Elucidating the genetic control of morphogenesis and cell differentiation during tooth development is crucial to our understanding of the pathogenesis and treatment of genetic and acquired diseases that involve dentition. Of these anomalies, missing teeth (hypodontia) constitutes the most common defect encountered by dentists. The lack of permanent teeth due to congenital absence or loss in adult life is an important public health concern of high clinical relevance. Little is known about the genetic basis of missing teeth in humans. Our long term goal is to elucidate factors important for tooth development in humans and to dissect their biology in in vitro and in vivo model systems. Here we propose to identity a gene important for tooth development in humans. We will accomplish this by clinically evaluating and collecting blood samples from all available members of a large kindred segregating a unique form of hypodontia. Twenty two of 58 members of the family evaluated are missing at least one complete set of molars and on average, at least two pairs of molars. A genome scan will be conducted with highly polymorphic microsatellite markers on genomic DNA from members of the hypodontia kindred in order to determine the chromosomal location of the hypodontia locus. To identity the hypodontia gene, """"""""strong"""""""" candidates will be selected from all known genes and expressed sequence tags (ESTs) that map within the candidate interval. Mutation analysis will be conducted on the latter by chemical cleavage and direct DNA sequencing. We will also make a concerted effort to refine the candidate interval by expanding the family, and identifying cDNAs for anonymous STSs mapping to the region and systematically conducting mutation analysis. These efforts are expected to allow us to identity a gene for a new hypodontia locus in humans, and will in the future, allow us to study its biology and interplay with other known factors important for tooth development.
| Das, Parimal; Hai, Mehreen; Elcock, Claire et al. (2003) Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia. Am J Med Genet A 118A:35-42 |
