Xena Marie Mapel

Last Name

Mapel

First Name

Xena Marie

ORCID

0000-0002-7501-578X

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09575 - Pausch, Hubert / Pausch, Hubert

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Publications 1 - 10 of 17

Graph construction method impacts variation representation and analyses in a bovine super-pangenome
Leonard, Alexander; Crysnanto, Danang; Mapel, Xena Marie; et al. (2023)
Genome Biology
Background Several models and algorithms have been proposed to build pangenomes from multiple input assemblies, but their impact on variant representation, and consequently downstream analyses, is largely unknown. Results We create multi-species super-pangenomes using pggb, cactus, and minigraph with the Bos taurus taurus reference sequence and eleven haplotype-resolved assemblies from taurine and indicine cattle, bison, yak, and gaur. We recover 221 k nonredundant structural variations (SVs) from the pangenomes, of which 135 k (61%) are common to all three. SVs derived from assembly-based calling show high agreement with the consensus calls from the pangenomes (96%), but validate only a small proportion of variations private to each graph. Pggb and cactus, which also incorporate base-level variation, have approximately 95% exact matches with assembly-derived small variant calls, which significantly improves the edit rate when realigning assemblies compared to minigraph. We use the three pangenomes to investigate 9566 variable number tandem repeats (VNTRs), finding 63% have identical predicted repeat counts in the three graphs, while minigraph can over or underestimate the count given its approximate coordinate system. We examine a highly variable VNTR locus and show that repeat unit copy number impacts the expression of proximal genes and non-coding RNA. Conclusions Our findings indicate good consensus between the three pangenome methods but also show their individual strengths and weaknesses that need to be considered when analysing different types of variants from multiple input assemblies.
Taurine pangenome uncovers a segmental duplication upstream of KIT associated with depigmentation in white-headed cattle
Milia, Sotiria; Leonard, Alexander; Mapel, Xena Marie; et al. (2025)
Genome Research
Cattle have been selectively bred for coat color, spotting, and depigmentation patterns. The assumed autosomal dominant inherited genetic variants underlying the characteristic white head of Fleckvieh, Simmental, and Hereford cattle have not been identified yet, although the contribution of structural variation upstream the KIT gene has been proposed. Here, we construct a graph pangenome from 24 haplotype assemblies representing seven taurine cattle breeds to identify and characterize the white head-associated locus for the first time based on long-read sequencing data and pangenome analyses. We introduce a pangenome-wide association mapping approach which examines assembly path similarities within the graph to reveal an association between two most likely serial alleles of a complex structural variant 66 kb upstream KIT and facial depigmentation. The complex structural variant contains a variable number of tandemly duplicated 14.3 kb repeats, consisting of LTRs, LINEs, and other repetitive elements, leading to misleading alignments of short and long reads when using a linear reference. We align 250 short-read sequencing samples spanning 15 cattle breeds to the pangenome graph, further validating that the alleles of the structural variant segregate with head depigmentation. We estimate an increased count of repeats in Hereford relative to Simmental and other white-headed cattle breeds from the graph alignment coverage, suggesting a large under-assembly in the current Hereford-based cattle reference genome which had fewer copies. Our work shows that exploiting assembly path similarities within graph pangenomes can reveal trait-associated complex structural variants.
Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue
Bhati, Meenu; Mapel, Xena Marie; Lloret i Villas, Audald; et al. (2023)
Genetics
Structural variants (SVs) and short tandem repeats (STRs) are significant sources of genetic variation. However, the impacts of these variants on gene regulation have not been investigated in cattle. Here, we genotyped and characterized 19,408 SVs and 374,821 STRs in 183 bovine genomes and investigated their impact on molecular phenotypes derived from testis transcriptomes. We found that 71% STRs were multiallelic. The vast majority (95%) of STRs and SVs were in intergenic and intronic regions. Only 37% SVs and 40% STRs were in high LD (R2 > 0.8) with surrounding SNPs/Indels, indicating that SNP-based association testing and genomic prediction are blind to a non-negligible portion of genetic variation. We showed that both SVs and STRs were more than two-fold enriched among expression and splicing QTL (e/sQTL) relative to SNPs/Indels and were often associated with differential expression and splicing of multiple genes. Deletions and duplications had larger impacts on splicing and expression than any other type of structural variant. Exonic duplications predominantly increased gene expression either through alternative splicing or other mechanisms, whereas expression- and splicing-associated STRs primarily resided in intronic regions and exhibited bimodal effects on the molecular phenotypes investigated. Most e/sQTL resided within 100 kb of the affected genes or splicing junctions. We pinpoint candidate causal STRs and SVs associated with the expression of SLC13A4 and TTC7B, and alternative splicing of a lncRNA and CAPP1. We provide a catalogue of STRs and SVs for taurine cattle and show that these variants contribute substantially to gene expression and splicing variation.
