Multicenter initiative seeking critical genes in respiratory papillomatosis.
OBJECTIVE
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.


METHODS
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.
Buchinsky
Farrel J
FJ
Center for Genomic Sciences, Allegheny Singer Research Institute, 320 E. North Avenue, Pittsburgh, PA 15212-4772, USA. fbuchins@wpahs.org
Derkay
Craig S
CS
Leal
Suzanne M
SM
Donfack
Joseph
J
Ehrlich
Garth D
GD
Post
J Christopher
JC
D002648:Child; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006078:Government Programs; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D010212:Papilloma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012141:Respiratory Tract Infections / Q000235:genetics*; D014481:United States
D005819:Genetic Markers