Whole-genome sequencing in a large cohort of PID patients

Reference: Thaventhiran, J.E.D., Lango Allen, H., Burren, O.S. et al. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature (2020).

Journal: Nature

Summary: 1. Whole genome was sequenced for 1318 familial and sporadic PID patients with most of them being adult onset CVID and CID

2. Bayesian inference (BeviMed) was used to study if cohort based WGS identifies new genetic associations

3. WGS can detect compound Hets and non-coding cis-regulatory element region deletions

4. GWAS of common single nucleotide polymorphisms, reinforced precious associations of MHC locus and 16p13.13 region and also suggested association in promoter region of EOMES with 3p24.1 and 18p11.21 proximal to PTPN2 

5. GWAS also identified protein truncating variants in ETS1, SOCS1 and PTPN2 in PID patients

6.  Patient with novel heterozygous variant SOCS1 presented with CVID phenotype and lung and liver inflammation 

7. Patient with novel stop-gain variant in PTPN2 presented with polyarthropathy, recurrent bacterial infections and inflammatory lungs with CVID phenotype

Bottom line: Cohort based WGS can identify known genetic defects as well as discover novel coding and non-coding variants associated with Primary Immunodeficiency disorders

germ, bacteria, infection