Biology subjects

Noskova, A.

Publications and source records attributed to Noskova, A..

4 recordsLinked to original sources

bioRxiv2021

Characterization of a haplotype-reference panel for genotyping by low-pass sequencing in Swiss Large White pigs

BackgroundThe key-ancestor approach has been frequently applied to prioritize individuals for whole-genome sequencing based on their marginal genetic contribution to current populations. Using this approach, we selected 70 key ancestors from two lines of the Swiss Large White breed that have been selected divergently for fertility and fattening traits and sequenced their genomes with short paired-end reads. ResultsUsing pedigree records, we estimated the effective population size of the dam and sire line to 72 and 44, respectively. In order to assess sequence variation in both lines, we sequenced the genomes of 70 boars at an average coverage of 16.69-fold. The boars explained 87.95 and 95.35% of the genetic diversity of the breeding populations of the dam and sire line, respectively. Reference-guided variant discovery using the GATK revealed 26,862,369 polymorphic sites. Principal component, admixture and FST analyses indicated considerable genetic differentiation between the lines. Genomic inbreeding quantified using runs of homozygosity was higher in the sire than dam line (0.28 vs 0.26). Using two complementary approaches (CLR and iHS), we detected 51 signatures of selection. However, only six signatures of selection overlapped between both lines. We used the sequenced haplotypes of the 70 key ancestors as a reference panel to call 22,618,811 genotypes in 175 pigs that had been sequenced at very low coverage (1.11-fold) using GLIMPSE. The genotype concordance, non-reference sensitivity and non-reference discrepancy between thus inferred and Illumina PorcineSNP60 BeadChip-called genotypes was 97.60, 98.73 and 3.24%, respectively. The low-pass sequencing-derived genomic relationship coefficients were highly correlated (r > 0.99) with those obtained from microarray genotyping. ConclusionsWe assessed genetic diversity within and between two lines of the Swiss Large White pig breed. Our analyses revealed considerable differentiation, even though the split into two populations occurred only few generations ago. The sequenced haplotypes of the key ancestor animals enabled us to implement genotyping by low-pass sequencing which offers an intriguing cost-effective approach to increase the variant density over current array-based genotyping by more than 350-fold.

genomics↗

bioRxiv2020

Deletion of an intronic polypyrimidine tract of porcine DNAH17 perturbs splicing and causes defective sperm flagella

Artificial insemination in pig (Sus scrofa domesticus) breeding involves the evaluation of the semen quality of breeding boars. Ejaculates that fulfill predefined quality requirements are processed, diluted and used for inseminations. Within short time, eight Swiss Large White boars producing immotile sperm that had multiple morphological abnormalities of the sperm flagella were noticed at a semen collection center. The eight boars were inbred on a common ancestor suggesting that the novel sperm flagella defect is a recessive trait. Transmission electron microscopy cross-sections revealed that the immotile sperm had disorganized flagellar axonemes. Haplotype-based association testing involving microarray-derived genotypes at 41,094 SNPs of six affected and 100 fertile boars yielded strong association (P=4.22 x 10-15) at chromosome 12. Autozygosity mapping enabled us to pinpoint the causal mutation on a 1.11 Mb haplotype located between 3,473,632 and 4,587,759 bp. The haplotype carries an intronic 13-bp deletion (Chr12:3,556,401-3,556,414 bp) that is compatible with recessive inheritance. The 13-bp deletion excises the polypyrimidine tract upstream exon 56 of DNAH17 (XM_021066525.1:c.8510-17_8510-5del) encoding dynein axonemal heavy chain 17. Transcriptome analysis of the testis of two affected boars revealed that the loss of the polypyrimidine tract causes exon skipping which results in the in-frame loss of 89 amino acids from DNAH17. Disruption of DNAH17 impairs the assembly of the flagellar axoneme and manifests in multiple morphological abnormalities of the sperm flagella. Direct gene testing may now be implemented to monitor the defective allele in the Swiss Large White population and prevent the frequent manifestation of a sterilizing sperm tail disorder in breeding boars.

genomics↗

bioRxiv2020

Deletion of porcine BOLL causes defective acrosomes and subfertility in Yorkshire boars

A recessively inherited sperm defect of Finnish Yorkshire boars was detected more than a decade ago. Affected boars produce ejaculates that contain many spermatozoa with defective acrosomes resulting in low fertility and small litters. The acrosome defect was mapped to porcine chromosome 15 but the causal mutation has not been identified. We re-analyzed microarray-derived genotypes of affected boars and performed a haplotype-based association study. Our results confirmed that the acrosome defect maps to a 12.24 Mb segment of porcine chromosome 15 (P=3.38 x 10-14). In order to detect the mutation causing defective acrosomes, we sequenced the genomes of two affected and three unaffected boars to an average coverage of 11-fold. Read-depth analysis revealed a 55 kb deletion that segregates with the acrosome defect. The deletion encompasses the BOLL gene encoding the boule homolog, RNA binding protein which is an evolutionarily highly conserved member of the DAZ (deleted in azoospermia) gene family. Lack of BOLL expression causes spermatogenic arrest and sperm maturation failure in many species. Our study reveals that absence of BOLL is associated with a sperm defect also in pigs. The acrosomes of boars that carry the deletion in the homozygous state are defective suggesting that lack of porcine BOLL compromises acrosome formation. Our findings warrant further research to investigate the precise function of BOLL during spermatogenesis and sperm maturation in pigs.

genomics↗

bioRxiv2020

A 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita

Arthrogryposis multiplex congenita (AMC) is a recessively inherited fatal disease detected almost 20 years ago in the Swiss Large White pig population. A diagnostic marker test enabled the identification of carrier animals, but the underlying causal mutation remains unknown. To identify the mutation underlying AMC, we collected whole-genome genotyping and sequencing data for 11 affected piglets and 23 healthy pigs. Haplotype-based case-control association testing using 47,829 SNPs confirmed that AMC maps to SSC5 (P = 9.4 x10-13). Subsequent autozygosity mapping revealed a common 6.06 Mb region (from 66,757,970 to 72,815,151 bp) of extended homozygosity in 11 piglets affected by AMC. We detected a 63-bp insertion in the second exon of KIF21A gene encoding Kinesin Family Member 21A using whole-genome sequences of a carrier boar, two of its affected and two heterozygous piglets. This insertion was compatible with the recessive inheritance of AMC. The 63-bp insertion likely represents a loss-of-function allele because it is predicted to introduce a premature stop codon in KIF21A gene (p.Val41_Phe42insTer) that truncates 1,614 amino acids ([~] 97%) from the protein. Lack of KIF21A protein is lethal in mice, thus providing additional evidence that a loss-of function allele of KIF21A might cause fatal AMC in pigs. We found that this deleterious allele still segregates at low frequency in the Swiss Large White pig population. The unambiguous detection of carrier animals can now facilitate the eradication of the deleterious allele from the population.

genomics↗