GENOMIC APPROACHES AND TOOL DEVELOPMENT

The ability to determine the complete DNA sequence or genome of an organism is transforming biology and medicine.  Pacific Hybreed founder Hedgecock has played an active role in the development of genome-based tools for mapping genes of interest in the oyster and was a co-author on the publication of the genome of the Pacific oyster in 2012, a landmark in shellfish biology.

Centromere-mapping in triploid families of the Pacific oyster Crassostrea gigas (Thunberg)

Hubert, S., E. Cognard, and D. Hedgecock. 2009. Centromere-mapping in triploid families of the Pacific oyster Crassostrea gigas (Thunberg). Aquaculture 288:172–183.

This paper helped to improve the genetic linkage map for the Pacific oyster and aided subsequent efforts to map genes underlying traits of commercial importance, such as hybrid vigor, sex determination, and survival. This research was supported by grants from the National Sea Grant College Program and the National Science Foundation.

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De novo assembly of the Manila clam Ruditapes philippinarum transcriptome provides new insights into expression bias, mitochondrial doubly uniparental inheritance and sex determination

Ghiselli, F., L. Milani, P. L. Chang, D. Hedgecock, J. P. Davis, S. V. Nuzhdin, and M. Passamonti. 2012. De novo assembly of the Manila clam Ruditapes philippinarum transcriptome provides new insights into expression bias, mitochondrial doubly uniparental inheritance and sex determination. Molecular Biology and Evolution 29: 771-786.

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Expression of the Pacific oyster mitochondrial genome: Variation among loci and evidence for regulation by nuclear-cytoplasmic interaction

Curole, J. P., E. Meyer, D. T. Manahan and D. Hedgecock. 2009. Expression of the Pacific oyster mitochondrial genome: Variation among loci and evidence for regulation by nuclear-cytoplasmic interaction. Biological Bulletin 218:122-131.

In this paper, an outgrowth of the transcriptome study (Hedgecock et al 2007, below), we focused on the expression of genes in the oyster mitochondrial genome. We showed that mitochondrial genes, despite being transcribed as a unit, have very different levels of expression (i.e. abundances of messenger RNA vary by orders of magnitude). We also provided evidence that this variation in mitochondrial gene expression depends in part on the nuclear genotype. Such nuclear-cytoplasmic interactions may underlie the significant differences that we often see between reciprocal hybrids (i.e. hybrid AB ≠ hybrid BA), even though both hybrids have, in principle, have very similar nuclear genes. Hedgecock and Davis (2007) provided substantial evidence that reciprocal differences are a significant component of yield variance. This work was supported by grants from the USDA and the NSF.

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Inheritance of high-resolution melting profiles in assays targeting single nucleotide polymorphisms in protein-coding sequences of the Pacific oyster Crassostrea gigas:

Sun, X.J., G. Shin, and D. Hedgecock. 2015. Inheritance of high-resolution melting profiles in assays targeting single nucleotide polymorphisms in protein-coding sequences of the Pacific oyster Crassostrea gigas: Implications for parentage assignment of experimental and commercial broodstocks. Aquaculture 437: 127-139.

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Second-generation linkage maps for the Pacific oyster Crassostrea gigas reveal errors in assembly of genome scaffolds

Hedgecock, D., G. Shin, A.Y. Gracey, D. Van Den Berg and M.P. Samanta. 2015. Second-generation linkage maps for the Pacific oyster Crassostrea gigas reveal errors in assembly of genome scaffolds. G3: Genes Genomes Genetics 5: 2007-2019.

A continuation of a decade-long effort to construct genetic linkage maps for the Pacific oyster, this paper not only provided a consensus, high-density genetic map but also provided definitive evidence that the genome assembly provided by Zhang et al (2012, below) has many errors that need to be corrected.

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The Case for Sequencing the Pacific Oyster Genome

Hedgecock, D., P. M. Gaffney, P. Goulletquer, X. Guo, K. Reece, and G. W. Warr. 2005. The case for sequencing the Pacific oyster genome. Journal of Shellfish Research 24:429-441.

This “white paper” was the first to advocate for the sequencing of the Pacific oyster genome. The paper describes the biological and genomic resources available (at that time) to support a genome sequencing project, including the fourth-generation inbred line 51, from which a BAC DNA library was constructed and which ultimately provided the oyster whose genome was sequenced by the Beijing Genome Institute (Zhang et al. 2012). Also mentioned are the 51 × 35 F1 and F2 hybrids, which have been used extensively for research on heterosis and inbreeding depression; this research provided a framework for genomic approaches to understanding heterosis and its applications to shellfish breeding and, thus, a compelling rationale for sequencing the genome.

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The Oyster Genome Reveals Stress Adaptation and Complexity of Shell Formation.

Zhang, G., X. Fang, X. Guo, L. Li, R. Luo, F. Xu, P. Yang, L. Zhang, X. Wang, H. Qi, Z. Xiong, H. Que, Y. Xie, P. W. H. Holland, J. Paps, Y. Zhu, F. Wu, Y. Chen, J. Wang, C. Peng, J. Meng, L. Yang, J. Liu, B. Wen, N. Zhang, Z. Huang, Q. Zhu, Y. Feng, A. Mount, D. Hedgecock, Z. Xu, Y. Liu, T. Domazet-Lošo, Y. Du, X. Sun, S. Zhang, B. Liu, P. Cheng, X. Jiang, J. Li, D. Fan, W. Wang, W. Fu, T. Wang, B. Wang, J. Zhang, Z. Peng, Y. Li, N. Li, J. Wang, M. Chen, Y. He, F. Tan, X. Song, Q. Zheng, R. Huang, H. Yang, X. Du, L. Chen, M. Yang, P. M. Gaffney, S. Wang, L. Luo, Z. She, Y. Ming, W. Huang, S. Zhang, B. Huang, Y. Zhang, T. Qu, P. Ni, G. Miao, J. Wang, Q. Wang, C. E. W. Steinberg, H. Wang, N. Li, L. Qian, G. Zhang, X. Liu, Y. Li, Y. Yin, and J. Wang. 2012. The oyster genome reveals stress adaptation and complexity of shell formation. Nature 490:49-52 (4 October 2012).

This is the publication of the genome sequence of the Pacific oyster. Hedgecock and Davis supplied the fourth-generation inbred oyster whose genome was sequenced. Hedgecock, a co-author, confirmed the pedigree of the oyster, using genetic markers, and provided advice on the overall project, the rationale for which was established by Hedgecock et al (2005, below). The development of this inbred line was made possible by grants from the USDA.

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Transcriptomic Analysis of Growth Heterosis in Larval Pacific Oysters (Crassostrea Gigas)

Hedgecock, D., J.-Z. Lin, S. DeCola, C. Haudenschild, E. Meyer, D. T. Manahan, and B. Bowen. 2007. Transcriptomic analysis of growth heterosis in larval Pacific oysters (Crassostrea gigas). Proceedings of the National Academy of Sciences, U.S.A. 104:2313-2318.

Published in the prestigious journal, Proceedings of the National Academy of Sciences, this paper reported the first analysis of sequences of transcribed or expressed genes in a marine animal. It was one of the first such studies, comparing inbre and hybrid families of any organism.

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