Gece kuşu uyku düzenine neden olan genetik mutasyon bulundu

Bilkent Üniversitesi’nden Tayfun Özçelik ve Rockefeller Üniversitesi’nden Michael Young’ın önderliğinde yürütülen araştırma “gecikmiş uyku fazı” ile ilgili olarak gece kuşu olarak tanımlanan ilk gen olma niteliğini taşımaktadır.

Bazı insanların geceleri geç saatlere kadar uyuyamadıkları, sabahları da erken kalkmakta zorlandıkları iyi bilinmektedir. 6 Nisan tarihli Cell dergisinde yayınlanan bir araştırmaya göre bu kişilerin biyolojik saatleri genetik olarak yavaş çalışmaya programlanmıştır. Bunun nedeni ise Kriptokrom 1 – CRY1 olarak adlandırılan genlerinde mutasyon taşımaları ve biyolojik saatlerinde yaklaşık 2-2.5 saatlik bir gecikme yaşanmasıdır.

Bilkent, Rockefeller ve Cornell Üniversiteleri’nin ortaklaşa yürüttükleri araştırmaya göre “Mutasyon taşıyıcılarının bir günü dünyanın bir günü ile kıyaslandığında biraz daha uzun olmakta ve bu nedenle tüm yaşamları uyku düzeni üzerinden bir kovalamacaya dönüşmektedir”.

Gece Kuşu olarak biliniyor

Halk arasında “gece kuşu” olarak da adlandırılan böyle kişiler aslında “gecikmiş uyku fazı” veya kısaca DSPD (delayed sleep phase disorder) olarak adlandırılan bir hastalıktan etkilenmiştir. Çeşitli ülkelerde yürütülen kapsamlı klinik araştırmalara göre uyku kliniklerinde kesin tanısı konabilen bu davranış şekli toplumun yüzde 10’a kadar çıkabilen önemli bir bölümünde görülebilmektedir. Bilkent Üniversitesi’nden Tayfun Özçelik ve Rockefeller Üniversitesi’nden Michael Young’ın önderliğinde yürütülen araştırma “gecikmiş uyku fazı” ile ilgili olarak tanımlanan ilk gen olma niteliğini taşımaktadır.

DSPD tanısı alan kişiler genellikle geceleri uykuya dalmakta çok zorlanırlar. Bazen uyku o kadar gecikir ki gün boyunca uzun şekerlemeler şeklinde parçalanmış bir düzene dönüşebilir. DSPD gibi uyku bozuklukları genellikle anksiyete, depresyon, dikkat eksikliği, kalp-damar hastalıkları, obezite ve şeker hastalığı ile birlikte gözükebilir. DSPD’den etkilenen kişiler aynı zamanda çalışma hayatına ve sosyal ortamlara uyumda da önemli zorluklar yaşayabilirler.  Öyle ki, bu (gece kuşu) mutasyonu taşıyan kişiler sanki sürekli bir jetlag yaşıyor gibi hissedebilir, sabah olduğunda yeni günü karşılamaya henüz hazır olmayabilirler.

100 milyon kişi CRY1 taşıyıcısı olabilir

Dr. Özçelik “CRY1 geninde tanımladığımız mutasyon aralarında Türkiye’nin de bulunduğu Avrupa toplumları ve Akdeniz coğrafyasında her 75-100 kişiden birinde görüldüğü için toplumun önemli bir kısmını etkiliyor” diyor. Buna göre ülkemizde yaklaşık 1 milyon, Avrupa’da 10 milyon ve dünya genelinde 100 milyon kişi CRY1mutasyonu taşıyıcısı olabilir. Ailesel hiperkolesterolemi, polikistik böbrek hastalığı, orak hücreli anemi, kistik fibrosis, fenilketonüri veya kas erimeleri gibi sayıları yaklaşık 5,000 adet olan tek gen hastalıklarının tümü bir bütün olarak değerlendirildiğinde her 100 kişiden birini etkilendiği düşünülürse CRY1mütasyonunun ne kadar sık olduğu daha net olarak ortaya çıkmaktadır.

