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BMC Med Genomics. 2016 Sep 13;9(1):59. doi: 10.1186/s12920-016-0220-7.

Immunoseq: the identification of functionally relevant variants through targeted capture and sequencing of active regulatory regions in human immune cells.

Author information

1
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
2
McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada.
3
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
4
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden.
5
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
6
Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
7
Department of Human Genetics, McGill University, Montréal, Quebec, Canada. tomi.pastinen@mcgill.ca.
8
McGill University and Genome Québec Innovation Centre, Montréal, Quebec, Canada. tomi.pastinen@mcgill.ca.

Abstract

BACKGROUND:

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".

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Capture; Gene expression; Immune disease; Next-generation sequencing; Rare variants

PMID:
27624058
PMCID:
PMC5022205
DOI:
10.1186/s12920-016-0220-7
[Indexed for MEDLINE]
Free PMC Article

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