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A 0.5-Mbp deletion on bovine chromosome 23 is a strong candidate for stillbirth in Nordic Red cattle.

Sahana G, Iso-Touru T, Wu X, Nielsen US, de Koning DJ, Lund MS, Vilkki J, Guldbrandtsen B - Genet. Sel. Evol. (2016)

Bottom Line: Among this haplotype's alleles, HAPQTL had a large negative effect on stillbirth.No animals were found to be homozygous for HAPQTL.A deleted region of approximately 500 kb that spans three genes on BTA23 was identified and is a strong candidate QTL with a large effect on BI by increasing stillbirth.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, 8830, Tjele, Denmark. goutam.sahana@mbg.au.dk.

ABSTRACT

Background: A whole-genome association study of 4631 progeny-tested Nordic Red dairy cattle bulls using imputed next-generation sequencing data revealed a major quantitative trait locus (QTL) that affects birth index (BI) on Bos taurus autosome (BTA) 23. We analyzed this QTL to identify which of the component traits of BI are affected and understand its molecular basis.

Results: A genome-wide scan of BI in Nordic Red dairy cattle detected major QTL on BTA6, 14 and 23. The strongest associated single nucleotide polymorphism (SNP) on BTA23 was located at 13,313,896 bp with [Formula: see text]. Analyses of component traits showed that the QTL had a large effect on stillbirth. Based on the 10 most strongly associated SNPs with stillbirth, we constructed a haplotype. Among this haplotype's alleles, HAPQTL had a large negative effect on stillbirth. No animals were found to be homozygous for HAPQTL. Analysis of stillbirth records that were categorized by carrier status for HAPQTL of the sire and maternal grandsire suggested that this haplotype had a recessive mode of inheritance. Illumina BovineHD BeadChip genotypes and genotype intensity data indicated a chromosomal deletion between 12.28 and 12.81 Mbp on BTA23. An independent set of Illumina Bovine50k BeadChip genotypes identified a recessive lethal haplotype that spanned the deleted region.

Conclusions: A deleted region of approximately 500 kb that spans three genes on BTA23 was identified and is a strong candidate QTL with a large effect on BI by increasing stillbirth.

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Average genotype signal intensity per SNP for carriers (red) and noncarriers (blue) of the chromosomal deletion (CHRDEL), plotted against their genomic positions. Carrier status of an individual was predicted based on loss of genotype intensity and homozygosity using SNPs from the Illumina BovineHD genotyping array
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Fig7: Average genotype signal intensity per SNP for carriers (red) and noncarriers (blue) of the chromosomal deletion (CHRDEL), plotted against their genomic positions. Carrier status of an individual was predicted based on loss of genotype intensity and homozygosity using SNPs from the Illumina BovineHD genotyping array

Mentions: The plot of the average intensities from carriers and noncarriers of CHRDEL (Fig. 7) showed a clear reduction in signal intensities for SNPs in the region between 12,289,281 and 12,816,660 bp, which confirmed the existence of a chromosomal deletion. Since the deleted region harbored several repetitive elements, it was difficult to identify the exact breaking points from the position of the split reads of the sequence data. Amplification across the deleted region was unsuccessful because unique primers for its extremities could not be designed. Sequence coverage increased in depth at the end region of the breaking point (see Additional file 4: Figure S4), which could be due to assembly problems or the presence of repetitive elements. These data, combined with the individual HD SNP intensity data and sequence alignments (results not shown), indicate that either the bovine genome assembly of this region is incorrect, or that the structural variation is more complex than just a simple deletion.Fig. 7


A 0.5-Mbp deletion on bovine chromosome 23 is a strong candidate for stillbirth in Nordic Red cattle.

Sahana G, Iso-Touru T, Wu X, Nielsen US, de Koning DJ, Lund MS, Vilkki J, Guldbrandtsen B - Genet. Sel. Evol. (2016)

Average genotype signal intensity per SNP for carriers (red) and noncarriers (blue) of the chromosomal deletion (CHRDEL), plotted against their genomic positions. Carrier status of an individual was predicted based on loss of genotype intensity and homozygosity using SNPs from the Illumina BovineHD genotyping array
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835938&req=5

Fig7: Average genotype signal intensity per SNP for carriers (red) and noncarriers (blue) of the chromosomal deletion (CHRDEL), plotted against their genomic positions. Carrier status of an individual was predicted based on loss of genotype intensity and homozygosity using SNPs from the Illumina BovineHD genotyping array
Mentions: The plot of the average intensities from carriers and noncarriers of CHRDEL (Fig. 7) showed a clear reduction in signal intensities for SNPs in the region between 12,289,281 and 12,816,660 bp, which confirmed the existence of a chromosomal deletion. Since the deleted region harbored several repetitive elements, it was difficult to identify the exact breaking points from the position of the split reads of the sequence data. Amplification across the deleted region was unsuccessful because unique primers for its extremities could not be designed. Sequence coverage increased in depth at the end region of the breaking point (see Additional file 4: Figure S4), which could be due to assembly problems or the presence of repetitive elements. These data, combined with the individual HD SNP intensity data and sequence alignments (results not shown), indicate that either the bovine genome assembly of this region is incorrect, or that the structural variation is more complex than just a simple deletion.Fig. 7

Bottom Line: Among this haplotype's alleles, HAPQTL had a large negative effect on stillbirth.No animals were found to be homozygous for HAPQTL.A deleted region of approximately 500 kb that spans three genes on BTA23 was identified and is a strong candidate QTL with a large effect on BI by increasing stillbirth.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, 8830, Tjele, Denmark. goutam.sahana@mbg.au.dk.

ABSTRACT

Background: A whole-genome association study of 4631 progeny-tested Nordic Red dairy cattle bulls using imputed next-generation sequencing data revealed a major quantitative trait locus (QTL) that affects birth index (BI) on Bos taurus autosome (BTA) 23. We analyzed this QTL to identify which of the component traits of BI are affected and understand its molecular basis.

Results: A genome-wide scan of BI in Nordic Red dairy cattle detected major QTL on BTA6, 14 and 23. The strongest associated single nucleotide polymorphism (SNP) on BTA23 was located at 13,313,896 bp with [Formula: see text]. Analyses of component traits showed that the QTL had a large effect on stillbirth. Based on the 10 most strongly associated SNPs with stillbirth, we constructed a haplotype. Among this haplotype's alleles, HAPQTL had a large negative effect on stillbirth. No animals were found to be homozygous for HAPQTL. Analysis of stillbirth records that were categorized by carrier status for HAPQTL of the sire and maternal grandsire suggested that this haplotype had a recessive mode of inheritance. Illumina BovineHD BeadChip genotypes and genotype intensity data indicated a chromosomal deletion between 12.28 and 12.81 Mbp on BTA23. An independent set of Illumina Bovine50k BeadChip genotypes identified a recessive lethal haplotype that spanned the deleted region.

Conclusions: A deleted region of approximately 500 kb that spans three genes on BTA23 was identified and is a strong candidate QTL with a large effect on BI by increasing stillbirth.

Show MeSH