Deemster Parr's Abstract

Deemster John Parr's Abstract of Manx laws is an important source of Manx law dating from the late seventeenth century. It is also of more than passing interest to scholars of the legal history of the larger jurisdictions surrounding the Isle of Man. Although available in manuscript form in the Manx Museum, this document has never been published. This typescript was prepared and checked by Peter Edge from MS 03176 C

Manx Customary Laws

This document, catalogued in the Manx Museum as "Customary Lawes" appears to be the document referred to by Deemster Parr in the sidenotes to his Abstract. Certainly, the paragraph numbers tally with the references in those sidenotes. Accordingly, this document is included as an additional source for use with Deemster Parr's Abstract, also part of this collectio

Haplotype Assembly and Small Variant Calling using Emerging Sequencing Technologies

Short read DNA sequencing technologies from Illumina have made sequencing a human genome significantly more affordable, greatly accelerating studies of biological function and the association of genetic variants to disease. These technologies are frequently used to detect small genetic variants such as single nucleotide variants (SNVs) using a reference genome. However, short read sequencing technologies have several limitations. First, the human genome is diploid and short reads contain limited information for assembling haplotypes, or the sequences of alleles on homologous chromosomes. Moreover, there is significant input DNA required, which poses challenges for analyzing single cells. Further, there is limited ability to detect genetic variants inside long duplicated sequences that occur in the genome. As a result, there has been widespread development of novel methods to overcome these deficiencies using short reads. These include clone based sequencing, linked read sequencing, and proximity ligation sequencing, as well as various single cell sequencing methods. There are also entirely new sequencing technologies from Pacific Biosciences and Oxford Nanopore Technologies that produce significantly longer reads. While these emerging methods and technologies demonstrate improvements compared to short reads, they also have properties and error modalities that pose unique computational challenges. Moreover, there is a shortage of bioinformatics methods for accurate small variant detection and haplotype assembly using these approaches compared to short reads. This dissertation aims to address this problem with the introduction of several new algorithms for highly accurate haplotype assembly and SNV calling. First, it introduces HapCUT2, an algorithm that can rapidly assemble haplotypes using a broad range of sequencing technologies. Second, it introduces an algorithm for variant calling and haplotyping using SISSOR, a recently introduced microfluidics based technology for sequencing single cells. Finally, it introduces Longshot, an algorithm for detecting and phasing SNVs using error-prone long read technologies. In each case, the algorithms are benchmarked using multiple real whole-genome sequencing datasets and are found to be highly accurate. The methods introduced in this dissertation contribute to the goal of sequencing diploid genomes accurately and completely for a broad range of scientific and clinical purposes

Ordinary Theology amongst Church of England Volunteers: A Contribution to the Debate

This thesis explores the theological literacy of ordinary (not theologically trained) Christian Church of England volunteers who carry out volunteer work beyond their church congregations. I approach Jeff Astley’s “ordinary theology” in a way that enables the ordinary Christian volunteer to express their theological literacy. The cohort studied was of Christians whose vocation was to be an intentional Christian presence to those they supported in the context of prison or offender work and supporting chaplaincy with the deaf. I chose to approach this thesis in terms of Jeff Astley’s ordinary theology. This was in order to attend to how such Christian faith (or theology) had changed as a result of their work. I used Cameron’s “Theology in four voices”, attending to the volunteers “espoused” voice, pursuing their perception of “operant” theologies. I approached the study empirically, using a conversational hermeneutic as a researcher who was an “observer as participant”: a participant in the above fields not directly involved, yet sharing a horizon of understanding with the cohort. I pursued semi-structured questions which brought the underlying theology to the fore. Such theology included understanding of culture, the Bible, and aspects of faith such as Christian love, forgiveness and prayer. The conclusions derived from analysing the data in discussion with “ordinary theology” may encourage further academic exploration and expansion of this particular genre of practical theology, and in particular regarding those motivated by faith to work beyond the local church community. These findings could also provide a theological resource to the wider church, in its mission to engage with the world beyond local church congregations

