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PubMed2026

Integrative haplotype and SNP-based GWAS supports the identification of stable genomic loci controlling yield-related traits in soybean.

Soybean yield is vulnerable to environmental variation, therefore, it is important to detect and implement stable genomic regions associated with yield-related traits in soybean breeding programs. In this study, SNP and haplotype-based GWAS were conducted to reveal important candidate genomic regions and putative candidate genes associated with soybean yield-related traits. This study demonstrates that the integration of haplotype and SNP-based GWAS could improve the detection of genomic regions associated with complex traits, enhance statistical power, and facilitate the identification of biologically relevant candidate genes. Ten stable haplotype blocks and six stable SNPs were detected based on the integration of haplotype and SNP-based GWAS, respectively. Furthermore, multiple candidate genes associated with the yield-related traits were identified. For instance, six genes were identified as transporters, including Glyma.15G092800, encoding serine-type endopeptidase activity, Glyma.15G203300 encoding a major facilitator superfamily (MFS) sugar transporter, Glyma.04G163000, transmembrane transporter, and Glyma.04G164100, leucine-rich repeat receptor-like protein kinase (LRR-RLK), as the most promising candidate genes. Additionally, three genes involved in signaling and pathways of various phytohormones can be promising candidates for increasing seed yield through improving plant architecture in soybean plants. The identified superior haplotypes with favourable alleles will be useful for marker-assisted selection in future breeding programs in soybean.

DArT markers↗

PubMed2026

Haplotype-resolved 3D genome maps reveal RNAPII-mediated allelic regulation in hybrid rice.

To understand how the two parental genomes coordinate transcription in hybrids, chromatin architecture must be resolved at the haplotype level. Here, using phased Bridge-Linker Hi-C, we reconstructed a haplotype-resolved three-dimensional (3D) genome of the elite hybrid rice (Oryza sativa) line Shanyou 63 (SY63). We identified extensive allele-specific chromatin conformations. Furthermore, we generated allele-resolved RNAPII ChIA-PET maps and phased transcriptomes to explore how chromatin interactions contribute to allelic regulation. Although maternal and paternal homologs share broadly similar chromatin features, we detected widespread haplotype-biased RNAPII binding and chromatin looping at high resolution. These allele-specific RNAPII-mediated contacts were significantly associated with biased expression. Stronger RNAPII binding on one haplotype promoted the formation of long-range regulatory loops with distal genes, thereby contributing to allele-biased transcription at a subset of loci, even when promoter-proximal RNAPII occupancy was comparable between alleles. These results demonstrate that subtle differences in RNAPII engagement and 3D regulatory wiring between parental haplotypes can reshape transcriptional output in hybrids, providing new insights into the mechanisms underlying the allelic regulation of gene expression.

Allele-specific chromatin interactions↗

PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with systemic lupus erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within IRF7. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA-binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in interferon-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of the corresponding risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits.

ancient DNA↗

PubMed2026

Dissecting contributions of directional and balancing selection to trajectories of mitochondrial haplotype evolution in Drosophila melanogaster.

Emerging evidence suggests mtDNA haplotypes contribute to fitness variation and local adaptation, with directional thermal selection and negative frequency-dependent selection shaping haplotype diversity. However, their interplay remains unexplored. We conducted experimental evolution using Drosophila melanogaster populations from opposite ends of an Australian latitudinal cline (Melbourne and Townsville), exposing them to contrasting temperatures (17°C versus 27°C) and varying starting frequencies of two mtDNA haplotypes (A1 and B1) that occur at appreciable frequencies in these populations. We paired this with population genetic simulations to estimate selection and its influence on haplotype trajectories. Haplotype frequencies were influenced by interactions involving temperature, starting frequency, and nuclear genomic background (Melbourne, Townsville, or admixed). Although prior work predicted A1 should be favoured at the warmer temperature and B1 at the cooler temperature, A1 was generally favoured across both temperatures. Simulations supported directional selection in populations evolving at 17°C in the Melbourne background; otherwise dynamics were best explained by balancing selection shaped by negative frequency-dependent fitness effects. Patterns also varied across nuclear backgrounds, suggestive of mito-nuclear epistasis. These findings challenge a simple thermal adaptation model of mtDNA dynamics, suggesting that mtDNA evolution is shaped by interacting effects of temperature, frequency-dependence, nuclear background and experimental environment.

adaptation↗

PubMed1978

A haplotype study of HLA complex with special reference to the HLA-DR series and to Bf. C2 and glyoxalase I polymorphisms.

