Genetic mapping of new DNA probes at Xq27 defines a strategy for DNA studies in the fragile X syndrome.
The fragile X syndrome is the most common cause of familial mental retardation and is characterized by a fragile site at the end of the long arm of the X chromosome. The unusual genetics and cytogenetics of this X-linked condition make genetic counseling difficult. DNA studies were of limited value in genetic counseling, because the nearest polymorphic DNA loci had recombination fractions of 12% or more with the fragile X mutation, FRAXA. Five polymorphic loci have recently been described in this region of the X chromosome. The positions of these loci in relation to FRAXA were defined in a genetic linkage study of 112 affected families. The five loci--DXS369, DXS297, DXS296, IDS, and DXS304--had recombination fractions of 4% or less with FRAXA. The closest locus, DXS296, was distal to FRAXA and had a recombination fraction of 2%. The polymorphisms at these loci can be detected in DNA enzymatically digested with a limited number of restriction endonucleases. A strategy for DNA studies which is based on three restriction endonucleases and on five probes will detect one or more of these polymorphisms in 94% of women. This strategy greatly increases the utility of DNA studies in providing genetic advice to families with the fragile X syndrome.
Suthers
G K
GK
Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, Australia.
Mulley
J C
JC
Voelckel
M A
MA
Dahl
N
N
Väisänen
M L
ML
Steinbach
P
P
Glass
I A
IA
Schwartz
C E
CE
van Oost
B A
BA
Thibodeau
S N
SN
D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis*; D015342:DNA Probes; D005600:Fragile X Syndrome / Q000175:diagnosis*; D008040:Genetic Linkage; D006801:Humans; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic; D014960:X Chromosome
D015342:DNA Probes; D004247:DNA