{"id":6419,"date":"2026-10-19T09:48:53","date_gmt":"2026-10-19T09:48:53","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-kaan-okay\/"},"modified":"2026-10-19T09:48:53","modified_gmt":"2026-10-19T09:48:53","slug":"doktorsvorn-i-lif-og-laeknavisindum-kaan-okay","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-kaan-okay\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum \u2013 Kaan Okay"},"content":{"rendered":"
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Mi\u00f0vikudaginn 1. okt\u00f3ber 2025 ver Kaan Okay, doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: L\u00edft\u00f6lfr\u00e6\u00f0ileg n\u00e1lgun til a\u00f0 varpa lj\u00f3si \u00e1 hlutverk utangenaerf\u00f0akerfisins \u00ed \u00feroskun taugakerfisins. A bioinformatics approach to uncover the role of the epigenetic machinery in neurodevelopment.<\/p>\n

Andm\u00e6lendur eru dr. Bekim Sadikovic, pr\u00f3fessor vi\u00f0 Western University \u00ed Kanada, og dr. Kristinn P\u00e9tur Magn\u00fasson, pr\u00f3fessor vi\u00f0 H\u00e1sk\u00f3lann \u00e1 Akureyri.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var Hans T\u00f3mas Bj\u00f6rnsson, pr\u00f3fessor og me\u00f0lei\u00f0beinandi var Kasper Daniel Hansen, pr\u00f3fessor. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd\u00a0 Arnar P\u00e1lsson, pr\u00f3fessor, Bjarni V. Halld\u00f3rsson, d\u00f3sent, og P\u00e1ll Melsted, pr\u00f3fessor.\u00a0<\/p>\n

Stef\u00e1n \u00de. Sigur\u00f0sson, pr\u00f3fessor og varadeildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

\u00c1grip<\/strong><\/p>\n

Utangenaerf\u00f0a\u00fe\u00e6ttir gegna lykilhlutverki \u00ed a\u00f0 st\u00fdra litnisvirkni og tj\u00e1ningu gena. St\u00f6kkbreytingar \u00ed \u00feessum \u00fe\u00e1ttum valda Mendelskum r\u00f6skunum \u00e1 utangenaerf\u00f0akerfinu, sem lei\u00f0a til \u00feroskah\u00f6mlunar og vaxtatruflana. Einstaklingar me\u00f0 truflun \u00ed utangenaerf\u00f0akerfinu eru einnig oft me\u00f0 \u00f3e\u00f0lilegt DNA met\u00fdlunar (DNAm) mynstur \u00ed bl\u00f3\u00f0i. Hins vegar er enn \u00f3lj\u00f3st hvort \u00feetta DNAm fr\u00e1vik stu\u00f0li beint a\u00f0 \u00feeim sameiginlegu einkennum, \u00feroskah\u00f6mlun og vaxtatruflunum, sem finnast \u00ed m\u00f6rgum \u00feessum einstaklingum. \u00deessi doktorsranns\u00f3kn sneri a\u00f0 \u00fer\u00f3un og beitingu l\u00edfuppl\u00fdsingafr\u00e6\u00f0ilegra a\u00f0fer\u00f0a til a\u00f0 greina DNAm r\u00f6skun \u00ed taugafrumum \u00far drekasv\u00e6\u00f0i heila me\u00f0 \u00fatsl\u00e1tt \u00e1 \u00fdmsum utangenaerf\u00f0a\u00fe\u00e1ttum. \u00deessar taugafrumur voru einangra\u00f0ar \u00far m\u00fasum af tveimur stofnum (B6 \u00d7 FVB), sem gerir kleift a\u00f0 greina hvora sams\u00e6tu fyrir sig. Notu\u00f0 var ONT ra\u00f0greining og var tilg\u00e1tan a\u00f0 m\u00f6gulega v\u00e6ri s\u00f6mu raskanir eftir \u00fatsl\u00e1tt \u00fdmissa utangenaerf\u00f0a\u00fe\u00e1tta. Eitt markt\u00e6kt mismunandi met\u00fdlera\u00f0 sv\u00e6\u00f0i (DMR) fannst \u00ed 3\u2019 UTR sv\u00e6\u00f0i Zic4 gensins \u00ed taugafrumum \u00far m\u00fasum me\u00f0 B6 setr\u00f6\u00f0 eftir \u00fatsl\u00e1tt \u00e1 46 utangena\u00fe\u00e1ttum. Zic4 reyndist einnig hafa mismunandi tj\u00e1ningu \u00e1 tauga\u00feroskastigum \u00ed m\u00fasum me\u00f0 villiger\u00f0 sem er \u00e1hugavert. \u00de\u00e6ttir sem bindast DNMT1 og DNMT3A virtust hafa einkennandi mynstur \u00e1 DNAm \u00ed st\u00fdrisv\u00e6\u00f0um gena sem tengjast taugamyndun og \u00feroskun taugafrumna. Einnig fannst v\u00ed\u00f0t\u00e6k DNAm r\u00f6skun \u00ed frumum me\u00f0 \u00farfellingu \u00e1 DNMT1 en v\u00e6gari fr\u00e1vik \u00ed frumum me\u00f0 \u00farfellingu \u00e1 KMT2A geninu og engum sameiginlegum breytingum. Hins vegar s\u00e1st mj\u00f6g svipu\u00f0 truflun \u00ed tj\u00e1ningu gena eftir \u00farfellingu \u00e1 \u00feessum tveimur utangenaerf\u00f0agenum. Ranns\u00f3knin s\u00fdnir fram \u00e1 gildi sam\u00fe\u00e6ttrar notkunar Oxford Nanopore (ONT) ra\u00f0greiningar \u00e1 l\u00f6ngum r\u00f6\u00f0um og RNA-ra\u00f0greiningar til a\u00f0 rannsaka \u00e1hrif eftir \u00fatsl\u00e1tt utangenaerf\u00f0a\u00fe\u00e1tta \u00ed taugafrumum. Sl\u00edk samtvinnun \u00e1 a\u00f0fer\u00f0um leyfir uppg\u00f6tvun \u00e1 sm\u00e1v\u00e6gilegum en l\u00edffr\u00e6\u00f0ilega \u00fe\u00fd\u00f0ingarmiklum breytingum sem geta n\u00fdst sem hugsanleg me\u00f0fer\u00f0arm\u00f6rk e\u00f0a greiningarmerki fyrir sj\u00fakd\u00f3ma sem trufla utangenaerf\u00f0akerfi\u00f0.<\/p>\n

