[Development of a DNA chip screening mitochondrial DNA mutations in patients with diabetes mellitus] Export

@article{citeulike:1058471, abstract = {OBJECTIVE: To establish a rapid and precise high-throughput mitochondrial (mt) DNA chip and to investigate the relationship between mtDNA tRNA Leu (UUR) and ND1 gene mutations and diabetes mellitus. METHODS: A wild-type and mutant probes of 28 loci in tRNA Leu (UUR) and ND1 gene were immobilized on the Hybond N + nylon membrane by UV-crosslinking, then the mtDNA chips were used to detect 28 loci mutation in 200 cases of type 2 diabetes mellitus and 210 matched healthy controls. All the mutations were further confirmed by DNA sequencing. Mfold and Antherprot softwares were used to predict the secondary structures of the mutant gene and protein. RESULTS: The mtDNA chip, which could detect 28 loci mutations, was successfully developed. In diabetic group, there were 2 (1.0\%) cases of T3 290C mutation, 6 (3.0\%) of G3 316A (Ala-->Thr) mutation, 5 (2.5\%) of T 3 394C (Tyr-->His) mutation, 1 (0.5\%) of T3 593 C (Val-->Ala) mutation, 1 (0.5\%) of A3 606G (Leu-->Leu) mutation, 8 (4.0\%) of A4 164G (Met-->Met) mutation, 2 (1.0\%) of T4 216C (Met-->His) mutation. In the controls, 1 (0.5\%) carrier of G3 316A mutation and 5 (2.4\%) carriers of A4 164G mutation were found. There was significant difference between two groups for T3 394C mutation frequencies (P = 0.027). The secondary structures of the mutant proteins of G3 316A, T3 394C, T3 593C and T4 216C mutations were all different from those of the wild-types'. CONCLUSION: mtDNA chip is a rapid and reliable high-throughput method for mutations detection, and T3 394C mutation in ND1 gene might contribute to the pathogenesis of mitochondrial diabetes.}, address = {Genetic Diagnosis Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.}, author = {Liu, S. M. and Zhou, X. and Zheng, F. and Li, X. and Qin, H. and Zhang, H. M. and Li, D.}, citeulike-article-id = {1058471}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/17200023}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=17200023}, day = {31}, issn = {0376-2491}, journal = {Zhonghua Yi Xue Za Zhi}, keywords = {a3606g, a4164g, diabetes, g3316a, mt, nd1, t3290c, t3394c, t3593c, t4216c}, month = {October}, number = {40}, pages = {2853--2857}, posted-at = {2007-01-22 04:46:46}, priority = {5}, title = {[Development of a DNA chip screening mitochondrial DNA mutations in patients with diabetes mellitus]}, url = {http://view.ncbi.nlm.nih.gov/pubmed/17200023}, volume = {86}, year = {2006} }

TY - JOUR ID - citeulike:1058471 L3 - citeulike-article-id:1058471 N2 - OBJECTIVE: To establish a rapid and precise high-throughput mitochondrial (mt) DNA chip and to investigate the relationship between mtDNA tRNA Leu (UUR) and ND1 gene mutations and diabetes mellitus. METHODS: A wild-type and mutant probes of 28 loci in tRNA Leu (UUR) and ND1 gene were immobilized on the Hybond N + nylon membrane by UV-crosslinking, then the mtDNA chips were used to detect 28 loci mutation in 200 cases of type 2 diabetes mellitus and 210 matched healthy controls. All the mutations were further confirmed by DNA sequencing. Mfold and Antherprot softwares were used to predict the secondary structures of the mutant gene and protein. RESULTS: The mtDNA chip, which could detect 28 loci mutations, was successfully developed. In diabetic group, there were 2 (1.0%) cases of T3 290C mutation, 6 (3.0%) of G3 316A (Ala-->Thr) mutation, 5 (2.5%) of T 3 394C (Tyr-->His) mutation, 1 (0.5%) of T3 593 C (Val-->Ala) mutation, 1 (0.5%) of A3 606G (Leu-->Leu) mutation, 8 (4.0%) of A4 164G (Met-->Met) mutation, 2 (1.0%) of T4 216C (Met-->His) mutation. In the controls, 1 (0.5%) carrier of G3 316A mutation and 5 (2.4%) carriers of A4 164G mutation were found. There was significant difference between two groups for T3 394C mutation frequencies (P = 0.027). The secondary structures of the mutant proteins of G3 316A, T3 394C, T3 593C and T4 216C mutations were all different from those of the wild-types'. CONCLUSION: mtDNA chip is a rapid and reliable high-throughput method for mutations detection, and T3 394C mutation in ND1 gene might contribute to the pathogenesis of mitochondrial diabetes. IS - 40 JF - Zhonghua Yi Xue Za Zhi SN - 0376-2491 AD - Genetic Diagnosis Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. EP - 2857 TI - [Development of a DNA chip screening mitochondrial DNA mutations in patients with diabetes mellitus] VL - 86 SP - 2853 KW - a3606g KW - a4164g KW - diabetes KW - g3316a KW - mt KW - nd1 KW - t3290c KW - t3394c KW - t3593c KW - t4216c AU - Liu, SM AU - Zhou, X AU - Zheng, F AU - Li, X AU - Qin, H AU - Zhang, HM AU - Li, D PY - 2006/10/31/ UR - http://view.ncbi.nlm.nih.gov/pubmed/17200023 ER -