Genetic signatures of high-altitude adaptation and geographic distribution in Tibetan sheep

Most sheep breeding programs designed for the tropics and sub-tropics have to take into account the impacts of environmental adaptive traits. However, the genetic mechanism regulating the multiple biological processes driving adaptive responses remains unclear. In this study, we applied a selective sweep analysis by combing 1% top values of Fst and ZHp on both altitude and geographic subpopulations (APS) in 636 indigenous Tibetan sheep breeds. Results show that 37 genes were identified within overlapped genomic regions regarding Fst significantly associated with APS. Out of the 37 genes, we found that 8, 3 and 6 genes at chromosomes (chr.) 13, 23 and 27, respectively, were identified in the genomic regions with 1% top values of ZHp. We further analyzed the INDEL variation of 6 genes at chr.27 (X chromosome) in APS together with corresponding orthologs of 6 genes in Capra, Pantholops, and Bos Taurus. We found that an INDEL was located within 5′UTR region of HAG1 gene. This INDEL of HAG1 was strongly associated with the variation of APS, which was further confirmed by qPCR. Sheep breeds carrying “C-INDEL” of HAG1 have significantly greater body weight, shear amount, corpuscular hemoglobin and globulin levels, but lower body height, than those carrying “CA-INDEL” of HAG1. We concluded that “C-INDEL” variation of HAG1 gene confers better hypoxia tolerance in the highlands of Tibetan and explains well geographic distributions in this population. These results contribute to our understanding of adaptive responses to altitude and geographic adaptation in Tibetan sheep populations and will help to guide future conservation programs for Tibetan sheep native to Qinghai-Tibetan Plateau.

Determination of genetic variation within the <i>DYRK2</i> gene and its associations with milk traits in cattle

To speed up the progress of marker-assisted selection (MAS) in cattle breeding, the dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2), cadherin 2 (CDH2), and kinesin family member 1A (KIF1A) genes were chosen based on our pervious genome-wide association study (GWAS) analysis results. DYRK2 is a kinase that may participate in cell growth and/or development; it shows phosphorylation activity toward serine, threonine, and tyrosine fragments of proteins, and it is different from other protein kinases. The CDH2 gene encodes a classic cadherin, which is a member of the cadherin superfamily. The protein encoded by KIF1A is a member of the kinesin family and plays a role in the transportation of membrane organelles along axon microtubules. We detected insertion/deletion (InDel) variation in these three candidate genes in 438 individual cattle (Xinjiang Brown cattle and Wagyu × Luxi crossbreed cattle). Only DYRK2-P3-11 bp was polymorphic and genotyped. The polymorphism information content of DYRK2-P3-11 bp was 0.336. Correlation analyses showed that InDel polymorphism was significantly associated with six different milk traits. These findings may aid future analyses of InDel genotypes in cattle breeds, and speed up the progress of MAS in cattle breeding.

Novel RNASEH2C mutation in multiple members of a large family: insights into phenotypic spectrum of Aicardi-Goutières Syndrome

BackgroundAicardi-Goutières syndrome (AGS) is a genetic inflammatory disorder that presents with early infantile encephalopathy. We report the clinical and molecular details of multiple members of a family with AGS secondary to a novel RNASEH2C mutation, highlighting the evolution of phenotypic abnormalities in AGS.MethodsBetween February 2018 and June 2019, a pedigree tree was constructed for 141 members of a family. The clinical and radiological details of 14 symptomatic children were chronicled and compared with the asymptomatic family members. Genetic analysis was performed on 23 individuals (six symptomatic). This involved whole exome sequencing for one patient and confirmation of the identified indel variant in other family members.ResultsThe symptomatic children were diagnosed as AGS secondary to a novel indel variation in exon 2 of the RNASEH2C gene (chr11:65487843_65487846delinsGCCA). Clinically, between the ages of 2 and 6 months, the symptomatic children developed irritability (14/14), unexplained fever (9/14), chill blains (12/14), sleep irregularities (14/14) and developmental delay (14/14), with deterioration to vegetative state at a median (IQR) age of 10.5 months (9.25–11). In addition, chill blains were observed in 5/17 (29.4%) carrier individuals. Neuroimaging demonstrated a gradual progression of calcification involving basal ganglia, periventricular white matter and dentate nucleus. Three patients also demonstrated presence of subependymal germinolytic cysts.ConclusionThis report highlights a novel founder RNASEH2C mutation and the phenotypic evolution of AGS. In addition, we report chill blains in one-third of RNASEH2C mutation carriers. Neuroradiologically, the report illustrates novel MRI findings and demonstrates a progression pattern of disease. These findings will aid in earlier suspicion and diagnosis of AGS.