Abstract<\/strong><\/p>\n

Components of the epigenetic machinery (EM) play a critical role in regulating chromatin states and controlling gene expression. Mutations in these components cause Mendelian disorders of the epigenetic machinery (MDEMs), which are associated with intellectual disability (ID) and growth abnormalities. Individuals diagnosed with MDEMs often present with DNA methylation (DNAm) abnormalities (epi-signatures) in peripheral blood cells. However, it remains unclear whether the DNAm abnormality functionally contributes to the shared phenotypes of ID and growth dysregulation seen in multiple MDEMs. This thesis focuses on developing and applying bioinformatics methods to identify shared DNAm dysregulation across MDEMs in murine hippocampal neuronal cells (B6 x FVB) in haplotype-resolved manner. We successfully developed and applied bioinformatics methods to identify shared DNAm dysregulation across multiple MDEMs. A genome-wide significant differentially methylated region (DMR) in 3\u2019 UTR of Zic4 gene was identified across 46 B6-haplotyped EM knockouts. Zic4 was also differentially expressed in murine neurodevelopment. In addition, we discovered that DNMT1 and DNMT3A-interacting EM components may regulate promoter DNAm of neurogenesis and neuronal differentiation-associated genes in neurons. We also discovered drastic genome-wide DNAm dysregulation in Dnmt1 knockout cells and subtle DNAm dysregulation in Kmt2a knockouts cells. Intriguingly, a more significant overlap of differentially expressed genes was observed between these two EM knockouts. These findings demonstrate the value of integrating Oxford Nanopore (ONT) whole genome sequencing and RNA sequencing to study DNAm and gene expression dynamics in EM knockout-neurons. This integrative framework provides a powerful approach for detecting subtle but biologically relevant changes that could represent potential therapeutic targets or diagnostic markers for MDEMs.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Kaan Okay f\u00e6ddist \u00ed \u0130zmir \u00ed Tyrklandi \u00ed apr\u00edl 1995. Eftir a\u00f0 hann \u00fatskrifa\u00f0ist \u00far menntask\u00f3la \u00e1ri\u00f0 2013 stunda\u00f0i hann n\u00e1m \u00ed sameindal\u00edffr\u00e6\u00f0i og erf\u00f0afr\u00e6\u00f0i vi\u00f0 Atat\u00fcrk h\u00e1sk\u00f3lann. Kaan var d\u00fax, b\u00e6\u00f0i \u00ed menntask\u00f3la og h\u00e1sk\u00f3la. Hann \u00fatskrifa\u00f0ist svo me\u00f0 meistaragr\u00e1\u00f0u \u00ed sameindal\u00edffr\u00e6\u00f0i og erf\u00f0afr\u00e6\u00f0i fr\u00e1 Dokuz Eyl\u00fcl h\u00e1sk\u00f3lanum \u00ed \u0130zmir, sem leiddi til \u00fatg\u00e1fu tveggja v\u00edsindagreina. Hann kom til \u00cdslands \u00ed \u00e1g\u00fast 2021 til a\u00f0 hefja doktorsn\u00e1m undir handlei\u00f0slu Hans T\u00f3masar Bj\u00f6rnssonar og Kaspers Daniels Hansen.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5806,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2025-10-01T13:00:00+00:00","_phd_date_end":"2025-10-01T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"L\u00edft\u00f6lfr\u00e6\u00f0ileg n\u00e1lgun til a\u00f0 varpa lj\u00f3si \u00e1 hlutverk utangenaerf\u00f0akerfisins \u00ed \u00feroskun taugakerfisins. 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