Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome.
Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8 (DXS98), and St14 (DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Etude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies (theta) corresponding to maximum LOD scores (Z) were obtained by two-point linkage analysis for a number of linkage groups, including: DXS51-F9 (Z = 5.94, theta = 0.03), F9-DXS98 (Z = 0.51, theta = 0.26), F9-DXS52 (Z = 0.84, theta = 0.27), and DXS98-DXS52 (Z = 0.32, theta = 0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 (Z = 9.96, theta = 0) and F9-DXS52 (Z = 0.07, theta = 0.45) as well as for the groups DXS51-FRAXA (Z = 2.42, theta = 0.15), F9-FRAXA (Z = 1.30, theta = 0.18), DXS98-FRAXA (Z = 0.05, theta = 0.36), and DXS52-FRAXA (Z = 2.42, theta = 0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P less than 0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.
Thibodeau
S N
SN
Children's Hospital, Department of Pathology, Denver, Colorado.
Dorkins
H R
HR
Faulk
K R
KR
Berry
R
R
Smith
A C
AC
Hagerman
R
R
King
A
A
Davies
K E
KE
D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic; D012016:Reference Values; D012729:Sex Chromosome Aberrations / Q000235:genetics*
D004247:DNA