RT Journal
A1 Tan, Iris K.L.
A1 Mackin, Leanne
A1 Wang, Nancy
A1 Papenfuss, Anthony T.
A1 Elso, Colleen M.
A1 Ashton, Michelle P.
A1 Quirk, Fiona
A1 Phipson, Belinda
A1 Bahlo, Melanie
A1 Speed, Terence P.
A1 Smyth, Gordon K.
A1 Morahan, Grant
A1 Brodnicki, Thomas C.
T1 A recombination hotspot leads to sequence variability within a novel gene (AK005651) and contributes to type 1 diabetes susceptibility
JF Genome Research 
JO Genome Research 
YR 2010 
FD December 01 
VO 20 
IS 12 
SP 1629 
OP 1638 
DO 10.1101/gr.101881.109 
UL http://genome.cshlp.org/content/20/12/1629.abstract 
AB More than 25 loci have been linked to type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse, but identification of the underlying genes remains challenging. We describe here the positional cloning of a T1D susceptibility locus, Idd11, located on mouse chromosome 4. Sequence analysis of a series of congenic NOD mouse strains over a critical 6.9-kb interval in these mice and in 25 inbred strains identified several haplotypes, including a unique NOD haplotype, associated with varying levels of T1D susceptibility. Haplotype diversity within this interval between congenic NOD mouse strains was due to a recombination hotspot that generated four crossover breakpoints, including one with a complex conversion tract. The Idd11 haplotype and recombination hotspot are located within a predicted gene of unknown function, which exhibits decreased expression in relevant tissues of NOD mice. Notably, it was the recombination hotspot that aided our mapping of Idd11 and confirms that recombination hotspots can create genetic variation affecting a common polygenic disease. This finding has implications for human genetic association studies, which may be affected by the approximately 33,000 estimated hotspots in the genome.