Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.

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Cleft lip and palate: understanding genetic and environmental influences.

The genomic era of biomedical research has given rise to the genome-wide association study (GWAS) approach, which attempts to discover novel genes affecting an outcome by testing a large number (i.e., hundreds of thousands to millions) of genetic variants for association. This article discusses the issues surrounding the GWAS approach with emphasis on the prospects and challenges relevant to the oral health research community.

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Genome-wide Association Studies Prospects and Challenges for Oral Health

Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.

https://projects.nfstc.org/dnamix/2011/presentations/forensics_article.pdf

Improving human forensics through advances in genetics, genomics and molecular biology

Objectives
This study presents the global burden of major oral diseases with an exegetical commentary on their current profiles, the critical issues in oral healthcare and future perspectives.

Methods
A narrative overview of current literature was undertaken to synthesise the contexts with critical elaboration and commentary.

Results
Oral disease is one of the most common public health issues worldwide with significant socio-economic impacts, and yet it is frequently neglected in public health policy. The oral data extracted from the Global Burden of Disease Study in 2010 (Murray et al, 2012) show that caries, periodontal disease, edentulism, oral cancer and cleft lip/palate collectively accounted for 18 814 000 disability-adjusted life-years; and the global burden of periodontal disease, oral cancer and caries increased markedly by an average of 45.6% from 1990 to 2010 in parallel with the major non-communicable diseases like diabetes by 69.0%. Oral diseases and non-communicable diseases are closely interlinked through sharing common risk factors (e.g. excess sugar consumption and tobacco use) and underlying infection/inflammatory pathways.

Conclusions
Oral disease remains a major public health burden worldwide. It is of great importance to integrate oral health into global health agenda via the common risk factor approach. The long-term sustainable strategy for global oral health should focus on health promotion and disease prevention through effective multidisciplinary teamwork.

Global burden of oral diseases: emerging concepts, management and interplay with systemic health.

Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in individuals with these birth defects and their family members: from subclinical phenotypes to associated syndromic features that is mirrored by the many genes that contribute to the etiology of these disorders. Identification of these genes and loci has been the result of decades of research using multiple genetic approaches. Significant progress has been made recently due to advances in sequencing and genotyping technologies, primarily through the use of whole exome sequencing and genome-wide association studies. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies.

/pdf/genetics-of-cleft-lip-and-cleft-palate-564cknrkwj.pdf

Genetics of cleft lip and cleft palate.

Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 x 10(-12)) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.

/pdf/a-genome-wide-association-study-of-cleft-lip-with-and-cjxcoj56ea.pdf

James M. Scott

Papers

A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4