Estonia is a state in the Baltic region of Northern Europe. It is bordered to the north by the Gulf of Finland, to the west by the Baltic Sea. The Estonians are a Finnic people, and the sole official language, Estonian, is closely related to Finnish.
There is a large geographical variation in the birth prevalence rate for all orofacial clefts. Cp prevalence varys between 3-5 per 10 000 in Europe. The highest reported prevalence rate for CP in the world is that of Finland 10-14 cases per 10 000. Proportions for different cleft types for Caucasians are given by Fogh-Andersen. But for many registries in Europe, the cleft palate ratio is little bit more around 1,5-1,7 Last year in Estonia we had 15 000 newborns and 14 cleft children were born with clefts
In our first study a total of 585 health files of patients with OCs had been preserver. There were more boys then girls. CP was almost as common as CLP.
Approximately 50% of CP cases are isolated, nonsyndromic OCs . Recent years have witnessed considerable success in the mapping of loci for nonsyndromic CP, with additional genes to include TBX22, TCOF1, FOXE1 and SUMO1 among other genes contributing increased risk for NSCP. A genom-wide linkage scan of NSCP in Finnish multiplex families produced suggestive evidence of linkage for three chromosomal loci . Evidence of linkage was obtained for the 4q21-q26 locus in genome-wide linkage scan in families of Central European descent with nonsyndromic oral clefts.
Because of genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported clefting candidate genes and chromosomal loci to the risk of NSCP in the Estonian population.
Cleft sample was collected from surgical clinics in Estonia (North Estonia Medical Centre, Tallinn, and Tartu University Hospital). Unaffected unrelated individuals without a family history of clefting, collected as randomly selected population-based controls from a Biobank of the Estonian Genome Center, University of Tartu We conducted a case-control association study to investigate the role of 40 candidate genes in predisposition to orofacial clefting. 630 tagSNPs were genotyped in a clefting sample, comprised of 53 patients with nonsyndromic cleft palate and 205 controls from Estonian population.
The Estonian Genome Center (EGC) is a research venture of the University of Tartu. It was founded by the Government of the Republic of Estonia in 2001 and was subsequently reorganized as a research institution affiliated with to the University of Tartu. The aim of the EGC is to create a database of health, genealogical and genome data representing 5% of Estonia’s population. The database will make it possible for researchers both in Estonia and outside Estonia to look for links between genes, environmental factors and common diseases (cancer, diabetes, depression, cardiovascular diseases, etc) From now we have 51 534 individuals with comprehensive health records, objective data and DNA, plasma and white blood cells sample.
We selected candidate genes on the basis of previously published findings from: association and linkage studies, gene expression patterns during craniofacial development, gene-knockout data from animal studies, genes that underlie Mendelian syndromic forms of clefting, and studies of chromosomal rearrangements associated with cleft phenotypes in humans. Selected Single Nucleotide Polymorphisms were selected based on the HapMap Phase II data, using HapMap CEU as a reference population. Multiple SNPs were selected for each gene, including of both upstream and downstream genomic sequences.
We genotyped 630 tagSNPs in 40 candidate genes related to orofacial clefting in 53 patients with nonsyndromic cleft palate and 205 unrelated controls from the Estonian population.
In case-control anlysis of the CP phenotype, 37 polymorphismsin 19 genes displayed nominal evidence of association with CP in Estonian sample. The most significant association with CP was found for SNps in MMP3 gene
, in Jagged 2 gene and in lipoxynase homology domains 1 gene within OFC 11 linkage region on Chr 18.
CONCLUSIONS : This study provides the evidence of the implication of JAG2 , MMP3 , MSX1 , OFC11 region and FGF1 in the occurrence of NSCP in Estonian population. Further independent studies in other populations with a substantially larger number of individuals should be conducted to verify and extend these results. D o to the small sample size of our patients group, we must emphasize that our study carries the risk of false-positive findings as a result of the large number of comparisons performed. Conversely, we cannot exclude the possibility that a modest effect of polymorphisms or haplotypes in disease predisposition may become apparent in larger sample. We have join our efforts with our neighbouring countries with Latvia and Lithuania and increased CP sample size and our results are published with the little bit large sample size. Baltics: we provided the evidence that variations in cartilage collagen II and XI genes, IRF6 and Wnt nad FGF signaling pathway genes are likely involved in the etiology of CP in Notheaster European populations.
Mari Nelis. Genetic structure of Europeans: A view from North-East.
Candidate genes contribute to therisk of nonsyndromic cleft palate in Estonia.Triin Jagomägi | Tiit Nikopensius | Mare Saag | Andres Metspalu
• Population of 1.34 million• The Estonians are a Finnic people, and the sole official language, Estonian, is closely related to Finnish.
Prevalence of CP• CL:CLP:CP for Caucasians 1:2:1• Finland 10-14 CP cases per 10 000• Estonia 2011 – 15 000 newborns – 14 clefts • 3 CL • 5 CLP • 6 CP – 1:2:2
Estonian Genome Center• University of Tartu• Founded in 2001• The AIM – to create a database of health, genealogical and genome data representing 5% of Estonia’s population.• 51 534 individuals with health records, objective data and DNA, plasma and white blood cell samples.
Methods• Genes and SNP selection – association and linkage studies – gene expression pattern – gene-knockout data – genes that underlie Mendelian syndromic forms of clefting – chromosomal rearrangements – SNPs with minor allele frequencies >0.05 and r2>0.08 – HapMap CEU