Fifty-three French families were typed for alleles at seven loci of the HLA complex (HLA-A, -B, -C, -DR, -Bf, -C2 and -GLO) and 212 haplotypes were demonstrated. Eleven recombinations were observed (two A/B, two A/C, two B/Bf, one Bf/D and four D/GLO). The linkage disequilibrium was calculated not only between two alleles (delta) but between three, four...seven alleles (D). In order to compare the intensity of D values in the various haplotypes, the influence of the differences in gene frequencies was eliminated by the introduction of the standardized Ds (Ds = D/D max). The number of haplotypes in disequilibrium is relatively limited since most of the significant Ds involved about 17 haplotypes. For some haplotypes, the disequilibrium covered the whole distance from A to GLO but the stronger disequilibrium concerns the C to Bf or C to DR segment. Three hypotheses (isolation, admixture of population and selection) concerning the formation and maintenance of the disequilibria are discussed.

Epitopes↗

PubMed2026

Haplotype Blocks Are Associated With Rapid Local Adaptation to Environmental Shifts in Wild Barley.

Genomic mechanisms of local adaptation must be highly responsive in geographic regions where climate is changing rapidly. The Levant region is a critical biodiversity hotspot and the distribution edge for many species, including the wild ancestor of domesticated barley. This region is under an accelerated desertification process, thus enforcing a rapid genomic response to the projected environmental changes. To elucidate the genomic basis of rapid local adaptation, we studied wild barley populations using an ecological-genetic sampling design that decouples environmental variation from demographic background. We collected and sequenced 300 wild barley individuals and evaluated the phenotypes of 3600 progeny plants over 3 years. Our genomic analyses revealed that local adaptation is associated with clusters of candidate genes forming haplotype blocks. These clusters are enriched with environment and stress responsive genes, including flowering time regulators, drought and heat responsive genes. We identified six candidate adaptive haplotype blocks which span 1-8 Mbp and are distributed across chromosomes 1H, 2H, 4H and 5H, each segregating as two major haplotypes. Additionally, we integrated over 2600 occurrence records into ecological and evolutionary modelling to assess the genomic vulnerability of populations to projected future climates. Our study identifies candidate genomic regions and environmental drivers of local adaptation in wild barley and highlights the advantage of haplotype blocks architecture in orchestrating an efficient response to rapid environmental change. We highlight the ecological factors most strongly associated with the observed evolutionary responses and provide insights and guidelines for biodiversity conservation and implementation of crop wild relatives in breeding.

Hordeum↗

PubMed2026

Haplotype-specific expression of a terpene synthase underlies linalool variation in the grapevine cultivar Riesling.

Grapevine cultivars vary widely in monoterpenoid content, yet the genetic and regulatory mechanisms underlying this variation remain poorly characterized beyond highly aromatic Muscat types. We profiled free volatiles and monoterpenoid glycosides in a Riesling × Cabernet Sauvignon F1 mapping population, revealing extensive variation and transgressive segregation consistent with multigenic control. QTL mapping identified 70 significant loci associated with 48 volatile compounds and monoterpene glycosides, including two major QTLs explaining 33.6% and 33.4% of phenotypic variance in (3S)-linalool accumulation. Integration of haplotype-resolved transcriptomics with metabolite data, enabled by a chromosome-scale diploid Riesling genome assembly, resolved a (3S)-linalool/nerolidol synthase cluster on chromosome 10 and identified VviTPS54 as the strongest candidate underlying linalool variation. VviTPS54 exhibited haplotype-specific expression strongly correlated with (3S)-linalool accumulation across genotypes, while no QTL was detected at the 1-deoxy-D-xylulose-5-phosphate synthase 1 (VviDXS1) locus previously identified in Muscat cultivars. In addition, VviDXS1 expression was not correlated with terpene levels, indicating that regulatory variation within terpene synthase clusters, rather than methylerythritol phosphate (MEP) pathway flux, drives monoterpenoid composition in this population. These results establish regulatory variation of terpene synthases as a key mechanism underlying monoterpenoid diversity in grapevine and demonstrate that resolving such variation requires haplotype-phased genome assemblies coupled with haplotype-resolved transcriptomics to detect allele-specific expression differences at complex, heterozygous loci.