Bull fertility and semen quality are not correlated with dairy and production traits in Brown Swiss cattle
Mapel, Xena Marie; Hiltpold, Maya; Kadri, Naveen Kumar; et al. (2022)
JDS Communications
Undisturbed reproduction is key for successful breeding of beef and dairy cattle. Improving reproductive ability can be difficult because of antagonistic relationships with other economically relevant traits. In cattle, thorough investigation of female fertility revealed unfavorable genetic correlations with various production phenotypes. However, the correlation between male reproductive ability and production traits remains poorly understood. Here, we investigated the genetic relationships among and between male fertility characteristics and economically relevant traits in a population of Brown Swiss cattle. We performed GWAS with imputed genotypes at nearly 12 million sequence variants for semen quality (sperm head and tail anomalies, motility, concentration, and volume), male fertility, and 57 production phenotypes. Allele substitution effects were then correlated on a trait-by-trait basis to estimate genetic correlations. Correlations between male reproductive characteristics and traits of economic value were small and ranged from −0.0681 to 0.0787. Among the semen quality parameters, sperm motility was negatively correlated with anomalies (head: r = −0.7083 ± 0.0002; tail: r = −0.7739 ± 0.0002) and volume (r = −0.1266 ± 0.0003), whereas volume was negatively correlated with concentration (r = −0.3503 ± 0.0002). Sire nonreturn rate was negatively correlated with sperm anomalies (head: r = −0.1640 ± 0.0002; tail: r = −0.1580 ± 0.0002) and positively correlated with motility (r = 0.1598 ± 0.0002). A meta-analysis of male reproductive traits identified 2 quantitative trait loci: a previously described region on chromosome 6 showed pleiotropic effects and a novel region on chromosome 11 was associated with sperm head anomalies. In conclusion, our results suggest that selection for economically important dairy and production phenotypes has little impact on semen quality and fertility of Brown Swiss bulls.
The bovine and human branch point sequence is depleted for variants
Kadri, Naveen Kumar; Mapel, Xena Marie; Pausch, Hubert (2021)
Identifying variants and molecular phenotypes associated with male fertility
Mapel, Xena Marie (2025)
A 1-bp deletion in bovine QRICH2 causes low sperm count and immotile sperm with multiple morphological abnormalities
Hiltpold, Maya; Janett, Fredi; Mapel, Xena Marie; et al. (2022)
Genetics Selection Evolution
BACKGROUND: Semen quality and insemination success are monitored in artificial insemination bulls to ensure high male fertility rates. Only ejaculates that fulfill minimum quality requirements are processed and eventually used for artificial inseminations. We examined 70,990 ejaculates from 1343 Brown Swiss bulls to identify bulls from which all ejaculates were rejected due to low semen quality. This procedure identified a bull that produced 12 ejaculates with an aberrantly small number of sperm (0.2 ± 0.2 × 109 sperm per mL) which were mostly immotile due to multiple morphological abnormalities. RESULTS: The genome of this bull was sequenced at a 12× coverage to investigate a possible genetic cause. Comparing the sequence variant genotypes of this bull with those from 397 fertile bulls revealed a 1-bp deletion in the coding sequence of the QRICH2 gene which encodes the glutamine rich 2 protein, as a compelling candidate causal variant. This 1-bp deletion causes a frameshift in translation and a premature termination codon (ENSBTAP00000018337.1:p.Cys1644AlafsTer52). The analysis of testis transcriptomes from 76 bulls showed that the transcript with the premature termination codon is subject to nonsense-mediated mRNA decay. The 1-bp deletion resides in a 675-kb haplotype that includes 181 single nucleotide polymorphisms (SNPs) from the Illumina BovineHD Bead chip. This haplotype segregates at a frequency of 5% in the Brown Swiss cattle population. Our analysis also identified another bull that carried the 1-bp deletion in the homozygous state. Semen analyses from the second bull confirmed low sperm concentration and immotile sperm with multiple morphological abnormalities that primarily affect the sperm flagellum and, to a lesser extent, the sperm head. CONCLUSIONS: A recessive loss-of-function allele of the bovine QRICH2 gene likely causes low sperm concentration and immotile sperm with multiple morphological abnormalities. Routine sperm analyses unambiguously identify homozygous bulls for this allele. A direct gene test can be implemented to monitor the frequency of the undesired allele in cattle populations.
Review: Genetic mutations affecting bull fertility
Pausch, Hubert; Mapel, Xena Marie (2023)
Animal
