Greater physical activity is associated with neuroretinal thinning in glaucomatous and normative cohorts

Ella Claire Berry, Henry Marshall, Sean Mullany, Santiago Diaz Torres, Joshua Schmidt, Daniel Thomson, Mark Hassall, Stewart R Lake, Richard A Mills, John Landers, Stuart MacGregor, Robert Casson, Owen Siggs, Jamie E Crai

High polygenic risk is associated with earlier treatment initiation and escalation in glaucoma suspects

Abstract #A0360Henry Marshall, Xikun Han, Sean Mullany, Georgie Hollitt, Ella Claire Berry, Lachlan Knight, Richard A Mills, John Landers, Paul Healey, Alex W Hewitt, Stuart L Graham, Robert Casson, Stuart MacGregor, Owen Siggs, Jamie E Crai

A polygenic risk score predicts functional progression in early primary open-angle glaucoma

Abstract #A0353Owen Siggs, Ayub Qassim, Xikun Han, Henry Marshall, Sean Mullany, Emmanuelle Souzeau, Anna Galanopoulos, Ashish Agar, John Landers, Robert Casson, Alex W Hewitt, Paul Healey, Stuart L Graham, Stuart MacGregor, Jamie Crai

Multitrait analysis of glaucoma, intraocular pressure and vertical cup to disc ratio identifies many new loci and enables a polygenic genetic risk score strongly predictive of disease susceptibility in the population, and disease progression and treatment intensity in the clinic

Plenary: Best Paper Presentations #P0404Jamie Craig, Xikun Han, Ayub Qassim, Mark Hassall, Robert Casson, Stuart Graham, John Landers, Colin Willoughby, Andrew Lotery, Janey Wiggs, Owen Siggs, Anna Galanopoulos, Paul Mitchell, Richard Mills, Ashish Agar, Paul Healey, Andrea Vincent, David Mackey, Emmanuelle Souzeau, Alex Hewitt, Stuart MacGrego

Forward genetic analysis of mammalian immunity

Mutation, whether spontaneous or induced, is the premier tool for understanding gene function. One approach is to create mutations in a specific gene, and then use the resulting cell or organism to search for a phenotype. An alternative is to create mutations at random, and focus first on the identification of phenotypes. The mutation that underlies a phenotype can then be tracked down, forming the foundation of testable hypotheses. Using random chemical mutagenesis in mice, I have identified 20 heritable phenotypes affecting either the innate or adaptive branches of immunity. The genetic basis of 18 of these phenotypes was solved, caused by mutations in at least 16 unique genes. Five of these genes were not previously known to be involved in immunity, and a detailed analysis of four of them is provided in this thesis. These include genes encoding the following proteins: the inactive rhomboid protease iRhom2, which is specifically required for the secretion of tumour necrosis factor alpha; the hypothetical phospholipid flippase ATP11C, required for B cell development in the adult bone marrow; the folliculin-interacting protein FNIP1, also required for B cell development; and the zinc finger transcription factor ZBTB1, essential for the development of all lymphocyte lineages. These findings uncover new entry points for the understanding of mammalian immunity, and highlight the value of mouse forward genetics in the understanding of mammalian phenomena in general.</p

Dissecting mammalian immunity through mutation

Although mutation and natural selection have given rise to our immune system, a well-placed mutation can also cripple it, and within an expanding population we are recognizing more and more cases of single-gene mutations that compromise immunity. These mutations are an ideal tool for understanding human immunology, and there are more ways than ever to measure their physiological effects. There are also more ways to create mutations in the laboratory, and to use these resources to systematically define the function of every gene in our genome. This review focuses on the discovery and creation of mutations in the context of mammalian immunity, with an emphasis on the use of genome-wide chemical and CRISPR/Cas9 mutagenesis to reveal gene function. © 2014 Australasian Society for Immunology Inc

The BTB-ZF transcription factors.

The BTB-ZF (broad-complex, tramtrack and bric-à-brac--zinc finger) proteins are encoded by at least 49 genes in mouse and man and commonly serve as sequence-specific silencers of gene expression. This review will focus on the known physiological functions of mammalian BTB-ZF proteins, which include essential roles in the development of the immune system. We discuss their function in terminally differentiated lymphocytes and the progenitors that give rise to them, their action in hematopoietic malignancy and roles beyond the immune system