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Research Progress of Three-dimensional Genomics in Animal Genetics and Breeding
CHEN Yi-he,LI Xin-miao,PENG Wei,LEI Chu-zhao,ZHAO Huang-qing,ZHANG Zi-jing,LIU Xian,HUANG Yong-zhen
China Biotechnology ›› 2022, Vol. 42 ›› Issue (4) : 78-84.
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Research Progress of Three-dimensional Genomics in Animal Genetics and Breeding
({{custom_author.role_en}}), {{javascript:window.custom_author_en_index++;}}Three-dimensional genomics is a newly developed subject that studies the three-dimensional space and structure of genome. Based on considering genome sequence, gene structure and its regulatory elements, it studies the functions of gene replication, transcription, repair and regulation in biological processes and the three-dimensional structure of genome sequence in the nucleus. With the emergence and improvement of high-throughput sequencing technology, the research of three-dimensional genomics has developed rapidly. This paper focuses on the development process, research technology and structural level of three-dimensional genomics, and summarizes the application of three-dimensional genomics in animal genetics and breeding in recent years.
Three-dimensional genome / Chromatin spatial structure / Animal genetics and breeding {{custom_keyword}} /
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Transcription regulation in higher eukaryotes is controlled by regulatory elements such as enhancers that are recognized by transcription factors. In many cases regulatory elements can be located at distances up to several megabases from their target genes. Recent evidence shows that long-range control of gene expression can be mediated through direct physical interactions between genes and these regulatory elements. Such looping interactions can be detected using the chromosome conformation capture (3C) methodology. Although 3C is experimentally straightforward, to draw meaningful conclusions one must carefully design 3C experiments and implement the conscientious use of controls. The general guidelines presented here should help experimental design and minimize misinterpretation of 3C experiments.
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We performed a genome-wide association study (GWAS) and candidate gene analysis to: (i) evaluate the effectiveness of the GWAS in our small population by performing GWAS for carcass weight (CW) and fatty acid composition; (ii) detect novel candidate regions affecting non-CW carcass traits, chemical composition and sugar; and (iii) evaluate the association of the candidate genes previously detected in CW and fatty acid composition with other economically important traits. A total of 574 Japanese Black cattle and 40 657 Single nucleotide polymorphisms were used. In addition, candidate gene analyses were performed to evaluate the association of three CW-related genes and two fatty acid-related genes with carcass traits, fatty acid composition, chemical composition and sugar. The significant regions with the candidate genes were detected for CW and fatty acid composition, and these results showed that a significant region would be detectable despite the small sample size. The novel candidate regions were detected on BTA23 for crude protein and on BTA19 for fructose. CW-related genes associated with the rib-eye area and fatty acid composition were identified, and fatty acid-related genes had no relationship with other traits. Moreover, the favorable allele of CW-related genes had an unfavorable effect on fatty acid composition.© 2016 Japanese Society of Animal Science.
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The oocyte cytoplasm can reprogram the somatic cell nucleus into a totipotent state, but with low efficiency. The spatiotemporal chromatin organization of somatic cell nuclear transfer (SCNT) embryos remains elusive. Here, we examine higher order chromatin structures of mouse SCNT embryos using a low-input Hi-C method. We find that donor cell chromatin transforms to the metaphase state rapidly after SCNT along with the dissolution of typical 3D chromatin structure. Intriguingly, the genome undergoes a mitotic metaphase-like to meiosis metaphase II-like transition following activation. Subsequently, weak chromatin compartments and topologically associating domains (TADs) emerge following metaphase exit. TADs are further removed until the 2-cell stage before being progressively reestablished. Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. These defects are partially caused by inherited H3K9me3, and can be rescued by Kdm4d overexpression. These observations provide insight into chromatin architecture reorganization during SCNT embryo development.
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