Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Commun ; 10(1): 2557, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186421

RESUMO

Facial recognition from DNA refers to the identification or verification of unidentified biological material against facial images with known identity. One approach to establish the identity of unidentified biological material is to predict the face from DNA, and subsequently to match against facial images. However, DNA phenotyping of the human face remains challenging. Here, another proof of concept to biometric authentication is established by using multiple face-to-DNA classifiers, each classifying given faces by a DNA-encoded aspect (sex, genomic background, individual genetic loci), or by a DNA-inferred aspect (BMI, age). Face-to-DNA classifiers on distinct DNA aspects are fused into one matching score for any given face against DNA. In a globally diverse, and subsequently in a homogeneous cohort, we demonstrate preliminary, but substantial true (83%, 80%) over false (17%, 20%) matching in verification mode. Consequences of future efforts include forensic applications, necessitating careful consideration of ethical and legal implications for privacy in genomic databases.


Assuntos
Identificação Biométrica , Face/anatomia & histologia , Reconhecimento Facial , Genótipo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estatura , Peso Corporal , Estudos de Coortes , Bases de Dados de Ácidos Nucleicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
2.
Genet Epidemiol ; 43(6): 704-716, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31172578

RESUMO

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes-cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a "cleft map" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.

3.
Am J Orthod Dentofacial Orthop ; 155(5): 693-701, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31053285

RESUMO

INTRODUCTION: Datasets of soft-tissue craniofacial anthropometric norms collected with the use of different methods are available, but there is little understanding of how the measurements compare. Here we compare a set of standard facial measurements between 2 large datasets: the 3D Facial Norms (3DFN) dataset collected with the use of 3D stereophotogrammetry (n = 2454), and the Farkas craniofacial norms collected with the use of direct anthropometry (n = 2326). METHODS: A common set of 24 craniofacial linear distances were compared by computing standardized effect sizes (Cohen d) for each measurement to describe the overall direction and magnitude of the difference between the 2 datasets. RESULTS: Variables with higher mean d values (suggesting greater discrepancy across datasets) included measurements involving the ear landmark tragion, the landmark nasion, the width of nasolabial structures, the vermilion portion of the lips, and palpebral fissure length. Variables with lower mean d values included smaller midline measurements involving the lips and lower face and horizontal distance measures between the eyes. Eight measurements showed a significant negative correlation (P < 0.05) between Cohen d and age, indicating greater similarity across the 2 datasets as age increased. CONCLUSIONS: There are considerable differences between the 3DFN and Farkas norms. In addition to the measurement methods, other factors accounting for discrepancies may include secular trends in craniofacial morphology or differences in ethnic composition.


Assuntos
Antropometria/métodos , Face/anatomia & histologia , Imagem Tridimensional , Fotogrametria/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Bases de Dados Factuais , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , América do Norte , Valores de Referência
4.
Orthod Craniofac Res ; 22 Suppl 1: 207-212, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31074157

RESUMO

There is ample evidence from heritability studies, genetic syndromes and experimental animal models that facial morphology is strongly influenced by genes. In this brief review, we present an up-to-date overview of the efforts to identify genes associated with the size and shape of human facial features. We discuss recent methodological advances that have led to breakthroughs, but also the multitude of challenges facing the field. We offer perspective on possible applications of this line of research, particularly in the context of the precision genomics movement.

5.
Laryngoscope ; 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30977521

RESUMO

OBJECTIVES/HYPOTHESIS: Individuals with orofacial clefts often experience respiratory problems because of nasopharyngeal abnormalities. Pharyngeal airway morphology is thought to differ among the various cleft types. We measured three-dimensional (3D) airway volume using cone-beam computed tomography (CBCT) analysis to evaluate and compare pharyngeal airways in Japanese preschoolers with and without orofacial clefts. STUDY DESIGN: Retrospective case-control study. METHODS: We enrolled 83 subjects (37 boys, 46 girls; mean age = 4.66 ± 0.56 years) with nonsyndromic orofacial clefts and 16 noncleft healthy subjects (seven boys, nine girls; mean age = 5.30 ± 0.52 years) as controls. The subjects were divided into five groups. Four groups were based on the cleft type: isolated cleft palate, unilateral cleft lip and alveolus), unilateral cleft lip and palate, and bilateral cleft lip and palate. The fifth group included the noncleft controls. All subjects were examined with CBCT, and the 3D airway volume was measured. We analyzed group differences statistically using analysis of covariance with the Bonferroni post hoc pairwise comparison tests for the corrected means. RESULTS: Compared with the noncleft group, each cleft group exhibited significantly decreased total and nasal airway volumes and increased superior and inferior pharyngeal airway volumes. The differences were all statistically significant. CONCLUSIONS: Our findings suggest that anatomical differences exist in pharyngeal airway volumes among various cleft groups and in those without a cleft. LEVEL OF EVIDENCE: 3b.

6.
Am J Med Genet A ; 179(3): 467-474, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30582786

RESUMO

Genome-wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low-frequency variants may account for some of the "missing" heritability. Therefore, we scanned low-frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP-Seq studies in craniofacial tissues or cell lines contained multiple low-frequency (0.01-1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low-frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p-value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p-value = .001). These findings suggest that low-frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs.

7.
Front Genet ; 9: 497, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405702

RESUMO

Many factors influence human facial morphology, including genetics, age, nutrition, biomechanical forces, and endocrine factors. Moreover, facial features clearly differ between males and females, and these differences are driven primarily by the influence of sex hormones during growth and development. Specific genetic variants are known to influence circulating sex hormone levels in humans, which we hypothesize, in turn, affect facial features. In this study, we investigated the effects of testosterone-related genetic variants on facial morphology. We tested 32 genetic variants across 22 candidate genes related to levels of testosterone, sex hormone-binding globulin (SHGB) and dehydroepiandrosterone sulfate (DHEAS) in three cohorts of healthy individuals for which 3D facial surface images were available (Pittsburgh 3DFN, Penn State and ALSPAC cohorts; total n = 7418). Facial shape was described using a recently developed extension of the dense-surface correspondence approach, in which the 3D facial surface was partitioned into a set of 63 hierarchically organized modules. Each variant was tested against each of the facial surface modules in a multivariate genetic association-testing framework and meta-analyzed. Additionally, the association between these candidate SNPs and five facial ratios was investigated in the Pittsburgh 3DFN cohort. Two significant associations involving intronic variants of SHBG were found: both rs12150660 (p = 1.07E-07) and rs1799941 (p = 6.15E-06) showed an effect on mandible shape. Rs8023580 (an intronic variant of NR2F2-AS1) showed an association with the total and upper facial width to height ratios (p = 9.61E-04 and p = 7.35E-04, respectively). These results indicate that testosterone-related genetic variants affect normal-range facial morphology, and in particular, facial features known to exhibit strong sexual dimorphism in humans.

8.
Front Genet ; 9: 502, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410503

RESUMO

Objectives: Orofacial clefting is one of the most prevalent craniofacial malformations. Previous research has demonstrated that unaffected relatives of patients with non-syndromic cleft lip with/without cleft palate (NSCL/P) show distinctive facial features, which can be an expression of underlying NSCL/P susceptibility genes. These results support the hypothesis that genes involved in the occurrence of a cleft also play a role in normal craniofacial development. In this study, we investigated the influence of genetic variants associated with NSCL/P on normal-range variation in facial shape. Methods: A literature review of genome wide association studies (GWAS) investigating the genetic etiology of NSCL/P was performed, resulting in a list of 75 single nucleotide polymorphisms (SNPs) located in 38 genetic loci. Genotype data were available for 65 of these selected SNPs in three datasets with a combined sample size of 7,418 participants of European ancestry, whose 3D facial images were also available. The effect of each SNP was tested using a multivariate canonical correlation analysis (CCA) against 63 hierarchically-constructed facial segments in each of the three datasets and meta-analyzed. This allowed for the investigation of associations between SNPs known to be involved in NSCL/P and normal-range facial shape variations in a global-to-local perspective, without preselecting specific facial shape features or characteristics. Results: Six NSCL/P SNPs showed significant associations with variation in normal-range facial morphology. rs6740960 showed significant effects in the chin area (p = 3.71 × 10-28). This SNP lies in a non-coding area. Another SNP, rs227731 near the NOG gene, showed a significant effect in the philtrum area (p = 1.96 × 10-16). Three SNPs showed significant effects on the shape of the nose. rs742071 (p = 8.71 × 10-14), rs34246903 (p = 6.87 × 10-12), and rs10512248 (p = 8.4 × 10-9). Respectively, these SNPs are annotated to PAX7, MSX1, and PTCH1. Finally, rs7590268, an intron variant of THADA, showed an effect in the shape of the supraorbital ridge (p = 3.84 × 10-7). Conclusions: This study provides additional evidence NSCL/P-associated genetic variants influence normal-range craniofacial morphology, with significant effects observed for the chin, the nose, the supraorbital ridges and the philtrum area.

9.
Genet Epidemiol ; 42(7): 664-672, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30277614

RESUMO

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G × S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G × S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test ( p < 1.00 × 10 -5 ) by examining the G × S effects from the same model. Out of the 133 loci with suggestive results ( p < 1.00 × 10 -5 ) for the joint test, we observed one genome-wide significant G × S effect in the 10q21 locus (rs72804706; p = 6.69 × 10 -9 ; OR = 2.62 CI [1.89, 3.62]) and 16 suggestive G × S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.


Assuntos
Alelos , Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Caracteres Sexuais , Estudos de Casos e Controles , Epistasia Genética , Feminino , Frequência do Gene/genética , Loci Gênicos , Humanos , Masculino , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
10.
PLoS Genet ; 14(10): e1007675, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30286078

RESUMO

The mechanisms that regulate post-natal growth of the craniofacial complex and that ultimately determine the size and shape of our faces are not well understood. Hippo signaling is a general mechanism to control tissue growth and organ size, and although it is known that Hippo signaling functions in neural crest specification and patterning during embryogenesis and before birth, its specific role in postnatal craniofacial growth remains elusive. We have identified the transcription factor FoxO6 as an activator of Hippo signaling regulating neonatal growth of the face. During late stages of mouse development, FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo expansion of the face, frontal cortex, olfactory component and skull. Enlargement of the mandible and maxilla and lengthening of the incisors in FoxO6-/- mice are associated with increases in cell proliferation. In vitro and in vivo studies demonstrated that FoxO6 activates Lats1 expression, thereby increasing Yap phosphorylation and activation of Hippo signaling. FoxO6-/- mice have significantly reduced Hippo Signaling caused by a decrease in Lats1 expression and decreases in Shh and Runx2 expression, suggesting that Shh and Runx2 are also linked to Hippo signaling. In vitro, FoxO6 activates Hippo reporter constructs and regulates cell proliferation. Furthermore PITX2, a regulator of Hippo signaling is associated with Axenfeld-Rieger Syndrome causing a flattened midface and we show that PITX2 activates FoxO6 expression. Craniofacial specific expression of FoxO6 postnatally regulates Hippo signaling and cell proliferation. Together, these results identify a FoxO6-Hippo regulatory pathway that controls skull growth, odontogenesis and face morphology.

11.
Arch Oral Biol ; 96: 33-38, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30172943

RESUMO

OBJECTIVE: The aim of the present study is to explore genetic factors determining difference of cleft side using whole-genome sequencing and evaluation of craniofacial morphology using cephalometric analysis between Japanese monozygotic (MZ) twins with mirror-image cleft lip and palate (CLP). DESIGN: We selected a Japanese MZ twin pair (MZ-A and MZ-B) affected with unilateral CLP who are discordant for cleft side (left/right) and conducted whole-genome sequencing to identify genetic factors determining cleft side. Moreover, we compared their craniofacial morphologies using cephalograms. RESULTS: Whole-genome sequencing results suggested that no discordant DNA variants were found between MZ-A and MZ-B. The comparison of craniofacial morphology between the MZ twins revealed that MZ-B had maxillary deficiency and slightly more mandibular protrusion than MZ-A. CONCLUSIONS: It is indicated that environmental factors might be a critical factor that influences the determination of difference of cleft side in orofacial clefts. In addition, we found some differences in craniofacial morphology between MZ-A and MZ-B. Our findings suggest that various environmental factors, such as epigenetics, might be a critical factor that influences the determination of difference of cleft side in CLP rather than inherited genetic factors.

12.
PLoS Genet ; 14(8): e1007501, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30067744

RESUMO

There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum.

14.
Oral Dis ; 24(7): 1303-1309, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29873870

RESUMO

OBJECTIVE: Orofacial clefts (OFCs) are common and etiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole-genome sequencing. SUBJECTS AND METHODS: One co-twin (MZ-1) presented with nonsyndromic bilateral cleft lip and palate; the other co-twin (MZ-2) had nonsyndromic bilateral cleft lip and unilateral left-sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole-genome sequencing, respectively. RESULTS: Morphologically, MZ-1 had a smaller vertical mandibular height, compared to MZ-2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harbored rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. CONCLUSION: The observed differences between MZ-1 and MZ-2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development.

15.
Sci Rep ; 8(1): 8470, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855589

RESUMO

Velopharyngeal dysfunction (VPD) occurs when the muscular soft palate (velum) and lateral pharyngeal walls are physically unable to separate the oral and nasal cavities during speech production leading to hypernasality and abnormal speech reduction. Because VPD is often associated with overt or submucous cleft palate, it could be present as a subclinical phenotype in families with a history of orofacial clefting. A key assumption to this model is that the overt and subclinical manifestations of the orofacial cleft phenotype exist on a continuum and therefore share common etiological factors. We performed a genome-wide association study in 976 unaffected relatives of isolated CP probands, 54 of whom had VPD. Five loci were significantly (p < 5 × 10-8) associated with VPD: 3q29, 9p21.1, 12q21.31, 16p12.3 and 16p13.3. An additional 15 loci showing suggestive evidence of association with VPD were observed. Several genes known to be involved in orofacial clefting and craniofacial development are located in these regions, such as TFRC, PCYT1A, BNC2 and FREM1. Although further research is necessary, this could be an indication for a potential shared genetic architecture between VPD and cleft palate, and supporting the hypothesis that VPD is a subclinical phenotype of orofacial clefting.

16.
Am J Hum Biol ; 30(4): e23133, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29744967

RESUMO

OBJECTIVES: We compared digital 3D stereophotogrammetry to more traditional measurement methods (direct anthropometry and 2D scanning) to capture digit lengths and ratios. METHODS: The length of the second and fourth digits was measured by each method and the second-to-fourth ratio was calculated. For each digit measurement, intraobserver agreement was calculated for each of the three collection methods. Further, measurements from the three methods were compared directly to one another. Agreement statistics included the intraclass correlation coefficient (ICC) and technical error of measurement (TEM). RESULTS: Intraobserver agreement statistics for the digit length measurements were high for all three methods; ICC values exceeded 0.97 and TEM values were below 1 mm. For digit ratio, intraobserver agreement was also acceptable for all methods, with direct anthropometry exhibiting lower agreement (ICC = 0.87) compared to indirect methods. For the comparison across methods, the overall agreement was high for digit length measurements (ICC values ranging from 0.93 to 0.98; TEM values below 2 mm). For digit ratios, high agreement was observed between the two indirect methods (ICC = 0.93), whereas indirect methods showed lower agreement when compared to direct anthropometry (ICC < 0.75). CONCLUSIONS: Digit measurements and derived ratios from 3D stereophotogrammetry showed high intraobserver agreement (similar to more traditional methods) suggesting that landmarks could be placed reliably on 3D hand surface images. While digit length measurements were found to be comparable across all three methods, ratios derived from direct anthropometry tended to be higher than those calculated indirectly from 2D or 3D images.

