A 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock
; ; Charlier, Carole et al
in PLoS Genetics (2014), 10(1), 1004049
In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has ... [more ▼]
In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has concomitantly severely declined. It is generally assumed that this reduction is primarily due to the negative energy balance of high-producing cows at the peak of lactation. We herein describe the fine-mapping of a major fertility QTL in Nordic Red cattle, and identify a 660-kb deletion encompassing four genes as the causative variant. We show that the deletion is a recessive embryonically lethal mutation. This probably results from the loss of RNASEH2B, which is known to cause embryonic death in mice. Despite its dramatic effect on fertility, 13%, 23% and 32% of the animals carry the deletion in Danish, Swedish and Finnish Red Cattle, respectively. To explain this, we searched for favorable effects on other traits and found that the deletion has strong positive effects on milk yield. This study demonstrates that embryonic lethal mutations account for a non-negligible fraction of the decline in fertility of domestic cattle, and that associated positive effects on milk yield may account for part of the negative genetic correlation. Our study adds to the evidence that structural variants contribute to animal phenotypic variation, and that balancing selection might be more common in livestock species than previously appreciated. [less ▲]Detailed reference viewed: 16 (3 ULg)
Hard Selective Sweep and Ectopic Gene Conversion in a Gene Cluster Affording Environmental Adaptation
Hanikenne, Marc ; ; et al
in PLoS Genetics (2013), 9Detailed reference viewed: 23 (4 ULg)
A splice site variant in the bovine RNF11 gene compromises growth and regulation of the inflammatory response.
Sartelet, Arnaud ; Druet, Tom ; Michaux, Charles et al
in PLoS Genetics (2012), 15(3), 1002581
We herein report association mapping of a locus on bovine chromosome 3 that underlies a Mendelian form of stunted growth in Belgian Blue Cattle. By resequencing positional candidates, we identify the ... [more ▼]
We herein report association mapping of a locus on bovine chromosome 3 that underlies a Mendelian form of stunted growth in Belgian Blue Cattle. By resequencing positional candidates, we identify the causative c124-2A>G splice variant in intron 1 of the RNF11 gene, for which all affected animals are homozygous. We make the remarkable observation that 26% of healthy Belgian Blue animals carry the corresponding variant. We demonstrate in a prospective study design that approximately one third of homozygous mutants die prematurely with major inflammatory lesions, hence explaining the rarity of growth-stunted animals despite the high frequency of carriers. We provide preliminary evidence that heterozygous advantage for an as of yet unidentified phenotype may have caused a selective sweep accounting for the high frequency of the RNF11 c124-2A>G mutation in Belgian Blue Cattle. [less ▲]Detailed reference viewed: 45 (25 ULg)
Co-Evolution of Mitochondrial tRNA Import and Codon Usage Determines Translational Efficiency in the Green Alga Chlamydomonas
; Duby, Franceline ; Larosa, Véronique et al
in PLoS Genetics (2012), 8(9),Detailed reference viewed: 39 (9 ULg)
Genetic variants in REC8, RNF212, and PRDM9 influence male recombination in cattle.
Sandor, Cynthia ; Li, Wanbo ; Coppieters, Wouter et al
in PLoS Genetics (2012), 8(7), 1002854
We use >250,000 cross-over events identified in >10,000 bovine sperm cells to perform an extensive characterization of meiotic recombination in male cattle. We map Quantitative Trait Loci (QTL ... [more ▼]
We use >250,000 cross-over events identified in >10,000 bovine sperm cells to perform an extensive characterization of meiotic recombination in male cattle. We map Quantitative Trait Loci (QTL) influencing genome-wide recombination rate, genome-wide hotspot usage, and locus-specific recombination rate. We fine-map three QTL and present strong evidence that genetic variants in REC8 and RNF212 influence genome-wide recombination rate, while genetic variants in PRDM9 influence genome-wide hotspot usage. [less ▲]Detailed reference viewed: 26 (6 ULg)
Balancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle.
Fasquelle, Corinne ; Sartelet, Arnaud ; et al
in PLoS Genetics (2009), 5(9), 1000666
We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals ... [more ▼]
We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed. [less ▲]Detailed reference viewed: 111 (49 ULg)
Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.
Libioulle, Cécile ; Louis, Edouard ; Hansoul, Sarah et al
in PLoS Genetics (2007), 3(4), 538-543
To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three ... [more ▼]
To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(-6) and 10(-9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(-7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 x 10(-4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4. [less ▲]Detailed reference viewed: 95 (9 ULg)