Examining genotype-phenotype associations of GRAM domain proteins using GWAS, PheWAS and literature review in cattle, human, pig, mouse and chicken

Kunej, Tanja (author), Šimon, Martin (author), Luštrek, Barbara (author), Horvat, Simon (author), Potočnik, Klemen (author)

The GRAMD genes are involved in maintaining cholesterol homeostasis, apoptosis, cancer and production traits in livestock. A lipid-binding GRAM domain is implicated in lipid transport and metabolism. The functions of GRAMD proteins remain incompletely understood. The aim of the present study was therefore to investigate the associations between six GRAMD genes in cattle using data from the international genomic evaluation of the Interbull InterGenomics Centre and to evaluate genotype-phenotype associations in human, cattle, pig, mouse and, chicken. Genotyping of 55,013 bulls was performed using DNA microarrays and 11 SNPs were mapped to the five GRAMD genes. A phenome-wide association study (PheWAS) tested associations between the 11 SNPs and 36 traits. The integrated analysis of SNP effects, rankings, and clustering patterns revealed their potential for improving cattle productivity, health, and robustness, and established a baseline for the targeted improvement of cattle traits. This study lays the groundwork for functional experiments aimed at uncovering the mechanism of action of GRAMD genes and to evaluate the potential of using GRAMD sequence variants for selection programs in dairy cattle. The study presents an example of how the combination of GWAS and the PheWAS offers a promising toolbox for the systematic functional annotation of vertebrate genomes.

• Language: English
• Keywords: cattle, GRAM domain, GWAS, PheWAS, single nucleotide polymorphism (SNP), mouse
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 17 str.
• Numbering: Vol. 14, art. 28889
• PID: 20.500.12556/RUL-165404
• UDC: 575
• ISSN on article: 2045-2322
• DOI: 10.1038/s41598-024-80117-7
• COBISS.SI-ID: 216061955
• Publication date in RUL: 05.12.2024

KUNEJ, Tanja, ŠIMON, Martin, LUŠTREK, Barbara, HORVAT, Simon and POTOČNIK, Klemen, 2024, Examining genotype-phenotype associations of GRAM domain proteins using GWAS, PheWAS and literature review in cattle, human, pig, mouse and chicken. Scientific reports [online]. 2024. Vol. 14, no. 28889. [Accessed 18 May 2025]. DOI 10.1038/s41598-024-80117-7. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=165404

Record is a part of a journal

• Title: Scientific reports
• Shortened title: Sci. rep.
• Publisher: Nature Publishing Group
• ISSN: 2045-2322
• COBISS.SI-ID: 18727432

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: genetika, geni, GRAMD, genotip, fenotip

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P4-0092
• Name: Zdravje živali, okolje in varna hrana

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P4-0220
• Name: Primerjalna genomika in genomska biodiverziteta