title: HapMap scanning of novel human minor histocompatibility antigens.
abstract: Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.
authors.affiliation: Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Michi
authors.initials: M
authors.lastname: Kamei
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nannya
authors.forename: Hiroki
authors.initials: H
authors.lastname: Torikai
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Taura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.forename: Taro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Yazaki
authors.forename: Satoko
authors.initials: S
authors.lastname: Morishima
authors.forename: Kunio
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kuzushima
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D018604:Epitope Mapping / Q000379:methods; D005819:Genetic Markers; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009369:Neoplasms / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014181:Transplantation Immunology
chemical_list: D005819:Genetic Markers; D015778:Minor Histocompatibility Antigens