Spatially dense 3D facial heritability and modules of co-heritability in a father-offspring design

Introduction: The human face is a complex trait displaying a strong genetic component as illustrated by various studies on facial heritability. Most of these start from sparse descriptions of facial shape using a limited set of landmarks. Subsequently, facial features are preselected as univariate measurements or principal components and the heritability is estimated for each of these features separately. However, none of these studies investigated multivariate facial features, nor the co-heritability between different facial features. Here we report a spatially dense multivariate analysis of facial heritability and co-heritability starting from data from fathers and their children available within ALSPAC. Additionally, we provide an elaborate overview of related craniofacial heritability studies. Methods: In total, 3D facial images of 762 father-offspring pairs were retained after quality control. An anthropometric mask was applied to these images to establish spatially dense quasi-landmark configurations. Partial least squares regression was performed and the (co-)heritability for all quasi-landmarks (∼7160) was computed as twice the regression coefficient. Subsequently, these were used as input to a hierarchical facial segmentation, resulting in the definition of facial modules that are internally integrated through the biological mechanisms of inheritance. Finally, multivariate heritability estimates were obtained for each of the resulting modules. Results: Nearly all modular estimates reached statistical significance under 1,000,000 permutations and after multiple testing correction (p ≤ 1.3889 × 10-3), displaying low to high heritability scores. Particular facial areas showing the greatest heritability were similar for both sons and daughters. However, higher estimates were obtained in the former. These areas included the global face, upper facial part (encompassing the nasion, zygomas and forehead) and nose, with values reaching 82% in boys and 72% in girls. The lower parts of the face only showed low to moderate levels of heritability. Conclusion: In this work, we refrain from reducing facial variation to a series of individual measurements and analyze the heritability and co-heritability from spatially dense landmark configurations at multiple levels of organization. Finally, a multivariate estimation of heritability for global-to-local facial segments is reported. Knowledge of the genetic determination of facial shape is useful in the identification of genetic variants that underlie normal-range facial variation

Spatially Dense 3D Facial Heritability and Modules of Co-heritability in a Father-Offspring Design

Introduction: The human face is a complex trait displaying a strong genetic component as illustrated by various studies on facial heritability. Most of these start from sparse descriptions of facial shape using a limited set of landmarks. Subsequently, facial features are preselected as univariate measurements or principal components and the heritability is estimated for each of these features separately. However, none of these studies investigated multivariate facial features, nor the co-heritability between different facial features. Here we report a spatially dense multivariate analysis of facial heritability and co-heritability starting from data from fathers and their children available within ALSPAC. Additionally, we provide an elaborate overview of related craniofacial heritability studies.Methods: In total, 3D facial images of 762 father-offspring pairs were retained after quality control. An anthropometric mask was applied to these images to establish spatially dense quasi-landmark configurations. Partial least squares regression was performed and the (co-)heritability for all quasi-landmarks (∼7160) was computed as twice the regression coefficient. Subsequently, these were used as input to a hierarchical facial segmentation, resulting in the definition of facial modules that are internally integrated through the biological mechanisms of inheritance. Finally, multivariate heritability estimates were obtained for each of the resulting modules.Results: Nearly all modular estimates reached statistical significance under 1,000,000 permutations and after multiple testing correction (p ≤ 1.3889 × 10-3), displaying low to high heritability scores. Particular facial areas showing the greatest heritability were similar for both sons and daughters. However, higher estimates were obtained in the former. These areas included the global face, upper facial part (encompassing the nasion, zygomas and forehead) and nose, with values reaching 82% in boys and 72% in girls. The lower parts of the face only showed low to moderate levels of heritability.Conclusion: In this work, we refrain from reducing facial variation to a series of individual measurements and analyze the heritability and co-heritability from spatially dense landmark configurations at multiple levels of organization. Finally, a multivariate estimation of heritability for global-to-local facial segments is reported. Knowledge of the genetic determination of facial shape is useful in the identification of genetic variants that underlie normal-range facial variation

Subdividing Y-chromosome haplogroup R1a1 reveals Norse Viking dispersal lineages in Britain