17.
PLoS One ; 13(4): e0196148, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29698431

RESUMO

The shape of the cranial vault, a region comprising interlocking flat bones surrounding the cerebral cortex, varies considerably in humans. Strongly influenced by brain size and shape, cranial vault morphology has both clinical and evolutionary relevance. However, little is known about the genetic basis of normal vault shape in humans. We performed a genome-wide association study (GWAS) on three vault measures (maximum cranial width [MCW], maximum cranial length [MCL], and cephalic index [CI]) in a sample of 4419 healthy individuals of European ancestry. All measures were adjusted by sex, age, and body size, then tested for association with genetic variants spanning the genome. GWAS results for the two cohorts were combined via meta-analysis. Significant associations were observed at two loci: 15p11.2 (lead SNP rs2924767, p = 2.107 × 10-8) for MCW and 17q11.2 (lead SNP rs72841279, p = 5.29 × 10-9) for MCL. Additionally, 32 suggestive loci (p < 5x10-6) were observed. Several candidate genes were located in these loci, such as NLK, MEF2A, SOX9 and SOX11. Genome-wide linkage analysis of cranial vault shape in mice (N = 433) was performed to follow-up the associated candidate loci identified in the human GWAS. Two loci, 17q11.2 (c11.loc44 in mice) and 17q25.1 (c11.loc74 in mice), associated with cranial vault size in humans, were also linked with cranial vault size in mice (LOD scores: 3.37 and 3.79 respectively). These results provide further insight into genetic pathways and mechanisms underlying normal variation in human craniofacial morphology.


Assuntos
Estudo de Associação Genômica Ampla , Crânio/metabolismo , Adulto , Animais , Proteínas de Transporte de Cátions/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Ligação Genética , Loci Gênicos , Genótipo , Humanos , Fatores de Transcrição MEF2/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição SOXC/genética , Crânio/anatomia & histologia , Adulto Jovem
18.
Am J Med Genet A ; 176(6): 1296-1303, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29663709

RESUMO

The biological relatives of offspring with nonsyndromic orofacial clefts have been shown to exhibit distinctive facial features, including excess asymmetry, which are hypothesized to indicate the presence of genetic risk factors. The significance of excess soft tissue nasal asymmetry in at-risk relatives is unclear and was examined in the present study. Our sample included 164 unaffected parents from families with a history of orofacial clefting and 243 adult controls. Geometric morphometric methods were used to analyze the coordinates of 15 nasal landmarks collected from three-dimensional facial surface images. Following generalized Procrustes analysis, Procrustes ANOVA and MANOVA tests were applied to determine the type and magnitude of nasal asymmetry present in each group. Group differences in mean nasal asymmetry were also assessed via permutation testing. We found that nasal asymmetry in both parents and controls was directional in nature, although the magnitude of the asymmetry was greater in parents. This was confirmed with permutation testing, where the mean nasal asymmetry was significantly different (p < .0001) between parents and controls. The asymmetry was greatest for midline structures and the nostrils. When subsets of parents were subsequently analyzed and compared (parents with bilateral vs. unilateral offspring; parents with left vs. right unilateral offspring), each group showed a similar pattern of asymmetry and could not be distinguished statistically. Thus, the side of the unilateral cleft (right vs. left) in offspring was not associated with the direction of the nasal asymmetry in parents.

19.
J Anat ; 233(1): 46-54, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29611183

RESUMO

An estimated 3% of US pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1000 pregnancies being complicated by overactive maternal thyroid levels. Excess thyroid hormones are linked to neurological impairment and excessive craniofacial variation, affecting both endochondral and intramembranous bone. Using a geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Canonical variate analysis utilized 16 unilateral mandibular landmarks obtained from 3D micro-computed tomography to assess shape changes between unexposed controls (n = 63) and exposed mice (n = 178). By evaluating shape changes in the mandible among three age groups (15, 20 and 25 days postnatal) and different dosage levels (low, medium and high), this study found that excess maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners. Group differences in overall shape were significant (P < 0.001), and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter the cranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development, as well as the medical implications of craniofacial growth and development.

20.
Nat Genet ; 50(3): 414-423, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29459680

RESUMO

Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA