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Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus

Summary: Positional cloning of Sorcs1, a type 2 diabetes quantitative
trait locus
Susanne M Clee1, Brian S Yandell2,3, Kathryn M Schueler1, Mary E Rabaglia1, Oliver C Richards1,
Summer M Raines1, Edward A Kabara1, Daniel M Klass1, Eric T-K Mui1, Donald S Stapleton1,
Mark P Gray-Keller1, Matthew B Young1, Jonathan P Stoehr1, Hong Lan1, Igor Boronenkov1,
Philipp W Raess1, Matthew T Flowers1 & Alan D Attie1
We previously mapped the type 2 diabetes mellitus-2
locus (T2dm2), which affects fasting insulin levels, to distal
chromosome 19 in a leptin-deficient obese F2 intercross
derived from C57BL/6 (B6) and BTBR T+ tf/J (BTBR) mice1.
Introgression of a 7-Mb segment of the B6 chromosome 19
into the BTBR background (strain 1339A) replicated the
reduced insulin linked to T2dm2. The 1339A mice have
markedly impaired insulin secretion in vivo and disrupted islet
morphology. We used subcongenic strains derived from 1339A
to localize the T2dm2 quantitative trait locus (QTL) to a
242-kb segment comprising the promoter, first exon and most
of the first intron of the Sorcs1 gene. This was the only gene
in the 1339A strain for which we detected amino acid
substitutions and expression level differences between mice


Source: Attie, Alan D. - Department of Biochemistry, University of Wisconsin at Madison
Yandell, Brian S. - Departments of Statistics & Horticulture, University of Wisconsin at Madison


Collections: Biology and Medicine; Mathematics