Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage

Abstract

Multiple endocrine neoplasis type 2A (MEN2A) is one of several kinds of cancers that appear to be inherited in an autosomally dominant fashion. We have assigned the MEN2A locus to chromosome 10 by linkage with a new DNA marker (D10S5). The linkage led us to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene. The D10S5 locus was sublocalized to 10q21.1 by hybridization in situ and the IRBP gene to p11.2----q11.2 with a secondary site at q24----q25. The linkages were established using 292 members of five families, three different restriction fragment length polymorphisms (RFLPs) at D10S5 and two RFLPs recognized by the IRBP probe. The recombination frequencies from pairwise linkage analysis between the disease and two marker loci D10S5 and IRBP were 0.19 and 0.11, with maximum lod scores of 3.6 and 8.0 respectively. Ordering of the three loci by multipoint analysis placed the IRBP gene approximately midway between the disease and D10S5 loci.

Preclinical detection of men 2A gene carrier using linked DNA markers

“…Both RBP3 and FNRB are linked to the MEN-2A locus, and the MEN2A locus lies between these markers (Meyers et aI., 1989). The linkage data analyzed from Japanese MEN 2A families is consistent with that ef European Caucasian kindreds (Mathew et al, 1987;Simpson et al, 1987;Yamamoto et al, 1989;Meyers et al, 1989). The recombination fraction (Om=Of) at maximum lod scores between MEN2A and these markers is calculated to be 0.045. for RI~P3 (Zm,x=13.t), and 0.063 for FNRB (Zm~x=13.2) (Wu et al, 1990), respectively.…”

“…Although the mechanism of tumorigenesis of MEN 2A has not been clarified yet, the gene for MEN 2A has been localized to the pericentromeric region of chromosome 10 by linkage studies (Mathew et aI., 1987;Simpson et al, 1987;Sobol et al, 1988;Yamamoto et al, 1989). Both RBP3 and FNRB are linked to the MEN-2A locus, and the MEN2A locus lies between these markers (Meyers et aI., 1989).…”

An epidemiologic approach to gene‐environment interaction

“…This "ideal" design for testing the models can be applied only to diseases for which linkage to a genetic marker has been demonstrated (e.g., X-linked manic depression [Baron et al, 1987], familial polyposis coli [Leppert et al, 1987], and multiple endocrine neoplasia type 2A [Simpson et al, 1987]). In this case, even though the susceptibility gene itself has not been isolated or characterized, information from the linked marker can be used to classify individuals according to their probabilities of carrying the disease gene.…”

An overview of molecular abnormalities leading to thyroid carcinogenesis: A 1993 perspective

“…In 1987, two groups reported linkage to a centromeric chromosome 10 locus [3,41. There has been a considerable amount of work since that time in mapping the genetic locus with the acquisition of a large number of polymorphic DNA sequences within the region.…”