Fzd6, Matn2 and Slc25A32, Possible Candidate Genes In Nonsyndromic Cleft Lip and Palate

<p>Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with a multifactorial etiology. Despite decades of research, the genetic underpinnings of NSCLP still remain largely unexplained. A genome wide association study (GWAS) of a large NSCLP African American family with seven affected individuals across three generations found evidence for linkage at 8q21.3-24.12 (LOD = 2.98). This region contained three biologically relevant candidate genes: <em>Frizzled-6 (FZD6) </em>(LOD = 2.8), <em>Matrilin-2 (MATN2)</em> (LOD = 2.3), and <em>Solute Carrier Family 25, Member 32</em> <em>(SLC26A32</em>) (LOD = 1.6). Sequencing of the coding regions and the 5’ and 3’ UTRs of these genes in two affected family members identified a rare intronic variant, rs138557689 (c.-153+432A>C), in <em>FZD6. </em>The rs138557689/C allele segregated with the NSCLP phenotype; <em>in silico</em> analysis predicted and EMSA analysis showed that the 138557689/C allele creates new DNA binding sites. <em>FZD6</em> is part of the WNT pathway, which is involved in craniofacial development, including midface development and upper lip fusion. Our novel findings suggest that an alteration in <em>FZD6</em> gene regulation may perturb this tightly controlled biological pathway and in turn contribute to the development of NSCLP in this family. Studies are underway to further define how the rs138557689/C variant affects expression of <em>FZD6</em>.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2012

Author dc:creator

• Cvjetkovic, Nevena

Contributors dc:contributor

• Jacqueline T. Hecht, PhD
• Eric C. Swindell, PhD
• John F. Teichgraeber, MD

• Frizzled 6 (FZD6)
• Matrilin 2 (MATN2)
• Solute Carrier Family 25
• Member 32 (SLC26A32)
• candidate genes
• nonsyndromic cleft lip and palate
• rare variant
• Genetics and Genomics
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/281

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1278