Using Whole-Genome Sequences of the LG/J and SM/J Inbred Mouse Strains to Prioritize Quantitative Trait Genes and Nucleotides

Authors

Igor Nikolskiy
Donald F. Conrad
Sung Chun
Justin C. Fay
James M. Cheverud, Loyola University ChicagoFollow
Heather A. Lawson

Document Type

Article

Publication Date

5-2015

Publication Title

BMC Genomics

Volume

16

Issue

415

Pages

1-12

Publisher Name

BMC Genomics

Abstract

Background

The laboratory mouse is the most commonly used model for studying variation in complex traits relevant to human disease. Here we present the whole-genome sequences of two inbred strains, LG/J and SM/J, which are frequently used to study variation in complex traits as diverse as aging, bone-growth, adiposity, maternal behavior, and methamphetamine sensitivity.

Results

We identified small nucleotide variants (SNVs) and structural variants (SVs) in the LG/J and SM/J strains relative to the reference genome and discovered novel variants in these two strains by comparing their sequences to other mouse genomes. We find that 39% of the LG/J and SM/J genomes are identical-by-descent (IBD). We characterized amino-acid changing mutations using three algorithms: LRT, PolyPhen-2 and SIFT. We also identified polymorphisms between LG/J and SM/J that fall in regulatory regions and highly informative transcription factor binding sites (TFBS). We intersected these functional predictions with quantitative trait loci (QTL) mapped in advanced intercrosses of these two strains. We find that QTL are both over-represented in non-IBD regions and highly enriched for variants predicted to have a functional impact. Variants in QTL associated with metabolic (231 QTL identified in an F16 generation) and developmental (41 QTL identified in an F34generation) traits were interrogated and we highlight candidate quantitative trait genes (QTG) and nucleotides (QTN) in a QTL on chr13 associated with variation in basal glucose levels and in a QTL on chr6 associated with variation in tibia length.

Conclusions

We show how integrating genomic sequence with QTL reduces the QTL search space and helps researchers prioritize candidate genes and nucleotides for experimental follow-up. Additionally, given the LG/J and SM/J phylogenetic context among inbred strains, these data contribute important information to the genomic landscape of the laboratory mouse.

Comments

Author Posting. © 2015 Nikolskiy et al. This article is posted here by permission of the authors for personal use, not for redistribution. The article was published in BMC Genomics, Volume 16, Issue 415, 2015, http://dx.doi.org/10.1186/s12864-015-1592-3

Recommended Citation

Nikolskiy, Igor; Conrad, Donald F.; Chun, Sung; Fay, Justin C.; Cheverud, James M.; and Lawson, Heather A.. Using Whole-Genome Sequences of the LG/J and SM/J Inbred Mouse Strains to Prioritize Quantitative Trait Genes and Nucleotides. BMC Genomics, 16, 415: 1-12, 2015. Retrieved from Loyola eCommons, Biology: Faculty Publications and Other Works, http://dx.doi.org/10.1186/s12864-015-1592-3

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright Statement

© 2015 Nikolskiy et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.