Integration of a Single-step Genome-wide Association Study with a Multi-tissue Transcriptome Analysis Provides Novel Insights into the Genetic Basis of Wool and Weight Traits in Sheep

Overview

Journal Genet Sel Evol

Publisher Biomed Central

Specialties Biology
Genetics

Date 2021 Jul 1

PMID 34193030

Citations 17

Authors

Bingru Zhao

Hanpeng Luo

Xixia Huang

Chen Wei

Jiang Di

Yuezhen Tian

Xuefeng Fu

Bingjie Li

George E Liu

Lingzhao Fang

Shengli Zhang

Kechuan Tian

Affiliations

Soon will be listed here.

Abstract

Background: Genetic improvement of wool and growth traits is a major goal in the sheep industry, but their underlying genetic architecture remains elusive. To improve our understanding of these mechanisms, we conducted a weighted single-step genome-wide association study (WssGWAS) and then integrated the results with large-scale transcriptome data for five wool traits and one growth trait in Merino sheep: mean fibre diameter (MFD), coefficient of variation of the fibre diameter (CVFD), crimp number (CN), mean staple length (MSL), greasy fleece weight (GFW), and live weight (LW).

Results: Our dataset comprised 7135 individuals with phenotype data, among which 1217 had high-density (HD) genotype data (n = 372,534). The genotypes of 707 of these animals were imputed from the Illumina Ovine single nucleotide polymorphism (SNP) 54 BeadChip to the HD Array. The heritability of these traits ranged from 0.05 (CVFD) to 0.36 (MFD), and between-trait genetic correlations ranged from - 0.44 (CN vs. LW) to 0.77 (GFW vs. LW). By integrating the GWAS signals with RNA-seq data from 500 samples (representing 87 tissue types from 16 animals), we detected tissues that were relevant to each of the six traits, e.g. liver, muscle and the gastrointestinal (GI) tract were the most relevant tissues for LW, and leukocytes and macrophages were the most relevant cells for CN. For the six traits, 54 quantitative trait loci (QTL) were identified covering 81 candidate genes on 21 ovine autosomes. Multiple candidate genes showed strong tissue-specific expression, e.g. BNC1 (associated with MFD) and CHRNB1 (LW) were specifically expressed in skin and muscle, respectively. By conducting phenome-wide association studies (PheWAS) in humans, we found that orthologues of several of these candidate genes were significantly (FDR < 0.05) associated with similar traits in humans, e.g. BNC1 was significantly associated with MFD in sheep and with hair colour in humans, and CHRNB1 was significantly associated with LW in sheep and with body mass index in humans.

Conclusions: Our findings provide novel insights into the biological and genetic mechanisms underlying wool and growth traits, and thus will contribute to the genetic improvement and gene mapping of complex traits in sheep.

Citing Articles

Combined Genome-Wide Association Study and Haplotype Analysis Identifies Candidate Genes Affecting Growth Traits of Inner Mongolian Cashmere Goats.

Ao X, Rong Y, Han M, Wang X, Xia Q, Shang F Vet Sci. 2024; 11(9).

PMID: 39330807 PMC: 11435611. DOI: 10.3390/vetsci11090428.

Population structure and selection signal analysis of indigenous sheep from the southern edge of the Taklamakan Desert.

Han Z, Yang R, Zhou W, Zhang L, Wang J, Liu C BMC Genomics. 2024; 25(1):681.

PMID: 38982349 PMC: 11232224. DOI: 10.1186/s12864-024-10581-y.

Weighted single-step genome-wide association study for direct and maternal genetic effects associated with birth and weaning weights in sheep.

Khazaei-Koohpar H, Gholizadeh M, Hafezian S, Esmaeili-Fard S Sci Rep. 2024; 14(1):13120.

PMID: 38849438 PMC: 11161479. DOI: 10.1038/s41598-024-63974-0.

A High-Quality Blue Whale Genome, Segmental Duplications, and Historical Demography.

Bukhman Y, Morin P, Meyer S, Chu L, Jacobsen J, Antosiewicz-Bourget J Mol Biol Evol. 2024; 41(3).

PMID: 38376487 PMC: 10919930. DOI: 10.1093/molbev/msae036.

Characterization of heterozygosity-rich regions in Italian and worldwide goat breeds.

Chessari G, Criscione A, Marletta D, Crepaldi P, Portolano B, Manunza A Sci Rep. 2024; 14(1):3.

PMID: 38168531 PMC: 10762050. DOI: 10.1038/s41598-023-49125-x.

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