Approaches to localizing disease genes as applied to cystic fibrosis.
Using chromosome jumping and walking and restriction fragment length polymorphism (RFLP) analysis, we have defined the region which must contain the cystic fibrosis gene. DNA segments spanning approximately 250 kb in the direction of the gene were isolated and used to identify several new polymorphisms informative in cystic fibrosis families. These RFLPs include a highly polymorphic, CA/GT repeat, and a 10 bp insertion uncovered using the polymerase chain reaction. By analyzing a family with a recombination near the gene, we can exclude this region as containing the mutation. Data on the extent of linkage disequilibrium of these markers provides additional information on where the gene is located.
Dean
M
M
Biological Carcinogenesis and Development Program, NCl-Frederick Cancer Research Facility, MD 21701.
Drumm
M L
ML
Stewart
C
C
Gerrard
B
B
Perry
A
A
Hidaka
N
N
Cole
J L
JL
Collins
F S
FS
Iannuzzi
M C
MC
D001483:Base Sequence; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D003001:Cloning, Molecular; D003550:Cystic Fibrosis / Q000235:genetics*; D004247:DNA / Q000235:genetics; D015247:Deoxyribonuclease HindIII; D005260:Female; D015723:Gene Library; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D015345:Oligonucleotide Probes; D004247:DNA; D015247:Deoxyribonuclease HindIII