PUBLICATION

Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate

Authors
Ma, L., Lou, S., Miao, Z., Yao, S., Yu, X., Kan, S., Zhu, G., Yang, F., Zhang, C., Zhang, W., Wang, M., Wang, L., Pan, Y.
ID
ZDB-PUB-201028-10
Date
2020
Source
Journal of Cellular and Molecular Medicine   24(23): 13669-13678 (Journal)
Registered Authors
Keywords
association signals, molecular genetics, orofacial clefts, susceptibility, zebrafish
MeSH Terms
  • Phenotype
  • Alleles
  • Molecular Sequence Annotation
  • Genome-Wide Association Study
  • Quantitative Trait Loci*
  • Genotype
  • Zebrafish
  • Genetic Association Studies*/methods
  • Odds Ratio
  • Gene Editing
  • Cleft Lip/diagnosis*
  • Cleft Lip/genetics*
  • Cleft Palate/diagnosis*
  • Cleft Palate/genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Animals
  • Computational Biology/methods
  • Disease Models, Animal
  • Case-Control Studies
  • Polymorphism, Single Nucleotide
  • Humans
  • Male
(all 23)
PubMed
33108691 Full text @ J. Cell. Mol. Med.
Abstract
Although several genome-wide association studies (GWAS) of non-syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in-depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case-parent trios and another in-house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3' of SERTAD4, P = 6.44 × 10-14 ; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10-13 and 2.80 × 10-11 , respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10-6 ; rs2095293: intron of NR6A1, P = 2.98 × 10-5 ). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10-16 ). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down-regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
Human Disease Fish Conditions Evidence
orofacial cleftTAS
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Sequence Targeting Reagents
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Fish
Antibodies
Name Type Antigen Genes Isotypes Host Organism
Ab13-sox2monoclonalIgG1Mouse
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Orthology
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Engineered Foreign Genes
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Mapping
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