| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
The pathogenesis of nonsyndromic cleft lip with or without cleft palate (NSCL±P) and nonsyndromic cleft palate only (NSCP) is thought to associate with genetic factors. Here we conducted mutation analysis using a Next Generation Sequencer. We selected 10 genes (IRF6, TP63, WNT5A, MSX1, TFAP2A, PAX9, WNT9B, MN1, DLX3 and DLX4) from genome-wide association study and candidate gene analyses, performed targeted resequencing in 78 Japanese patients with NSCL±P, and 14 Japanese patients with NSCP. The single nucleotide variants found on IRF6 and DLX4 were missense mutations, and on WNT5A, TFAP2A, WNT9B, TP63, and PAX9 were rare variants in the non-coding region, but no de novo mutation was found in trio samples. The amino acid change on DLX4 was found within the highly conserved homeodomain and predicted as a deleterious impact on the protein function in-silico analysis. The DLX4 missense mutation c.359C>T (Pro120Leu) was found in one Japanese with NSCL±P, was located in the homeodomain.
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