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Cover Page The handle http://hdl.handle.net/1887/59527 holds various files of this Leiden University dissertation.

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The handle http://hdl.handle.net/1887/59527 holds various files of this Leiden University dissertation.

Author: Jong, V.M. de

Title: Functional genetics of type 1 diabetes: between genes and disease

Issue Date: 2018-01-17

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FUNCTIONAL GENETICS OF TYPE 1 DIABETES:

Between Genes and Disease

Vincent Martijn de Jong

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The financial contribution of Novo Nordisk

Alrijne Zorggroep.

is gratefully acknowledged.

Cover and illustration design by Bas van Os

Layout and printed by Off Page, Amsterdam, The Netherlands ISBN: 978-94-6182-867-5

Copyright © Vincent M. de Jong, Leiden, The Netherlands. All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, without prior written permission of the author.

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FUNCTIONAL GENETICS OF TYPE 1 DIABETES:

Between Genes and Disease

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op woensdag 17 januari 2018

klokke 16:15 uur

door

Vincent Martijn de Jong geboren te Rotterdam

in 1986

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Dr. B.P.C. Koeleman Dr. A. Zaldumbide

Promotiecommissie

Prof. dr. J.J. Zwaginga Prof. dr. P.J. van den Elsen Prof. dr. C. van Kooten

Prof. dr. C. Mathieu Katholieke Universiteit Leuven Dr. H.J. Aanstoot Diabeter

Dr. T. Nikolic

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TABLE OF CONTENTS

Chapter 1 Introduction 7 Chapter 2 Alternative splicing and differential expression of 27

the islet-autoantigen IGRP between pancreas and

thymus contributes to immunogenicity of pancreatic islets but not diabetogenicity in humans

Chapter 3 Survival of autoreactive T-lymphocytes by microRNA-mediated 47 regulation of apoptosis through TRAIL and Fas in type 1 diabetes

Chapter 4 Posttranscriptional control of candidate risk genes for 69 type 1 diabetes by rare genetic variants

Chapter 5 Variation in the CTLA4 3’UTR has phenotypic consequences for 85 autoreactive T-cells and associates with genetic risk for

type 1 diabetes

Chapter 6 General discussion and summary 99

Addendum Nederlandse samenvatting 117

Curriculum vitae 124

List of publications 125

Dankwoord 126

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