Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2.
Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted.
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. jzeiger@jhmi.edu
Joanna S
JS
Zeiger
Jacqueline B
JB
Hetmanski
Terri H
TH
Beaty
Craig A
CA
VanderKolk
Diego F
DF
Wyszynski
Joan E
JE
Bailey-Wilson
Rosa Ortiz
RO
de Luna
Claudia
C
Perandones
Marie M
MM
Tolarova
Terezie
T
Mosby
Ricardo
R
Bennun
Mabel
M
Segovia
Pavel
P
Calda
Elizabeth W
EW
Pugh
Kim
K
Doheny
Iain
I
McIntosh
D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats
D005819:Genetic Markers