Kriptokrom genleri ilk olarak 1970’li yıllarda Aziz Sancar tarafından bakterilerde tanımlanmış ve biyolojik saat ile ilişkisi gösterilmiştir. Rockefeller Üniversitesi’nden Dr. Young’ın meyva sineğinde yürüttüğü araştırmalarla ise kriptokrom genlerinin bozulması ile uyku sorununun ortaya çıktığı gözlenmiştir. Araştırmanın insan uyku bozuklukları ile ilişkilendirilmesi ise Bilkent ve Cornell Üniversiteleri’nde gerçekleşmiştir. Örneğin

CRY1 mütasyonu taşıyan kişilerden alınan deri biyopsilerinde biyolojik saatin düzeninin değiştiği gösterilmiştir.

Biyolojik saat dünya üzerinde yaşayan tüm canlılarda, mikroorganizmalarda, bitkilerde, hayvanlarda, insanlarda bulunmaktadır. Güneşin etrafında ve bir gece/gündüz döngüsünde olan dünyamızda yaşam biyolojik saat üzerinden düzenlenmektedir. Bu düzenin temel mekanizması ise tüm canlılarda korunmuştur.

CRY1 (gece kuşu) durdurucu görevi yapmaktadır

Normal şartlar altında “başlatıcı-aktivatör” olarak adlandırılan bir grup proteinin hücre içinde birikmesi ile saat çalışmaya başlamaktadır. Diğer yandan başlatıcı proteinler kendilerini durduracak proteinlerin de hücre içinde sentezlenmesini tetiklemektedir. Böylece ortaya çıkan döngü biyolojik saati oluşturur.

CRY1 geni bu düzende durdurucu olarak görev yapmaktadır. Bilkent ve Rockefeller’li araştırmacıların tanımladıkları mütasyon CRY1 geninde tek bir nükleotidin değişmesi ile ortaya çıkmıştır. Bunun sonucunda ise CRY1 gerekenden daha çok çalışmakta ve biyolojik saatin düzeninde gecikmeye neden olmaktadır.

Bilkent Üniversitesi’nde yürütülen araştırma kapsamında 3-4 neslin bir arada olduğu 6 adet büyük aile incelenmiştir. Toplam 39 adet mütasyon taşıyıcısı ve 31 adet aile içi kontrol bireyinin genotiplendirilmesi ile CRY1 mütasyonu taşıyanların uyku orta noktalarının sabah saat 4, hatta parçalanmış uyku sorunu olanlarda sabah 6-8 gibi olduğu gösterilmiştir. Dominant olarak kalıtılan yani baskın bir nitelik taşıyan mutasyon anne veya babadan kalıtım yolu ile alındığında uyku gecikmesi ortaya çıkmaktadır. Akraba evliliği gibi nedenlerle hem anne hem de babadan mutasyonu alan homozigot bireylerde klinik tablo değişmemekte, uyku gecikmesi aynen dominant kişilerde olduğu gibi kliniğe yansımaktadır. Nitekim 39 adet mutasyon taşıyıcısının 8 tanesi homozigot olarak bulunmuştur.

Biyolojik saatin uyku bozukluğuyla ilişkilendirilmesi ve doğuştan gelen bir mutasyonun gösterilmesiyle yakın bir zamanda yaygın kullanıma girmesi beklenen yeni bir biyoişaretleyici, bir genetik tanı testi bulunmuştur. Biyolojik saat aynı zamanda direkt olarak güneş ışıklarından kaynaklanan fotonların etkilediği genlerle düzenlendiği için uyku hijyeni ve doğru dalga boyunda ışığın tedavi edici özellikleri moleküler düzeyde ortaya konmuştur.

 

Kaynak:

Bu araştırma Bilkent Üniversitesi, Türkiye Bilimler Akademisi, Rockefeller Üniversitesi, Cornell Üniversitesi, Amerika Birleşik Devletleri Ulusal Sağlık Enstitüsü (National Institutes of Health-NIH), Calico Yaşam Bilimleri-LLC Şirketi ve Beyin ve Davranış Araştırma Vakfı tarafından desteklenmiştir.

Cell, Patke, et al.: “Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder.” http://www.cell.com/cell/fulltext/S0092-8674(17)30346-X DOI: 10.1016/j.cell.2017.03.027

 

Araştırma iletişimi:
Prof. Dr. Tayfun Özçelik
Bilkent Üniversitesi Moleküler Biyoloji ve Genetik Bölümü
0312 266 4380
tozcelik@bilkent.edu.tr

Ahmet Doğan
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Ahmet Doğan

Araştırmacı - Yazar
Elektrik - Elektronik Mühendisliğinden 2014'te mezun oldu. Aynı alanda Yüksek Lisans eğitimine devam ederken, aynı zamanda ULUSLARARASI İLİŞKİLER lisans bölümünü okumaktadır. İnsan Hakları alanında ve Mülteci alanında Uluslararası bir Sivil Toplum Kuruluşunda çalışmaktadır.
Ahmet Doğan
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Ahmet Doğan

Araştırmacı - Yazar Elektrik - Elektronik Mühendisliğinden 2014'te mezun oldu. Aynı alanda Yüksek Lisans eğitimine devam ederken, aynı zamanda ULUSLARARASI İLİŞKİLER lisans bölümünü okumaktadır. İnsan Hakları alanında ve Mülteci alanında Uluslararası bir Sivil Toplum Kuruluşunda çalışmaktadır.

Gece kuşu uyku düzenine neden olan genetik mutasyon bulundu” için 105 yorum

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  • 23 Haziran 2018 tarihinde, saat 08:06
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  • 23 Haziran 2018 tarihinde, saat 22:25
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  • 24 Haziran 2018 tarihinde, saat 10:05
    Permalink

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  • 25 Haziran 2018 tarihinde, saat 00:49
    Permalink

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  • 26 Haziran 2018 tarihinde, saat 02:51
    Permalink

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  • 26 Haziran 2018 tarihinde, saat 14:01
    Permalink

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  • 27 Haziran 2018 tarihinde, saat 05:26
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  • 27 Haziran 2018 tarihinde, saat 22:18
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  • 28 Haziran 2018 tarihinde, saat 02:38
    Permalink

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  • 28 Haziran 2018 tarihinde, saat 07:36
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  • 28 Haziran 2018 tarihinde, saat 09:55
    Permalink

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  • 28 Haziran 2018 tarihinde, saat 13:02
    Permalink

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  • 29 Haziran 2018 tarihinde, saat 03:28
    Permalink

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  • 29 Haziran 2018 tarihinde, saat 08:59
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  • 29 Haziran 2018 tarihinde, saat 14:25
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  • 29 Haziran 2018 tarihinde, saat 19:50
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  • 29 Haziran 2018 tarihinde, saat 20:03
    Permalink

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  • 30 Haziran 2018 tarihinde, saat 00:01
    Permalink

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  • 30 Haziran 2018 tarihinde, saat 04:15
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  • 30 Haziran 2018 tarihinde, saat 09:39
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  • 30 Haziran 2018 tarihinde, saat 15:05
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  • 30 Haziran 2018 tarihinde, saat 20:46
    Permalink

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  • 1 Temmuz 2018 tarihinde, saat 01:14
    Permalink

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  • 1 Temmuz 2018 tarihinde, saat 04:47
    Permalink

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  • 1 Temmuz 2018 tarihinde, saat 17:16
    Permalink

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  • 1 Temmuz 2018 tarihinde, saat 22:09
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  • 2 Temmuz 2018 tarihinde, saat 02:06
    Permalink

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  • 2 Temmuz 2018 tarihinde, saat 06:07
    Permalink

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  • 2 Temmuz 2018 tarihinde, saat 11:38
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  • 2 Temmuz 2018 tarihinde, saat 14:42
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  • 2 Temmuz 2018 tarihinde, saat 16:40
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  • 3 Temmuz 2018 tarihinde, saat 01:43
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  • 3 Temmuz 2018 tarihinde, saat 15:28
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  • 3 Temmuz 2018 tarihinde, saat 20:46
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  • 3 Temmuz 2018 tarihinde, saat 22:45
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  • 4 Temmuz 2018 tarihinde, saat 00:53
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  • 4 Temmuz 2018 tarihinde, saat 05:00
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  • 4 Temmuz 2018 tarihinde, saat 21:16
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  • 5 Temmuz 2018 tarihinde, saat 01:07
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  • 5 Temmuz 2018 tarihinde, saat 14:44
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  • 5 Temmuz 2018 tarihinde, saat 20:29
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  • 6 Temmuz 2018 tarihinde, saat 00:56
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  • 6 Temmuz 2018 tarihinde, saat 05:06
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  • 6 Temmuz 2018 tarihinde, saat 15:58
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  • 8 Temmuz 2018 tarihinde, saat 20:11
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