Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle

Mapel, Xena Marie; Kadri, Naveen Kumar; Leonard, Alexander S.; He, Qiang; Lloret-Villas, Audald; Bhati, Meenu; Hiltpold, Maya; Pausch, Hubert

doi:10.1101/2023.06.29.547066

Cited by 3 publications

(2 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further investigations are needed to explore the integration of molecular QTL cohorts and GWAS cohorts through transcriptome-wide association testing. This approach holds the potential to reveal SVs and STRs associated with specific traits ( Mapel et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue

Bhati,

Mapel,

Lloret-Villas

et al. 2023

Genetics

Self Cite

View full text Add to dashboard Cite

Structural variants (SVs) and short tandem repeats (STRs) are significant sources of genetic variation. However, the impacts of these variants on gene regulation have not been investigated in cattle. Here, we genotyped and characterized 19,408 SVs and 374,821 STRs in 183 bovine genomes and investigated their impact on molecular phenotypes derived from testis transcriptomes. We found that 71% STRs were multiallelic. The vast majority (95%) of STRs and SVs were in intergenic and intronic regions. Only 37% SVs and 40% STRs were in high LD (R2 > 0.8) with surrounding SNPs/Indels, indicating that SNP-based association testing and genomic prediction are blind to a non-negligible portion of genetic variation. We showed that both SVs and STRs were more than two-fold enriched among expression and splicing QTL (e/sQTL) relative to SNPs/Indels and were often associated with differential expression and splicing of multiple genes. Deletions and duplications had larger impacts on splicing and expression than any other type of structural variant. Exonic duplications predominantly increased gene expression either through alternative splicing or other mechanisms, whereas expression- and splicing-associated STRs primarily resided in intronic regions and exhibited bimodal effects on the molecular phenotypes investigated. Most e/sQTL resided within 100 kb of the affected genes or splicing junctions. We pinpoint candidate causal STRs and SVs associated with the expression of SLC13A4 and TTC7B, and alternative splicing of a lncRNA and CAPP1. We provide a catalogue of STRs and SVs for taurine cattle and show that these variants contribute substantially to gene expression and splicing variation.

show abstract

Section: Discussionmentioning

confidence: 99%

Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue

Bhati,

Mapel,

Lloret-Villas

et al. 2023

Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…High-throughput RNA sequencing (RNA-seq) has been frequently applied for measuring gene expression levels (1), assembling de novo transcriptomes (2), detecting copy number alterations (3), and identifying genomic variants that influence gene expression (4). Genotypes called from RNA-seq have also been used to determine population structure (5,6).…”

Section: Introductionmentioning

confidence: 99%

RNA sequencing variants are enriched for eQTL in cattle tissues

Leonard,

Mapel,

Pausch

2024

Preprint

Self Cite

View full text Add to dashboard Cite

Association testing between molecular phenotypes and genomic variants can help to understand how genotype affects phenotype. RNA sequencing provides access to molecular phenotypes such as gene expression and alternative splicing while DNA sequencing or microarray genotyping are the prevailing options to obtain genomic variants. Here we genotype variants for 74 male Braunvieh cattle from both DNA and deep total RNA sequencing from three tissues. We show that RNA sequencing calls approximately 40% of variants (7-10 million) called from DNA sequencing, with over 80% precision, rising to over 92% of variants called with nearly 98% precision in highly expressed coding regions. Allele-specific expression and putative post-transcriptional modifications negatively impact variant genotyping accuracy from RNA sequencing and contribute to RNA-DNA differences. Variants called from RNA sequencing detect roughly 75% of eGenes identified using variants called from DNA sequencing, demonstrating a nearly 2-fold enrichment of eQTL variants. We observe a moderate-to-strong correlation in nominal association p-values (Spearman ρ2~0.6), although only 9% of eGenes have the same top associated variant. We also find several highly significant RNA variant-only eQTL, demonstrating that caution must be exercised beyond filtering for variant quality or imputation accuracy when analysing or imputing variants called from RNA sequencing.

show abstract

Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue

Bhati

Mapel

Lloret-Villas

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Structural variants (SVs) and short tandem repeats (STRs) are significant sources of genetic variation. However, the impacts of these variants on gene expression and splicing have not been investigated in cattle. Here, we genotyped and characterized 19,408 SVs and 374,821 STRs in 183 bovine genomes and investigated their impact on molecular phenotypes derived from testis transcriptomes. We found that 71% short tandem repeats (STRs) were multiallelic. The vast majority (95%) of STRs and SVs were in intergenic and intronic regions. Additionally, 37% of SVs and 40% of STRs were in high LD (R2>0.8) with surrounding SNPs/Indels. Both SVs and STRs were more than two-fold enriched among expression and splicing QTL (e/sQTL) relative to SNPs/Indels and were often associated with differential expression and splicing of multiple genes. Deletions and duplications had larger impacts on splicing and expression than any other type of structural variant. Exonic duplications predominantly increased gene expression either through alternative splicing or other mechanisms, whereas expression- and splicing-associated STRs primarily resided in intronic regions and exhibited bimodal effects on the molecular phenotypes investigated. Most e/sQTL resided within 100 kb of the affected genes or splicing junctions. We pinpoint candidate causal STRs and SVs associated with the expression of SLC13A4 and TTC7B, and alternative splicing of a lncRNA and CAPP1. Our results provide a comprehensive catalogue of polymorphic STRs and SVs in the bovine genome and show that they contribute substantially to gene expression and splicing variation in cattle.

show abstract

Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle

Cited by 3 publications

References 95 publications

Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue

Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue

RNA sequencing variants are enriched for eQTL in cattle tissues

Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue

Contact Info

Product

Resources

About