No evidence for linkage and association between 4q microsatellite markers and nonsyndromic cleft lip and palate in chilean case-parents trios.
OBJECTIVE
Nonsyndromic cleft lip/palate (NSCLP) has the characteristics of a complex genetic trait. Linkage and association studies have suggested that one or more clefting loci may be located on chromosome 4q. The goal of this study was to evaluate the possible linkage and association due to linkage disequilibrium between five microsatellite markers located on 4q28 to 4q33 and NSCLP, using the case-parent trio design.


METHODS
A total of 56 Chilean families (32 simplex and 24 multiplex) were recruited. Microsatellite markers were analyzed using polymerase chain reaction with fluorescent-labeled forward primers, followed by electrophoresis on a laser-fluorescent sequencer. Case-parents trios were ascertained to assess linkage and linkage disequilibrium through a multistage procedure. Transmission disequilibrium tests for multiple alleles were carried out to assess the statistical significance of 4q28 to 4q33 microsatellite markers.


RESULTS
Only weak evidence for linkage was obtained for the FGA marker (asymptotic uncorrected p value = .08 and empirical p value = .05). Only the FGA and UCP1 markers were selected for association analysis in trios, with unrelated cases achieving a nearly significant result for the UCP1 marker (asymptotic uncorrected p value = .07 and empirical p value = .19).


CONCLUSIONS
Though the FGA and UCP1 markers showed nearly significant p values for linkage and association, respectively, the results of the present study provided insufficient evidence of the existence of a major susceptibility locus in the 4q region that was analyzed in the present study.
Blanco
Rafael
R
Human Genetics Program, ICBM, School of Medicine, University of Chile. rblanco@med.uchile.cl
Suazo
José
J
Santos
José Luis
JL
Carreño
Hernán
H
Palomino
Hernán
H
Jara
Lilian
L
D002352:Carrier Proteins / Q000235:genetics; D002677:Chile; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005192:Family Health; D005340:Fibrinogen / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D007473:Ion Channels; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D024101:Mitochondrial Proteins; D017422:Sequence Analysis, DNA; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; C464794:fibrinogen Aalpha; D005340:Fibrinogen