Chromosome 17: gene mapping studies of cleft lip with or without cleft palate in Chinese families.
OBJECTIVE
Involvement of loci on chromosome 17, including retinoic acid receptor alpha (RARA) in nonsyndromic oral clefts has been reported in Caucasian populations, although never investigated in Asian populations. The purpose of the present study was to investigate several loci on chromosome 17, including RARA, in Chinese families.


METHODS
Thirty-six multiplex families (310 individuals), ascertained through nonsyndromic cleft lip with or without cleft palate surgical probands from hospitals in Shanghai, China, participated in the present study. There were 23 families whose probands had cleft lip and cleft palate (CLP) and 13 with cleft lip alone (CL).


RESULTS
Seventeen markers, spanning chromosome 17 and about 10 cM apart were assessed. Logarithm of odds ratio (LOD) scores (two point and multipoint), model-free linkage analyses, and allelic association tests (transmission/disequilibrium, Fisher's exact tests, and chi-square) were performed on the total family sample, families with CLP probands (CLP subgroup), and families with CL probands (CL subgroup). LOD scores from the two-point analyses were inconclusive. Multipoint analyses rejected linkage except for a few regions in the CL subgroup. However, positive results were found using the model-free linkage and association methods (p < .05). The markers with positive results varied across the CL and CLP subgroups. However, the RARA region and loci nearby yielded consistently positive results.


CONCLUSIONS
Genetic variation within the RARA locus or nearby appears to be involved in the pathogenesis of nonsyndromic oral clefts in this population. Furthermore, based on the differing pattern of results in the CL versus CLP subgroups, it appears that the formation of CL and CLP is because of either differing alleles at the same genetic locus or different but related (and/or linked) genes that modify the severity and expression of oral clefting.
Peanchitlertkajorn
Supakit
S
School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261-4004, USA.
Cooper
Margaret E
ME
Liu
You-e
YE
Field
L Leigh
LL
Marazita
Mary L
ML
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D002681:China; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004247:DNA / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008957:Models, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D013223:Statistics as Topic
D005819:Genetic Markers; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D004247:DNA