Browsing by Author "Williams L"

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    Fine mapping highlights ITGAL and MUS81 loss-of-function mutations modulating recessive impacts in dairy cattle
    (John Wiley and Sons Ltd on behalf of Stichting International Foundation for Animal Genetics, 2025-08-01) Duntsch L; Jivanji S; Lopdell T; Reynolds EGM; Williams L; Littlejohn MD
    We recently described several major-effect recessive loci impacting anatomical and lactation traits in dairy cattle. Two of these loci in particular presented multiple candidate causative variants, comprising tightly linked coding variants that could not be easily differentiated on a statistical or functional basis. Here, we re-examine the candidacy of these variants by leveraging a dataset of 1 million genotyped animals. Assessing lactation and bodyweight effects in conjunction with rare, recombined genotypes for the IL4R, KIAA0556, ITGAL, DPF2, and MUS81 candidates, we highlight ITGAL and MUS81 as the most likely causative genes for the two QTL. Recombinant homozygotes for these genes present larger, more significant effects than other candidates at the same loci, with both representing premature stop mutations anticipated to inactivate ITGAL and MUS81. We further examined homozygotes for the ITGAL mutation to better understand the range of phenotypes impacted. While outwardly normal, ITGAL mutants showed significant differences in the number and composition of circulating leukocytes, consistent with the role of ITGAL as a key mediator of leukocyte signalling, adhesion, and migration. These results demonstrate how near-perfectly linked candidate mutations can be differentiated given population-scale data, and highlight the ITGAL and MUS81 mutations as diagnostic targets to help manage the frequency of these variants.
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    Survey of functional Mendelian variants in New Zealand Huntaway and Heading dog breeds
    (John Wiley and Sons Ltd on behalf of Stichting International Foundation for Animal Genetics, 2025-10-01) Smith F; Lopdell T; Stephen M; Henry M; Dittmer K; Hunt H; Sneddon N; Williams L; Rolfe J; Garrick D; Littlejohn MD
    New Zealand (NZ) Huntaway and Heading dogs are working breeds that play active roles on farms across NZ. While these breeds are common in NZ, they are not well-known elsewhere, and little is understood about their genetic make-up. Here, we used whole genome sequencing to provide a comprehensive genomic view of 249 working dogs. As first use of this resource, we report the allele frequencies of provisionally functional variants aggregated from the Online Mendelian Inheritance in Animals (OMIA) database. Of 435 “probably causal” variants, 27 segregated in our sample. Notable examples of disease variants potentially actionable for selection include those in the CUBN, CLN8, SGSH, SOD1, VWF, and VPS13B genes. These findings will enable genetic testing and selection opportunities to help improve the health and performance of future generations of these unique breeds.
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    Understanding children's perceptions of, and priorities for, healthy neighbourhoods in Aotearoa New Zealand: study protocol for a cross-sectional study
    (BMJ Publishing Group, 2021-06-21) Egli V; Mandic S; Pocock T; Narayanan A; Williams L; Clark T; Spasic L; Wilson A; Witten K; Smith M
    Introduction Neighbourhood environments can have significant and enduring impacts on children’s physical, psychological and social health. Environments can impact health through promoting or hindering physical activity, active travel, and healthy eating in addition to opportunities for social interaction, cognitive development, rest and relaxation. There is a paucity of research that has examined neighbourhood and health priorities, strengths and needs from the perspectives of the community, and even less that has focused on the perspectives of children within communities. The aim of this article is to describe the research protocol for a project to gather child-identified needs and strengths-based solutions for promoting child health and well-being in urban neighbourhood environments. Methods and analysis This participatory research project is designed to partner with children in school settings in Tāmaki Makaurau Auckland and Ōtepoti Dunedin, Aotearoa New Zealand. An abundant communities approach will be used with children to identify needs and strengths related to neighbourhoods and health. Specific methods including collaborative, creative, play-based methods such as concept-mapping activities and co-creation of final dissemination material on the key messages are described. Plans for researcher reflections, data analysis and dissemination are also detailed. Ethics and dissemination This research has been approved by the University of Auckland Human Participants Ethics Committee. Results will be disseminated through child and researcher co-created output, a technical report and academic journal articles. By using evidence-based child-centred approaches to knowledge generation, we anticipate the research will generate new localised insights about children’s preferences and needs for healthy neighbourhoods which will be shared with stakeholders in planning and practice. The detailed session protocol including critical researcher reflections is shared in this manuscript for application, development and refinement in future research.