rescue of progeria in trichothiodystrophy by homozygous lethal xpd alleles救援trichothiodystrophy的早衰症xpd等位基因纯合子的致命.pdfVIP

PLoS BIOLOGY Rescue of Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles 1¤a 1¤b 1 2 1 1 Jaan-Olle Andressoo , Judith Jans , Jan de Wit , Frederic Coin , Deborah Hoogstraten , Marieke van de Ven , 1 3 4 5 1¤c 2 Wendy Toussaint , Jan Huijmans , H. Bing Thio , Wibeke J. van Leeuwen , Jan de Boer , Jean-Marc Egly , 1 1 1* Jan H. J. Hoeijmakers , Gijsbertus T. J. van der Horst , James R. Mitchell 1 Medical Genetics Center, Department of Cell Biology and Genetics, Center of Biomedical Genetics, Erasmus Medical Center, Rotterdam, Netherlands, 2 Institut de Genetique et de Biologie et Cellulaire, Strasbourg, France, 3 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands, 4 Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands, 5 Department of Experimental Radiology, Erasmus Medical Center, Rotterdam, Netherlands 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