ABSTRACT
Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend = 9.70E-10 and Ptrend = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Brain/abnormalities , Cleft Lip/genetics , Cleft Palate/genetics , Membrane Proteins/genetics , Brain/pathology , Cleft Lip/pathology , Cleft Palate/pathology , Discs Large Homolog 1 Protein , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Polymorphism, Single Nucleotide/geneticsABSTRACT
Achievement of the goal to eliminate measles by 2015 set by the European region of the World Health Organization (WHO) necessitates an increase in the willingness of German nationals to get vaccinated. To identify influential factors on vaccination behavior as the basis for communication measures specific to target groups, the Federal Centre for Health Education (BZgA) has conducted two representative surveys on attitude, knowledge, and practice concerning vaccination among parents of children between 0 and 13 years as well as among adolescents and adults. The parents' survey (n = 3,002) revealed that more than one-third see measles as a harmless disease. The survey of adolescents and adults (n = 4,483, 16-85 years) also shows that about one-quarter of the interviewees between 16 and 44 years regarded vaccination against measles as not very important. Moreover, 81 % of adults born after 1970 without sufficient existing vaccine protection were not aware of the new measles vaccination recommendation for this age group. Personal consultation with the physician was regarded as the major source of vaccination information in both surveys. About half of all persons interviewed intended to obtain information about vaccinations on the Internet. The results of these studies were used for the development of a nationwide multilevel BZgA campaign on vaccination protection against measles, its goal being to support medical professionals with comprehensive information and to enable adolescents and young adults via different communication measures to make well-informed vaccination decisions.
