A sequence-ready PAC contig of a 550-kb region on rat chromosome 4 including the diabetes susceptibility gene Lyp.
The Lyp locus controls diabetes development in rats. The diabetogenic allele in diabetes-prone BB rats is responsible for T cell lymphopenia characterized by the absence of regulatory T cells. We present refined genetic and radiation hybrid maps of the Lyp region on rat chromosome 4, a single 800-kb rat yeast artificial chromosome and a rat P1-derived artificial chromosome (PAC) contig corresponding to approximately 550 kb, both encompassing the entire candidate region. The contig, consisting of 48 PACs, gives 3- to 12-fold coverage. Genetic, radiation hybrid, and physical data were all in agreement and supported the same marker order. Nine genes and ESTs were identified in the contig in addition to a rat EST from the University of Iowa rat EST database-all possible candidate genes for Lyp. Alignment of our rat PAC contig with sequenced human PAC/BAC contigs confirms the position within the region of 3 of the 10 candidates and identifies an additional 8 genes/ESTs as candidates. These data will facilitate identification of Lyp.
Hornum
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Hagedorn Research Institute, Niels Steensens Vej 6, Gentofte, DK-2820, Denmark.
Markholst
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D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D018244:Chromosomes, Artificial, Yeast; D020451:Contig Mapping; D006224:Cricetinae; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D051381:Rats; D011913:Rats, Inbred BB; D011914:Rats, Inbred BN
C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases; C516766:Ptpn22 protein, mouse