Cattle are a well-suited “model organism” to study the genetic underpinnings of variation in male reproductive performance. The adoption of artificial insemination and genomic prediction in many cattle breeds provide access to microarray-derived genotypes and repeated measurements for semen quality and insemination success in several thousand bulls. Similar-sized mapping cohorts with phenotypes for male fertility are not available for most other species precluding powerful association testing. The repeated measurements of the artificial insemination bulls’ semen quality enable the differentiation between transient and biologically relevant trait fluctuations, and thus, are an ideal source of phenotypes for variance components estimation and genome-wide association testing. Genome-wide case-control association testing involving bulls with either aberrant sperm quality or low insemination success revealed several causal recessive loss-of-function alleles underpinning monogenic reproductive disorders. These variants are routinely monitored with customised genotyping arrays in the male selection candidates to avoid the use of subfertile or infertile bulls for artificial insemination and natural service. Genome-wide association studies with quantitative measurements of semen quality and insemination success revealed quantitative trait loci for male fertility, but the underlying causal variants remain largely unknown. Moreover, these loci explain only a small part of the heritability of male fertility. Integrating genome-wide association studies with gene expression and other omics data from male reproductive tissues is required for the fine-mapping of candidate causal variants underlying variation in male reproductive performance in cattle.
Complex histories of gene flow and a mitochondrial capture event in a nonsister pair of birds
Andersen, Michael J.; McCullough, Jenna M.; Gyllenhaal, Ethan F.; et al. (2021)
Molecular Ecology
Hybridization, introgression, and reciprocal gene flow during speciation, specifically the generation of mitonuclear discordance, are increasingly observed as parts of the speciation process. Genomic approaches provide insight into where, when, and how adaptation operates during and after speciation and can measure historical and modern introgression. Whether adaptive or neutral in origin, hybridization can cause mitonuclear discordance by placing the mitochondrial genome of one species (or population) in the nuclear background of another species. The latter, introgressed species may eventually have its own mtDNA replaced or “captured” by other species across its entire geographical range. Intermediate stages in the capture process should be observable. Two nonsister species of Australasian monarch-flycatchers, Spectacled Monarch (Symposiachrus trivirgatus) mostly of Australia and Indonesia and Spot-winged Monarch (S. guttula) of New Guinea, present an opportunity to observe this process. We analysed thousands of single nucleotide polymorphisms (SNPs) derived from ultraconserved elements of all subspecies of both species. Mitochondrial DNA sequences of Australian populations of S. trivirgatus form two paraphyletic clades, one being sister to and presumably introgressed by S. guttula despite little nuclear signal of introgression. Population genetic analyses (e.g., tests for modern and historical gene flow and selection) support at least one historical gene flow event between S. guttula and Australian S. trivirgatus. We also uncovered introgression from the Maluku Islands subspecies of S. trivirgatus into an island population of S. guttula, resulting in apparent nuclear paraphyly. We find that neutral demographic processes, not adaptive introgression, are the most likely cause of these complex population histories. We suggest that a Pleistocene extinction of S. guttula from mainland Australia resulted from range expansion by S. trivirgatus.
Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle
Mapel, Xena Marie; Kadri, Naveen Kumar; Leonard, Alexander; et al. (2024)
Nature Communications
Breeding bulls are well suited to investigate inherited variation in male fertility because they are genotyped and their reproductive success is monitored through semen analyses and thousands of artificial inseminations. However, functional data from relevant tissues are lacking in cattle, which prevents fine-mapping fertility-associated genomic regions. Here, we characterize gene expression and splicing variation in testis, epididymis, and vas deferens transcriptomes of 118 mature bulls and conduct association tests between 414,667 molecular phenotypes and 21,501,032 genome-wide variants to identify 41,156 regulatory loci. We show broad consensus in tissue-specific and tissue-enriched gene expression between the three bovine tissues and their human and murine counterparts. Expression- and splicing-mediating variants are more than three times as frequent in testis than epididymis and vas deferens, highlighting the transcriptional complexity of testis. Finally, we identify genes (WDR19, SPATA16, KCTD19, ZDHHC1) and molecular phenotypes that are associated with quantitative variation in male fertility through transcriptome-wide association and colocalization analyses.

Publications 1 - 10 of 17

Xena Marie Mapel

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