Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole-genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms (SNPs), ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7068586C) in the 3’-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed pre-historical migrations from the Near Eastern domestication center to South-and-Southeast Asia, and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation and selection of sheep.

The spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically associating domains (TADs), within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. We present OnTAD, an optimized nested TAD caller from Hi-C data, to identify hierarchical TADs. OnTAD reveals new biological insights into the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. OnTAD is available at https://github.com/anlin00007/OnTAD.

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here we conducted a comprehensive genomic analysis of diversity, interspecies introgression and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600k and 50k genome-wide SNP data from 3447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248302667-248306614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

BackgroundPast studies have shown that robot-based intervention was effective in improving gestural use in children with autism spectrum disorders (ASD). The present study examined whether children with ASD could catch up to the level of gestural production found in age-matched children with typical development and whether they showed an increase in verbal imitation after the completion of robot-based training. We also explored the cognitive and motor skills associated with gestural learning.MethodsChildren with ASD were randomly assigned to two groups. Four- to 6-year-old children with ASD in the intervention group (N = 15) received four 30-min robot-based gestural training sessions. In each session, a social robot, NAO, narrated five stories and gestured (e.g., both hands clapping for an awesome expression). Children with ASD were told to imitate the gestures during training. Age-matched children with ASD in the wait-list control group (N = 15) and age-matched children with typical development (N = 15) received the gestural training after the completion of research. Standardized pretests and posttests (both immediate and delayed) were administered to assess the accuracy and appropriateness of gestural production in both training and novel stories. Children’s language and communication abilities, gestural recognition skills, fine motor proficiencies, and attention skills were also examined.ResultsChildren with ASD in the intervention condition were more likely to produce accurate or appropriate intransitive gestures in training and novel stories than those in the wait-list control. The positive learning outcomes were maintained in the delayed posttests. The level of gestural production accuracy in children with ASD in the delayed posttest of novel stories was comparable to that in children with typical development, suggesting that children with ASD could catch up to the level of gestural production found in children with typical development. Children with ASD in the intervention condition were also more likely to produce verbal markers while gesturing than those in the wait-list control. Gestural recognition skills were found to significantly predict the learning of gestural production accuracy in the children with ASD, with such relation partially mediated via spontaneous imitation.ConclusionsRobot-based intervention may reduce the gestural delay in children with ASD in their early childhood.

These findings show that miR-29a exerts as a novel regulator in the fibrogenesis of keloid, suggesting that miR-29a might be a novel marker for keloid.

Variations in ear size can be observed in livestock such as sheep; however, the genetic basis of variable ear size in sheep is still poorly understood. To investigate causative genes associated with ear size in sheep, a genome-wide association study was performed in 115 adult Duolang sheep with different-sized floppy ears using the Ovine Infinium HD BeadChip. We found 38 significant SNPs at the genome-wide or chromosome-wise 5% significance level after Bonferroni correction. The most significant association (P = 1.61 × 10 ) was found at SNP rs402740419, located in the DCC gene, which plays a critical role in ear development. Also, we observed two additional significant SNPs, rs407891215 in PTPRD and rs407769095 in SOX5, both of which are functionally associated with ear developmental processes. Our results are useful for future sheep breeding and provide insights into the genetic basis of ear size development in sheep and other livestock.

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