scholarly journals Long‐read nanopore DNA sequencing can resolve complex intragenic duplication/deletion variants, providing information to enable preimplantation genetic diagnosis

2022 ◽  
Author(s):  
Christopher M. Watson ◽  
Deborah L. Holliday ◽  
Laura A. Crinnion ◽  
David T. Bonthron
Keyword(s):  
Dna Sequencing ◽  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis ◽  
Long Read ◽  
Intragenic Duplication ◽  
Nanopore Dna Sequencing

scholarly journals Long-read sequencing identified a causal structural variant in an exome-negative case and enabled preimplantation genetic diagnosis

2018 ◽  
Author(s):  
Hefan Miao ◽  
Jiapeng Zhou ◽  
Qi Yang ◽  
Fan Liang ◽  
Depeng Wang ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis ◽  
Glycogen Storage Disease Type ◽  
Pathogenic Variant ◽  
Mendelian Disease ◽  
Vitro Fertilization ◽  
Alu Elements ◽  
Negative Case ◽  
Long Read

AbstractFor a proportion of individuals judged clinically to have a recessive Mendelian disease, only one pathogenic variant can be found from clinical whole exome sequencing (WES), posing a challenge to genetic diagnosis and genetic counseling. Here we describe a case study, where WES identified only one pathogenic variant for an individual suspected to have glycogen storage disease type Ia (GSD-Ia), which is an autosomal recessive disease caused by bi-allelic mutations in the G6PC gene. Through Nanopore long-read whole-genome sequencing, we identified a 7kb deletion covering two exons on the other allele, suggesting that complex structural variants (SVs) may explain a fraction of cases when the second pathogenic allele is missing from WES on recessive diseases. Both breakpoints of the deletion are within Alu elements, and we designed Sanger sequencing and quantitative PCR assays based on the breakpoints for preimplantation genetic diagnosis (PGD) for the family planning on another child. Four embryos were obtained after in vitro fertilization (IVF), and an embryo without deletion in G6PC was transplanted after PGD and was confirmed by prenatal diagnosis, postnatal diagnosis, and subsequent lack of disease symptoms after birth. In summary, we present one of the first examples of using long-read sequencing to identify causal yet complex SVs in exome-negative patients, which subsequently enabled successful personalized PGD.

Increased enquiries for preimplantation genetic diagnosis (PGD)

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
KJ Heiliger ◽  
D Gutknecht ◽  
C Adelfalk ◽  
A Eder ◽  
M Bals-Pratsch ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis
Sign in / Sign up

Export Citation Format

Share Document