Nonsyndromic cleft lip with or without cleft palate in China: assessment of candidate regions.
OBJECTIVE
Although Asians have the highest birth prevalence of oral-facial clefts, the majority of gene mapping studies of cleft lip with or without cleft palate (CL/P) have been in European or American Caucasians. Therefore, the objective of this study of Chinese families was to evaluate linkage and association between CL/P and 10 genetic markers in five chromosomal regions that have shown positive results in Caucasians.


METHODS
Families were ascertained through nonsyndromic CL/P surgical probands from hospitals throughout Shanghai, China.


METHODS
Study participants included 671 individuals from 60 families with two or more members affected with oral-facial clefts. Of the 671 total individuals, 145 were affected.


RESULTS
Ten markers from chromosomes 2, 4, 6, 17, and 19 were assessed (TGFA, MSX1, D4S194, D4S175, F13A1, GATA185H, D17S250, D17S579, D19S49, APOC2). LOD scores were calculated between each of the 10 markers and CL/P as well as model-free statistics of linkage (SimIBD) and association (TDT). None of the markers showed significantly positive LOD scores with CL/P. A significantly positive result (p =.01) was seen using SimIBD for APOC2 on chromosome 19, and a positive TDT result (p =.004) was obtained for D19S49, near APOC2.


CONCLUSIONS
This is the first gene mapping study of CL/P in China. These results indicate that most of the genetic regions with positive results in Caucasian families may not be involved in CL/P found in China, although there is some positive evidence for the candidate region on chromosome 19.
Marazita
Mary L
ML
Division of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261-1931, USA. marazita@sdmgenetics.pitt.edu.
Field
L Leigh
LL
Cooper
Margaret E
ME
Tobias
Rose
R
Maher
Brion S
BS
Peanchitlertkajorn
Supakit
S
Liu
You-e
YE
D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008126:Lod Score; D051957:MSX1 Transcription Factor; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics
D005819:Genetic Markers; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha