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Annual Review of Genomics and Human Genetics

Volume 23, 2022

Decoding the Human Face: Progress and Challenges in Understanding the Genetics of Craniofacial Morphology

Abstract

Variations in the form of the human face, which plays a role in our individual identities and societal interactions, have fascinated scientists and artists alike. Here, we review our current understanding of the genetics underlying variation in craniofacial morphology and disease-associated dysmorphology, synthesizing decades of progress on Mendelian syndromes in addition to more recent results from genome-wide association studies of human facial shape and disease risk. We also discuss the various approaches used to phenotype and quantify facial shape, which are of particular importance due to the complex, multipartite nature of the craniofacial form. We close by discussing how experimental studies have contributed and will further contribute to our understanding of human genetic variation and then proposing future directions and applications for the field.

Keyword(s): craniofacial, development, gene regulation, genome-wide association study, GWAS, phenotyping, syndromes
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/content/journals/10.1146/annurev-genom-120121-102607
2022-08-31
2024-04-25
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Decoding the Human Face: Progress and Challenges in Understanding the Genetics of Craniofacial Morphology
Annual Review of Genomics and Human Genetics 23, 383 (2022); https://doi.org/10.1146/annurev-genom-120121-102607
/content/journals/10.1146/annurev-genom-120121-102607
/content/journals/10.1146/annurev-genom-120121-102607
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Supplemental Material

Supplementary Data

  • Download Supplemental Tables 1-3 (XLSX).

    Supplemental Table descriptions:

    Supplemental Table 1. Genes and pathways mutated in rare craniofacial disorders with Mendelian inheritance. Genes were identified by searching the Online Mendelian Inheritance in Man (OMIM) database for the term ‘craniofacial,’ and then manually reviewing clinical synopses to confirm a craniofacial defect in the accompanying syndrome. Genes implicated by GWAS were identified through literature review of all facial shape and nsCL/P GWAS (Supplementary Tables 2 and 3). Genes for which mouse mutants have craniofacial phenotypes were identified by searching the Mouse Genome Informatics database (MGI; http://www.informatics.jax.org/allele) for the phenotype term ‘craniofacial’ and further screening entries for loss-of-function mutations.

    Supplemental Table 2. SNPs associated with normal-range facial variation through GWAS. SNPs as well as corresponding candidate genes were collected from previously published GWAS.

    Supplemental Table 3. SNPs associated with orofacial clefts through GWAS. SNPs as well as corresponding candidate genes were collected from previously published GWAS.

  • Article Type: Review Article

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