Biology subjects

Brekke, C.

Publications and source records attributed to Brekke, C..

6 recordsLinked to original sources

bioRxiv2026

PRDM9 Alleles Guide Distinct Patterns of Recombination Localization in Atlantic Salmon

Meiotic recombination in many vertebrate lineages is directed to genomic regions by the DNA-binding protein PRDM9. To date, PRDM9 research has focused primarily on mammals, and its role in recombination localization has only recently been established in salmonids. PRDM9 binding specificity is determined by a tandemly repeated zinc-finger array that exhibits extensive allelic diversity within and between species. However, the extent to which PRDM9 variation shapes recombination landscapes in salmonids remains poorly understood. Here, we performed large-scale genotyping of PRDM9 in an aquaculture population of Atlantic salmon (Salmo salar) using long-read sequencing. By integrating PRDM9 genotypes with pedigree information and genome-wide recombination data, we generated PRDM9-specific linkage maps and sets of inferred crossover events. We show that the presence of specific PRDM9 alleles is associated with differences in recombination localization and identify patterns consistent with dominance interactions between alleles. Using population-averaged recombination rate estimates, we further link a previously described sequence motif enriched in European recombination hotspots to the presence of a common PRDM9 zinc-finger array allele (RPT6a). Together, our results demonstrate functional differences between PRDM9 alleles which contribute to divergence in recombination landscapes in Atlantic salmon, paralleling patterns observed in mammals. The broad geographic distribution of Atlantic salmon, combined with extensive pedigree data generated through aquaculture, highlights its potential as a powerful model for studying PRDM9 function and evolution beyond mammals.

genetics↗

bioRxiv2026

Imputed graph-genotyped structural variants identify regulatory haplotypes associated with gene expression in Atlantic salmon

Structural variants (SVs) can affect gene regulation, but they are difficult to include in expression genetic studies when large RNA-seq cohorts lack whole-genome sequencing. This is common in non-human and non-model systems, where whole-genome sequencing at population scale remains costly. As a result, expression quantitative trait locus (eQTL) studies often rely on single nucleotide polymorphism (SNP) markers. These analyses can identify expression-associated regions, but often provide limited biological interpretation of the underlying regulatory mechanisms. Here, we used Atlantic salmon as a study system to test whether graph-genotyped SVs can be imputed into a SNP-array-genotyped RNA-seq cohort and used to interpret regulatory haplotypes. SVs were discovered from two long-read-sequenced individuals, supplemented with short-read SV and SNP calls from a 112-individual whole-genome-sequenced reference panel, graph-genotyped, jointly phased with SNPs, and imputed into 906 offspring with gill RNA-seq and SNP-array genotypes. After size filtering, the imputed SV catalogue contained 100,269 variants and showed nonuniform genomic distributions associated with sex-specific recombination landscapes. Association testing identified 51 SV-eQTL candidates, including 35 cis and 16 trans associations. These candidates were enriched for short-read-derived variants, indicating that short-read supplementation can recover regulatory variants missed by small-scale long-read discovery. SV-eQTL candidates were more strongly tagged by nearby SNPs than non-associated variants generally, but individual SNP lead markers often failed to capture the same eQTL signals in conditional regression. Retained candidates after the conditional analysis included target-gene-overlapping deletions, nearby local variants without target-gene overlap, trans associations, and short insertions with opposite effects on gene expression. These results show that imputed graph-genotyped SVs can add biological interpretation to possible regulatory haplotypes.

genomics↗

bioRxiv2025

A major locus on chromosome 14 impacts developmental variation of Atlantic salmon smoltification

BackgroundSmoltification in anadromous Atlantic salmon is a complex developmental process involving physiological and cellular changes that enable freshwater fish to adapt to seawater. Central to this transformation is the functional transformation of the gill to manage osmoregulatory demands. While environmental cues like photoperiod are known to influence smolt development, the genetic architecture underlying smolt development -- particularly related to gill physiology -- remains poorly understood. ResultsA large-scale eQTL analysis across 3,000 Atlantic salmon subjected to three photoperiod regimes, identified over 45,000 significant SNP-gene expression associations in gill tissue. Notably, we discovered a 0.5 Mbp large trans-eQTL hotspot on chromosome 14. This hub-locus was associated with expression of more than 2,000 genes across the genome which were significantly enriched for gill cell type specific markers. In addition we found that the hub-locus was associated with somatic growth. Our findings support a "local tissue effect" model, where cis-regulatory or protein sequence variants within the hub-locus modulate cell proliferation and differentiation of gill cell types. ConclusionThis work advances our understanding of the genetic basis of smoltification in Atlantic salmon and provides a foundation for future studies using single-cell approaches to resolve cell-type specific mechanisms underlying genetic variation in smolt development.

genetics↗

bioRxiv2025

Phenotypic sex determines recombination rate and distribution in sex-reversed Rainbow Trout Oncorhynchus mykiss

