Povzetek
Alternative polyadenylation (APA) determines mRNA stability, localisation, translation and protein function. Several diseases, including obesity, have been linked to APA. Studies have shown that single nucleotide polymorphisms in polyadenylation signals (PAS-SNPs) can influence APA and affect phenotype and disease susceptibility. However, these studies focussed on associations between single PAS-SNP alleles with very large effects and phenotype. Therefore, we performed a genome-wide screening for PAS-SNPs in the polygenic mouse selection lines for fatness and leanness by whole-genome sequencing. The genetic variants identified in the two lines were overlapped with locations of PAS sites obtained from the PolyASite 2.0 database. Expression data for selected genes were extracted from the microarray expression experiment performed on multiple tissue samples. In total, 682 PAS-SNPs were identified within 583 genes involved in various biological processes, including transport, protein modifications and degradation, cell adhesion and immune response. Moreover, 63 of the 583 orthologous genes in human have been previously associated with human diseases, such as nervous system and physical disorders, and immune, endocrine, and metabolic diseases. In both lines, PAS-SNPs have also been identified in genes broadly involved in APA, such as Polr2c, Eif3e and Ints11. Five PAS-SNPs within 5 genes (Car, Col4a1, Itga7, Lat, Nmnat1) were prioritised as potential functional variants and could contribute to the phenotypic disparity between the two selection lines. The developed PAS-SNPs catalogue presents a key resource for planning functional studies to uncover the role of PAS-SNPs in APA, disease susceptibility and fat deposition.
Ključne besede
debelost;mišji modeli;debela linija;vitka linija;genetika;alternativna poliadenilacija;
Podatki
Jezik: |
Angleški jezik |
Leto izida: |
2023 |
Tipologija: |
1.01 - Izvirni znanstveni članek |
Organizacija: |
UL BF - Biotehniška fakulteta |
UDK: |
575 |
COBISS: |
130569475
|
ISSN: |
1432-1777 |
Št. ogledov: |
15 |
Št. prenosov: |
2 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Slovenski jezik |
Sekundarne ključne besede: |
debelost;mišji modeli;debela linija;vitka linija;genetika;alternativna poliadenilacija; |
Vrsta dela (COBISS): |
Članek v reviji |
Strani: |
str. 12-31 |
Letnik: |
ǂVol. ǂ34 |
Zvezek: |
[ǂiss. ǂ1] |
Čas izdaje: |
2023 |
DOI: |
10.1007/s00335-022-09967-8 |
ID: |
18487309 |