Identification of candidate genes in the type 2 diabetes modifier locus using expression QTL.
To identify new genetic determinants relevant to type 2 diabetes (T2D), diabetic F2 progeny were generated by intercrossing F1 mice obtained from a cross of BKS.Cg-Lepr(db)+/+m and DBA/2, and T2D-related phenotypes were measured. In the F2 population, increased susceptibility to diabetes and obesity was observed. We also detected the major quantitative trait loci (QTL) modifying the severity of diabetes on chromosome 9, where peaks of logarithm of odds (LOD) overlapped for three traits. To identify candidate genes in the QTL intervals, we combined "expression QTL" (eQTL), taking mRNA levels as quantitative traits, and "interstrain sequence variations, including cSNPs." As a result, four genes were identified from cosegregation of clinical QTL with eQTL and 13 genes were found from interstrain cSNPs as candidates in the T2D modifier QTL. Our combined approach shows the acceleration of the discovery of candidate genes in the QTL of interest, spanning several megabases.
Yaguchi
Hiroshi
H
Division of Genetic Information, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
Togawa
Katsuhiko
K
Moritani
Maki
M
Itakura
Mitsuo
M
D000818:Animals; D001823:Body Composition; D001835:Body Weight; D003433:Crosses, Genetic; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D008126:Lod Score; D051379:Mice; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D017931:DNA Primers; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin