scholarly journals Next‐generation sequence‐based preimplantation genetic testing for monogenic disease resulting from maternal mosaicism

2021 ◽  
Author(s):  
Xiao Hu ◽  
Wen‐Bin He ◽  
Shuo‐Ping Zhang ◽  
Ke‐Li Luo ◽  
Fei Gong ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Monogenic Disease ◽  
Next Generation ◽  
Preimplantation Genetic Testing

scholarly journals Haplotyping by linked-read sequencing (HLRS) of the genetic disease carriers for preimplantation genetic testing without a proband or relatives

2020 ◽  
Author(s):  
Qing Li ◽  
Yan Mao ◽  
Shaoying Li ◽  
Hongzi Du ◽  
Wenzhi He ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Disease ◽  
De Novo ◽  
Monogenic Disease ◽  
Nucleotide Polymorphisms ◽  
De Novo Mutations ◽  
Preimplantation Genetic Testing ◽  
Linkage Analyses ◽  
Alpha Thalassemia ◽  
Polar Bodies

Abstract Background: In order to mitigate the risk of allele dropout (ADO) and ensure the accuracy of preimplantation genetic testing for monogenic disease (PGT-M), it is necessary to construct parental haplotypes.. Typically, haplotype resolution is obtained by genotyping multiple polymorphic markers in both parents and a proband or a relative. Sometimes, single sperm typing, or tests on the polar bodies may also be useful. Nevertheless, this process is time-consuming. At present, there was no simple linkage analysis strategy for patients without affected relatives.Method: To solve this problem, we established a haplotyping by linked-read sequencing (HLRS) method without the requirement for additional relatives. First, the haplotype of the genetic disease carriers in the family was constructed by linked-read sequencing, and then the informative single nucleotide polymorphisms (SNPs) in upstream and downstream mutation region were selected to construct the embryo haplotype and to determine whether the embryo was carrying the mutation. Two families were selected to validate this method; one with alpha thalassemia and the other with NDP gene disorder.Results: The haplotyping by linked-read sequencing (HLRS) method was successfully applied to construct parental haplotypes without recruiting additional family members; the method was also validated for PGT-M. The mutation carriers in these families were sequenced by linked-read sequencing, and their haplotypes were successfully phased. Adjacent SNPs of the mutation gene were identified. The informative SNPs were chosen for linkage analyses to identify the carrier embryos. For the alpha thalassemia family, a normal blastocyst was transferred to the uterus and the accuracy of PGT-M was confirmed by amniocentesis at 16 weeks of gestation. Conclusions: Our results suggest that HLRS can be applied for PGT-M of monogenic disorders or de novo mutations where the mutations haplotype cannot be determined due to absence of affected relatives. Keywords: Preimplantation Genetic Testing for monogenic disease, Linked-read sequencing, Linkage analyses, Haplotype

68. PREIMPLANTATION GENETIC TESTING OF MONOGENIC DISEASE: EXPERIENCE IN RUSSIA

2019 ◽  
Vol 39 ◽  
pp. e68-e69
Author(s):  
S. Zhikrivetskaya Olegovna ◽  
Y. Volkova Leonidovna ◽  
E. Musatova Valerievna ◽  
Y. Sofronova Vladislavovna ◽  
N. Shirokova Anatolievna ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Monogenic Disease ◽  
Preimplantation Genetic Testing ◽  
Disease Experience
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