Biotechnical Faculty, Department of Animal Science, University of Ljubljana, Groblje 3, Domžale, SI-1230, Slovenia.
Sci Rep. 2024 Nov 21;14(1):28889. doi: 10.1038/s41598-024-80117-7.
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.
GRAMD 基因参与维持胆固醇动态平衡、细胞凋亡、癌症和家畜生产性状。一个脂质结合的 GRAM 结构域参与脂质运输和代谢。GRAMD 蛋白的功能仍不完全清楚。因此，本研究的目的是利用国际公牛基因组评估 Interbull 基因组中心的数据，对牛的 6 个 GRAMD 基因进行关联分析，并在人类、牛、猪、鼠和鸡中评估基因型-表型关联。使用 DNA 微阵列对 55013 头公牛进行了基因分型，将 11 个 SNP 映射到五个 GRAMD 基因上。表型全基因组关联研究（PheWAS）测试了 11 个 SNP 与 36 个性状之间的关联。对 SNP 效应、排名和聚类模式的综合分析揭示了它们在提高牛的生产力、健康和稳健性方面的潜力，并为有针对性地改进牛的性状建立了基线。本研究为功能实验奠定了基础，旨在揭示 GRAMD 基因的作用机制，并评估使用 GRAMD 序列变异进行奶牛选择计划的潜力。该研究展示了 GWAS 和 PheWAS 相结合如何为脊椎动物基因组的系统功能注释提供一个很有前途的工具包。