Lisvane's legacy? Constitutional reform in the Isle of Man

The Isle of Man is a largely autonomous dependent territory of the UK. In 2016, Lord Lisvane was commissioned to report on the functioning of the principal organ of governance, the Tynwald. This Lisvane Review has led to substantial constitutional reform within this small democracy, particularly in relation to the unelected second chamber of Tynwald, the Legislative Council. This reflects an ancient tension within the Manx constitution between the House of Keys, since the mid-nineteenth century a directly elected chamber, and the unelected Legislative Council. The Lisvane period saw important changes to the composition and powers of the Legislative Council, as well as gender diversity within Tynwald as a whole. Placing the Manx experience within a broader small democracy theoretical and comparative framework demonstrates not only the possibility of constitutional reform, but also provides insights into resources for constitutional development, the special challenges of managing intimacy, and the dangers of over-concentration of power in a small democracy

InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms.

Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/

The work of a religious representative in a democratic legislature: A case study of the Lord Bishop of Sodor and Man in Tynwald, 1961-2001

The Isle of Man is a largely autonomous territory of the United Kingdom Crown, whose dominant constitutional body is the Tynwald. Tynwald, although meeting regularly as a single body, is for most purposes divided into two Branches – a directly elected House of Keys, and the Legislative Council. The latter includes among its members the Lord Bishop of Sodor and Man. This study draws upon the legislative debates of Tynwald between 1961 and 2001 to examine the nature of the Bishop’s role. Analysis shows that the Bishop was expected to contribute to debate in two major areas – moral issues and technical issues concerning the Manx Church. Additionally, the Bishops operated within expectations as to their modes of contribution. The strongest of these was that the Bishop should not become entangled in party politics. There was also a strong expectation that the Bishop should represent the Manx Church and Christianity more generally, although this expectation does not seem to have been realised in relation to non-Christian religions. There is also evidence that the Bishop was also entitled to use both secular and religious modes of argumentation, and that he should not have expected to the be the only religious voice in Tynwald, or even the uncontested voice of the Manx Church

Freedom of religion under the European Convention on Human Rights: Foreshadowing interpretative dilemmas

This chapter focuses on those provisions of the European Convention on Human Rights (ECHR) most clearly relevant to freedom of religion: Article 9, and Article 2 of the First Protocol. These provisions are placed in context, both in terms of the development of freedom of religion at the international level, and in terms of the history of the drafting of the provisions. The exposition function was particularly important in a text on freedom of religion or belief. It was the first full-length text providing a sustained consideration of freedom of religion under the ECHR, as opposed to in international law more generally. A lack of sympathy, or perhaps better put, a failure of judicial imagination when considering the position of atheists within a religious rights regime, materialised in Lautsi v Italy. Eweida removed the initial hurdle in making a religion or belief claim, a second hurdle is immediately encountered: the margin of appreciation

Ultraaccurate genome sequencing and haplotyping of single human cells.

Accurate detection of variants and long-range haplotypes in genomes of single human cells remains very challenging. Common approaches require extensive in vitro amplification of genomes of individual cells using DNA polymerases and high-throughput short-read DNA sequencing. These approaches have two notable drawbacks. First, polymerase replication errors could generate tens of thousands of false-positive calls per genome. Second, relatively short sequence reads contain little to no haplotype information. Here we report a method, which is dubbed SISSOR (single-stranded sequencing using microfluidic reactors), for accurate single-cell genome sequencing and haplotyping. A microfluidic processor is used to separate the Watson and Crick strands of the double-stranded chromosomal DNA in a single cell and to randomly partition megabase-size DNA strands into multiple nanoliter compartments for amplification and construction of barcoded libraries for sequencing. The separation and partitioning of large single-stranded DNA fragments of the homologous chromosome pairs allows for the independent sequencing of each of the complementary and homologous strands. This enables the assembly of long haplotypes and reduction of sequence errors by using the redundant sequence information and haplotype-based error removal. We demonstrated the ability to sequence single-cell genomes with error rates as low as 10-8 and average 500-kb-long DNA fragments that can be assembled into haplotype contigs with N50 greater than 7 Mb. The performance could be further improved with more uniform amplification and more accurate sequence alignment. The ability to obtain accurate genome sequences and haplotype information from single cells will enable applications of genome sequencing for diverse clinical needs