A nonsense mutation in the<i>COL7A1</i>gene causes epidermolysis bullosa in Vorderwald cattle

Pausch, Hubert; Ammermueller, Simon; Wurmser, Christine; Hamann, H.; Tetens, Jens; Droegemueller, Cord; Fries, R.

doi:10.1101/062968

Cited by 10 publications

(12 citation statements)

References 45 publications

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“…In agreement with previous studies in cattle [21], missense deleterious and high impact variants occurred predominantly at low allele frequency likely indicating that variants which disrupt physiological protein functions are removed from the population through purifying selection [65]. However, deleterious variants may reach high frequency in livestock populations due to, e.g., the frequent use of individual carrier animals in artificial insemination [66], hitchhiking with favorable alleles under artificial selection [67,68], or demography effects such as population bottlenecks [69]. Because we predicted functional consequences of missense variants using computational inference, they have to be treated with caution in the absence of experimental validation [70].…”

Section: Discussionsupporting

confidence: 89%

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

Bhati

Kadri

Crysnanto

et al. 2019

Preprint

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Background: Local cattle breeds represent an important source of genetic variation because they might carry alleles that enable them to adapt to harsh environments and scarce food conditions. One such local Swiss cattle breed is Original Braunvieh (OB) which is used for beef and milk production in alpine areas. Using whole-genome sequencing data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. Results:We annotated 15.7 million SNPs and 1.5 million Indels including 10,738 and 2,763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive xanthinuria and albinism. The average nucleotide diversity (1.6 × 10 -3 ) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding (F ROH =0.14) was relatively low in OB cattle. However, genomic inbreeding increased in recent years due to a higher number of long (> 1 Mb) runs of homozygosity in cattle born in more recent generations. Using two complementary approaches, i.e., composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (p < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus. Conclusions:We provide a comprehensive overview of genomic variation segregating in Swiss OB cattle. Using whole-genome sequencing data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds.Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to harsh environments. Considering the low population size and increasing rates of genomic inbreeding in the past generations, the implementation and adoption of genomic mating programs seems warranted to maintain genetic diversity in the Swiss OB cattle population.

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Section: Discussionsupporting

confidence: 89%

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

Bhati

Kadri

Crysnanto

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

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“…In agreement with previous studies in cattle [14,27], missense deleterious and high impact variants occurred predominantly at low allele frequency likely indicating that variants which disrupt physiological protein functions are removed from the population through purifying selection [28]. However, deleterious variants may reach high frequency in livestock populations due to the frequent use of individual carrier animals in artificial insemination [29], hitchhiking with favorable alleles under artificial selection [30,31], or demography effects such as population bottlenecks [32]. Because we predicted functional consequences of missense variants using computational inference, they have to be treated with caution in the absence of experimental validation [33].…”

Section: Discussionsupporting

confidence: 89%

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

et al. 2020

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Background: Autochthonous cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution. Results: We annotated 15,722,811 SNPs and 1,580,878 Indels including 10,738 and 2763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive xanthinuria and albinism. The average nucleotide diversity (1.6 × 10 − 3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding derived from runs of homozygosity (ROH) was relatively low (F ROH = 0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in OB cattle of more recent generations (F ROH = 0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus. Conclusions: We provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.

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“…However, both bulls were housed at the AI center under controlled environmental conditions at the same time as many fertile bulls and their health and andrological parameters were normal indicating that non-genetic factors were less likely to cause this condition. Previous studies showed that autozygosity mapping is a powerful approach to identify genomic regions associated with recessive conditions even if only few affected individuals with genotype information are available [13], [33]. Using autozygosity mapping in the two affected bulls, we identified a 2.98 Mb segment of extended homozygosity located at chromosome 25 that was identical by descent in both bulls.…”

Section: Discussionmentioning

confidence: 97%

A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle

Iso-Touru

Wurmser

Venhoranta

et al. 2018

Preprint

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Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarrayderived genotypes are available for many artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected.Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8,557 fertile bulls although five homozygous haplotype carriers were expected (P=0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5' splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle. Conclusions:Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermiaassociated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

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A nonsense mutation in theCOL7A1gene causes epidermolysis bullosa in Vorderwald cattle

Cited by 10 publications

References 45 publications

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle

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