OBJECTIVES: To determine the host genes that govern susceptibility to recurrent respiratory papillomatosis (RRP). RRP is caused by human papillomavirus (HPV) 6 and 11. Millions of babies are exposed during the birthing process, but relatively few develop the disease and the aggressiveness of the course is highly variable. Genetically encoded host susceptibility is postulated. Determining the host genes that govern susceptibility will enhance our understanding not only of RRP but also of host-viral interaction in general. STUDY DESIGN: A genome-wide association study on familial triads consisting of an RRP-affected child and his or her parents. Using the HapMap data from the human genome project, we will identify those alleles that are over-transmitted by the parents to their affected offspring as compared to those alleles that are under-transmitted. METHODS: Approximately 400 patients and their parents will be recruited through a collaboration between the Center for Genomic Sciences and the RRP Task Force. DNA will be extracted from blood specimens and viral typing will be performed on biopsy specimens. Patients will be genotyped using single nucleotide polymorphism (SNP) markers and compared to their respective parents' genotype using the transmission disequilibrium test. Both a genome scan and a candidate gene approach will be utilized. RESULTS Institutional Review Board authorization has been obtained at three hospitals and the process is underway at 18 more. Patient and parent recruitment has begun. Specimens have been forwarded to Pittsburgh, Pennsylvania, where the DNA has been extracted and is being stored. CONCLUSIONS: A novel approach combining a nationwide patient resource and the mapping power of the sub-centimorgan human haplotype map has been developed to elucidate the biological mechanisms of RRP by determining the genetically encoded susceptibilities of host-virus interaction.
OBJECTIVES: To determine the host genes that govern susceptibility to recurrent respiratory papillomatosis (RRP). RRP is caused by human papillomavirus (HPV) 6 and 11. Millions of babies are exposed during the birthing process, but relatively few develop the disease and the aggressiveness of the course is highly variable. Genetically encoded host susceptibility is postulated. Determining the host genes that govern susceptibility will enhance our understanding not only of RRP but also of host-viral interaction in general. STUDY DESIGN: A genome-wide association study on familial triads consisting of an RRP-affected child and his or her parents. Using the HapMap data from the human genome project, we will identify those alleles that are over-transmitted by the parents to their affected offspring as compared to those alleles that are under-transmitted. METHODS: Approximately 400 patients and their parents will be recruited through a collaboration between the Center for Genomic Sciences and the RRP Task Force. DNA will be extracted from blood specimens and viral typing will be performed on biopsy specimens. Patients will be genotyped using single nucleotide polymorphism (SNP) markers and compared to their respective parents' genotype using the transmission disequilibrium test. Both a genome scan and a candidate gene approach will be utilized. RESULTS Institutional Review Board authorization has been obtained at three hospitals and the process is underway at 18 more. Patient and parent recruitment has begun. Specimens have been forwarded to Pittsburgh, Pennsylvania, where the DNA has been extracted and is being stored. CONCLUSIONS: A novel approach combining a nationwide patient resource and the mapping power of the sub-centimorgan human haplotype map has been developed to elucidate the biological mechanisms of RRP by determining the genetically encoded susceptibilities of host-virus interaction.
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Authors: F Z Hu; R A Preston; J C Post; G J White; L W Kikuchi; X Wang; S M Leal; M A Levenstien; J Ott; T W Self; G Allen; R S Stiffler; C McGraw; E A Pulsifer-Anderson; G D Ehrlich Journal: JAMA Date: 2000-07-19 Impact factor: 56.272
Authors: F Scasso; G Ferrari; G C DE Vincentiis; A Arosio; S Bottero; M Carretti; A Ciardo; S Cocuzza; A Colombo; B Conti; A Cordone; M DE Ciccio; E Delehaye; L Della Vecchia; I DE Macina; C Dentone; P DI Mauro; R Dorati; R Fazio; A Ferrari; G Ferrea; S Giannantonio; I Genta; M Giuliani; D Lucidi; L Maiolino; G Marini; P Marsella; D Meucci; T Modena; B Montemurri; A Odone; S Palma; M L Panatta; M Piemonte; P Pisani; S Pisani; L Prioglio; A Scorpecci; L Scotto DI Santillo; A Serra; C Signorelli; E Sitzia; M L Tropiano; M Trozzi; F M Tucci; L Vezzosi; B Viaggi Journal: Acta Otorhinolaryngol Ital Date: 2018-04 Impact factor: 2.124
Authors: Regina Helena Garcia Martins; Norimar H Dias; Elisa Aparecida Gregório; Mariângela Alencar Marques; Márcia Guimarães da Silva; João Manuel Grisi Candeias Journal: Braz J Otorhinolaryngol Date: 2008 Jul-Aug
Authors: Farrel J Buchinsky; William L Valentino; Nicole Ruszkay; Evan Powell; Craig S Derkay; Riaz Y Seedat; Virgilijus Uloza; Frederik G Dikkers; David E Tunkel; Sukgi S Choi; Anthony J Mortelliti; Paolo Campisi; Juan C Ospina; Adam J Donne; Robert T Sataloff; Stephen F Conley; John E McClay; Ellen M Friedman; Lisa Elden; Dale A Tylor; Clark A Rosen; Libby J Smith; Graeme J Copley; David E Karas; John M Schweinfurth; Charles M Myer; Brian J Wiatrak; Joseph E Dohar; Steven E Sobol; Robert W Bastian; Richard J H Smith; Marshall E Smith; Abebe M Wassie; James C Post; Garth D Ehrlich Journal: PLoS One Date: 2019-06-13 Impact factor: 3.240
Authors: Farrel J Buchinsky; Joseph Donfack; Craig S Derkay; Sukgi S Choi; Stephen F Conley; Charles M Myer; John E McClay; Paolo Campisi; Brian J Wiatrak; Steven E Sobol; John M Schweinfurth; Domingos H Tsuji; Fen Z Hu; Howard E Rockette; Garth D Ehrlich; J Christopher Post Journal: PLoS One Date: 2008-05-28 Impact factor: 3.240