title: Opposite effects on facial morphology due to gene dosage sensitivity.
abstract: Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, opposing difference from a matched norm, as a basis for investigating the effects of gene dosage on craniofacial development. We use dense surface modelling techniques to match any face (or part of a face) to a facial norm of unaffected individuals of matched age, sex and ethnicity and then we reverse the individual's face shape differences from the matched norm to produce the normative inversion. We demonstrate for five genomic regions, 4p16.3, 7q11.23, 11p15, 16p13.3 and 17p11.2, that such inversion for individuals with a duplication or (epi)-mutation produces facial forms remarkably similar to those associated with a deletion or opposite (epi-)mutation of the same region, and vice versa. The ability to visualise and quantify face shape effects of gene dosage is of major benefit for determining whether a CNV is the cause of the phenotype of an individual and for predicting reciprocal consequences. It enables face shape to be used as a relatively simple and inexpensive functional analysis of the gene(s) involved.
authors.affiliation: Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford St, London, WC1N 1EH, UK, p.hammond@ucl.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Hammond
authors.forename: Shane
authors.initials: S
authors.lastname: McKee
authors.forename: Michael
authors.initials: M
authors.lastname: Suttie
authors.forename: Judith
authors.initials: J
authors.lastname: Allanson
authors.forename: Jan-Maarten
authors.initials: JM
authors.lastname: Cobben
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Maas
authors.forename: Oliver
authors.initials: O
authors.lastname: Quarrell
authors.forename: Ann C M
authors.initials: AC
authors.lastname: Smith
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lewis
authors.forename: May
authors.initials: M
authors.lastname: Tassabehji
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sisodiya
authors.forename: Teresa
authors.initials: T
authors.lastname: Mattina
authors.forename: Raoul
authors.initials: R
authors.lastname: Hennekam
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002885:Chromosomes, Human, Pair 16; D002886:Chromosomes, Human, Pair 17; D002894:Chromosomes, Human, Pair 4; D002897:Chromosomes, Human, Pair 7; D056915:DNA Copy Number Variations; D005145:Face / Q000002:abnormalities / Q000033:anatomy & histology*; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D010641:Phenotype; D017384:Sequence Deletion; D044465:White People / Q000235:genetics