GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Andressoo, JO, Jans, J, de Wit, J, Coin, F, Hoogstraten, D, van de Ven, M, Toussaint, W, Huijmans, J, Thio, HB, van Leeuwen, WJ, de Boer, J, Egly, JM, Hoeijmakers, JH, van der Horst, GT and Mitchell, JR (2006) Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles. PLoS Biol. 4:e322


Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.


PubMed PMC1584416 Online version:10.1371/journal.pbio.0040322


Alleles; Animals; DNA Damage; Genes, Lethal; Genes, Recessive; Growth Disorders/genetics; Growth Disorders/pathology; Hair Diseases/genetics; Homozygote; Humans; Ichthyosis/genetics; Mice; Mice, Inbred C57BL; Phenotype; Progeria/genetics; Progeria/metabolism; Transcription Factor TFIIH/genetics; Transcription Factor TFIIH/metabolism; Transcription, Genetic; Ultraviolet Rays; Xeroderma Pigmentosum Group D Protein/genetics