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Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders.

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Ho, Minh 
Thompson, Brian 
Fisk, Jeffrey Nicholas 
Nebert, Daniel W 


Intermediate filament (IntFil) genes arose during early metazoan evolution, to provide mechanical support for plasma membranes contacting/interacting with other cells and the extracellular matrix. Keratin genes comprise the largest subset of IntFil genes. Whereas the first keratin gene appeared in sponge, and three genes in arthropods, more rapid increases in keratin genes occurred in lungfish and amphibian genomes, concomitant with land animal-sea animal divergence (~ 440 to 410 million years ago). Human, mouse and zebrafish genomes contain 18, 17 and 24 non-keratin IntFil genes, respectively. Human has 27 of 28 type I "acidic" keratin genes clustered at chromosome (Chr) 17q21.2, and all 26 type II "basic" keratin genes clustered at Chr 12q13.13. Mouse has 27 of 28 type I keratin genes clustered on Chr 11, and all 26 type II clustered on Chr 15. Zebrafish has 18 type I keratin genes scattered on five chromosomes, and 3 type II keratin genes on two chromosomes. Types I and II keratin clusters-reflecting evolutionary blooms of keratin genes along one chromosomal segment-are found in all land animal genomes examined, but not fishes; such rapid gene expansions likely reflect sudden requirements for many novel paralogous proteins having divergent functions to enhance species survival following sea-to-land transition. Using data from the Genotype-Tissue Expression (GTEx) project, tissue-specific keratin expression throughout the human body was reconstructed. Clustering of gene expression patterns revealed similarities in tissue-specific expression patterns for previously described "keratin pairs" (i.e., KRT1/KRT10, KRT8/KRT18, KRT5/KRT14, KRT6/KRT16 and KRT6/KRT17 proteins). The ClinVar database currently lists 26 human disease-causing variants within the various domains of keratin proteins.



Gene Family Update, Keratin, Intermediate filament, Evolutionary blooms, Gene expression, Gene duplications, Synteny, Markov-chain Monte Carlo (MCMC), MrBayes program to estimate phylogeny

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Hum Genomics

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Springer Science and Business Media LLC
National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08 AR070290, R03 AR076484, R01 AR079428)
National Institutes of Health (R01 EY017963)
National Center for Advancing Translational Sciences (TL1 TR001864)
National Eye Institute (EY022313)
National Human Genome Research Institute (U24 HG003345)
Wellcome Trust (UK 208349/Z/17/Z)
National Institute of Environmental Health Sciences (P30 ES006096)