Titre du document / Document title

Mapping by genetic interaction: High-resolution congenic mapping of the type 1 diabetes loci Idd10 and Iddl8 in the NOD mouse

Auteur(s) / Author(s)

LYONS Paul A. ⁽¹⁾ ; ARMITAGE Nicola ⁽¹⁾ ; LORD C. J. ^{(1 2)} ; PHILLIPS Michael S. ⁽³⁾ ; TODD John A. ⁽¹⁾ ; PETERSON Laurence B. ⁽⁴⁾ ; WICKER Linda S. ^{(1 5)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge University, Cambridge, ROYAUME-UNI
⁽²⁾ Institute of Cancer Research, Chester Beatty Laboratories, London, ROYAUME-UNI
⁽³⁾ Department of Human Genetics, Merck Research Laboratories, West Point, Pennsylvania, ETATS-UNIS
⁽⁴⁾ Department of Pharmacology, Merck Research Laborato-ries, Rahway, New Jersey, ETATS-UNIS
⁽⁵⁾ Departments of Immunology and Rheumatol-ogy, Merck Research Laboratories, Rahway, New Jersey, ETATS-UNIS

Résumé / Abstract

As many of the linked chromosome regions that predispose to type 1 diabetes in the NOD mouse have been dissected, it has become apparent that the initially observed effect is in fact attributable to several loci. One such cluster of loci on distal chromosome 3, originally described as Idd10, is now known to comprise three separate loci, Idd10, Idd17, and Iddl8. Although these loci have a significant combined effect on diabetes development, their individual effects are barely detectable when diabetes is used as a read-out, which makes fine-mapping them by use of a conventional congenic approach impractical. In this study, we demonstrate that it is possible to map loci, with modest effects, to regions small enough for systematic gene identification by capitalizing on the fact that the combined loci provide more profound, measurable protection. We have mapped the Idd10 and Iddl8 loci to 1.3- and 2.0-cM intervals, respectively, by holding the Idd3 allele constant. In addition, we have excluded Csfl and Nras as candidates for both loci.

Revue / Journal Title

Diabetes   ISSN 0012-1797   CODEN DIAEAZ 

Source / Source

2001, vol. 50, n^o11, pp. 2633-2637 (18 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Diabetes Association, Alexandria, VA, ETATS-UNIS  (1952) (Revue)

Mots-clés anglais / English Keywords

Vertebrata ; Mammalia ; Rodentia ; Endocrinopathy ; Autoimmune disease ; Immunopathology ; Mouse ; Insulin dependent diabetes ; Congenic ; Genetic mapping ; Animal ;

Mots-clés français / French Keywords

Vertebrata ; Mammalia ; Rodentia ; Endocrinopathie ; Maladie autoimmune ; Immunopathologie ; Souris ; Diabète insulinodépendant ; Congénique ; Carte génétique ; Animal ;

Mots-clés espagnols / Spanish Keywords

Vertebrata ; Mammalia ; Rodentia ; Endocrinopatía ; Enfermedad autoinmune ; Inmunopatología ; Ratón ; Diabetes insulinodependiente ; Congénico ; Mapa genético ; Animal ;

Localisation / Location

INIST-CNRS, Cote INIST : 8261, 35400009988560.0300