Microsatellites in the HLA region: 1999 update.

In this third update of a series of reviews on microsatellites in the HLA region or close to it we report 155 microsatellites, corresponding to 51 newly described markers, in addition to the 103 reported in the 1997 and 1998 reviews. This work is based both on a literature review and on data publicly available in molecular databases on the internet (http://www.gdb.org; http://bioinfo.weizmann.ac.il/cards/; http://cedar.genetics.soton.ac.uk/) up to September 1999. Thanks to numerous studies involving major histocompatibility complex (MHC) microsatellites, documentation on HLA region is proposed, including information on microsatellites described through MHC sequence projects and presenting documented location, polymorphism and amplification condition, together with additional information on previously described microsatellites when available and information on data in the literature regarding gametic associations between HLA region loci and alleles and microsatellite alleles. As basic information are presented various documents: i) a table showing the following characteristics of the 155 microsatellites: name, localisation, polymorphism, primer sequences, reference; ii) an integrated map of some HLA region genes and the 155 microsatellites considered; and iii) a summary table on HLA and microsatellites association patterns. In addition, an overview on HLA microsatellite analysis application is presented, with a special focus on disease genetics studies in the form of recent references where the use of microsatellites of the HLA region was a key tool. This review aims at providing the human immunogenetics community with a tool for helping optimal choice of microsatellites to be used in various studies.

Microsatellites in the HLA region: 1998 update.

In order to update the review published in Tissue Antigens in 1997, we present here a new overview on microsatellites in the HLA region, including additional information, with focus on the following points: * Description of 103 microsatellite characteristics in the HLA region, 50 markers having been newly described since 1996. * An integrated map of the HLA region, including microsatellites and some HLA genes, revealing an important microsatellite density in the MHC (Class I, Class II and Class III regions). * A synthesis of microsatellite analysis in disease studies, summarizing results of microsatellite approaches in 24 pathologies, including autoimmune diseases, HLA-associated or HLA-linked diseases and cancers. * Other applications of HLA region microsatellites in population or transplantation studies.

Microsatellites in the HLA region: on overview.

Microsatellites are repeats of a DNA base motif (1-6 bp, mostly CA repeats) up to 100 times; they are distributed regularly all over the genome. Many of them are polymorphic and their high polymorphism is based upon a variable number of repeats. They are widely used for genetic mapping, linkage analysis, population genetics, evolutionary studies and in forensic medicine. Such markers have also been described in the HLA region since 1991, and a growing interest in their potential applications is being expressed. The aims of this review are: 1) to outline the presently available information from literature and molecular databases concerning 53 microsatellites in the HLA region (localization, type of repeat, number of alleles, heterozygosity, primers used for amplification); 2) to address the question of technical pitfalls when using such markers; 3) to discuss specific features such as their mutation rate (10 (-3) to 10 (-6), which is higher than that reported for HLA genes, and their linkage disequilibrium with HLA alleles; 4) to present an integrated map of microsatellites and genes of this region; and 5) to provide a synopsis of their different applications in HLA-related fields (disease studies, population genetics, recombination point studies, HLA region mapping, transplantation) along with perspectives for future use. Although some HLA region microsatellites have already been applied to the analysis of more than 10 diseases, it is now evident that their use in population genetics and the determination of genomic compatibility in bone marrow transplantation represent growing areas of application.

Localization of the recombination points in a family with two DR/DP recombinations.

In a family with a maternal DR/GLO recombination, cellular DP typing showed it to be located between DR and DP. RFLP studies done during the 9th international histocompatibility workshop gave anomalous segregation patterns of DPA and DPB bands that could be interpreted as being due to a second, paternal DR/DP recombination. This assumption was confirmed later by PCR-SSO typing. A more precise mapping has been done by new markers showing the maternal recombination to be within the TAP2 locus and the paternal recombination to be between DQB1 and DQB3. This supports earlier suggestions of a hot spot of recombination in the TAP region. The recombinations involve parental haplotypes that presently show DR/DP linkage disequilibrium in the French population and it is proposed that DR/DP recombinations occur randomly while B/DR recombinations preferentially occur on haplotypes without strong linkage disequilibrium. Existing DR/DP linkage disequilibria in a given population will thus be broken down with time. The mixed lymphocyte culture response towards an isolated DP difference was tested in this and another DR/DP recombinant family. It showed that an alloresponse towards DP may be highly variable and this suggests that it might be important to define the rules for the strength of this reaction and the possible implications for allotransplantation.