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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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Genes located within the targeted region based on the Ensembl Bos taurus version 78 (UMD3.1, http://www.ensembl.org/)
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Fig9: Genes located within the targeted region based on the Ensembl Bos taurus version 78 (UMD3.1, http://www.ensembl.org/)

Mentions: Three genes are located within the deleted region: (1) BTB (POZ) domain containing 9 (BTBD9, 12,405,340–12,462,065 bp), (2) glyoxalase I (GLO1, 12,483,468–12,509,232 bp) and (3) dynein, axonemal, heavy chain 8 (DNAH8, 12,550,367–12,883,939 bp) (Fig. 9). Which, if any, of these genes causes stillbirth if deleted is not obvious from their known gene functions. Phenotypes of BTBD9 knockout mice suggest that BTBD9 is involved in synaptic plasticity, learning, memory and protein alterations associated with vesicle recycling and endocytosis [35]. When glyoxalase I activity decreased in situ through aging and oxidative stress, levels of glycation and tissue damage increased. These effects may be associated with a risk of developing vascular complications due to diabetes and uremia [36]. Overexpression of glyoxalase 1 in bone marrow cells reversed defective neovascularization in streptozotocin-induced diabetic mice [37]. Diseases associated with DNAH8 include myosin storage myopathy and reduced body myopathy (http://www.genecards.org/cgi-bin/carddisp.pl?gene=DNAH8, accessed 23 December 2014). The most well-known disease associated with dynein malfunction in humans is polycystic kidney disease (PCD; also known as Kartagener syndrome), which is characterized by malfunctioning of the cilia and sperm, as well as respiratory problems. Around half of the PCD patients also have situs inversus. Extreme defects in laterality may be diagnosed as heterotaxy with asplenia or polysplenia [38].Fig. 9


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)

Genes located within the targeted region based on the Ensembl Bos taurus version 78 (UMD3.1, http://www.ensembl.org/)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig9: Genes located within the targeted region based on the Ensembl Bos taurus version 78 (UMD3.1, http://www.ensembl.org/)
Mentions: Three genes are located within the deleted region: (1) BTB (POZ) domain containing 9 (BTBD9, 12,405,340–12,462,065 bp), (2) glyoxalase I (GLO1, 12,483,468–12,509,232 bp) and (3) dynein, axonemal, heavy chain 8 (DNAH8, 12,550,367–12,883,939 bp) (Fig. 9). Which, if any, of these genes causes stillbirth if deleted is not obvious from their known gene functions. Phenotypes of BTBD9 knockout mice suggest that BTBD9 is involved in synaptic plasticity, learning, memory and protein alterations associated with vesicle recycling and endocytosis [35]. When glyoxalase I activity decreased in situ through aging and oxidative stress, levels of glycation and tissue damage increased. These effects may be associated with a risk of developing vascular complications due to diabetes and uremia [36]. Overexpression of glyoxalase 1 in bone marrow cells reversed defective neovascularization in streptozotocin-induced diabetic mice [37]. Diseases associated with DNAH8 include myosin storage myopathy and reduced body myopathy (http://www.genecards.org/cgi-bin/carddisp.pl?gene=DNAH8, accessed 23 December 2014). The most well-known disease associated with dynein malfunction in humans is polycystic kidney disease (PCD; also known as Kartagener syndrome), which is characterized by malfunctioning of the cilia and sperm, as well as respiratory problems. Around half of the PCD patients also have situs inversus. Extreme defects in laterality may be diagnosed as heterotaxy with asplenia or polysplenia [38].Fig. 9

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