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Cleft lip and palate: understanding genetic and environmental influences

Cleft lip and palate: understanding genetic and environmental influences Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP affects approximately 1 in 700 live births, with wide variability across geographic origin, racial and ethnic groups, as well as environmental exposures and socioeconomic status. CLP can occur in syndromic or non-syndromic forms. This Review focuses on the latter. Although twin studies and familial clustering studies have provided compelling evidence for a genetic component to non-syndromic CLP, few pedigrees show clear-cut Mendelian inheritance and many cases appear to be sporadic. Accurate phenotyping is crucial to understanding both the epidemiology and aetiology of any congenital malformation because the power to detect effects is weakened when heterogeneous groups are treated as a single entity. To date, genetic approaches to non-syndromic CLP have included: linkage analysis using large, multiplex families or smaller but inbred families, or analysis of affected relative pairs; association studies using case–parent trios or case–control samples; identification of chromosomal anomalies or micro-deletions in cases; and direct sequencing of affected individuals. Genome-wide association studies have provided recent major advances in our understanding of genes and pathways that have a role in the aetiology of CLP. There is remarkable heterogeneity by ancestry in the relative contributions by genes found with common variants contributing to CLP. There is evidence that environmental factors have a role in CLP risk and interactions of the environment with certain genetic variants have been identified. The next critical phase of statistical analyses will be to examine the heterogeneity underlying the aetiology of oral clefts and to investigate the gene–gene and gene–environment interactions that control risk. Integration of genetic and environmental risk using epigenetics, systems biology, gene expression and epidemiology will be required to generate a synthesis that will both better characterize aetiologies and eventually lead to improvements in prevention and clinical care. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Genetics Springer Journals

Cleft lip and palate: understanding genetic and environmental influences

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References (184)

Publisher
Springer Journals
Copyright
Copyright © 2011 by Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1471-0056
eISSN
1471-0064
DOI
10.1038/nrg2933
Publisher site
See Article on Publisher Site

Abstract

Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP affects approximately 1 in 700 live births, with wide variability across geographic origin, racial and ethnic groups, as well as environmental exposures and socioeconomic status. CLP can occur in syndromic or non-syndromic forms. This Review focuses on the latter. Although twin studies and familial clustering studies have provided compelling evidence for a genetic component to non-syndromic CLP, few pedigrees show clear-cut Mendelian inheritance and many cases appear to be sporadic. Accurate phenotyping is crucial to understanding both the epidemiology and aetiology of any congenital malformation because the power to detect effects is weakened when heterogeneous groups are treated as a single entity. To date, genetic approaches to non-syndromic CLP have included: linkage analysis using large, multiplex families or smaller but inbred families, or analysis of affected relative pairs; association studies using case–parent trios or case–control samples; identification of chromosomal anomalies or micro-deletions in cases; and direct sequencing of affected individuals. Genome-wide association studies have provided recent major advances in our understanding of genes and pathways that have a role in the aetiology of CLP. There is remarkable heterogeneity by ancestry in the relative contributions by genes found with common variants contributing to CLP. There is evidence that environmental factors have a role in CLP risk and interactions of the environment with certain genetic variants have been identified. The next critical phase of statistical analyses will be to examine the heterogeneity underlying the aetiology of oral clefts and to investigate the gene–gene and gene–environment interactions that control risk. Integration of genetic and environmental risk using epigenetics, systems biology, gene expression and epidemiology will be required to generate a synthesis that will both better characterize aetiologies and eventually lead to improvements in prevention and clinical care.

Journal

Nature Reviews Genetics – Springer Journals

Published: Feb 18, 2011

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