NDLI: Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains

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Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains

Content Provider	Springer Nature Link
Author	Dumas, Laura Dickens, C. Michael Anderson, Nathan Davis, Jonathan Bennett, Beth Radcliffe, Richard A. Sikela, James M.
Copyright Year	2014
Abstract	It has been well documented that genetic factors can influence predisposition to develop alcoholism. While the underlying genomic changes may be of several types, two of the most common and disease associated are copy number variations (CNVs) and sequence alterations of protein coding regions. The goal of this study was to identify CNVs and single-nucleotide polymorphisms that occur in gene coding regions that may play a role in influencing the risk of an individual developing alcoholism. Toward this end, two mouse strains were used that have been selectively bred based on their differential sensitivity to alcohol: the Inbred long sleep (ILS) and Inbred short sleep (ISS) mouse strains. Differences in initial response to alcohol have been linked to risk for alcoholism, and the ILS/ISS strains are used to investigate the genetics of initial sensitivity to alcohol. Array comparative genomic hybridization (arrayCGH) and exome sequencing were conducted to identify CNVs and gene coding sequence differences, respectively, between ILS and ISS mice. Mouse arrayCGH was performed using catalog Agilent 1 × 244 k mouse arrays. Subsequently, exome sequencing was carried out using an Illumina HiSeq 2000 instrument. ArrayCGH detected 74 CNVs that were strain-specific (38 ILS/36 ISS), including several ISS-specific deletions that contained genes implicated in brain function and neurotransmitter release. Among several interesting coding variations detected by exome sequencing was the gain of a premature stop codon in the alpha-amylase 2B (AMY2B) gene specifically in the ILS strain. In total, exome sequencing detected 2,597 and 1,768 strain-specific exonic gene variants in the ILS and ISS mice, respectively. This study represents the most comprehensive and detailed genomic comparison of ILS and ISS mouse strains to date. The two complementary genome-wide approaches identified strain-specific CNVs and gene coding sequence variations that should provide strong candidates to contribute to the alcohol-related phenotypic differences associated with these strains.
Starting Page	235
Ending Page	243
Page Count	9
File Format	PDF
ISSN	09388990
Journal	Mammalian Genome
Volume Number	25
Issue Number	5-6
e-ISSN	14321777
Language	English
Publisher	Springer US
Publisher Date	2014-02-20
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell Biology Anatomy Zoology
Content Type	Text
Resource Type	Article
Subject	Genetics

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