Identifikacija kandidatnih genomskih regij in primer zasnove transgenega modela za motnje avtističnega spektra

Sladič Oblak, Sabina (author), Dovč, Peter (mentor), Zorc, Minja (co-mentor)

Motnje avtističnega spektra (MAS), so kompleksen fenotip v razvoju človeka, s specifičnimi posebnostmi v komunikaciji, socialni interakciji in s ponavljajočimi se vedenjskimi vzorci. Sindrom je heterogen, z vplivom tako okoljskih kot genetskih dejavnikov. Geni, povezani z motnjami avtističnega spektra, lahko služijo za razvoj in vitro modelov za MAS, identifikacijo MAS v celični nevrobiologiji ter zdravstveni diagnostiki, kot tudi biooznačevalci za zgodnejšo in natančnejšo detekcijo. Geni so urejeni v različnih internetnih zbirkah, izmed katerih smo za to nalogo izbrali znanstveno podprte in prosto dostopne vire, iz njih pa z metodami ločevanja po izbranih kriterijih, prišli do kandidatnega lokusa ANOS1. V literaturi je že dokazana povezava proteina anozmin-1 z VEFGR2 in njegov vpliv na nekatere signalne molekule v signalni poti VEGF. Nov aspekt predstavlja povezava koncentracije kalcija, z genom ANOS1, ki še ni opisana v literaturi. Sprememba koncentracije kalcija deluje na razvoj osrednjega živčevja in je tako povezana s pojavom MAS. Na osnovi CRISPR/Cas9 tehnologije, smo zasnovali celični model z astrociti za preučevanje vpliva gena ANOS1 na koncentracijo kalcija v VEGF signalni poti. Na osnovi pozitivnih rezultatov nameravamo celični model nadgraditi s kunčjim transgenim modelom.

• Language: Slovenian
• Keywords: motnje avtističnega spektra, bioinformacijska orodja, gen ANOS1, sistem CRISPR/Cas9, VEGF signalna pot, astrociti, modelni organizem
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: BF - Biotechnical Faculty
• Publisher: [S. Sladič Oblak]
• Year: 2020
• PID: 20.500.12556/RUL-119430
• UDC: 606:616.896:601.4:577.21:575.112(043.2)
• COBISS.SI-ID: 32289795
• Publication date in RUL: 09.09.2020

Secondary language

• Language: English
• Title: Identification of candidate genome regions for autism spectrum disorder and example of transgene model construction

Abstract

Autism spectrum disorders (ASD) are a complex developmental condition with abnormalities in communication, social interaction and repetitive behaviour. It is a heterogeneous phenotype, influenced by environmental and genetic factors. Genes associated with ASD can serve to develop ASD in vitro models, identify ASD specific parameters in cellular neurobiology and medical diagnostics as well as biomarkers for earlier and more accurate detection of ASD. Genes associated with ASD are collected in various internet resources from which ANOS1 gene was extracted using selection criteria defined in the research strategy. The interaction of the anosmin-1 protein with VEGFR2 and its effect on some signalling molecules in the VEGF signalling pathway, has already been demonstrated in the literature. We propose a new association of the ANOS1 gene with the concentration of calcium which was not documented yet. The change in calcium concentration affects the development of the central nervous system, having a possible effect on development of ASD. Based on CRISPR/Cas9 technology, we designed a model to study the effect of ANOS1 gene on calcium concentration in astrocytes in the VEGF signalling pathway. Based on these results, we plan to develop a transgenic rabbit model.

• Keywords: autism spectrum disorders, bioinformatic tools, gene ANOS1, CRISPR/Cas9 system, VEGF signalling pathway, astrocytes, model organism