May 20, 2008
Scientists estimate that anywhere from 3 to 14 loci, or fixed markers on a chromosome or gene, interact as a baby develops in the womb to produce an abnormal cleft lip and/or palate. To identify these contributory loci, a key step in beginning to decipher the genetics of clefts, scientists have attempted to cast a wide epidemiological and technological net. However, their results have been only modestly successful to date. This has led a team of NIDCR grantees to hypothesize that perhaps a more informative route is to pursue clefting subphenotypes, or inherited familial traits that involve not only a cleft but also characteristic dental anomalies.
Published online on April 28 in the American Journal of Medical Genetics, the scientists present some preliminary data using genome-wide association studies, or GWAS. A melding of genomics with relatively low-cost DNA sequencing technology, GWAS studies can produce rapid genome scans of large cohorts of people with a predisposition to a specific disease. Computer algorithms then scan the sequence data and sometimes detect shared variations in genes that would have been undetectable by other approaches. In this paper, the scientists present their gene linkage data, the first step in the pinpointing genes with shared variations, in a study of 46 Filipino families with histories of clefts. The preliminary data support their hypothesis that some loci may contribute to both clefts and inherited dental anomalies, such as missing, extra, or undersized teeth. As the authors concluded, "This approach appears to be a promising one and may help in the identification of genetic variants that increase cleft susceptibility, which would be a crucial step that may allow better estimates of recurrence risks for individual families.
Read more about this study by Marazita ML, Vieira AR, et. al
In related work, the scientists also recently published the first GWAS scans for loci involved in dental caries. Their preliminary linkage data, which involved these same 46 Filipino families, are published in the May issue of the Journal of Dental Research.
Read more about this work by Goldstein-McHenry, Vieira, AR, and Marazita, ML.