Isolation of a new DNA marker in linkage disequilibrium with cystic fibrosis, situated between J3.11 (D7S8) and IRP.
A cosmid library of recombinants containing nonmethylated CpG sites for rare-cutter restriction enzymes was used previously to isolate the gene IRP and four polymorphic DNA markers (pPT-3, pXV-2c, pCS.7, and pKM.19) which are close to and in linkage disequilibrium with the cystic fibrosis (CF) mutation. We have analyzed several new clones from the same library and have isolated a further cosmid, cNX.6d, which maps approximately 160 kb from CS.7, in the J3.11 direction. A DNA fragment (pMP6d-9) (D7S399) derived from cosmid cNX.6d detects a frequent polymorphism with MspI. Strong linkage disequilibrium between CF and MP6d-9 is found in European populations. Recombinations in two families suggest that CF is between the MspI polymorphic site recognized by pMP6d-9 and the polymorphism recognized by pJ3.11. The new marker is the closest, to date, to CF and will be useful for prenatal diagnosis and carrier testing.
Estivill
X
X
Molecular Genetics Unit, Fundació d'Investigació Santa Creu i Sant Pau, Barcelona, Spain.
McLean
C
C
Nunes
V
V
Casals
T
T
Gallano
P
P
Scambler
P
P
Williamson
R
R
D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003360:Cosmids; D003550:Cystic Fibrosis / Q000235:genetics*; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length