; next-generation sequencing.