Analiza genetske variabilnosti gena IL21 pri kokoši

Rode, Jerneja (author), Kunej, Tanja (mentor), Narat, Mojca (co-mentor)

Interlevkin 21 (IL21) je imunomodulatorni citokin, ki deluje na prirojeni in pridobljeni imunski odziv. Povezan je z nastankom različnih bolezenskih stanj. Študije so pokazale, da ima povečanje ali zaviranje aktivnosti IL21 pozitivni učinek pri zdravljenju širokega spektra bolezni. Bolezenska stanja so posledica odstopanja v sintezi/aktivnosti IL21, do katerih lahko pride med drugim tudi zaradi sprememb v zaporedju DNA. Zanimiv model za raziskave IL21 v povezavi z bolezenskimi stanji je kokoš, saj lahko pri tej vrsti v eksperimentalnih, kontroliranih pogojih induciramo avtoimunski artritis z bakterijo Mycoplasma synoviae. Cilj te raziskave je bil preučiti genetsko variabilnost gena IL21 pri kokoši in preveriti, če se te variante nahajajo znotraj regulatornih regij. Določili smo zaporedje dela gena IL21 pri trajni celični liniji kokošjih makrofagov HD-11. Eksperimentalno smo potrdili prisotnost osmih že znanih različic nukleotidnega zaporedja (SNP-jev). Z uporabo bioinformacijskih metod smo napovedali 16 motivov in tri domene v zaporedju proteina, štiri mesta za vezavo mikro RNA ter lokacije in dolžine α-vijačnic. Naredili smo tudi pregled genetskih variant pri človeku, ki so bile povezane z avtoimunskimi boleznimi. Ena se nahaja v regiji, ki ima ortologno zaporedje v genu IL21 pri kokoši, vendar na tej regiji pri kokoši še ni opisanih genetskih variant. Rezultati te študije bodo omogočili nadaljevanje preučevanja gena IL21 pri kokoši in njegove morebitne povezave z nastankom avtoimunskih bolezni.

• Language: Slovenian
• Keywords: interlevkin 21, genetska variabilnost, različica nukleotidnega zaporedja, avtoimunske bolezni, kokoš
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Place of publishing: Ljubljana
• Publisher: [J. Rode]
• Year: 2022
• PID: 20.500.12556/RUL-135691
• UDC: 601.4:577.21:575.112:577.27(043.2)
• COBISS.SI-ID: 102786819
• Publication date in RUL: 26.03.2022

Secondary language

• Language: English
• Title: Analysis of genetic variability of IL21 gene in chicken

Abstract

Interleukin 21 (IL21) is an immunomodulatory cytokine that is part of innate and adaptive immune response. It has been associated with the onset of various inflammatory and autoimmune diseases. Studies have demonstrated that increasing or inhibiting IL21 activity has a positive effect in the treatment of a wide range of diseases. Changes in DNA sequence are one of the causes for differences in IL21 synthesis and/or activity. Chicken is an interesting model for studies of IL21 and its association with diseases, as in this species autoimmune arthritis can be induced by the bacterium Mycoplasma synoviae under experimental, controlled conditions. The aim of the present study was to examine genetic variability of the IL21 gene in chicken and to analyze if these variants are located within regulatory regions. We determined the sequence of part of the IL21 gene in macrophage-like immortalized cell line derived from chicken bone; HD-11. Eight previously known single nucleotide polymorphisms (SNPs) were experimentally confirmed. With the use of bioinformatic tools we identified 16 predicted motifs and three domains in IL21 protein sequence in chicken. We predicted four miRNA binding sites and locations and lengths of α-helixes. We also performed the review of genetic variants of IL21 gene in human that were associated with autoimmune diseases. One human variant is located in a region that has an orthologous sequence in the IL21 gene in chicken. The results of this study present a baseline for continuation of the study of the IL21 gene in chicken and its possible association with the development of autoimmune diseases.

• Keywords: interleukin 21, genetic variability, single nucleotide polymorphism, autoimmune diseases, chicken