Genome-Wide Association Analysis of Litter Size Trait in Four Goat Breeds in Southwest China

doi:10.13560/j.cnki.biotech.bull.1985.2025-0982

Abstract

Abstract:

Objective Litter size is one of the most important economic traits in goats. This study aimed to identify genetic variants and candidate genes significantly associated with goat litter size. Method Four goat breeds from southwestern China (Youzhou Dark goats, Dazu Black goats, Chuanzhong Black goats, and Qianbei Ma goats) were used as experimental subjects. Historical lambing records from conservation farms were collected, and blood samples from 60 high-yielding and 54 low-yielding ewes were subjected to whole-genome resequencing at an average depth of 27.10×. Population genetic differentiation index (Fst) and genome-wide association study (GWAS) methods were employed to identify loci strongly associated with the target trait. The most likely candidate genes were identified through gene annotation, haplotype analysis, and GO and KEGG enrichment analyses. Result A total of 65 candidate SNPs were identified, distributed within four Fst-significant selective sweep regions on chromosome 2, 4, and X. Five candidate genes potentially associated with the litter size trait were predicted. Among them, the COL4A5 and COL4A6 genes were significantly enriched in signaling pathways such as the ECM-receptor interaction and PI3K-Akt. The significant variant sites annotated to the COL4A6 and ETV1 genes each formed a haplotype block. Furthermore, Hap1 showed highly significant differences in litter size compared to other haplotypes (P<0.01). Conclusion Multiple variant loci significantly associated with litter size traits were detected. Genes such as COL4A5, COL4A6, ETV1, SP3, and PLS3 were identified as potential candidate genes influencing goat litter size traits, which may provide new perspectives for the genetic improvement and selective breeding of high-fertility goats in southwestern China.

Key words: genome-wide association study (GWAS), litter size trait, goats, population genetic differentiation index (Fst), whole-genome resequencing

JIANG Jing, LYU Shi-peng, CHEN Hao-lin, XIONG Ting, SUN Xiao-yan, LI Jie, CHEN Can-can, WANG Gao-fu, REN Hang-xing. Genome-Wide Association Analysis of Litter Size Trait in Four Goat Breeds in Southwest China[J]. Biotechnology Bulletin, 2026, 42(7): 341-350.

Figures/Tables 7

Table 1 Descriptive statistics of litter size traits in high and low litter size groups

分组

Grouping

样本量

Sample size

最大值

Max

最小值

Min

平均值

Mean

标准差

Standard deviation

变异系数

CV （%）

高产组 High litter size group

低产组 Low litter size group

Fig. 1 Results of the population analysisA: Distribution density of SNPs on each chromosome. B: PCA of populations. C: LD attenuation diagram of populations. D: Kinship matrix heatmap

Fig. 2 Manhattan plots of population genetic differentiation index (Fst) and GWAS, along with the GWAS Q-Q plotA: Manhattan plot of population genetic differentiation index (Fst). B: Manhattan plot of genome-wide association study (GWAS). C: Q-Q plot of GWAS

Table 2 Fst and GWAS analysis results of litter size traits in goats

染色体 Chromosome	Fst显著选择区域 Fst significant selection regions	平均Fst值 Average Fst value	显著关联的变异位点数量 Number of significantly associated variant sites	相对基因位置 Location relative to gene	区域内基因 Genes in the region
2	chr2：113 280 001-113 460 000	0.04	36	Downstream	SP3
4	chr4：98 210 001-98 430 000	0.05	5	Upstream， Intron	ETV1
X	chrX：26 050 001-26 470 000	0.08	2	Upstream	PLS3
X	chrX：34 890 001-35 350 000	0.07	24	Upstream， Intron	COL4A5、COL4A6

Fig. 3 Bar plot of GO and KEGG enrichment analysis for candidate genes

Fig. 4 Bubble plot of KEGG enrichment analysis of the candidate genes

Fig. 5 Haplotype-based association analysis of ETV1 and COL4A6 genesA: Haplotype block diagram of 5 significant SNPs annotated to the ETV1 gene. B: Violin plot of the major haplotypes annotated to the ETV1 gene. C: Haplotype block diagram of 24 significant loci annotated to the COL4A6 gene. D: Violin plot of the major haplotypes annotated to the COL4A6 gene

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