Original Article
Heredity (2005) 95, 158–165. doi:10.1038/sj.hdy.6800701; published online 1 June 2005
Evidence for a major gene affecting the transition from normoglycaemia to hyperglycaemia in Psammomys obesus
J Hillel1, D Gefel2, R Kalman3, G Ben-Ari1, L David1, O Orion4, M W Feldman5, H Bar-On6, S Blum1, I Raz6, T Schaap7, I Shpirer8, U Lavi9, E Shafrir6 and E Ziv6
- 1The Robert H Smith Institute of Plant Sciences & Genetics, The Hebrew University of Jerusalem, Rehovot 76100, Israel
- 2Department of Medicine-C, Barzilai Medical Center, Ashkelon 78306, Israel
- 3The Authority for Research Animals, The Hebrew University of Jerusalem, Israel
- 4Institute of Evolution, University of Haifa, Mt. Carmel, Haifa 31905, Israel
- 5Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
- 6Diabetes Research Center, Hadassah University Hospital, Jerusalem 91120, Israel
- 7Department of Human Genetics, Hadassah Medical Center, Jerusalem 91120, Israel
- 8Pulmonary Institute, Assaf Harofeh Medical Center, PO Beer Yaacov, Zerifin 70300, Israel
- 9Institute of Horticulture, ARO-Volcani Center, PO Box 6, Bet-Dagan 50250, Israel
Correspondence: J Hillel, The Robert H Smith Institute of Plant Sciences & Genetics, The Hebrew University of Jerusalem, Rehovot 76100, Israel. E-mail: Hillel@agri.huji.ac.il
Received 23 July 2004; Accepted 13 April 2005; Published online 1 June 2005.
Abstract
We investigated the mode of inheritance of nutritionally induced diabetes in the desert gerbil Psammomys obesus (sand rat), following transfer from low-energy (LE) to high-energy (HE) diet which induces hyperglycaemia. Psammomys selected for high or low blood glucose level were used as two parental lines. A first backcross generation (BC1) was formed by crossing F1 males with females of the diabetes-prone line. The resulting 232 BC1 progeny were assessed for blood glucose. All progeny were weaned at 3 weeks of age (week 0), and their weekly assessment of blood glucose levels proceeded until week 9 after weaning, with all progeny maintained on HE diet. At weeks 1 to 9 post weaning, a clear bimodal distribution statistically different from unimodal distribution of blood glucose was observed, normoglycaemic and hyperglycaemic at a 1:1 ratio. This ratio is expected at the first backcross generation for traits controlled by a single dominant gene. From week 0 (prior to the transfer to HE diet) till week 8, the hyperglycaemic individuals were significantly heavier (4–17%) than the normoglycaemic ones. The bimodal blood glucose distribution in BC1 generation, with about equal frequencies in each mode, strongly suggests that a single major gene affects the transition from normo- to hyperglycaemia. The wide range of blood glucose values among the hyperglycaemic individuals (180 to 500 mg/dl) indicates that several genes and environmental factors influence the extent of hyperglycaemia. The diabetes-resistant allele appears to be dominant; the estimate for dominance ratio is 0.97.
Keywords:
Psammomys obesus, backcross, bimodal distribution, QTL, type-2 diabetes, major gene
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