Association of class II MHC restriction fragment length polymorphisms (RFLPs) with seropositive rheumatoid arthritis (RA)

Abstract Restriction fragment length polymorphisms (RFLPs) are being used to construct complete linkage maps for many eukaryotic genomes. These RFLP maps can be used to predict the inheritance of important phenotypic loci and will assist in the molecular cloning of linked gene(s) which affect phenotypes of scientific, medical and agronomic importance. However, genetic linkage implies very little about the actual physical distances between loci. An assay is described which uses genetic recombinants to measure physical distance from a DNA probe to linked phenotypic loci. We have defined the subset of all RFLPs which have polymorphic restriction sites at both ends as class II RFLPs. The frequency of class II RFLPs is computed as a function of sequence divergence and total RFLP frequency for highly divergent genomes. Useful frequencies exist between organisms which differ by more than 7% in DNA sequence. Recombination within class II RFLPs will produce fragments of novel sizes which can be assayed by pulsed field electrophoresis to estimate physical distance in kilobase pairs between linked RFLP and phenotypic loci. This proposed assay should have particular applications to crop plants where highly divergent and polymorphic species are often genetically compatible and thus, where class II RFLPs will be most frequent.

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Detection of HLA Class II Restriction Fragment Length Polymorphisms in Multiple Sclerosis Using Pooled DNA Samples

Virology and Immunology in Multiple Sclerosis: Rationale for Therapy ◽

10.1007/978-3-642-73032-0_9 ◽

1988 ◽

pp. 55-63

Author(s):

R. N. S. Heard ◽

I. A. Dodi ◽

A. W. Downie ◽

D. A. Francis ◽

J. E. C. Hern ◽

...

Keyword(s):

Multiple Sclerosis ◽

Restriction Fragment ◽

Fragment Length ◽

Class Ii ◽

Restriction Fragment Length Polymorphisms ◽

Hla Class Ii ◽

Length Polymorphisms ◽

Pooled Dna ◽

Restriction Fragment Length

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Major histocompatibility complex restriction fragment length polymorphisms define three diabetogenic haplotypes in BB and BBN rats.

Journal of Experimental Medicine ◽

10.1084/jem.162.2.444 ◽

1985 ◽

Vol 162 (2) ◽

pp. 444-458 ◽

Cited By ~ 11

Author(s):

J B Buse ◽

R Rifai-Haddad ◽

S Lees ◽

H Taniguchi ◽

D Chaplin ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Restriction Fragment ◽

Fragment Length ◽

Class Ii ◽

Restriction Fragment Length Polymorphisms ◽

Class I ◽

Histocompatibility Complex ◽

Bb Rats ◽

Length Polymorphisms ◽

Restriction Fragment Length

Class I and II major histocompatibility complex (MHC) probes can be used to subdivide diabetes-prone BB rats and their BBN control strain, coderived from the same outbred colony by selection against diabetes. Class II probes (A-alpha in particular) distinguish four restriction fragment length polymorphisms (RFLP), termed 1a, 1b, 2a, and 2b, in the BBN population, only one of which (2a) is found in BB rats. The degree of class II RFLP in the population studied is RT1.B-alpha greater than or equal to RT1.B-beta greater than RT1.D-alpha greater than or equal to RT1.D-beta, suggesting that intra-class II region dynamics may be different in rats compared with mice. A class I probe (S16) absolutely distinguished BB from BBN rats, since all BB rats exhibit an RFLP pattern termed 2a0, while 2a BBN rats can be subdivided into 2a1 and 2a2 forms. Serologic evaluation has shown that 2a0, 2a1, and 2a2 rats express RT1.AuBu, 1a rats express RT1.AaDa, and 1b rats express neither RT1a nor RT1u at the loci tested. A breeding study was carried out to determine the diabetogenicity of the MHC-defined RFLP's. As expected, the BB-derived 2a0 is diabetogenic. The BBN-derived 2a1 and 2a2 RFLPs are also diabetogenic, while 1a and 1b rats do not carry MHC-linked diabetogenic genes. The MHC-linked diabetes gene acts in a functionally recessive manner, since there is a 10-fold higher incidence in homozygotes than in heterozygotes. Analysis of the RFLP patterns leads us to hypothesize that the 2a1 RFLP results from a crossover between 1a and 2a0 MHCs and that the diabetogenic MHC-linked gene is on the class II side of Qa and T1. The availability of three diabetogenic MHC haplotypes should help localize the MHC-linked diabetogenic gene of rats.

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