Rett syndrome is a severe neurodevelopmental disorder that is usually caused by mutations in Methyl-CpG-binding Protein 2 (MECP2). Four of the eight common disease causing mutations in MECP2 are nonsense mutations and are responsible for over 35% of all cases of RTT. A strategy to overcome disease-causing nonsense mutations is treatment with nonsense mutation suppressing drugs that allow expression of full length proteins from mutated genes with premature in-frame stop codons.
Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation. To date, it has been revealed that a nonsynonymous polymorphism in EDAR has effects on the morphological variation in both hair and teeth. Previous association studies have confirmed that single nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology.
A fundamental question in evolutionary genetics concerns the roles of mutational pleiotropy and epistasis in shaping trajectories of protein evolution. This question can be addressed most directly by using site-directed mutagenesis to explore the mutational landscape of protein function in experimentally defined regions of sequence space.
The triggering receptor expressed on myeloid 2 (TREM2) is an immune phagocytic receptor expressed on brain microglia known to trigger phagocytosis and regulate the inflammatory response. Homozygous mutations in TREM2 cause Nasu–Hakola disease, a rare recessive form of dementia.