Prof. Dr. Aslı TOLUN

Boğaziçi University
Molecular Biology and Genetics
Kuzey Park, 301
34342 Bebek - Istanbul
+90 (212) 359 6472
• Aslı Tolun's full publication record
• Aslı Tolun's full resume


Identification of disease genes and population genetics

The research area of my team is identification of novel human disease genes. We are studying several families afflicted with different diseases, ranging from neurological disorders to eye diseases and male infertility. A new gene function identified sheds light on the related cellular mechanism.

The most certain route to the identification of the function of a gene is via clinically investigating affected individuals with defects in that particular gene. Because experiments on humans cannot be performed, molecular genetic studies are performed instead. In a large family in which the parents are related, the genetic research aims to find the answer to the question “which gene is defective in the patients so that such a novel disease manifests?” In the search for the gene mutation that underlies a novel disease in a family, we first find the chromosomal localization of the disease gene, and then evaluate the results of exome sequencing (sequencing of all coding regions of the genome) via bioinformatics tools and perform the necessary genetic analyses.

The first disease gene we identified is associated with pulmonary alveolar microlithiasis. Tiny stones form in the lungs; they grow large in time and lead to severe damage. It was known that the disease was frequent in our country, and the underlying cause was believed to be a yet unidentified environmental factor. We found that mutations in gene SLC34A2 underlie the disease and thus showed that the basis of the disease was completely genetic and due to consanguineous marriages. In another family afflicted with split hand/foot malformation, we found the gene responsible for the condition and showed that the inheritance of the trait was complex.

Ayhan et al., 2014

Among the other genes we identified are some that are responsible for brain development and function. Additionally, we work on population genetics to understand the relation of our population to other populations or to uncover ancient migration routes.

Selected Publications

  • Yıldız Bölükbaşı E, Afzal M, Mumtaz S, Ahmad N, Malik S, Tolun A (2017) Progressive SCAR14 with unclear speech, developmental delay, tremor, and behavioral problems caused by a homozygous deletion of the SPTBN2 pleckstrin homology domain. Am J Med Genet A. Jun 21.

  • Mumtaz S, Yıldız E, Lal K, Tolun A, Malik S (2017). Complex postaxial polydactyly types A and B with camptodactyly, hypoplastic third toe, zygodactyly and other digit anomalies caused by a novel GLI3 mutation. Eur J Med Genet. 60:268-274.

  • Kara B, Köroğlu Ç, Peltonen K, Steinberg RC, Maraş Genç H, Hölttä-Vuori M, Güven A, Kanerva K, Kotil T, Solakoğlu S, Zhou Y, Olkkonen VM, Ikonen E, Laiho M, Tolun A (2017). Severe neurodegenerative disease in brothers with homozygous mutation in POLR1A. Eur J Hum Genet. 25:315-323.

  • Durmuş H, Ayhan Ö, Çırak S, Deymeer F, Parman Y, Franke A, Eiber N, Chevessier F, Schlötzer-Schrehardt U, Clemen CS, Hashemolhosseini S, Schröder R, Hemmrich-Stanisak G, Tolun A, Serdaroğlu-Oflazer P (2016). Neuromuscular endplate pathology in recessive desminopathies: Lessons from man and mice. Neurology 87:799-805.

  • Balestrini S, Milh M, Castiglioni C, Lüthy K, Finelli MJ, Verstreken P, Cardon A, Stražišar BG, Holder JL Jr, Lesca G, Mancardi MM, Poulat AL, Repetto GM, Banka S, Bilo L, Birkeland LE, Bosch F, Brockmann K, Cross JH, Doummar D, Félix TM, Giuliano F, Hori M, Hüning I, Kayserili H, Kini U, Lees MM, Meenakshi G, Mewasingh L, Pagnamenta AT, Peluso S, Mey A, Rice GM, Rosenfeld JA, Taylor JC, Troester MM, Stanley CM, Ville D, Walkiewicz M, Falace A, Fassio A, Lemke JR, Biskup S, Tardif J, Ajeawung NF, Tolun A, Corbett M, Gecz J, Afawi Z, Howell KB, Oliver KL, Berkovic SF, Scheffer IE, de Falco FA, Oliver PL, Striano P, Zara F, Campeau PM, Sisodiya SM. TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features (2017). Neurology 87:77-85.

  • Durlu YK, Köroğlu Ç, Tolun A.
    Novel recessive cone-rod dystrophy caused by POC1B mutation.
    JAMA Ophthalmic. 2014 Oct;132(10):1185-91.

  • Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GM, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG.
    Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.
    Science. 2014. 343:506-11.

  • Ayhan Ö, Balkan M, Guven A, Hazan R, Atar M, Tok A, Tolun A.
    Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia.
    J Med Genet. 2014. 51:239-44.

  • Köroğlu Ç, Seven M, Tolun A.
    Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with facial dysmorphism.
    J Med Genet. 2013. 50:515-20.

  • Corut A, Senyigit A, Ugur SA, Altin S, Ozcelik U, Calisir H, Yildirim Z, Gocmen A, Tolun A.
    Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis.
    Am J Hum Genet. 2006. 79:650-6.