Diagnosis and molecular basis of mitochondrial respiratory chain disorders: exome sequencing for disease gene identification.

Mitochondrial disorders have the highest incidence among congenital metabolic diseases, and are thought to occur at a rate of 1 in 5000 births. About 25% of the diseases diagnosed as mitochondrial disorders in the field of pediatrics have mitochondrial DNA abnormalities, while the rest occur due to defects in genes encoded in the nucleus. The most important function of the mitochondria is biosynthesis of ATP. Mitochondrial disorders are nearly synonymous with mitochondrial respiratory chain disorder, as respiratory chain complexes serve a central role in ATP biosynthesis. By next-generation sequencing of the exome, we analyzed 104 patients with mitochondrial respiratory chain disorders. The results of analysis to date were 18 patients with novel variants in genes previously reported to be disease-causing, and 27 patients with mutations in genes suggested to be associated in some way with mitochondria, and it is likely that they are new disease-causing genes in mitochondrial disorders. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

Nucleotide compositional constraints on genomes generate alanine-, glycine-, and proline-rich structures in transcription factors.

Correlation between amino acid composition and nucleotide composition is examined. Class III POU transcription factors having higher third GC contents showed higher contents of alanine, glycine, and proline residues encoded by GC-rich nucleotides, and vice versa. This correlation was observed even among various types of transcription factors from vertebrates and invertebrates regardless of functional and structural constraints inherent to each protein. Furthermore, reptile class III POU sequences revealed no evolutionary directionality increasing the GC contents from cold- to warm-blooded vertebrates.