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

Sahana, Goutam; Iso-Touru, Terhi; Wu, Xiaoping; Nielsen, U.; Koning, Dirk-Jan de; Lund, Mogens Sandø; Vilkki, Johanna; Guldbrandtsen, Bernt

doi:10.1186/s12711-016-0215-z

Cited by 18 publications

(17 citation statements)

References 38 publications

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“…The frequency of this haplotype was 4.07%. This region has been previously reported to be related to stillbirth (Sahana et al, 2016;Mesbah-Uddin et al, 2018). However, we observed a significant harmful effect on later NRR (at 100 and 150 d), also indicating evidence for prenatal death.…”

Section: Three Haplotypes Detected In Rdc Overlap Known Recessive Letsupporting

confidence: 72%

Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle

Uddin

Guldbrandtsen

et al. 2020

Journal of Dairy Science

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Haplotypes that are common in a population but not observed as homotypes in living animals may harbor lethal alleles that compromise embryo survival. In this study, we searched for homozygous-deficient haplotypes in the genomes of 19,309 Nordic Red Dairy (RDC) and 4,291 Danish Jersey (JER) cattle genotyped using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). For statistically significant deficient haplotypes, we evaluated the effect on nonreturn rate in at-risk matings (mating between carrier bull and daughter of carrier sire) versus not-at-risk matings (mating between noncarrier bull and daughter of noncarrier sire). Next, we analyzed whole-genome sequence variants from the 1000 Bull Genomes Project to identify putative causal variants underlying these haplotypes. In RDC, we identified 3 homozygous-deficient regions (HDR) that overlapped with known recessive lethal mutations: a 662-kb deletion on chromosome 12 in RDC [Online Mendelian Inheritance in Animals (OMIA) 001901-9913), a missense mutation in TUBD1, g.11063520T>C, in Braunvieh cattle (OMIA 001939-9913), and a 525-kb deletion on chromosome 23 in RDC (OMIA 001991-9913)]. In addition, we identified 15 novel HDR and their tag haplotypes for the underlying causative variants. The tag haplotype located between 39.2 and 40.3 Mbp on chromosome 18 had a negative effect on nonreturn rate in at-risk mating, confirming embryonic lethality. In Danish Jersey, we identified 12 novel HDR and their tag haplotypes for underlying causative variants. For 3 of these 12 tag haplotypes, insemination records of at-risk mating showed a negative effect on nonreturn rate, confirming the association with early embryonic mortality. Cattle that had both genotype and whole-genome sequence data were analyzed to detect the causative variants underlying each tag haplotype. However, none of the functional variants or deletions showed concordance with carrier status of the novel tag haplotypes. Carrier status of these detected haplotypes can be used to select bulls to reduce the frequencies of lethal alleles in the population and to avoid at-risk matings.

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Section: Three Haplotypes Detected In Rdc Overlap Known Recessive Letsupporting

confidence: 72%

Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle

Uddin

Guldbrandtsen

et al. 2020

Journal of Dairy Science

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“…We validated a previously reported ∼525 KB deletion segregating in Nordic Red Cattle 10 using PCR and amplicon sequencing. Genomic DNA was extracted as described previously by Miller et al 31 from semen sample of two bulls carrying the deletion and two non-carriers.…”

Section: Methodsmentioning

confidence: 78%

“…We then experimentally validated breakpoints for ‘Chr23:12,291,761-12,817,087’ deletion, previously reported to be associated with stillbirth in Nordic Red Cattle 10 . Four animals were used for PCR validation: two carriers and two non-carriers.…”

Section: Resultsmentioning

confidence: 99%

“…BEDTools (v2.26.0) software 46 is used for identifying the overlap between deletion calls and other genomic features, such as, ‘UMD3.1 ’ assembly gaps (from ‘UCSC Table Browser ’ ), CNVs from dbVar database 47 , three known deletions from 7 , 9 , 10 , QTL from QTLdb . VCFtools (v0.1.15) software and PLINK (v1.90p) software were used for analysing the VCF file.…”

Section: Methodsmentioning

confidence: 99%

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Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle

et al. 2017

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Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp–773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the dbVar database. Breakpoint sequence analyses revealed that majority (24 of 29 tested) of the deletions contain microhomology/homology at breakpoint, and therefore, most likely generated by microhomology-mediated end joining. We observed higher differentiation among breeds for deletions in some genic-regions, such as ABCA12, TTC1, VWA3B, TSHR, DST/BPAG1, and CD1D. The genes overlapping deletions are on average evolutionarily less conserved compared with known mouse lethal genes (P-value = 2.3 × 10−6). We report 167 natural gene knockouts in cattle that are apparently nonessential as live homozygote individuals are observed. These genes are functionally enriched for immunoglobulin domains, olfactory receptors, and MHC classes (FDR = 2.06 × 10−22, 2.06 × 10−22, 7.01 × 10−6, respectively). We also demonstrate that deletions are enriched for health and fertility related quantitative trait loci (2-and 1.5-fold enrichment, Fisher’s P-value = 8.91 × 10−10 and 7.4 × 10−11, respectively). Finally, we identified and confirmed the breakpoint of a ∼525 KB deletion on Chr23:12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8), causing stillbirth in Nordic Red Cattle.

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“…Deletions are indeed a cause of productive and reproductive problems in cattle (for example, a 500‐kb deletion in BTA23 is a strong candidate for stillbirth; Sahana et al . ). However, there is no reported evidence of any health problems in the Hereford cow L1 Dominette 01449.…”

Section: Discussionmentioning

confidence: 97%

Characterization of a deletion in the Hsp70 cluster in the bovine reference genome

et al. 2017

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The 70 kilodalton heat shock proteins (Hsp70) are highly conserved molecular chaperones which have a crucial role in the stress response of the cell. In mammals, the Hsp70 proteins are encoded by a cluster of three genes: HSPA1A, HSPA1B and HSPA1L. In bovines, this cluster is located on chromosome 23 downstream of the major histocompatibility complex (BoLA). We detected inconsistencies in the location of markers on the Hsp70 genes reported in the literature that pointed to a potential deletion in the bovine reference genome UMD 3.1.1. An in silico analysis of the bovine genomic region of the Hsp70 cluster, using available information from public databases, confirmed the existence of a deletion of 11.1-kb spanning the HSPA1B gene and the intergenic region between HSPA1B and HSPA1A. Although we originally considered this an assembly error, it is most likely a particular condition of L1 Dominette 01449, the cow sequenced in the Bovine Genome Project. Moreover, we suggest a new classification of bovine Hsp70 sequences reported in NCBI and a reassignment of the location of SNPs from dbSNP that map to the deletion on BTA23. We also compared the location of selected transcription factor binding sites on the promoters of HSPA1A and HSPA1B. The results generated in the present work could be helpful to refine the reference genome of an important livestock species and also to understand the role and the regulation of the bovine Hsp70 genes.

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

Cited by 18 publications

References 38 publications

Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle

Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle

Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle

Characterization of a deletion in the Hsp70 cluster in the bovine reference genome

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