A Genome‐Wide Linkage Scan for Quantitative Trait Loci Influencing the Craniofacial Complex in Humans (<i>Homo sapiens sapiens</i>)

Sherwood, Richard J.; Duren, Dana L.; Mahaney, Michael C.; Blangero, John; Dyer, Thomas D.; Cole, Shelley A.; Czerwinski, Stefan A.; Chumlea, Wm. Cameron; Choh, Audrey C.; Nahhas, Ramzi W.; Lee, Miryoung; Towne, Bradford

doi:10.1002/ar.21337

Cited by 18 publications

(20 citation statements)

References 67 publications

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“…In humans, visual phenotype matching has been reported. Many facial features are heritable, and close relatives often resemble one another (for recent quantitative genetic studies see [36]–[38] and references therein). In experimental games people exhibit greater trust and cooperation toward computer-generated images that resemble themselves, as well as judging the sexual attractiveness of opposite-sex self-resembling images to be lower [39].…”

Section: Introductionmentioning

confidence: 99%

Visual Phenotype Matching: Cues to Paternity Are Present in Rhesus Macaque Faces

Kazem

Widdig

2013

PLoS ONE

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The ability to recognize kin and thus behaviourally discriminate between conspecifics based on genetic relatedness is of importance both in acquiring inclusive fitness benefits and to enable optimal inbreeding. In primates, mechanisms allowing recognition of paternal relatives are of particular interest, given that in these mating systems patrilineal information is unlikely to be available via social familiarity. Humans use visual phenotype matching based on facial features to identify their own and other's close relatives, and recent studies suggest similar abilities may be present in other species. However it is unclear to what extent familial resemblances remain detectable against the background levels of relatedness typically found within demes in the wild – a necessary condition if facial cues are to function in kin recognition under natural conditions. Here, we experimentally investigate whether parent-offspring relationships are discernible in rhesus macaque (Macaca mulatta) faces drawn from a large free-ranging population more representative of the latter scenario, and in which genetic relatedness has been well quantified from pedigrees determined via molecular markers. We used the human visual system as a means of integrating multiple types of facial cue simultaneously, and demonstrate that paternal, as well as maternal, resemblance to both sons and daughters can be detected even by human observers. Experts performed better than participants who lacked previous experience working with nonhuman primates. However the finding that even naïve individuals succeeded at the task underlines the strength of the phenotypic cues present in faces.

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Section: Introductionmentioning

confidence: 99%

Visual Phenotype Matching: Cues to Paternity Are Present in Rhesus Macaque Faces

Kazem

Widdig

2013

PLoS ONE

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“…Participants were not selected for any disease or bone-related trait, and therefore represent normal variation in such traits. For the age range of interest (7–35 years), the examination protocol was to see participants every 6 months until age 18 or until they reach skeletal maturity, and every 2 years thereafter [36]. Each study exam included collecting measures of body habitus (e.g., stature, weight, and BMI), a hand-wrist radiograph, and a detailed health history (including menstrual history) via questionnaire.…”

Section: Methodsmentioning

confidence: 99%

The influence of age at menarche on cross-sectional geometry of bone in young adulthood

Šešelj

Nahhas

Sherwood

et al. 2012

Bone

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Elucidating the somatic and maturational influences on the biomechanical properties of bone in children is crucial for a proper understanding of bone strength and quality in childhood and later life, and has significant potential for predicting adult fracture and osteoporosis risks. The ability of a long bone to resist bending and torsion is primarily a function of its cross-sectional geometric properties, and is negatively impacted by smaller external bone diameter. In pubescent girls, elevated levels of estrogen impede subperiosteal bone growth and increase endosteal bone deposition, resulting in bones averaging a smaller external and internal diameter relative to boys. In addition, given a well-documented secular trend for an earlier menarche, the age at which the rate of subperiosteal bone deposition decreases may also be younger in more recent cohorts of girls.In this study we examined the relationship between pubertal timing and subsequent bone strength in girls. Specifically, we investigated the effects of age at menarche on bone strength indicators (polar moment of inertia and section modulus) determined from cross-sectional geometry of the second metacarpal (MC2) using data derived from serial hand-wrist radiographs of female participants (N=223) in the Fels Longitudinal Study, with repeated measures of MC2 between the ages of 7 and 35 years. Using multivariate regression models, we evaluated the effects of age at menarche on associations between measures of bone strength in early adulthood and the same measures at a prepubertal age. Results indicate that later age at menarche is associated with stronger adult bone (in torsion and bending) when controlling for prepubertal bone strength (R 2 ranged between 0.54 and 0.70, p<0.001). Since cross-sectional properties of bone in childhood may have long lasting implications, they should be considered along with pubertal timing in assessing risk for future fracture and in clinical recommendations.

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“…While subtle modulation of this pathway can produce a dose-dependent phenotypic continuum during embryonic development, the effect is non-linear such that the range of “normal” variation is quite narrow and even slight changes in Shh levels can result in major malformations such as clefting in adults (Young, et al 2010). This experiment may explain why this gene has yet to be identified in studies of normal facial variation (Boehringer, et al 2011; Liu, et al 2012; Paternoster, et al 2012; Sherwood, et al 2011). As pointed out by Hallgrimsson and colleagues (Hallgrimsson, et al 2014), it is quite possible (and even likely) that genes not identified by embryonic mutagenesis screens are contributing to the majority of normal facial variation in humans.…”

Section: The Limitations Of Induced Mutationsmentioning

confidence: 99%

Cichlid fishes as a model to understand normal and clinical craniofacial variation

Powder

Albertson

2016

Developmental Biology

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We have made great strides towards understanding the etiology of craniofacial disorders, especially for ‘simple’ Mendelian traits. However, the facial skeleton is a complex trait, and the full spectrum of genetic, developmental, and environmental factors that contribute to its final geometry remain unresolved. Forward genetic screens are constrained with respect to complex traits due to the types of genes and alleles commonly identified, developmental pleiotropy, and limited information about the impact of environmental interactions. Here, we discuss how studies in an evolutionary model – African cichlid fishes – can complement traditional approaches to understand the genetic and developmental origins of complex shape. Cichlids exhibit an unparalleled range of natural craniofacial morphologies that model normal human variation, and in certain instance mimic human facial dysmorphologies. Moreover, the evolutionary history and genomic architecture of cichlids make them an ideal system to identify the genetic basis of these phenotypes via quantitative trait loci (QTL) mapping and population genomics. Given the molecular conservation of developmental genes and pathways, insights from cichlids are applicable to human facial variation and disease. We review recent work in this system, which has identified lbh as a novel regulator of neural crest cell migration, determined the Wnt and Hedgehog pathways mediate species-specific bone morphologies, and examined how plastic responses to diet modulate adult facial shapes. These studies have not only revealed new roles for existing pathways in craniofacial development, but have identified new genes and mechanisms involved in shaping the craniofacial skeleton. In all, we suggest that combining work in traditional laboratory and evolutionary models offers significant potential to provide a more complete and comprehensive picture of the myriad factors that are involved in the development of complex traits.

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A Genome‐Wide Linkage Scan for Quantitative Trait Loci Influencing the Craniofacial Complex in Humans (Homo sapiens sapiens)

Cited by 18 publications

References 67 publications

Visual Phenotype Matching: Cues to Paternity Are Present in Rhesus Macaque Faces

Visual Phenotype Matching: Cues to Paternity Are Present in Rhesus Macaque Faces

The influence of age at menarche on cross-sectional geometry of bone in young adulthood

Cichlid fishes as a model to understand normal and clinical craniofacial variation

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