NBDC Research ID: hum0439.v1

 

SUMMARY

Aims: Familial hypercholesterolemia (FH) is an inherited disorder caused by mutations in the low-density lipoprotein (LDL) receptor-related gene. FH patients have a significantly increased LDL-C compared to non-genetic hypercholesterolemia, the progression of atherosclerosis is more rapid, and the associated organ damage is more severe. FH heterozygotes are found in more than 1 in 500 people and homozygotes are found in more than 1 in 1 million people, and the total number of FH patients in Japan is estimated to be more than 250,000. Among various inherited metabolic diseases, FH is one of the most frequent and frequently encountered diseases in daily medical practice, but patients heterozygous for FH are not always correctly diagnosed. Therefore, we decided to perform genetic testing in the diagnosis of FH.

Methods: For the LDLR and PCSK9 genes, the genome is cut out using the CRISPR-Cas method, and only that portion is analyzed using a nanopore sequencer.

Participants/Materials: Genome sequence information from nanopore sequencing of LDLR and PCSK9 genes in 5 FH patients and 1 control

 

Dataset IDType of DataCriteriaRelease Date
DRA017996 NGS (Target Capture) Unrestricted-access 2024/02/27

*Release Note

*When the research results including the data which were downloaded from NHA/DRA, are published or presented somewhere, the data user must refer the papers which are related to the data, or include in the acknowledgment. Learn more

 

MOLECULAR DATA

DRA017996

Participants/Materials

FH (ICD10: E780): 5 cases

1 Control

Targets Target Capture
Target Loci for Capture Methods

LDLR (Low-Density Lipoprotein Receptor): Chr19: 11089463-11133820

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): Chr1: 55039548-55064852

* LDLR and PCSK9 genes were selectively excised from the entire genome using CRISPR-Cas9, followed by ligating sequencing adapters for targeted sequencing. The background DNA remains unremoved, which results in a small amount of reads from random regions.

Platform Nanopore [MinION]
Library Source DNAs extracted from peripheral blood cells
Cell Lines -
Library Construction (kit name) Cas9 Sequencing Kit (SQK-CS9109)
Fragmentation Methods -
Spot Type Single-end
Read Length (without Barcodes, Adaptors, Primers, and Linkers)

LDLR location: read length up to 46.2 kb

PCSK9 location: read length up to 26.5 kb

DDBJ Sequence Read Archive ID DRA017996
Total Data Volume 5.9 GB (fastq)
Comments (Policies) NBDC policy

 

DATA PROVIDER

Principal Investigator: Koh Ono

Affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

Project / Group Name: -

Funds / Grants (Research Project Number):

NameTitleProject Number
KAKENHI Grant-in-Aid for Scientific Research (B) Elucidation of the functions of long non-coding RNA in cardiovascular diseases JP20H03675

 

PUBLICATIONS

TitleDOIDataset ID
1 CRISPR-Cas9-guided amplification-free genomic diagnosis for familial hypercholesterolemia using nanopore sequencing. In submission DRA017996
2