Differential methylation patterns in paternally imprinted gene promoter regions in sperm from hepatitis B virus infected individuals.

BACKGROUND: Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underlying mechanisms driving this phenomenon remain elusive. This study aims to shed light on this issue by examining alterations in paternally imprinted genes within sperm. METHODS: A cohort of 35 individuals with normal semen analysis, comprising 17 hepatitis B surface antigen (HBsAg)-positive and 18 negative individuals, was recruited. Based on the previous research and the Online Mendelian Inheritance in Man database (OMIM, https://www.omim.org/ ), targeted promoter methylation sequencing was employed to investigate 28 paternally imprinted genes associated with various diseases. RESULTS: Bioinformatic analyses revealed 42 differentially methylated sites across 29 CpG islands within 19 genes and four differentially methylated CpG islands within four genes. At the gene level, an increase in methylation of DNMT1 and a decrease in methylation of CUL7, PRKAG2, and TP53 were observed. DNA methylation haplotype analysis identified 51 differentially methylated haplotypes within 36 CpG islands across 22 genes. CONCLUSIONS: This is the first study to explore the effects of HBV infection on sperm DNA methylation and the potential underlying mechanisms of intergenerational influence of paternal HBV infection.

Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep.

Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing ∼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated ß-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites.

Challenges in classifying recurrent Plasmodium vivax infections constrain surveillance of antimalarial efficacy and transmission. Recurrent infections may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or reinfection. Molecular inference of familial relatedness (identity-by-descent or IBD) can help resolve the probable origin of recurrences. As whole genome sequencing of P. vivax remains challenging, targeted genotyping methods are needed for scalability. We describe a P. vivax marker discovery framework to identify and select panels of microhaplotypes (multi-allelic markers within small, amplifiable segments of the genome) that can accurately capture IBD. We evaluate panels of 50-250 microhaplotypes discovered in a global set of 615 P. vivax genomes. A candidate global 100-microhaplotype panel exhibits high marker diversity in the Asia-Pacific, Latin America and horn of Africa (median HE = 0.70-0.81) and identifies 89% of the polyclonal infections detected with genome-wide datasets. Data simulations reveal lower error in estimating pairwise IBD using microhaplotypes relative to traditional biallelic SNP barcodes. The candidate global panel also exhibits high accuracy in predicting geographic origin and captures local infection outbreak and bottlenecking events. Our framework is open-source enabling customised microhaplotype discovery and selection, with potential for porting to other species or data resources.

Orthanq: transparent and uncertainty-aware haplotype quantification with application in HLA-typing.

BACKGROUND: Identification of human leukocyte antigen (HLA) types from DNA-sequenced human samples is important in organ transplantation and cancer immunotherapy and remains a challenging task considering sequence homology and extreme polymorphism of HLA genes. RESULTS: We present Orthanq, a novel statistical model and corresponding application for transparent and uncertainty-aware quantification of haplotypes. We utilize our approach to perform HLA typing while, for the first time, reporting uncertainty of predictions and transparently observing mutations beyond reported HLA types. Using 99 gold standard samples from 1000 Genomes, Illumina Platinum Genomes and Genome In a Bottle projects, we show that Orthanq can provide overall superior accuracy and shorter runtimes than state-of-the-art HLA typers. CONCLUSIONS: Orthanq is the first approach that allows to directly utilize existing pangenome alignments and type all HLA loci. Moreover, it can be generalized for usages beyond HLA typing, e.g. for virus lineage quantification. Orthanq is available under https://orthanq.github.io .

Local read haplotagging enables accurate long-read small variant calling.

Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy. However, using local haplotype information creates an overhead as variant calling needs to be performed multiple times which ultimately makes it difficult to extend to new data types and platforms as they get introduced. In this work, we have developed a local haplotype approximate method that enables state-of-the-art variant calling performance with multiple sequencing platforms including PacBio Revio system, ONT R10.4 simplex and duplex data. This addition of local haplotype approximation simplifies long-read variant calling with DeepVariant.

The first complete genome of the extinct European wild ass (Equus hemionus hydruntinus).

We present palaeogenomes of three morphologically unidentified Anatolian equids dating to the first millennium BCE, sequenced to a coverage of 0.6-6.4×. Mitochondrial DNA haplotypes of the Anatolian individuals clustered with those of Equus hydruntinus (or Equus hemionus hydruntinus), the extinct European wild ass, secular name 'hydruntine'. Further, the Anatolian wild ass whole genome profiles fell outside the genomic diversity of other extant and past Asiatic wild ass (E. hemionus) lineages. These observations suggest that the three Anatolian wild asses represent hydruntines, making them the latest recorded survivors of this lineage, about a millennium later than the latest observations in the zooarchaeological record. Our mitogenomic and genomic analyses indicate that E. h. hydruntinus was a clade belonging to ancient and present-day E. hemionus lineages that radiated possibly between 0.6 and 0.8 Mya. We also find evidence consistent with recent gene flow between hydruntines and Middle Eastern wild asses. Analyses of genome-wide heterozygosity and runs of homozygosity suggest that the Anatolian wild ass population may have lost genetic diversity by the mid-first millennium BCE, a possible sign of its eventual demise.

