Association between genes on chromosome 4p16 and non-syndromic oral clefts in four populations.
Isolated cleft lip with or without cleft palate and cleft palate are among the most common human birth defects. Several candidate gene studies on MSX1 have shown significant association between markers in MSX1 and risk of oral clefts, and re-sequencing studies have identified multiple mutations in MSX1 in a small minority of cases, which may account for 1-2% of all isolated oral clefts cases. We explored the 2-Mb region around MSX1, using a marker map of 393 single nucleotide polymorphisms (SNPs) in 297 cleft lip, with or without cleft palate, case-parent trios and 84 cleft palate trios from Maryland, Taiwan, Singapore, and Korea. Both individual markers and haplotypes of two to five SNPs showed several regions yielding statistical evidence for linkage and disequilibrium. Two genes (STK32B and EVC) yielded consistent evidence from cleft lip, with or without cleft palate, trios in all four populations. These two genes plus EVC2 also yielded suggestive evidence for linkage and disequilibrium among cleft palate trios. This analysis suggests that several genes, not just MSX1, in this region may influence risk of oral clefts.
Ingersoll
Roxann G
RG
Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD 21287, USA. rashwor2@jhmi.edu
Hetmanski
Jacqueline
J
Park
Ji-Wan
JW
Fallin
M Daniele
MD
McIntosh
Iain
I
Wu-Chou
Yah-Huei
YH
Chen
Philip K
PK
Yeow
Vincent
V
Chong
Samuel S
SS
Cheah
Felicia
F
Sull
Jae Woong
JW
Jee
Sun Ha
SH
Wang
Hong
H
Wu
Tao
T
Murray
Tanda
T
Huang
Shangzhi
S
Ye
Xiaoqian
X
Jabs
Ethylin Wang
EW
Redett
Richard
R
Raymond
Gerald
G
Scott
Alan F
AF
Beaty
Terri H
TH
D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005796:Genes; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007723:Korea; D015810:Linkage Disequilibrium; D051957:MSX1 Transcription Factor / Q000235:genetics; D008297:Male; D008396:Maryland; D008565:Membrane Proteins; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012846:Singapore; D013624:Taiwan
C406058:EVC protein, human; C473310:EVC2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D008565:Membrane Proteins; D011506:Proteins; D017346:Protein Serine-Threonine Kinases; C551917:STK32B protein, human