Sijie Wu

Combined effects of crystallographic orientation, stacking fault energy and grain size on deformation twinning in fcc crystals

The combined effects of crystallographic orientation, stacking fault energy (SFE) and grain size on deformation twinning behavior in several face-centred cubic (fcc) crystals were investigated experimentally and analytically. Three types of fcc crystals, Al single crystals, Cu single crystals and polycrystalline Cu–3% Si alloy with different SFEs and special crystallographic orientations, were selected. The orientations of the Al and Cu single crystals were designed with one of the twinning systems just perpendicular to the intersection plane of equal-channel angular pressing (ECAP). For Al single crystals, no deformation twins were observed after a one-pass ECAP, although a preferential crystallographic orientation was selected for twinning. For Cu single crystals, numerous deformation twins were found even when strained at room temperature and at low strain rate. For Cu–3% Si alloy, deformation twins were only observed in some grains; however, others with different orientations were full of dislocations, although it has the lowest SFE value of the three fcc crystal types. The experimental results provide evidence that SFE and crystallographic orientation have a remarkable influence on the behavior of deformation twinning in fcc crystals. The observations were subsequently analyzed based on fundamental dislocation mechanisms and the grain-size effect. The deformation conditions required for twinning and the variation in twinning stress with SFE, crystallographic orientation and grain size in fcc crystals are also discussed.

A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence

Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1.

Anisotropic compressive properties of iron subjected to single-pass equal-channel angular pressing

The anisotropic compressive properties and shear deformation mechanism of iron subjected to equal-channel angular pressing (ECAP) with single-pass have been investigated. It was found that the anisotropic compressive properties can be attributed to the effect of the ECAP shear plane. It is suggested that the ECAP shear plane induced by the first pass of ECAP is a relatively weak plane in terms of resisting subsequent shear deformation.

Nature of shear flow lines in equal-channel angular-pressed metals and alloys

The nature of shear flow lines in equal-channel angular-pressed (ECAPed) metals has been investigated experimentally and theoretically. Experimental results indicate that, for metals pressed in a right-angle die, the shear flow lines often have an angle of ∼27° with respect to the extrusion direction. It is suggested that the shear flow lines are composed of a group of elongated grains with an elongation direction that deviates slightly from that of the shear flow lines.

Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10−10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10−8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10−11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

Genome-wide variants of Eurasian facial shape differentiation and a prospective model of DNA based face prediction

It is a long-standing question as to which genes define the characteristic facial features among different ethnic groups. In this study, we use Uyghurs, an ancient admixed population to query the genetic bases why Europeans and Han Chinese look different. Facial traits were analyzed based on high-dense 3D facial images; numerous biometric spaces were examined for divergent facial features between European and Han Chinese, ranging from inter-landmark distances to dense shape geometrics. Genome-wide association studies (GWAS) were conducted on a discovery panel of Uyghurs. Six significant loci were identified, four of which, rs1868752, rs118078182, rs60159418 at or near UBASH3B, COL23A1, PCDH7 and rs17868256 were replicated in independent cohorts of Uyghurs or Southern Han Chinese. A prospective model was also developed to predict 3D faces based on top GWAS signals and tested in hypothetic forensic scenarios.

Towards broadening Forensic DNA Phenotyping beyond pigmentation: Improving the prediction of head hair shape from DNA