Grapevine↗

PubMed1977

Bf types of HLA haplotyped individuals in an isolated Newfoundland population.

Five hundred and fourteen individuals from an isolated NewFoundland population have been typed and haplotyped for HLA and Factor B (Bf locus). The Bf gene frequencies were: S0.704, F0.226, F1 0.052 and S1 0.018. Tracing the haplotypes backwards on the various pedigrees it was shown that 202 HLA/Bf haplotypes had been introduced into the study population. Some HLA alleles always appeared in association with particular Bf alleles and vice versa. Bf S1 had entered the population four times, always with HLA--A9, B12. Bf F1 had entered three times, always with HLA--B18. There were 17 entries of HLA--Al, B8 that had given rise to the 78 such haplotypes that were now present in the population; all were Bf S. There were 68 family units informative for Bf. They accounted for 240 children and 304 informative meioses. There were three recombinants in the HLA region but none could be shown to have occurred between the HLA-B and Bf loci.

Adult↗

PubMed1978

Serological studies of Cw1 and Cw3 expressed on the same haplotype.

A serological comparison has been made between individuals who are phenotypically Cw1 and Cw3. The first individual is Oriental and carries Cw1 and Cw3 on the same haplotype, the other individuals are Caucasian and carry either Cw1, Cw3 or Cw1 and Cw3 on different haplotypes. No unique specificities could be found on the Oriental Cw1, Cw3 haplotype by reciprocal absorption experiments, inhibition of complement dependent microcytotoxicity by F(ab') 2 fragments prepared from Cw1 and Cw3 antisera or by lysostrip experiments. The blocking and lysostrip experiments also suggested molecular independence of Cw1 and Cw3 determinants coded for by Oriental Cw1 haplotype. The results suggest a recent gene duplication in Oriental populations or two loci in the C region.

Cytotoxicity, Immunologic↗

PubMed1979

HLA haplotype associations with disease.

Interest recently has extended to the problem of looking for HLA haplotype associations with particular diseases. Higher order interactions, that is to say of particular haplotypes with a disease, are much more complicated than individual antigen associations, with which most disease studies have so far been concerned. Our aim in this work is to explain the concept of higher order interactions and to discuss the difficulties involved when trying to measure such haplotype associations. The main emphasis is to point out that it is not easily possible to detect haplotype associations if an individual antigen association with the disease exists.

Alleles↗

PubMed1977

Population and family studies to demonstrate Ir genes: HLA haplotype in atopic allergy.

47 normal healthy controls and 45 atopic individuals together with five families with allergic diathesis and sensitive to mite antigen were typed for 13 HLA antigens. In general population, HLA-A1 and HLA-A8 were found to be higher than in normal controls. But the difference was significant at a level of p 0.05 after correction was made for the number of HLA antigens used. In one family, an HLA-A1 -B8 haplotype seems to be linked to the manifestation of atopic disease. The pattern of association of an HLA-A9 -B7 haplotype with the disease process in another family indicates that multiple genes may be involved in the manifestation of a variety of allergic disorders. Although more than one HLA haplotype of HLA-associated Ir gene for one antigen have been postulated, we still do not have enough evidence to suggest linkage between HLA haplotypes and atopic allergy. Further studies utilizing mixed lymphocyte culture and carefully matched control with a large number of subjects and more families are in progress to study the genetic basis of allergic diseases.

Asthma↗

PubMed2026

Haplotype-resolved reconstruction and functional interrogation of cancer karyotypes.

Complex karyotype changes are widespread in cancer genomes. A major gap in cancer genome characterization is the resolution of rearranged chromosomes with chromosome-length continuity. Here, we describe a two-tiered approach to determine the segmental composition of rearranged chromosomes with haplotype resolution. First, we present refLinker, a bioinformatic method for robust determination of chromosomal haplotypes using cancer Hi-C data. By contrast with existing methods, refLinker is insensitive to the presence of large-scale DNA deletions, duplications, and high-level amplification in cancer genomes. Second, we demonstrate a computational strategy to determine the segmental structure of rearranged chromosomes using haplotype-specific Hi-C contacts. We apply these methods to breast cancer genomes and provide direct evidence for long-range transcriptional changes associated with rearrangements of the inactive X chromosome. Together, these results highlight refLinker's broad utility for studying the functional consequences of chromosomal rearrangements.

