Linkage analysis of candidate regions in Swedish nonsyndromic cleft lip with or without cleft palate families.
OBJECTIVE
To analyze linkage of five candidate regions for nonsyndromic cleft lip with or without palate (CLP) on chromosome 2p13, 4q, 6p23, and 19q13; in addition chromosome 1q32, the locus for van der Woude syndrome, on Swedish CLP families.


METHODS
Three to five linked microsatellite markers were selected from each candidate region. Polymerase chain reaction (PCR) with fluorescent-labeled microsatellite markers was performed on DNA samples from the participating families. Electrophoresis of the PCR products was performed on a laser-fluorescent DNA sequencer. The genotype data were analyzed with multipoint linkage analysis. Modes of inheritance tested included two autosomal dominant, an autosomal recessive, and a nonparametric model. Multipoint logarithm of odds (LOD) scores were also calculated by assuming genetic heterogeneity.


METHODS
Nineteen Swedish multigenerational families with at least two first-degree relatives affected with CLP. Greater than 50% of the families studied show vertical transmission of the clefting phenotype and both inter- and intrafamilial variability were noted.


RESULTS
Cumulative multipoint LOD scores for the whole group of families calculated under autosomal dominant modes of inheritance were negative in all regions and less than -2 except chromosome 6p23. LOD scores calculated under recessive inheritance and the nonparametric model were inconclusive. There was no significant evidence of genetic heterogeneity among the sample group.


CONCLUSIONS
The group of Swedish CLP families did not demonstrate significant linkage to any of the five candidate regions examined. This might suggest a new but yet unknown CLP locus or loci in this family group. However, because linkage could not be excluded in some individual families, they should still be tested with candidate genes from these regions.
Department of Orthodontics, Institute of Odontology, Karolinska Institute, Stockholm, Sweden. Fung-Ki.Wong@ofa.ki.se
F K
FK
Wong
C
C
Hagberg
A
A
Karsten
O
O
Larson
M
M
Gustavsson
J
J
Huggare
C
C
Larsson
B T
BT
Teh
S
S
Linder-Aronson
D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D013548:Sweden; D013577:Syndrome