Publication Details

Applying gene expression, proteomics and single-nucleotide polymorphism analysis for complex trait gene identification.

Authors:Stylianou IM, Affourtit JP, Shockley KR, Wilpan RY, Abdi FA, Bhardwaj S, Rollins J, Churchill GA, Paigen B
Title:Applying gene expression, proteomics and single-nucleotide polymorphism analysis for complex trait gene identification.
Journal:Genetics Mar 2008 , Vol 178 , pp. 1795-805
Abstract:Previous quantitative trait locus (QTL) analysis of an intercross involving the inbred mouse strains NZB/BlNJ and SM/J revealed QTL for a variety of complex traits. Many QTL have large intervals containing hundreds of genes, and methods are needed to rapidly sort through these genes for probable candidates. We chose nine QTL: the three most significant for high-density lipoprotein (HDL) cholesterol, gallstone formation, and obesity. We searched for candidate genes using three different approaches: mRNA microarray gene expression technology to assess >45,000 transcripts, publicly available SNPs to locate genes that are not identical by descent and that contain nonsynonymous coding differences, and a mass-spectrometry-based proteomics technology to interrogate nearly 1000 proteins for differential expression in the liver of the two parental inbred strains. This systematic approach reduced the number of candidate genes within each QTL from hundreds to a manageable list. Each of the three approaches selected candidates that the other two approaches missed. For example, candidate genes such as Apoa2 and Acads had differential protein levels although the mRNA levels were similar. We conclude that all three approaches are important and that focusing on a single approach such as mRNA expression may fail to identify a QTL gene.   PUBMED: 18245842
Ontological Annotations:
  • D011506: Proteins (Publication, NCBO Annotator)
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • MA:0000358: liver (Publication, NCBO Annotator)
  • D007062: Identification (Psychology) (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • D013672: Technology (Publication, NCBO Annotator)
  • D011110: Polymorphism, Genetic (Publication, NCBO Annotator)
  • GO:0010467: gene expression (Publication, NCBO Annotator)
  • D008074: Lipoproteins (Publication, NCBO Annotator)
  • D008099: Liver (Publication, NCBO Annotator)
  • D012333: RNA, Messenger (Publication, NCBO Annotator)
  • MP:0001261: obese (Publication, NCBO Annotator)
  • D042882: Gallstones (Publication, NCBO Annotator)
  • D008815: Mice, Inbred Strains (Publication, NCBO Annotator)
  • GO:0009058: biosynthetic process (Publication, NCBO Annotator)
  • D009765: Obesity (Publication, NCBO Annotator)
  • D008722: Methods (Publication, NCBO Annotator)
  • D020641: Polymorphism, Single Nucleotide (Publication, NCBO Annotator)
  • D059019: Clinical Coding (Publication, NCBO Annotator)
  • D040901: Proteomics (Publication, NCBO Annotator)
  • D002784: Cholesterol (Publication, NCBO Annotator)

8 GeneSets from this Publication:

Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier II Mouse 385 Genes GS135953: HDL QTL 20 (Hdlq20, Published QTL Chr 1)
Expand Tier II Mouse 394 Genes GS135957: HDL QTL 24 (Hdlq24, Published QTL Chr 6)
Expand Tier II Mouse 722 Genes GS136136: lithogenic gene 17 (Lith17, Published QTL Chr 5)
Expand Tier II Mouse 257 Genes GS136138: lithogenic gene 19 (Lith19, Published QTL Chr 8)
Expand Tier II Mouse 273 Genes GS136141: lithogenic gene 21 (Lith21, Published QTL Chr 10)
Expand Tier II Mouse 561 Genes GS136384: obesity and body weight QTL 3 (Obwq3, Published QTL Chr 6)
Expand Tier II Mouse 643 Genes GS136385: obesity and body weight QTL 4 (Obwq4, Published QTL Chr 17)
Expand Tier II Mouse 277 Genes GS136386: obesity and body weight QTL 5 (Obwq5, Published QTL Chr 19)