Genomics

Accuracies of genomic breeding values in American Angus beef cattle using K-means clustering for cross-validation

by Mahdi Saatchi

Genomic selection is a recently developed technology that is beginning to revolutionize animal breeding. The objective... more Genomic selection is a recently developed technology that is beginning to revolutionize animal breeding. The objective of this study was to estimate marker effects to derive prediction equations for direct genomic values for 16 routinely recorded traits of American Angus beef cattle and quantify corresponding accuracies of prediction. Deregressed estimated breeding values were used as observations in a weighted analysis to derive direct genomic values for 3570 sires genotyped using the Illumina BovineSNP50 BeadChip. These bulls were clustered into five groups using K-means clustering on pedigree estimates of additive genetic relationships between animals, with the aim of increasing within-group and decreasing between-group relationships. All five combinations of four groups were used for model training, with cross-validation performed in the group not used in training. Bivariate animal models were used for each trait to estimate the genetic correlation between deregressed estimated breeding values and direct genomic values. Accuracies of direct genomic values ranged from 0.22 to 0.69 for the studied traits, with an average of 0.44. Predictions were more accurate when animals within the validation group were more closely related to animals in the training set. When training and validation sets were formed by random allocation, the accuracies of direct genomic values ranged from 0.38 to 0.85, with an average of 0.65, reflecting the greater relationship between animals in training and validation. The accuracies of direct genomic values obtained from training on older animals and validating in younger animals were intermediate to the accuracies obtained from K-means clustering and random clustering for most traits. The genetic correlation between deregressed estimated breeding values and direct genomic values ranged from 0.15 to 0.80 for the traits studied. These results suggest that genomic estimates of genetic merit can be produced in beef cattle at a young age but the recurrent inclusion of genotyped sires in retraining analyses will be necessary to routinely produce for the industry the direct genomic values with the highest accuracy.

Application of Genomic and Proteomic Technologies in Biomarker Discovery

by Elana Fertig

EJ Fertig, R Slebos, and CH Chung. Application of Genomic and Proteomic Technologies in Biomarker Discovery. In: Govindan R, ed. 2012 ASCO Educational Book. Alexandria, VA: American Society of Clinical Oncology; 2012;377-382.

Overview: Sequencing of the human genome was completed in 2001. Building on the technology and experience of... more Overview: Sequencing of the human genome was completed in 2001. Building on the technology and experience of whole-exome sequencing, numerous cancer genomes have been sequenced, including head and neck squamous cell carcinoma (HNSCC) in 2011. Although DNA sequencing data reveals a complex genome with numerous mutations, the biologic interaction and clinical significance of the overall genetic aberrations are largely unknown. Comprehensive analyses of the tumors using genomics and proteomics beyond sequencing data can potentially accelerate the rate and number of biomarker discoveries to improve biology-driven classification of tumors for prognosis and patient selection for a specific therapy. In this review, we will summarize the current genomic and proteomic technologies, general biomarker-discovery paradigms using the technology and published data in HNSCC---including potential clinical applications and limitations.

Opportunities and challenges for genomic selection of beef cattle

by Mahdi Saatchi

The objective of genomic prediction is to characterize the impact of chromosomal fragments or marker alleles on... more The objective of genomic prediction is to characterize the impact of chromosomal fragments or marker alleles on variation in performance, a process known as training.  This characterization is then used to predict the merit of animals at a young age, without the need for individual phenotypic observations on these selection candidates.  A dataset comprising 803 Hereford animals with 50k marker genotypes and expected progeny differences was used to estimate and validate these techniques.  This population was partitioned at random, or based on genetic relatedness, in order to characterize on most of the individuals the effects of marker alleles for validation in the remaining animals.  Accuracy of prediction was measured as the correlation between genomic prediction and true merit. For birth weight, random partitioning resulted in accuracies of around 0.7, whereas partitioning using relatedness was poorer, at 0.44.  Accuracies for other growth and calving ease traits were lower than birth weight.  Prediction of genomic merit for the same traits in Angus animals, using effects estimated in Herefords had accuracies of 0.22 or less.  Genomic prediction in the near future will require the use of training populations that include all widely used sires in order to provide useful prediction within breed.  In the longer term, denser marker panels, and more research, may lead to predictions with across-breed utility.

De mens als genetisch geïnformeerde ondernemer?

by Hub Zwart

H. Zwart (2011) De mens als genetisch geïnformeerde ondernemer? Bespreking van Gen-ethische grensverkenningen vanuit filosofisch perspectief. Liberaal Reveil 52 (2), 77-82.

A Lab of Their Own: Genomic sovereignty as postcolonial science policy

by Ruha Benjamin

Chromosome-scale selective sweeps shape Caenorhabditis elegans genomic diversity

by Joshua Shapiro

Tissue sampling methods and standards for vertebrate genomics

by Robert Murphy

Wong, P.B.Y., E.O. Wiley, W.E. Johnson, O.A. Ryder, S.J. O'Brien, D. Haussler, K.-P. Koepfli, M.L. Houck, P. Perelman, G. Mastromonaco, A.C. Bentley, B. Venkatesh, Genome 10K Community of Scientists, Y.-p. Zhang, and R.W. Murphy. In press. Tissue sampling methods and standards for vertebrate genomics. GigaScence.

