Locating Genes for Oral Clefts in Humans

• Published in: Cleft Lip And Palate
• Main Author: Wyszynski, Diego F.
• Format: Book Chapter
• Language: English
• Published: New York, NY Oxford University Press 01.08.2002; Oxford University Press, Incorporated
• Subjects: Genetics and Genomics; Molecular Biology and Genetics; Otolaryngology (ENT); Relevance; Considered; Constitutional; Exploited; Genes
• ISBN: 0195139062; 9780195139068
• DOI: 10.1093/oso/9780195139068.003.0021

The identification of disease genes (genes whose aberrant alleles are responsible for defined clinical syndromes) has been a major focus of human genetics over the past 30 years as a natural consequence of significant improvements in DNA technology and genetic resources. To identify genes involved in inherited disease or predispositions, two general strategies are commonly applied: positional cloning and the candidate-gene approach. In the case of positional cloning, a physical map of the target region must be developed. All genes within the mapped region are considered candidates for the disease gene and are subject to screening for mutations in constitutional DNA from patients. In the candidate-gene approach, prior knowledge of specific genes is exploited by analyzing these genes for mutations (Groden and Albertsen, 1996). A subset of genes already shown to play an important role in the development of the head, with particular relevance to the development of the lip and palate, is listed in Table 21.1. Additional growth, signaling, and transcription factors that play a role in facial development include JAGGED1, sonic hedgehog, patched, cAMP response element (CRE)-binding protein, GLI3, fibroblast growth factor receptor 1 (FGFRl), calcium/calmodulindependent serine protein kinase (CASK), treacle, fibroblast grown factor receptor 2 (FGFR2), distalless homeo box (DLX)5/6, and paired box gene 3 (PAX3) (Schutte and Murray, 1999).