These radicals were able to attack major cellular macromolecules (lipids, proteins, DNA) and caused direct destruction of cell membranes, abnormality in the activation or inactivation of enzymes, and extensive mutations on the gene structure [ 52].
BimS is an intrinsically unstructured protein that tolerates extensive mutation of its BH3 sequence, and BimSBH3 chimeras display the prosurvival protein specificity profile of the replacement BH3 domain.
Moreover, genes within AT-isochores are affected by RIP, which can occasionally overrun the repeated region into adjacent single-copy genes, resulting in extensive mutation of the affected genes [ 16– 16].
Extensive mutation screening of 11 genes in a large cohort of 77 unrelated patients with neuropathy with onset in the first year of life revealed pathogenic sequence variants in 35 patients, representing 45% of the total cohort.
Therefore, we performed an extensive mutation analysis of oncocytic tumor biopsies, previously characterized for the presence of mtDNA mutations.
To make Mutation@A Glance a reliable and general mutation analysis platform for other various genetic diseases in the future, we consider that data sharing with experts in particular diseases will be highly important as in the case of PID; otherwise it would take a long time to accumulate extensive mutation data of all human disease genes to an acceptable level for clinical use.
These two missense variants were not present in the SDHB orthologous amino acid positions in other organisms in GenBank, in over 200 human chromosomes that we previously sequenced, and have not been reported as population variants in extensive mutation surveys of PGL [3].
Extensive mutation analyses of other positional candidate genes identified mutation in the nearby GRN gene [ 7, 28].
Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses.
Extensive mutation analyses of positional candidate genes identified an expanded noncoding G4C2 hexanucleotide repeat in C9orf72 explaining linkage and association [ 33, 55, 128].
