A strategy using SNP linkage analysis for monogenic diseases PGD combined with HLA typing
A strategy using SNP linkage analysis for monogenic diseases PGD combined with HLA typing
复制标题
单基因疾病PGD结合HLA分型SNP连锁分析策略
DOI：
10.1111/cge.13770
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发表时间：
2020-05-25
影响因子：
3.5
通讯作者：
Yan, Liying
中科院分区：
文献类型：
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作者：
Wang, Yuqian;Qin, Meng;Yan, Liying
遗传性疾病的植入前遗传学诊断（PGD）结合人类白细胞抗原（HLA）分型（PGD-HLA）是一种有用的技术，以获得与造血干细胞移植（HSCT）相容的健康后代来治疗其遗传性疾病。在这里，我们报告了一种新的策略，使用单核苷酸多态性（SNP）连锁分析单基因疾病PGD结合HLA分型，同时获得染色体非整倍体，靶突变和HLA分型的信息，通过一个单一的低深度下一代测序（NGS）程序。在这项研究中，五对夫妇的先证者进行SNP连锁分析PGD-HLA分型招募。在这五对夫妇中，两对夫妇幸运地与他们的兄弟姐妹收获了四个未受影响且HLA匹配的胚胎。胚胎移植后，两个健康的新生儿成功出生。随后，从这两个新生儿中获得的脐带血造血干细胞被收集并冷冻用于治疗他们患病的兄弟姐妹。这种新的策略可以为每个家族提供丰富而特异的SNP，因此邻近甚至在HLA簇内的连锁信息是显而易见的。本研究提供了一种高度灵活、精确的方法，可消除HLA基因染色体重组引起的误诊，从而提高造血干细胞移植的成功率。
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.