Figure 2
From: Identification of mutations through dominant screening for obesity using C57BL/6 substrains
Identification of a single nucleotide substitution in the Sim1 gene in the Obese-13 pedigree.
(a) The body weights of Obese-13 pedigree N2 littermates (bars) are deviated toward overweight compared with the body weight distribution of the screened F1 mice (line, same as in Fig. 1b, Mann-Whitney U test, p < 0.0001). (b) QTL analysis of the Obese-13 pedigree (n = 49) for body weight showed a single LOD score peak on chromosome 10. (c) Further QTL analysis using 172 N2 mice and focusing on chromosome 10 shows a single peak (LOD score, 25.6) located between rs13480575 and rs13480619. (d) Haplotype analysis of Obese-13 N2 mice indicates that the mutation falls between rs13480575 and rs13480619 (arrow) on chromosome 10. (e) Direct sequencing of the Sim1 gene identified a thymine (T)-to-adenine (A) substitution specific to obese mice of the Obese-13 pedigree. (f) The T-to-A substitution is located in exon 4 of the Sim1 gene. Black box indicates the coding region, while the white box indicates the non-coding region. (g) The methionine residue at position 136 located in the PAS A domain is substituted with lysine. (h) This methionine residue is well-conserved among vertebrates and invertebrates. The Fα region of the PAS A domain is indicated.
