Immunoseq: the identification of functionally relevant variants through targeted capture and sequencing of active regulatory regions in human immune cells.
The observation that the genetic variants identified in genome-wide association studies (GWAS) frequently lie in non-coding regions of the genome that contain cis-regulatory elements suggests that altered gene expression underlies the development of many complex traits. In order to efficiently make a comprehensive assessment of the impact of non-coding genetic variation in immune related diseases we emulated the whole-exome sequencing paradigm and developed a custom capture panel for the known DNase I hypersensitive site (DHS) in immune cells - "Immunoseq".



We performed Immunoseq in 30 healthy individuals where we had existing transcriptome data from T cells. We identified a large number of novel non-coding variants in these samples. Relying on allele specific expression measurements, we also showed that our selected capture regions are enriched for functional variants that have an impact on differential allelic gene expression. The results from a replication set with 180 samples confirmed our observations.



We show that Immunoseq is a powerful approach to detect novel rare variants in regulatory regions. We also demonstrate that these novel variants have a potential functional role in immune cells.
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.|McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Andréanne
A
Morin
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.|McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Tony
T
Kwan
McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Bing
B
Ge
McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Louis
L
Letourneau
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Maria
M
Ban
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden.
Karolina
K
Tandre
McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Maxime
M
Caron
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden.|Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Johanna K
JK
Sandling
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Jonas
J
Carlsson
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.|McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Guillaume
G
Bourque
Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
Catherine
C
Laprise
McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Alexandre
A
Montpetit
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Ann-Christine
AC
Syvanen
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden.
Lars
L
Ronnblom
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Stephen J
SJ
Sawcer
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.|McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
Mark G
MG
Lathrop
Department of Human Genetics, McGill University, Montréal, Quebec, Canada. tomi.pastinen@mcgill.ca.|McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada. tomi.pastinen@mcgill.ca.
Tomi
T
Pastinen
D000483:Alleles; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D058977:Molecular Sequence Annotation; D040641:Quantitative Trait Loci / Q000235:genetics; D017423:Sequence Analysis, RNA; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
Capture; Gene expression; Immune disease; Next-generation sequencing; Rare variants