The recent rise in speed and efficiency of new sequencing technologies have facilitated high-throughput sequencing of... more The recent rise in speed and efficiency of new sequencing technologies have facilitated high-throughput sequencing of genomes, assembly and analyses, advancing ongoing efforts to analyze genetic sequences across major vertebrate groups. Standardized procedures in acquiring high quality DNA and RNA and establishing cell lines from target species will facilitate these initiatives. We provide a legal and methodological guide according to four standards of acquiring and storing tissue for the Genome 10K project and similar initiatives as follows: four-star (banked tissue/cell cultures, RNA from multiple types of tissue for transcriptomes, and sufficient flash-frozen tissue for 1mg of DNA, all from a single individual); three-star (RNA as above and frozen tissue for 1mg of DNA); two-star (frozen tissue for at least 700μg of DNA); and one-star (ethanol-preserved tissue for 700μg of DNA or less of mixed quality). At a minimum, all tissues collected for the Genome 10K and other genomic projects should consider each species’ natural history and follow institutional and legal requirements. Associated documentation should detail as much information as possible about provenance to ensure representative sampling and subsequent sequencing. Hopefully, the procedures outlined here will not only encourage success in the Genome 10K project but also inspire the adaptation of standards by other genomic projects, including those involving other biota.

Strategies for transcriptome analysis in non-model plants

by Judson Ward

Authors: Ward JA, Ponnala L, Weber CA.

Even with recent reductions in sequencing costs, most plants lack the genomic resources required for successful... more Even with recent reductions in sequencing costs, most plants lack the genomic resources required for successful short-read transcriptome analyses as performed routinely in model species. Several approaches for the analysis of short-read transcriptome data are reviewed for nonmodel species for which the genome of a close relative is used as the reference genome. Two approaches using a data set from Phytophthora-challenged Rubus idaeus (red raspberry) are compared. Over 70000000 86-nt Illumina reads derived from R. idaeus roots were aligned to the Fragaria vesca genome using publicly available informatics tools (Bowtie/TopHat and Cufflinks). Alignment identified 16956 putatively expressed genes. De novo assembly was performed with the same data set and a publicly available transcriptome assembler (Trinity). A BLAST search with a maximum e-value threshold of 1.0 × 10−3 revealed that over 36000 transcripts had matches to plants and over 500 to Phytophthora. Gene expression estimates from alignment to F. vesca and de novo assembly were compared for raspberry (Pearson’s correlation = 0.730). Together, alignment to the genome of a close relative and de novo assembly constitute a powerful method of transcriptome analysis in nonmodel organisms. Alignment to the genome of a close relative provides a framework for differential expression testing if alignments are made to the predefined gene-space of a close relative and de novo assembly provides a more robust method of identifying unique sequences and sequences from other organisms in a system. These methods are considered experimental in nonmodel systems, but can be used to generate resources and specific testable hypotheses.

Karthick B, 2009. Genome sequencing of cells that live inside glass cages reveals their past history.

by Karthick Balasubramanian

Current Science, VOL. 96(3), 334-337.

SCRIPTed: Report of the Human Fertilisation and Embryology Act Workship

by Malcolm Smith

Co-authored with Dr Christine Knight. Published in SCRIPTed: A Journal of Law, Technology & Society (2011) 8(1), pp. 107-111

Event report following a multidisciplinary workshop at the Economic and Social Research Council's Genomics Policy and... more Event report following a multidisciplinary workshop at the Economic and Social Research Council's Genomics Policy and Research Forum, which took place at the University of Edinburgh on 20 January 2011.

X-chromosome recognition and spreading of the C. elegans Dosage Compensation Complex.

by Christina Whittle

The genomic distribution and function of NFI and histone variant H2A. Z during Caenorhabditis elegans development

by Christina Whittle

Parental information use in the context of newborn bloodspot screening. An exploratory mixed methods study.

by Stuart Nicholls

Co authored with Kevin W Southern. Published in Journal of Community Genetics

Objective: To investigate how parents select and use information sources when considering newborn bloodspot... more Objective: To investigate how parents select and use information sources when considering newborn bloodspot screening
Methods: Mixed methods approach using semi-structured interviews [n=18] and a selfcompletion
postal questionnaire [n=154] conducted with parents of children who had undergone newborn bloodspot screening. Qualitative data was assessed using a thematic analysis approach with quantitative data analyzed using multinomial logistic
regression.
Results: Parents used a limited range of information. In the UK, maternity services are largely delivered by the midwife and the healthcare practitioner was the main information source for parents, with only half of parents using official health service
leaflets. Barriers included the provision of information post-natally and with other nonhealthcare
materials. Neither number of children, age group, education level, nor income were significantly associated with the number of information sources used. Nor were they associated with the information source indicated as most important.
Conclusion: The midwife is well placed to act as a gatekeeper for parents seekinginformation about newborn bloodspot screening. Even when additional sources are used, the midwife remains a prominent source of information. Furthermore, the use of written materials is dependent upon appropriate delivery and consequently delivery is essential to information use.