Detection of genetic variations of five MMAF-related genes and their associations with litter size in goat

Background: Multiple morphological abnormalities of the sperm flagella (MMAF) makes an assignable contribution to male infertility, including QRICH2 , CFAP43 , CFAP44 , CFAP69 , CCDC39 , AKAP4 and DNAH1 gene. This work studied 28 putative indel mutations of MMAF related genes including QRICH2 , CFAP69 , CFAP43 , CCDC39 and DNAH1 gene and their correlation with the first-born litter sizes of 769 Shaanbei white cashmere (SBWC) goats. Results: Electrophoresis and DNA sequencing analysis showed the 11-bp indel within QRICH2 ( QRICH2 -P4), the three indel variations in CFAP69 ( CFAP69 -P4, CFAP69 -P6 and CFAP69 -P7) and the 27-bp indel of DNAH1 ( DNAH1 -P1) were found to be polymorphic. The 27-bp indel variation within DNAH1 was not in consistent with HWE and the other four indel of QRICH2 and CFAP69 were in consistent with HWE. The linkage disequilibrium (LD) analysis showed the 8-bp indel ( CFAP69 -P4) and the 6-bp indel ( CFAP69- P6) within CFAP69 were in complete LD with each other (D'=0.99, r 2 =1.00). The 27-bp indel mutation within DNAH1 was strongly significantly associated with first-born litter sizes of SBWC goats ( P ＜0.01) and the average litter size of II genotype was significantly greater than ID and DD genotypes ( P = 0.003). In single-lamb and multi-lamb of goat groups, the genotype distributions of the 27-bp indel was significantly different ( P = 0.002). While the 11-bp indel variation of QRICH2 and three indel mutations (P4, P6 and P7) of CFAP69 identified were not ( P ＞0.05). Conclusions: These findings suggest the 27-bp indels in the goat DNAH1 can be used as an effective molecular marker for marker-assisted selection of goats reproduction breeding in the future.

PyRAD: assembly ofde novoRADseq loci for phylogenetic analyses

Restriction-site associated genomic markers are a powerful tool for investigating evolutionary questions at the population level, but are limited in their utility at deeper phylogenetic scales where fewer orthologous loci are typically recovered across disparate taxa. While this limitation stems in part from mutations to restriction recognition sites that disrupt data generation, an alternative source of data loss comes from the failure to identify homology during bioinformatic analyses. Clustering methods that allow for lower similarity thresholds and the inclusion of indel variation will perform better at assembling RADseq loci at the phylogenetic scale.PyRADis a pipeline to assemblede novoRADseq loci with the aim of optimizing coverage across phylogenetic data sets. It utilizes a wrapper around an alignment-clustering algorithm which allows for indel variation within and between samples, as well as for incomplete overlap among reads (e.g., paired-end). Here I comparePyRADwith the programStacksin their performance analyzing a simulated RADseq data set that includes indel variation. Indels disrupt clustering of homologous loci inStacksbut not inPyRAD, such that the latter recovers more shared loci across disparate taxa. I show through re-analysis of an empirical RADseq data set that indels are a common feature of such data, even at shallow phylogenetic scales.PyRADutilizes parallel processing as well as an optional hierarchical clustering method which allow it to rapidly assemble phylogenetic data sets with hundreds of sampled individuals.