[Association between nonsyndromic cleft lip/palate and microsatellite markers located in 4q].
BACKGROUND
Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial defect. Association studies have suggested that a clefting locus is located on chromosome 4q at or near two microsatellite markers D4S175 and D4S192.


OBJECTIVE
To test the hypothesis on the possible presence of a clefting locus on chromosome 4q.


METHODS
We carried out an association study on a sample of unrelated NSCLP patients, of their unaffected relatives and in controls. Both probands and relatives were further analyzed depending if they originated from simplex or multiplex families. DNA was analyzed with two PCR markers close to the putative NSCLP locus, dinucleotide repeats D4S175 and D4S192. PCR products were resolved by PAGE and visualized by silver staining. Statistical analysis was performed by means of chi 2 log ratio.


RESULTS
Significant differences between NSCLP and controls were observed when comparing the allele frequency distribution of D4S192 both in the total sample as well as in NSCLP-multiplex and simplex cases. No significant differences for D4S175 were observed in any of the comparisons. Unaffected relatives showed significant differences with controls both for D4S175 and D4S192.


CONCLUSIONS
Our results support the hypothesis that a NSCLP locus maps on chromosome 4q close to the microsatellite marker D4S192. No differences were observed between NSCLP multiplex and simplex cases versus controls, implying that they do not represent different etiologic entities. The results of the present and previous studies in the same group of patients support the hypothesis that several major interacting genes participate in the etiology of NSCLP.
Paredes
M
M
Escuela de Postgrado, Facultad de Medicina, Universidad de Chile.
Carreño
H
H
Solá
J A
JA
Segú
J
J
Palomino
H
H
Blanco
R
R
D000483:Alleles; D016022:Case-Control Studies; D002677:Chile; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004247:DNA / Q000032:analysis; D018900:Dinucleotide Repeats / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016133:Polymerase Chain Reaction
D004247:DNA