title: Genetic associations of common deletion polymorphisms in families with Avellino corneal dystrophy.
abstract: Although the locations of many common deletion variants in the human genome are unknown, such deletions may be causative in rare disorders. Deletions can be mapped through the identification of Mendelian inconsistencies in pedigrees. Data for a total of 341,577 SNPs from an ACD family cohort (n=551) and 341,039 SNPs from a Korean-Vietnamese family cohort (n=554) were collected for a genome-wide association study using Illumina 370K-Duo Beadchips((R)). In the present study, a Mendelian inconsistency analysis of genotype data identified 1029 deletion variants in Korean and Korean-Vietnam family cohorts of 404 trios comprising 1105 individuals. Small-deletion copy number variations adjacent to 10 deletion variants were then validated by the real-time quantitative polymerase chain reaction. The expected copy numbers of each deletion variant were directly matched to its genotype cluster image. Deletion variants were also in strong linkage disequilibrium with nearby SNPs. To determine the overall contribution of the 1029 deletion variants, we analyzed case-control trio associations with the risk for Avellino corneal dystrophy. One SNP marker (rs885945) neighboring the gene encoding major histocompatibility complex class I F (HLA-F) was significantly associated with the risk of Avellino corneal dystrophy (P=0.0003). rs885945 showed high LD with SNPs within the HLA-F gene. Therefore, HLA-F may be a potential candidate gene for Avellino corneal dystrophy.
authors.affiliation: Center for Genome Sciences, National Institute of Health, Tongil-Lo, Eunpyung-Gu, Seoul, Republic of Korea. mpark@nih.go.kr
authors.forename: Miey
authors.initials: M
authors.lastname: Park
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Kwang Joong
authors.initials: KJ
authors.lastname: Kim
authors.forename: Chang Bum
authors.initials: CB
authors.lastname: Hong
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Han-Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Chung
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyung-Lae
authors.initials: HL
authors.lastname: Kim
mesh_terms: D003317:Corneal Dystrophies, Hereditary / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007723:Korea / Q000453:epidemiology; D015810:Linkage Disequilibrium; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion