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Advances in Felid Genetics and Genomics

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Advances in Felid Genetics and Genomics Advances in felid genetics and genomics Georgina Samaha Bachelor of Animal and Veterinary Biosciences (Hons I), Bachelor of Arts and Sciences Faculty of Science Sydney School of Veterinary Science A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy 2021 Acknowledgements I thank Assoc. Prof. Bianca Waud, my PhD supervisor and mentor. You instilled in me an enthusiasm for scientific practice that I will carry into future endeavours. A first-time experience for both of us, your door was always open, and you took everything in stride. While I am sure it was difficult to watch me flail at times, I am grateful for the freedom to get lost, make mistakes and come to things in my own time. I also thank my auxiliary supervisor, Prof. Claire Wade who was always there to thoughtfully tease out a problem. I am grateful to have been a beneficiary of your scientific acumen- I could always trust you to recognise a dead end and cut through the B.S. I am grateful to have been a member of the Wade-Waud laboratory and acknowledge the postgraduate students I studied alongside over the course of my candidature: Mitchell O’Brien, Bobbie Cansdale, Tracy Chew, Jessica Gurr, Niruba Kandasamy and Lillian Brancalion. I am especially appreciative of Mitchell’s friendship and collaboration. I also give sincere thanks to Trung Doan and Dr Maura Carrai for their technical expertise and support. I thank my internal collaborators: Dr Catherine Gruber, Prof. Julia Beatty and Dr Hamutal Mazrier who helped me develop my communication skills and taught me the value of interdisciplinary collaboration and lateral thinking in scientific practice. I also thank my external collaborators Prof. Leslie Lyons and Dr Linda Fleeman, and the services and computing resources that the University of Sydney’s High Performance Computing cluster, Sydney Informatics Hub and ICT department provided for all analyses presented here. I am also grateful to have been the recipient of an Australian Postgraduate Award and for the funding provided by the Jenna O’Grady Donley Fund. Finally, I give thanks to my friends and family. I thank my parents for their love and support in pursuing the path I chose, and my partner Emilia for her indulgence and patience. i Statement of originality I declare that this thesis is my own work and contains no material which has been accepted for the award of any other degree or diploma in my name at any other university or institution of tertiary education. To the best of my knowledge this thesis contains no material previously published or written by another person, except where referenced in the text. I certify that the intellectual content of this thesis is the product of my own work and that all assistance received in preparing this thesis and sources have been acknowledged. Georgina Samaha 28th February 2021 ii Table of Contents Abstract 1 Chapter 1: Introduction 2 1.1 A brief history of felid taxonomy 2 1.2 From wildcat to house cat 5 1.3 The expansion of feline genomics 8 1.4 The domestic cat as a model for mapping heritable diseases in humans 12 1.5 Felid conservation 15 1.6 Aims of thesis 19 1.7 References 20 Chapter 2: The domestic cat as a novel genetic model of complex disease 34 2.1 The Burmese cat as a genetic model of type 2 diabetes in humans 34 2.2 Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat 42 Chapter 3: Cross-species applications of the feline reference genome for the benefit of conservation research 55 3.1 Exploiting genomic synteny in Felidae using cross-species genome alignment and SNV discovery to inform conservation management in big cats 55 Chapter 4: Cross-species applications of low-density SNV discovery and genotyping techniques for the benefit of conservation research 83 4.1 Harnessing cross-species SNV methodologies for conservation genomics: A comparison of genotyping array and reduced-representation sequencing methods in wild felids 83 Chapter 5: Concluding remarks 109 Appendices 112 Appendix I: Supplementary data for chapter 2.2 112 Appendix II: Supplementary data for chapter 3 149 Appendix III: Supplementary data for chapter 4 170 iii Manuscripts and conference proceedings This thesis contains published manuscripts, manuscripts currently under review for publication and research that was presented at national and international conferences. They are as listed below. 2021 Under review: Samaha, G., Wade, C.M., Mazrier, H., Grueber, C.E., Haase, B. Harnessing cross- species SNP methodologies for conservation genomics: A comparison of genotyping array and reduced-representation sequencing methods in wild felids. Molecular Ecology Resources 2020 Under review: Samaha, G., Wade, C.M., Mazrier, H., Grueber, C. E., & Haase, B. Exploiting genomic synteny in Felidae: using cross-species genome alignment and SNP discovery to inform conservation management in big cats. BMC Genomics Samaha, G., Wade, C.M., Betty, J., Lyons, L.A., Fleeman, L.M., Haase, B. (2020) Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus). Scientific Reports 10, 19194 doi: 10.1038/s41598-020-766166-3 Samaha, G. Advances in Felid Genomics. Postgraduate conference, November 2020, Sydney School of Veterinary Science, The University of Sydney, NSW, Australia. 2019 Samaha, G., Beatty, J., Wade, C., Haase, B. (2019) The Burmese cat as a genetic model for type 2 diabetes. Animal Genetics 50(4) doi: 10.1111/age.12799 Samaha, G., Lamande, S., Haase, B. Exploring the functional role of TRPV4 variant c.2041G>A in osteochondrodysplasia in Scottish Fold cats. The 10th International Conference on Canine and Feline Genetics and Genomics, May 2019, Bern, Switzerland. 2017 Samaha, G., Beatty, J., Wade, C., Haase, B. The Burmese cat as a spontaneous model for type 2 diabetes. 2017 EMRC Conference, Charles Perkins Centre, Sydney, NSW, Australia. Samaha, G., Beatty, J., Lyons, L., Wade, C., Haase, B. Revealing the genetic basis of diabetes mellitus in Burmese cats. The 9th International Conference on Canine and Feline Genetics and Genomics, May 2017, Saint Paul, Minnesota, USA. 2016 Samaha, G. & Haase, B. Conservation genomics and genetic disorder management of threatened zoo felids. Postgraduate conference, November 2016, Faculty of Veterinary Science, The University of Sydney, NSW, Australia. iv Authorship Attribution Statement Chapter 2.1 of this thesis is published as Samaha, G., Beatty, J., Wade, C., Haase, B. (2019) The Burmese cat as a genetic model for type 2 diabetes. Animal Genetics 50(4) doi: 10.1111/age.12799 I wrote this review under the supervision of Assoc. Prof. Bianca Waud (Haase) and Prof. Claire Wade. Together with Assoc. Prof. Bianca Waud, Prof. Claire Wade and Prof. Julia Beatty, I conceptualised the research. I drafted the manuscript and developed the ideas and arguments within it. Critical revisions were made by myself, Assoc. Prof. Bianca Waud, Prof. Claire Wade and Prof. Julia Beatty. Chapter 2.2 of this thesis is published as Samaha, G., Wade, C.M., Betty, J., Lyons, L.A., Fleeman, L.M., Haase, B. (2020) Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus). Scientific Reports 10, 19194 doi: 10.1038/s41598-020-766166-3 I conceptualised this study with Assoc. Prof. Bianca Waud, Prof. Claire Wade and Prof. Julia Beatty, under the supervision of Assoc. Prof. Bianca Waud, Prof. Claire Wade. I performed all experimental work, data analysis and visualisation. Samples were provided by Prof. Julia Beatty, Prof. Leslie Lyons and Dr Linda Fleeman. Clinical diagnoses were performed by Prof. Julia Beatty and Dr Linda Fleeman. I drafted the original manuscript. Critical revisions were made by myself, Assoc. Prof. Bianca Waud, Prof. Claire Wade, Prof. Julia Beatty, Prof. Leslie Lyons and Dr Linda Fleeman. Chapter 3 of this thesis is currently under review with the journal BMC Genomics. It was submitted as Samaha, G., Wade, C.M., Mazrier, H., Grueber, C. E., & Haase, B. Exploiting genomic synteny in Felidae: using cross- species genome alignment and SNP discovery to inform conservation management in big cats. BMC Genomics. I conceptualised this study with Assoc. Prof Bianca Waud, Prof. Claire Wade, Dr Hamutal Mazrier and Dr Catherine Grueber and performed all experimental work, data analyses and visualisation under the supervision of Assoc. Prof. Bianca Waud and Prof. Claire Wade. I drafted the original manuscript and critical revisions were made by myself, Assoc. Prof Bianca Waud, Prof. Claire Wade, Dr Hamutal Mazrier and Dr. Catherine Grueber. Chapter 4 of this thesis is currently under review with the journal Molecular Ecology Resources. It was submitted as Samaha, G., Wade, C.M., Mazrier, H., Grueber, C.E., Haase, B. Harnessing cross-species SNP methodologies for conservation genomics: A comparison of genotyping array and reduced-representation sequencing methods in wild felids. Molecular Ecology Resources. v Georgina Samaha 28/02/21 As supervisor for the candidature upon which this thesis is based, I can confirm that the authorship attribution statements above are correct. Assoc. Prof. Bianca Waud 28/02/21 vi Abbreviations CVD Congenital vestibular disease FH Familial hypocholesterolaemia FDM Feline diabetes mellitus GWAS Genome-wide association studies IA Islet Amyloidosis IUCN International Union for the Conservation of Nature Kb Kilobase Kya Thousand years ago LCA Last common ancestor LD Linkage disequilibrium MAF Minor allele frequency Mb Megabase MDS Multidimensional scaling mtDNA Mitochondrial DNA MY Million
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