During meiotic cell division, homologous chromosomes align and exchange large segments of DNA through crossover recombination. Rates of recombination often show distinct differences between males and females, a phenomenon known as heterochiasmy. Despite decades of research documenting the presence of heterochiasmy across eukaryotes, the specific feature of sex leading to this curious sexual dimorphism remains to be explained. Some species, such as salmonids, also display extensive differences between the sexes in crossover positioning. A critical part of solving this puzzle is to establish whether heterochiasmy is driven by genetic sex or if it is a result of the physiological differences between producing sperm and eggs. In this study, we show that phenotypic sex determines recombination rate and distribution in hormonally sex-reversed rainbow trout. With pedigree and genotype information from 18 452 individuals and 33 913 SNP markers we map crossover events in families where the fathers were hatched as genetic XX females and sex-reversed as young trout fry with a masculinising hormone 17-methyltestosterone and compare the crossover patterns to those in families with normal XY male fathers. We find that recombination patterns in XX males resemble those of normal XY males with crossovers exclusively in sub-telomeric regions. Crossover count per gamete was 25.8{+/-}4.4 in XX females vs 19.5{+/-}3.9 and 19.9{+/-}4.0 in XY males and XX males, respectively. These results support the hypothesis that heterochiasmy arises from physiological differences between oogenesis and spermatogenesis rather than effects related to genetic sex and will aid in guiding the research on heterochiasmy going forward.

genetics↗

bioRxiv2024

Individual variation in meiotic crossover positioning, rate and interference are driven by distinct genetic processes in domestic pigs.

Meiotic crossovers are essential for proper chromosome segregation, and provide an important mechanism for adaptation through linking beneficial alleles and purging deleterious mutations. However, crossovers can also break apart beneficial alleles and are themselves a source of new mutations within the genome. The rate and distribution of crossovers shows huge variation both within and between chromosomes, individuals and species, yet the molecular and evolutionary causes and consequences of this variation remain poorly understood. A key step in understanding this variation is to understand the genetic architecture of how many crossovers occur, where they occur, and how they interfere, as this allows us to identify the degree to which these factors are governed by common or distinct genetic processes. Here, we investigate individual variation in crossover count, crossover interference ({nu}), and crossover positioning measured as both intra-chromosomal allelic shuffling and distance to telomere (Mb), in a large genotyped breeding population of domestic pigs. Using measures from 82,474 gametes from 4,704 mothers and 271 fathers, we show that crossover traits are heritable within each sex (h2 = 0.03 - 0.11), with the exception of male crossover interference. Crossover count and interference have a strongly shared genetic architecture in females, mostly driven by variants at RNF212. Female crossover positioning is mediated by variants at MEI4, PRDM9, and SYCP2. We also identify tentative associations at genomic regions corresponding to CTCF and REC114/REC8/CCNB1IP1 (crossover count), and ZCWPW1 and ZCWPW2 (crossover positioning). Our results show that crossover count and crossover positioning in female pigs have the capacity to evolve somewhat independently in our dataset.

genomics↗

bioRxiv2023

Genetic architecture of individual meiotic crossover rate and distribution in a large Atlantic Salmon (Salmo salar) breeding population.

Meiotic recombination through chromosomal crossovers ensures proper segregation of homologous chromosomes in meiosis, while also breaking down linkage disequilibrium and shuffling alleles at loci located on the same chromosome. Rates of recombination can vary between species, but also between and within individuals, sex and chromosomes within species. Indeed, the Atlantic salmon genome is known to have clear sex differences in recombination with female biased heterochiasmy and markedly different landscapes of crossovers between males and females. In male meiosis, crossovers occur strictly in the telomeric regions, whereas in female meiosis crossovers tend to occur closer to the centromeres. However, little is known about the genetic control of these patterns and how this differs at the individual level. Here, we investigate genetic variation in individual measures of recombination in >5000 large full-sib families of a Norwegian Atlantic salmon breeding population with high-density SNP genotypes. We show that females had 1.6x higher crossover counts (CC) than males, with autosomal linkage maps spanning a total of 2174 cM in females and 1483 cM in males. However, because of the extreme telomeric bias of male crossovers, female recombination is much more important for generation of new haplotypes with 8x higher intra-chromosomal genetic shuffling than males. CC was heritable in females (h2 = 0.11) and males (h2 = 0.10), and shuffling was also heritable in both sex but with a lower heritability in females (h2 = 0.06) than in males (h2 = 0.11). Inter-sex genetic correlations for both traits were close to zero, suggesting that rates and distribution of crossovers are genetically distinct traits in males and females, and that there is a potential for independent genetic change in both sexes in the Atlantic Salmon. Together, these findings give novel insights into the genetic architecture of recombination in salmonids and contribute to a better understanding of how rates and distribution of recombination may evolve in eukaryotes more broadly.

genetics↗