ABSTRACT: A novel nonsense mutation in DMP1 gene identified by a genome-wide association study is responsible for inherited rickets in Corriedale sheep
Project description:Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies suggest it is a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep including 17 affected and 3 carriers. A homozygous region of 199 consecutive single-nucleotide polymorphism (SNP) loci was identified in all the affected sheep, covering a region of 10Mbp on ovine chromosome 6. Among 91 candidate genes in this region, exon 6 of the dentin matrix protein 1 gene (DMP1) was sequenced to reveal 9 SNPs including a nonsense mutation 253T/C which introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed that, all 17 affected sheep were “T T” genotypes and the 27 phenotypically normal sheep were either “C T” or “C C”. This locus is not in complete linkage disequilibrium with the other 8 SNPs that can all be ruled out as candidates. Previous research has shown that mutations in DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice also exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” alleles. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep including 17 affected and 3 carriers to define homozygous regions with consecutive single-nucleotide polymorphism (SNP) loci only existing in all the affected sheep. Fine mapping was conducted by screening coding regions and splicing regions on the positional candidate genes within the homozygous regions by using more sheep
Project description:Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies suggest it is a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep including 17 affected and 3 carriers. A homozygous region of 199 consecutive single-nucleotide polymorphism (SNP) loci was identified in all the affected sheep, covering a region of 10Mbp on ovine chromosome 6. Among 91 candidate genes in this region, exon 6 of the dentin matrix protein 1 gene (DMP1) was sequenced to reveal 9 SNPs including a nonsense mutation 253T/C which introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed that, all 17 affected sheep were “T T” genotypes and the 27 phenotypically normal sheep were either “C T” or “C C”. This locus is not in complete linkage disequilibrium with the other 8 SNPs that can all be ruled out as candidates. Previous research has shown that mutations in DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice also exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” alleles. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis
Project description:We have completed the high quality reference genome for domestic sheep (Oar v3.1) and performed a detailed survey of gene expression across different tissues. RNA-seq data of 7 tissue types from the reference female Texel and skin tissue from a Gansu alpine fine wool sheep were sequenced.
Project description:We have completed the high quality reference genome for domestic sheep (Oar v3.1) and performed a detailed survey of gene expression across different tissues. RNA-seq data of 7 tissue types from the reference female Texel and skin tissue from a Gansu alpine fine wool sheep were sequenced. Here is the part of the RNA-seq data sequenced in BGI, including 7 tissue types from the reference female Texel and skin type from a Gansu alpine fine wool sheep.
Project description:We have completed the high quality reference genome for domestic sheep (Oar v3.1). Early-stage Illumina GA sequence platform sequenced less reads in high GC content regions than in other regions. To read through higher GC content regions, we generated 2 Gb MeDIP-seq data for filling gaps in sheep reference genome assembly.
Project description:Reproduction, as a physiologically complex process, can significantly affect the development of the sheep industry. However, a lack of overall understanding to sheep fecundity has long blocked the progress in sheep breeding and husbandry. Herein, in present study, we aimed to identify differentially expressed proteins (DEPs) from hypothalamus in sheep without FecB mutation in two comparison groups: polytocous (PF) versus (vs.) monotocous (MF) sheep at follicular phase and polytocous (PL) vs. monotocous (ML) sheep at luteal phase,expecting to provide an alternative method to identify DEPs associated with sheep prolificacy from the hypothalamus.
Project description:FecB (also known as BMPR1B) is a crucial gene in sheep reproduction, which has a mutation (A746G) that was found to increase the ovulation rate and litter size. The FecB mutation is associated with reproductive endocrinology, such mutation can control external estrous characteristics and affect follicle-stimulating hormone during the estrous cycle. Previous researches showed that the FecB mutation can regulate the transcriptomic profiles in the reproductive-related tissues including hypothalamus, pituitary, and ovary during the estrous cycle of Small Tailed Han sheep (STH). However, little research has been reported on the correlation between FecB mutation and the estrous cycle in STH sheep oviduct. To investigate the coding and non-coding transcriptomic profiles involved in the estrous cycle and FecB in the sheep oviduct, RNA sequencing was performed to analyze the transcriptomic profiles of mRNAs and long non-coding RNAs (lncRNAs) in the oviduct during the estrous cycle of STH sheep with mutant (FecBBB) and wild-type (FecB++) genotypes. In total, 21,863 lncRNAs and 43,674 mRNAs were screened.Together, our results can provide novel insights into the oviductal transcriptomic function against a FecB mutation background in sheep reproduction.
Project description:Here, we analyzed and identified the miRNA expression profile of three different intestinal tissues (i.e., duodenum, cecum, and colon) of sheep (Ovis aries) using high-throughput sequencing and bioinformatic methods. In total, 128 known miRNAs were identified, 526 novel miRNAs were predicted, and 202 differentially expressed miRNAs were found between the different tissues. Additionally, 4,422 candidate target genes were predicted, and 185 non-redundant GO annotation terms were identified using enrichment analysis. A total of 529 target genes were found to participate in 37 KEGG biological pathways, and 270 of these genes were significantly enriched in the metabolism category.
Project description:In the present study, we studied the effect of dietary selenium (Se) supplementation on the transcriptomic profile of sheep. The main objective was to evaluate the effect of Se-supplementation on the overall transcriptome of sheep, the altered pathways, and the biological processes related to it . A custom oligo microarray platform (AMADID: 070119) was designed, then used to profile gene expression from 20 samples from 10 sheep at two time points (T0; before Se-supplementation, and T40; at the end of a 40-d Se-supplementation period). Isolated and purified total RNAs were individually hybridized to the custom (4x44k) DNA microarray. The comparison of control and treated animal transcriptomes revealed a large set of differentially expressed genes. After functional analysis and qPCR validation, the result showed several pathways and biological processes that have been altered following Se-supplementation to the diet.