The influence of Viking-Age migrants to the British Isles is obvious in archaeological and place-names evidence, but their demographic impact has been unclear. Autosomal genetic analyses support Norse Viking contributions to parts of Britain, but show no signal corresponding to the Danelaw, the region under Scandinavian administrative control from the ninth to eleventh centuries. Y-chromosome haplogroup R1a1 has been considered as a possible marker for Viking migrations because of its high frequency in peninsular Scandinavia (Norway and Sweden). Here we select ten Y-SNPs to discriminate informatively among hg R1a1 sub-haplogroups in Europe, analyse these in 619 hg R1a1 Y chromosomes including 163 from the British Isles, and also type 23 short-tandem repeats (Y-STRs) to assess internal diversity. We find three specifically Western-European sub-haplogroups, two of which predominate in Norway and Sweden, and are also found in Britain; starlike features in the STR networks of these lineages indicate histories of expansion. We ask whether geographical distributions of hg R1a1 overall, and of the two sub-lineages in particular, correlate with regions of Scandinavian influence within Britain. Neither shows any frequency difference between regions that have higher (≥10%) or lower autosomal contributions from Norway and Sweden, but both are significantly overrepresented in the region corresponding to the Danelaw. These differences between autosomal and Y-chromosomal histories suggest either male-specific contribution, or the influence of patrilocality. Comparison of modern DNA with recently available ancient DNA data supports the interpretation that two sub-lineages of hg R1a1 spread with the Vikings from peninsular Scandinavia

The Y-Chromosome Tree Bursts into Leaf: 13,000 High-Confidence SNPs Covering the Majority of Known Clades

Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51x, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes

3D facial phenotyping by biometric sibling matching used in contemporary genomic methodologies

The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17–0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Peer reviewe

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Mediterranean Y-chromosome 2.0—why the Y in the Mediterranean is still relevant in the postgenomic era

<p><b>Context:</b> Due to its unique paternal inheritance, the Y-chromosome has been a highly popular marker among population geneticists for over two decades. Recently, the advent of cost-effective genome-wide methods has unlocked information-rich autosomal genomic data, paving the way to the postgenomic era. This seems to have announced the decreasing popularity of investigating Y-chromosome variation, which provides only the paternal perspective of human ancestries and is strongly influenced by genetic drift and social behaviour.</p> <p><b>Objective:</b> For this special issue on population genetics of the Mediterranean, the aim was to demonstrate that the Y-chromosome still provides important insights in the postgenomic era and in a time when ancient genomes are becoming exponentially available.</p> <p><b>Methods:</b> A systematic literature search on Y-chromosomal studies in the Mediterranean was performed.</p> <p><b>Results:</b> Several applications of Y-chromosomal analysis with future opportunities are formulated and illustrated with studies on Mediterranean populations.</p> <p><b>Conclusions:</b> There will be no reduced interest in Y-chromosomal studies going from reconstruction of male-specific demographic events to ancient DNA applications, surname history and population-wide estimations of extra-pair paternity rates. Moreover, more initiatives are required to collect population genetic data of Y-chromosomal markers for forensic research, and to include Y-chromosomal data in GWAS investigations and studies on male infertility.</p

The Y chromosome as the most popular marker in genetic genealogy benefits interdisciplinary research

The Y chromosome is currently by far the most popular marker in genetic genealogy that combines genetic data and family history. This popularity is based on its haploid character and its close association with the patrilineage and paternal inherited surname. Other markers have not been found (yet) to overrule this status due to the low sensitivity and precision of autosomal DNA for genetic genealogical applications, given the vagaries of recombination, and the lower capacities of mitochondrial DNA combined with an in general much lower interest in maternal lineages. The current knowledge about the Y chromosome and the availability of markers with divergent mutation rates make it possible to answer questions on relatedness levels which differ in time depth; from the individual and familial level to the surnames, clan and population level. The use of the Y chromosome in genetic genealogy has led to applications in several well-established research disciplines; namely in, e.g., family history, demography, anthropology, forensic sciences, population genetics and sex chromosome evolution. The information obtained from analysing this chromosome is not only interesting for academic scientists but also for the huge and lively community of amateur genealogists and citizen-scientists, fascinated in analysing their own genealogy or surname. This popularity, however, has also some drawbacks, mainly for privacy reasons related to the DNA donor, his close family and far-related namesakes. In this review paper we argue why Y-chromosomal analysis and its genetic genealogical applications will still perform an important role in future interdisciplinary research