Analiza prekrivanja genomskih regij za nalaganje maščobe pri sesalcih.

Mirič, Tajda (author), Kunej, Tanja (mentor)

Debelost je posledica prekomernega nalaganja maščobe v telesu in je povezana z razvojem različnih bolezni. Poleg človeka se študije nalaganja maščobe izvajajo tudi pri drugih vrstah sesalcev. Pogosta modelna organizma sta miš in podgana, pri rejnih živalih pa določamo genetske dejavnike, ki vplivajo na proizvodnjo mleka in kvaliteto mesa. Nalaganje maščobe je poligenska lastnost, zato je pomemben celosten pregled nad literaturo. Na tem področju manjka podatkovna zbirka, ki bi bila redno posodobljena in bi omogočala odkrivanje še neznanih genetskih vzrokov. Magistrska naloga je sestavljena iz treh delov: razvoja zbirke genov za nalaganje maščobe pri sesalcih, bioinformacijske analize za določanje zanesljivejših kandidatnih lokusov in določanja genov za količino maščobe v mleku na osnovi GWAS (angl. genome wide association study) pri govedu. Razvita zbirka vsebuje 855 lokusov za nalaganje maščobe pri človeku, miši, podgani in govedu. Dopolnili smo tudi predhodno razvito zbirko genov za debelost The Human Obesity Gene Map. Določili smo genomske lokacije z večjim številom genov povezanih z debelostjo. Z zbranimi geni je povezanih 73 bioloških poti pri človeku in 103 pri miši. Ena izmed njih je PPAR signalna pot, za katero smo opravili tudi reanalizo literature in zbirko dopolnili z novimi kandidatnimi geni. Določili smo štiri nove gene za količino maščobe v mleku pri govedu (SLC25A43, NAV3, BFAR, TMPRSS11F), potrdili povezavo za gen HS3ST6 ter našli prekrivanja značilno povezanih polimorfizmov s QTL-i (angl. quantitative trait loci). Debelost je kompleksna bolezen, pod vplivom številnih genov, ki so razpršeni po celotnem genomu in sodelujejo v različnih bioloških poteh. Izdelana zbirka je orodje za nadaljnje raziskave na tem področju, a bo potrebno opravljati redne posodobitve.

• Language: Slovenian
• Keywords: biotehnologija, debelost, nalaganje maščobe, sesalci, podatkovna zbirka, biološka pot, SNP- mikromreža
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Publisher: [T. Mirič]
• Year: 2017
• PID: 20.500.12556/RUL-99146
• UDC: 601.4:575.116.4:577.115(043.2)
• COBISS.SI-ID: 8894841
• Publication date in RUL: 24.12.2017

Secondary language

• Language: English
• Title: Analysis of overlapping genomic regions for fat deposition in mammals

Abstract

Excessive fat deposition causes obesity that is connected with different diseases. Research into fat deposition is not limited to humans but covers other mammals too. Mice and rats are frequently used model organisms but in the case of farmed animals’ genetic factors affecting milk production and meat quality are researched. As fat deposition is a polygenetic trait, a comprehensive overview of literature is of great significance. There is, however, no periodically updated database enabling the detection of still unknown genetic causes of fat deposition. This master's thesis is composed of the following three parts: the development of a database of mammalian genes for fat deposition, a bioinformatics analysis to define more reliable candidate loci, and the identification of milk fat yield genes in cattle based on GWAS (genome wide association study) approach. The database established in the thesis contains 855 loci for fat deposition in humans, mice, rats and cattle. Furthermore, the previously developed Human Obesity Gene Map was supplemented. In the thesis, genome locations with a higher number of obesity related genes were identified. It was also established that in humans 73 biological pathways are connected with catalogued obesity genes and 103 in mice. One such pathway is the PPAR signaling pathway with respect to which literature was reanalysed and the database supplemented with new candidate genes. Four new cattle genes for milk fat yield (SLC25A43, NAV3, BFAR, TMPRSS11F) were determined, for HS3ST6 the connection was confirmed. SNPs overlapping previously identified QTLs (quatitative trait loci) were detected. Obesity is a complex disease affected by many genes distributed throughout the genome and associated with different biological pathways. The developed database, if periodically updated, will be a useful tool for further research in this field.

• Keywords: biotechnology, obesity, fat deposition, mammals, database, pathway, SNP chip