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

  1. 1The Robert H Smith Institute of Plant Sciences & Genetics, The Hebrew University of Jerusalem, Rehovot 76100, Israel
  2. 2Department of Medicine-C, Barzilai Medical Center, Ashkelon 78306, Israel
  3. 3The Authority for Research Animals, The Hebrew University of Jerusalem, Israel
  4. 4Institute of Evolution, University of Haifa, Mt. Carmel, Haifa 31905, Israel
  5. 5Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
  6. 6Diabetes Research Center, Hadassah University Hospital, Jerusalem 91120, Israel
  7. 7Department of Human Genetics, Hadassah Medical Center, Jerusalem 91120, Israel
  8. 8Pulmonary Institute, Assaf Harofeh Medical Center, PO Beer Yaacov, Zerifin 70300, Israel
  9. 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.

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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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