Genetic and physical mapping of a novel region close to the fragile X site on the human X chromosome.
We report the isolation and characterization of a novel DNA marker (1A1) in Xqter in the region of the fragile X. Genetic studies in families segregating for the fragile X syndrome suggest that 1A1 lies between the disease mutation and the distal locus, DXS52. Studies in normal and fragile X families show that 1A1 is tightly linked to DXS52 (Zmax = 17.20; theta max = 0.03) and F8 (Zmax = 7.01; theta max = 0.08). Multipoint mapping of families supports the order Xcen-DXS105-FRAXA-1A1-DXS52-(F8, DXS115)-Xqter. Pulsed-field gel electrophoresis (PFGE) studies demonstrate that 1A1 defines a new region of at least 2 Mb of DNA not physically linked to DXS52 or F8, thus extending the physical map of Xq27-qter to over 4 Mb. Complex partial digestion PFGE patterns, probably due to differing degrees of methylation, are observed with 1A1 in unrelated normal and fragile-X-positive individuals, whereas other distal markers give uniform digestion profiles. Physical data suggest that 1A1 lies in a region less CpG rich than other distal markers in Xq27-qter.
Patterson
M N
MN
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, England.
Bell
M V
MV
Bloomfield
J
J
Flint
T
T
Dorkins
H
H
Thibodeau
S N
SN
Schaid
D
D
Bren
G
G
Schwartz
C E
CE
Wieringa
B
B
D000818:Animals; D002874:Chromosome Mapping; D004587:Electrophoresis, Agar Gel / Q000379:methods; D005600:Fragile X Syndrome / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D008126:Lod Score; D051379:Mice; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D014960:X Chromosome
D005819:Genetic Markers