Genetics of congenital heart diseases




Principal Investigator:

Gudny-Ella Thorlacius


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30599: Other Medical and Health Sciences not elsewhere specified




Pulmonary atresia with intact ventricular septum (PA/IVS) and hypoplastic left heart syndrome (HLHS) are severe congenital heart diseases that require life-saving surgical intervention in all cases. The causes of these diseases are unknown, however genetics are thought to play a role in mediating disease risk - with both inherited (familial) and de novo genetic variants being suspected. Nonetheless, studies on the genetic associations with these diseases have been few and far between. This in turn leaves methods such as whole-genome sequencing underutilized in the clinical setting for diagnosing these diseases. From 2014 samples from individuals affected by congenital heart diseases in Sweden have been collected in the Swedish national biobank for congenital heart diseases (Svensk nationell biobank för medfödda hjärtsjukdomar - Using samples from the SNAB-CHD biobank from individuals born with PA/IVS or HLHS, we hope to find novel genetic associations with PA/IVS and/or HLHS in Swedish individuals using whole genome sequencing. From the biobank, 48 saliva samples each from HLHS and PA/IVS were extracted, DNA isolated, and sent to the SNP&SEQ facility in Uppsala for whole genome sequencing using the Illumina TruSeq PCR-free library prep and unique dual indexes, targeting an insert size of 350bp. Paired-end 150bp read length sequencing (30x) is then performed using the NovaSeq 6000 on a S4 flowcell. At the sequencing facility, alignment, variant discovery and variant annotation is implemented using nf-core Sarek. Bioinformatics support has been obtained via the National Bioinformatics Support (NBIS) and most of the data processing will be handled via their service. The 48 individuals with PA/IVS have already been sequenced and the data is ready for delivery. The HLHS samples have been sent to the sequencing facility and library preps performed and are now waiting in the sequencing que. For this project, data delivery is imminent and with the help of the NBIS we hope to swiftly make the necessary analysis needed to complete the project within one year.