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Review
. 2005 Dec;17(6):731-9.
doi: 10.1097/01.mop.0000185138.65820.7f.

Progress toward discerning the genetics of cleft lip

Andrew C Lidral  1 , Lina M Moreno
Affiliations
Review

Progress toward discerning the genetics of cleft lip

Andrew C Lidral et al. Curr Opin Pediatr. 2005 Dec.

Abstract

Purpose of review: Orofacial clefts are common birth defects with a known genetic component to their etiology. Most orofacial clefts are nonsyndromic, isolated defects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate and (2) cleft palate only. Both are genetically complex traits, which has limited the ability to identify disease loci or genes. The purpose of this review is to summarize recent progress of human genetic studies in identifying causal genes for isolated or nonsyndromic cleft lip with or without cleft palate.

Recent findings: The results of multiple genome scans and a subsequent meta-analysis have significantly advanced our knowledge by revealing novel loci. Furthermore, candidate gene approaches have identified important roles for IRF6 and MSX1. To date, causal mutations with a known functional effect have not yet been described.

Summary: With the implementation of genome-wide association studies and inexpensive sequencing, future studies will identify disease genes and characterize both gene-environment and gene-gene interactions to provide knowledge for risk counseling and the development of preventive therapies.

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Figures

Figure 1
Figure 1. Summed dominant heterogeneity log odds ratio scores from seven different populations
The green arrows indicate the 1 and 2 log odds ratio intervals of linkage. Modified from [20].
Figure 2
Figure 2. Association plot of the TGFBR1 gene
Upper left, HapMap view of TGFBR1 single nucleotide polymorphisms (SNPs). Upper level shows SNP markers genotyped by the HapMap Project. Lowest level displays gene structure for TGFBR1. Right, Association plot of the TGFBR1 gene. Association of marker pairs is indicated by a red-white gradient, with red being highly associated and white being relatively unassociated. The location of the TGFBR1 gene is defined by the blue arrows. A hypothetical mutation is indicated by the red arrow and markers by black arrows Lower left, Haplotypes of TGFBR1 SNP markers showing association between the markers.
Figure 3
Figure 3. Association plot of the TP63 gene
The location of the TP63 gene is defined by the blue arrows. A hypothetical mutation is indicated by the red arrow and markers by black arrows.
See this image and copyright information in PMC

References

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