Table5_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table3_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table1_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table7_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table8_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table2_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table6_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Table4_Transcriptomic analysis of the upper lip and primary palate development in mice.XLSX

Background: Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.Methods: Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5— three key fusion stages—were acquired for RNA sequencing.Results: Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as Krt5, Pax1, Ambn, Hey2, and Tnmd, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including Tnn, Wnt3a, and Wnt16. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including Gtpbp8, Armcx1, Tle3, and Numa1. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem, etc.Conclusion: Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL/P.</p

Maternal Transmission Effect of a <em>PDGF-C</em> SNP on Nonsyndromic Cleft Lip with or without Palate from a Chinese Population

<div><p>Cleft lip with or without palate (CL/P) is a common congenital anomaly with a high birth prevalence in China. Based on a previous linkage signal of nonsyndromic CL/P (NSCL/P) on the chromosomal region 4q31–q32 from the Chinese populations, we screened the 4q31–q32 region for susceptibility genes in 214 trios of Han Chinese. <em>PDGF-C</em>, an important developmental factor, resides in the region and has been implicated in NSCL/P. However, in our family-based association test (transmission disequilibrium test; TDT), we could not conclude an association between <em>PDGF-C</em> and NSCL/P as previously suggested. Instead, we found strong evidence for parent-of-origin effect at a <em>PDGF-C</em> SNP, rs17035464, by a likelihood ratio test (unadjusted p-value = 0.0018; <em>I_m</em> = 2.46). The location of rs17035464 is 13 kb downstream of a previously reported, NSCL/P-associated SNP, rs28999109. Furthermore, a patient from our sample trios was observed with a maternal segmental uniparental isodisomy (UPD) in a region containing rs17035464. Our findings support the involvement of <em>PDGF-C</em> in the development of oral clefts; moreover, the UPD case report contributes to the collective knowledge of rare variants in the human genome.</p> </div

Scatter diagram of the p-values of FBAT and PLORT tests.

<p>Scatter diagram of the p-values (−log₁₀ (p-value)) of FBAT and POLRT tests. The p-value of rs17035464 exceeds the corrected threshold of multiple testing.</p