Humans↗

PubMed2026

Multiple local PfDHFR I164L haplotype expansions drive Plasmodium falciparum antifolate resistance in Uganda.

Mutations in the Plasmodium falciparum genes, pfdhfr and pfdhps, drive antifolate resistance and threaten malaria control in regions where sulfadoxine-pyrimethamine (SP) is the primary chemoprevention strategy. The spatial patterns and evolutionary dynamics of these mutations in high-transmission settings remain incompletely understood. Here we genotyped 11 resistance-associated mutations in pfdhfr and pfdhps in 4,725 P. falciparum isolates collected from 16 Ugandan health facilities as part of annual surveillance between 2016 and 2022. Notably, we show that the frequency of PfDHFR I164L, which confers higher pyrimethamine resistance, increased over time from 19.4% to 32.4%. Using identity-by-descent, haplotype structure, and extended haplotype homozygosity analyses, we show that PfDHFR I164L is present on multiple haplotype backgrounds and undergoes localised expansions, without detectable signatures of recent positive selection at all but one site. Our results suggest that the evolution of antifolate resistance, driven by PfDHFR I164L, is spatially heterogeneous and complex in regions that primarily use SP chemoprevention programmes.

Plasmodium falciparum↗

PubMed2025

Chromosome-level haplotype-resolved genome assembly of the giant honeycomb oyster, Hyotissa hyotis.

The giant honeycomb oyster, Hyotissa hyotis, a common bivalve inhabitant of tropical and subtropical coastal waters, holds significant ecological and economic importance due to its shell characteristics, rapid growth, and high-quality adductor muscle. However, the lack of high-quality genome has impeded the genetic study and artificial breeding of this species. In this study, we provided the first chromosomal-level haplotype-resolved assembly for the H. hyotis (2n = 20) by combining PacBio HiFi long-read and Hi-C sequencing. We obtained a haplotype-resolved assembly of 3.39 Gb in size, of which 96.69% were anchored to 20 chromosomes. The haplotype A and B genome (HapA and HapB) was 1,639.90 and 1,643.23 Mb in size, respectively. Accordingly, a total of 28,720 and 29,003 protein-coding genes were annotated from HapA and HapB. Through the BUSCO evaluation, the assembly and annotation results exhibited the completeness value of 94.65% and 94.03% for HapA, while 94.13% and 92.98% for HapB. This high-quality genome assembly provides valuable resource for further genetic studies and genetic improvement of the group of oysters.

Animals↗

PubMed2026

De novo haplotype-resolved genome assembly of the endemic kiwifruit Actinidia hubeiensis.

The genus Actinidia, which encompasses the widely cultivated kiwifruit, is characterized by its rich species diversity. Wild Actinidia species serve as invaluable germplasm reservoirs for crop improvement. As an important kiwifruit species, Actinidia hubeiensis represents a unique taxonomic group endemic to Hubei Province, contributing valuable genetic diversity to the genus Actinidia. Here, we present a haplotype-resolved genome assembly for A. hubeiensis. The two haplotype assemblies (Hap1 and Hap2) spanned 658.03 Mb (N50 = 23.16 Mb) and 597.19 Mb (N50 = 20.89 Mb), encoding 35,741 and 36,647 high-confidence protein-coding genes, respectively. Based on comprehensive assessments, both haplotypes demonstrated high completeness (BUSCO completeness > 99%), excellent continuity (LAI up to 21.67), low base-error rates (QV > 40), and nearly complete read mapping rates (> 98%). This genome assembly provides crucial genomic resources for the genus, enriching our understanding of kiwifruit biodiversity and offering new insights into the genetic background and evolutionary characteristics of this distinctive species.

Actinidia↗

PubMed2025

Enhancing the sensitivity of non-invasive cervical cancer detection using CpG methylation haplotype profiling.

