SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: no evidence for the involvement of common or rare variants in Central European patients.
OBJECTIVE
Studies in mice and humans have suggested that SUMO1, which codes for the small ubiquitin-related modifier 1 (SUMO1), is a promising candidate gene for non-syndromic cleft lip with or without cleft palate (NSCL/P). To investigate the possible involvement of this gene in NSCL/P patients from Central Europe, we performed: (i) a case control association study, and (ii) a resequencing study.


METHODS
Genotyping and the subsequent single marker and haplotype association analyses were performed for 413 NSCL/P patients and 412 controls. A total of 17 tagging single-nucleotide polymorphisms (SNPs) were used. In the resequencing study, the complete coding region and splice sites were sequenced in 65 index patients from multiply affected families.


RESULTS
One of the 17 tested SNPs (rs16838917) had a borderline significant P-value of 0.0416 in the single-marker association analysis. However, this result did not withstand correction for multiple testing (P(corr)=0.707). No association was observed for any haplotypic marker combination. Sequencing failed to identify any novel rare sequence variants.


CONCLUSIONS
The results of the present study do not support the hypothesis that common or rare variants in SUMO1 play a significant role in the development of NSCL/P in Central-European patients. However, smaller effects of common variants or the presence of rare high penetrance mutations in other non-investigated familial cases cannot be excluded. Further analysis of SUMO1 in independent samples from Central European and other populations is therefore warranted.
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Nilma Almeida
NA
de Assis
Stefanie
S
Nowak
Kerstin U
KU
Ludwig
Heiko
H
Reutter
Jennifer
J
Vollmer
Stefanie
S
Heilmann
Nadine
N
Kluck
Carola
C
Lauster
Bert
B
Braumann
Rudolf H
RH
Reich
Alexander
A
Hemprich
Michael
M
Knapp
Thomas F
TF
Wienker
Franz-Josef
FJ
Kramer
Per
P
Hoffmann
Markus M
MM
Nöthen
Elisabeth
E
Mangold
D000483:Alleles; D016022:Case-Control Studies; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005061:Europe, Eastern / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D025842:SUMO-1 Protein / Q000235:genetics*
D025842:SUMO-1 Protein; C495501:SUMO1 protein, human