Prof. Dr. Aslı TOLUN
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.
- A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing. Karacan İ, Diz Küçükkaya R, Karakuş FN, Solakoğlu S, Tolun A, Hançer VS, Turanlı ET. Turk J Haematol. 2019 Feb 7;36(1):29-36.
- STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16. Turkgenc B, Sanlidag B, Eker A, Giray A, Kutuk O, Yakicier C, Tolun A, Temel SG. Hum Mutat. 2018 Oct;39(10):1344-1348.
- LACC1 Gene Defects in Familial Form of Juvenile Arthritis. Karacan I, Uğurlu S, Şahin S, Everest E, Kasapçopur Ö, Tolun A, Özdoğan H, Turanli ET. J Rheumatol. 2018 May;45(5):726-728.
- Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility. Yıldırım Y, Ouriachi T, Woehlbier U, Ouahioune W, Balkan M, Malik S, Tolun A Eur J Hum Genet. 2018 Jun;26(6):876-885.
- Homozygous CHST11 mutation in chondrodysplasia, brachydactyly, overriding digits, clino-symphalangism and synpolydactyly. Shabbir RMK, Nalbant G, Ahmad N, Malik S, Tolun A. J Med Genet. 2018 Jul;55(7):489-496.
- WNT10B mutations associated with isolated dental anomalies. Kantaputra PN, Hutsadaloi A, Kaewgahya M, Intachai W, German R, Koparal M, Leethanakul C, Tolun A, Ketudat Cairns JR. Clin Genet. 2018 May;93(5):992-999.
- Other autoinflammatory disease genes in an FMF-prevalent population: a homozygous MVK mutation and a novel heterozygous TNFRSF1A mutation in two different Turkish families with clinical FMF. Karacan İ, Uğurlu S, Tolun A, Tahir Turanlı E, Ozdogan H. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):75-81.
- Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. Yıldız Bölükbaşı E, Mumtaz S, Afzal M, Woehlbier U, Malik S, Tolun A. J Med Genet. 2018 Mar;55(3):189-197.
- Karacan I, Uğurlu S, Şahin S, Everest E, Kasapçopur Ö, Tolun A, Özdoğan H, Turanli ET. LACC1 Gene Defects in Familial Form of Juvenile Arthritis. J Rheumatol.2018 May;45(5):726-728.
- Yıldırım Y, Ouriachi T, Woehlbier U, Ouahioune W, Balkan M, Malik S, Tolun A. Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility. Eur J Hum Genet. 2018 Jun;26(6):876-885.
- Shabbir RMK, Nalbant G, Ahmad N, Malik S, Tolun A. Homozygous CHST11 mutation in chondrodysplasia, brachydactyly, overriding digits, clino-symphalangism and synpolydactyly. J Med Genet. 2018 Jul;55(7):489-496.
- Kantaputra PN, Hutsadaloi A, Kaewgahya M, Intachai W, German R, Koparal M, Leethanakul C, Tolun A, Ketudat Cairns JR. WNT10B mutations associated with isolated dental anomalies. Clin Genet. 2018 May;93(5):992-999.
- Karacan İ, Uğurlu S, Tolun A, Tahir Turanlı E, Ozdogan H. Other autoinflammatory disease genes in an FMF-prevalent population: a homozygous MVK mutation and a novel heterozygous TNFRSF1A mutation in two different Turkish families with clinical FMF. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):75-81.
- Yıldız Bölükbaşı E, Mumtaz S, Afzal M, Woehlbier U, Malik S, Tolun A. Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. J Med Genet. 2018 Mar;55(3):189-197.
- 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.