DNA methylation is a critical epigenetic modification that regulates gene expression and plays a significant role in cancer development. This methylation signature can be detected in cancer-derived DNA from non-invasive samples, such as plasma, urine or Pap smears. However, in early-stage cancers-when detection is most critical-the concentration of cancer DNA is often low, limiting the sensitivity of current detection methods. Traditional DNA methylation detection techniques, which rely on methylation ratio-based measurements, may obscure subtle variations in methylation patterns, further reducing detection sensitivity. In this study, we analyzed cervical scraping specimens and examined whether detecting cancer-specific methylation patterns in cervical cancer could be enhanced using a Highly Methylated Haplotype (HMH) approach. This novel approach captures highly methylated haplotypes at single-molecule resolution using next-generation sequencing, providing greater detail than conventional methods. HMHs in specific DNA regions are a hallmark of cancer and stand out in contrast to sporadic methylation commonly observed in non-cancerous tissues. We applied HMH profiling to a gene panel of four biomarkers (CA10, DPP10, FMN2, and HAS1) previously validated in cervical cancer studies. At pre-specified cutoffs (99th percentile of normals), haplotype-based scoring achieved 89.9% sensitivity for invasive cancer at high specificity (~ 94-98%), outperforming median (78.0%) and single-CpG (71.6%) methods. For clinically relevant endpoints, the combined panel detected 51-52% of CIN2 + and 66-67% of CIN3 + cases, again exceeding the performance of median- and single-CpG-based scoring methods.These findings demonstrate the potential of HMH to substantially enhance sensitivity in cervical cancer detection, offering a promising approach for non-invasive diagnostics.

Humans↗

PubMed2026

A chromosome-level, haplotype-resolved genome assembly for the barn owl, Tyto alba.

Recent advances in long-read sequencing have enabled near telomere-to-telomere (T2T) assemblies across diverse taxa. However, avian genomes remain challenging due to numerous microchromosomes, small, typically < 20Mb, DNA molecules that are gene-, GC-, and repeat-rich. As a consequence, microchromosomes are often missing from genome assemblies. Here, we present a chromosome-level, haplotype-resolved genome assembly for the Western barn owl (Tyto alba). Using a trio-binning strategy with Illumina parental reads combined with PacBio HiFi and Oxford Nanopore Technologies data, we generated two phased contig sets. These were scaffolded into 40 linkage groups using a linkage map. Comparative analyses identified unplaced HiFi scaffolds corresponding to microchromosomes, which we integrated into six additional microchromosomes using long reads information. The two assemblies present 46 chromosomes, matching the karyotype of the species. They exhibit strong synteny between parental haplotypes, except for a ∼38 Mb complex region on chromosome 7 containing nested inversions. This high-quality reference provides a haplotype-resolved and chromosome-level genome for Strigiformes, enabling fine-scale studies of structural variation and avian genome evolution.

Tyto alba↗

PubMed2026

Haplotype-resolved genome of Forsythia suspensa reveals the reticulate evolution in Oleaceae and a novel gene cluster regulating stamen development.

The olive family (Oleaceae) comprises numerous species of economic, horticultural, and medicinal importance. Despite its significance, the evolutionary history of this complex family remains enigmatic. Here, we generated a high-quality haplotype-resolved genome of Forsythia suspensa, a distylous species that occupies a key phylogenetic position in Oleaceae. The 2 haplotypes exhibit significant allelic divergence with potential allele-specific regulation. We reconstructed the polyploidization history of Oleaceae by confirming and precisely dating a shared whole-genome triplication and an independent whole-genome duplication event. We revealed a complex reticulate evolution that gave rise to the tribe Oleeae: an initial hybridization between Forsythieae (♂) and Jasmineae (♀), a subsequent backcrossing event, and a final whole-genome duplication. We identified a novel tandemly duplicated pectin methylesterase inhibitor gene cluster that regulates filament length and pollen size via restricting cell elongation in the long-styled morph. Dosage augmentation via stepwise cluster formation (0.99 to 3.83 Mya) may contribute to maintaining stamen traits of the long-styled morph. These FsPMEIs are co-expressed with many cell wall-related genes, suggesting a functional link in cell wall modification. Our study reveals the reticulate evolution in Oleaceae and a novel gene cluster controlling stamen development in F. suspensa and provides valuable haplotype-resolved genomic resources for heterostylous species, offering novel framework and molecular pathways to understand plant adaptive evolution.

Forsythia↗