Human head hair shape, commonly classified as straight, wavy, curly or frizzy, is an attractive target for Forensic DNA Phenotyping and other applications of human appearance prediction from DNA such as in paleogenetics. The genetic knowledge underlying head hair shape variation was recently improved by the outcome of a series of genome-wide association and replication studies in a total of 26,964 subjects, highlighting 12 loci of which 8 were novel and introducing a prediction model for Europeans based on 14 SNPs. In the present study, we evaluated the capacity of DNA-based head hair shape prediction by investigating an extended set of candidate SNP predictors and by using an independent set of samples for model validation. Prediction model building was carried out in 9674 subjects (6068 from Europe, 2899 from Asia and 707 of admixed European and Asian ancestries), used previously, by considering a novel list of 90 candidate SNPs. For model validation, genotype and phenotype data were newly collected in 2415 independent subjects (2138 Europeans and 277 non-Europeans) by applying two targeted massively parallel sequencing platforms, Ion Torrent PGM and MiSeq, or the MassARRAY platform. A binomial model was developed to predict straight vs. non-straight hair based on 32 SNPs from 26 genetic loci we identified as significantly contributing to the model. This model achieved prediction accuracies, expressed as AUC, of 0.664 in Europeans and 0.789 in non-Europeans; the statistically significant difference was explained mostly by the effect of one EDAR SNP in non-Europeans. Considering sex and age, in addition to the SNPs, slightly and insignificantly increased the prediction accuracies (AUC of 0.680 and 0.800, respectively). Based on the sample size and candidate DNA markers investigated, this study provides the most robust, validated, and accurate statistical prediction models and SNP predictor marker sets currently available for predicting head hair shape from DNA, providing the next step towards broadening Forensic DNA Phenotyping beyond pigmentation traits.

Large-scale genome-wide scans do not support petaloid toenail as a Mendelian trait

Petaloid toenail, or accessory nail of the fifth toe, is a physical trait characterized by the presence of an additional tiny toenail on the small toe. Since it can occasionally cause disfigurement and tenderness while wearing tight shoes or walking, standard surgical matricectomy is often carried out to repair the petaloid toenail (Chi and Wang, 2004). Chinese legends recorded petaloid toenails as a trait unique to Han Chinese (Gao, 2010), but populationbased studies are largely absent. A recent study of petaloid toenail confirmed its prevalence in Han Chinese (Hao et al., 2005) and proposed a dominant Mendelian mode of inheritance. In this study, we examined the petaloid toenail trait in both Han Chinese and Uyghur populations in China, aiming to 1) obtain a more complete picture of the population prevalence of petaloid toenail; 2) find potential genes associated with petaloid toenail through genome-wide scans, thereby shedding light on the mode of inheritance of this trait. For this study, we collected 2980 Han Chinese samples and 721 Uyghur samples including 1349 males and 2352 females. The petaloid toenail phenotype was recorded as an ordered categorical variable scored as levels 0 to 2, following a previously established standard (Hao et al., 2005) (Fig. 1A and supplementary data). Apart from the three ordered categorical levels, we further derived two statistics combining the right and left foot statistics: Petaloid_E (“petaloid toenail exist”: the presence of a petaloid toenail on at least one foot), and Petaloid_D (“petaloid toenail double”: the presence of a petaloid toenail on both feet). We summarized the frequency of the petaloid toenail trait in Han Chinese and Uyghurs (Tables S1 and S2). The frequency of petaloid toenail in our Han Chinese population in the Jiangsu Province (58.97%) fits well with previous reports (Hao et al., 2005). While we confirmed the presence of the petaloid toenail trait in the Han Chinese population, we also found a substantial prevalence of this trait in Uyghurs (51.15%), suggesting that it is not unique to the Han Chinese. Furthermore, the petaloid toenail trait is not associated with the East Asian ancestral proportion in the Uyghurs (P1⁄4 0.357). Since the Uyghurs are a quite evenly admixed population with both eastern and western Eurasian ancestries (Xu and Jin, 2008), it is very likely that the frequency of the petaloid toenail in western Eurasian populations is also considerable. Future studies in western Eurasian populations shall provide unequivocal evidence. We found a significant correlation between the presence of a petaloid toenail on right and left feet in both Han Chinese (r 1⁄4 0.4684, P < 2.2e-16) and Uyghurs (r 1⁄4 0.5024, P < 2.2e-16). Nonetheless, the distribution of the trait is not symmetric. By