New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing

by Angela Graefen

Andreas Keller, Angela Graefen, Markus Ball, Mark Matzas, Valesca Boisguerin, Frank Maixner, Petra Leidinger, Christina Backes, Rabab Khairat, Michael Forster, Björn Stade, Andre Franke, Jens Mayer, Jessica Spangler, Stephen McLaughlin, Minita Shah, Clarence Lee, Timothy T. Harkins, Alexander Sartori, Andres Moreno-Estrada, Brenna Henn, Martin Sikora, Ornella Semino, Jacques Chiaroni, Siiri Rootsi, Natalie M. Myres, Vicente M. Cabrera, Peter A. Underhill, Carlos D. Bustamante, Eduard Egarter Vigl, Marco Samadelli, Giovanna Cipollini, Jan Haas, Hugo Katus, Brian D. O'Connor, Marc R.J. Carlson, Benjamin Meder, Nikolaus Blin, Eckart Meese, Carsten M. Pusch & Albert Zink

Nature Communications 3

The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the... more The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Ötztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to ~60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis.

Current State of Our Knowledge on Brain Tumor Epidemiology

by Quinn Ostrom

Co-authored with Jill S. Barnholtz-Sloan, PhD

The overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 person-years;... more The overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 person-years; 11.52 per 100,000 person-years for benign tumors and 7.19 per 100,000 person-years for malignant tumors. Incidence, response to treatment, and survival after diagnosis vary greatly by age at diagnosis, histologic type of tumor, and degree of neurologic compromise. The only established environmental risk factor for brain tumors is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor for brain tumor development. However, studies have been inconsistent and inconclusive due to systematic differences in study designs and difficulty of accurately measuring cell phone use. Recently studies of genetic risk factors for brain tumors have expanded to genome-wide association studies. In addition, genome-wide studies of somatic genetic changes in tumors show correlation with clinical outcomes.

Transcriptome profiling of adult zebrafish at the late stage of chronic tuberculosis due to Mycobacterium marinum infection

by Jeroen Bussmann

The Mycobacterium marinum–zebrafish infection model was used in this study for analysis of a host transcriptome... more The Mycobacterium marinum–zebrafish infection model was used in this study for analysis of a host transcriptome response to mycobacterium infection at the organismal level. RNA isolated from adult zebrafish that showed typical signs of fish tuberculosis due to a chronic progressive infection with M. marinum was compared with RNA from healthy fish in microarray analyses. Spotted oligonucleotide sets (designed by Sigma-Compugen and MWG) and Affymetrix GeneChips were used, in total comprising 45,465 zebrafish transcript annotations. Based on a detailed comparative analysis and quantitative reverse transcriptase-PCR analysis, we present a validated reference set of 159 genes whose regulation is strongly affected by mycobacterial infection in the three types of microarrays analyzed. Furthermore, we analyzed the separate datasets of the microarrays with special emphasis on the expression profiles of immune-related genes. Upregulated genes include many known components of the inflammatory response and several genes that have previously been implicated in the response to mycobacterial infections in cell cultures of other organisms. Different marker genes of the myeloid lineage that have been characterized in zebrafish also showed increased expression. Furthermore, the zebrafish homologs of many signal transduction genes with relationship to the immune response were induced by M. marinum infection. Future functional analysis of these genes may contribute to understanding the mechanisms of mycobacterial pathogenesis. Since a large group of genes linked to immune responses did not show altered expression in the infected animals, these results suggest specific responses in mycobacterium-induced disease.

Genomic natures read through posthumanisms

by Richard Twine

SEARCHING FOR THE 'WIN-WIN'? ANIMALS, GENOMICS AND WELFARE

by Richard Twine

The Escherichia coli K-12 ORFeome: a resource for comparative molecular microbiology

by Peter Uetz

Biased gene conversion affects patterns of codon usage and amino acid usage in the Saccharomyces sensu stricto group of yeasts

by Richard Harrison

Harrison RJ, Charlesworth B.
Mol Biol Evol. 2011 Jan;28(1):117-29. Epub 2010 Jul 23.

Patterns of synonymous codon usage vary between organisms and are controlled by neutral processes (such as drift and... more Patterns of synonymous codon usage vary between organisms and are controlled by neutral processes (such as drift and mutation) as well as by selection. Here we show that an additional neutral process, GC-biased gene conversion (gBGC), plays a part in shaping patterns of both synonymous codon usage and amino acid composition in a manner dependent upon the local recombination rate. We obtain estimates of the strength of gBGC acting on synonymous sites in five species of yeast, which we find to be a much weaker force than selection. We use this to correct estimates of the strength of selection on codon usage bias, which are normally confounded by the action of gBGC. Our estimate of the rate of gBGC agrees well with an experimentally determined value obtained from Saccharomyces cerevisiae. We also find that, contrary to expectation, codon usage bias is highest in areas of intermediate levels of recombination for GC-ending optimal codons. Possible reasons for this are discussed.