Rare variations within the serine/arginine-rich splicing factor PtoRSZ21 modulate stomatal size to determine drought tolerance in Populus.

Rare variants contribute significantly to the 'missing heritability' of quantitative traits. The genome-wide characteristics of rare variants and their roles in environmental adaptation of woody plants remain unexplored. Utilizing genome-wide rare variant association study (RVAS), expression quantitative trait loci (eQTL) mapping, genetic transformation, and molecular experiments, we explored the impact of rare variants on stomatal morphology and drought adaptation in Populus. Through comparative analysis of five world-wide Populus species, we observed the influence of mutational bias and adaptive selection on the distribution of rare variants. RVAS identified 75 candidate genes correlated with stomatal size (SS)/stomatal density (SD), and a rare haplotype in the promoter of serine/arginine-rich splicing factor PtoRSZ21 emerged as the foremost association signal governing SS. As a positive regulator of drought tolerance, PtoRSZ21 can recruit the core splicing factor PtoU1-70K to regulate alternative splicing (AS) of PtoATG2b (autophagy-related 2). The rare haplotype PtoRSZ21hap2 weakens binding affinity to PtoMYB61, consequently affecting PtoRSZ21 expression and SS, ultimately resulting in differential distribution of Populus accessions in arid and humid climates. This study enhances the understanding of regulatory mechanisms that underlie AS induced by rare variants and might provide targets for drought-tolerant varieties breeding in Populus.

Integrating high-throughput phenotyping and genome-wide association studies for enhanced drought resistance and yield prediction in wheat.

Drought, especially terminal drought, severely limits wheat growth and yield. Understanding the complex mechanisms behind the drought response in wheat is essential for developing drought-resistant varieties. This study aimed to dissect the genetic architecture and high-yielding wheat ideotypes under terminal drought. An automated high-throughput phenotyping platform was used to examine 28 392 image-based digital traits (i-traits) under different drought conditions during the flowering stage of a natural wheat population. Of the i-traits examined, 17 073 were identified as drought-related. A genome-wide association study (GWAS) identified 5320 drought-related significant single-nucleotide polymorphisms (SNPs) and 27 SNP clusters. A notable hotspot region controlling wheat drought tolerance was discovered, in which TaPP2C6 was shown to be an important negative regulator of the drought response. The tapp2c6 knockout lines exhibited enhanced drought resistance without a yield penalty. A haplotype analysis revealed a favored allele of TaPP2C6 that was significantly correlated with drought resistance, affirming its potential value in wheat breeding programs. We developed an advanced prediction model for wheat yield and drought resistance using 24 i-traits analyzed by machine learning. In summary, this study provides comprehensive insights into the high-yielding ideotype and an approach for the rapid breeding of drought-resistant wheat.

Association study between adiponectin gene variants, serum levels and the risk of type 2 diabetes in Tunisian women: Insights from BMI stratification.

Although prior studies have shown that adiponectin synthesis is genetically determined and that its levels influence susceptibility to T2D, the results in this regard have been inconsistent. This study aims, to investigate the relationship between adiponectin gene variants with the risk of developing T2D among Tunisian women and in relation to their BMI status. A cohort of 491 Tunisian T2D women and 373 non-diabetic subjects participated in the study. Nine ADIPOQ variants namely rs16861194, rs17300539, rs266729, rs822395, rs822396, rs2241766, rs1501299, rs2241767 and rs3774261 were selected and genotyped using the TaqMan® SNP genotyping assay. Fasting serum adiponectin levels were quantified using ELISA. The results showed that only the rs17300539 variant exhibited a significant association with the risk of T2D. However, upon considering T2D group stratification based on BMI (normal weight [18-24.99 Kg/m2], overweight [25-29.99 Kg/m2] and obese [30-34.99 Kg/m2]), the ADIPOQ rs2241766 variant emerged as a contributing risk factor for increased BMI in obese women with T2D. Linear regression analysis revealed that the minor allele (A), (GA) and (AA) genotypes of rs17300539 as well as the (G) allele and (GG) genotype of rs2241766 were significantly associated with hypoadiponectinemia in T2D subjects. Two haplotypes namely GGCAATGAA and AGCCGTGGA, were identified as conferring a higher risk of T2D with the GGCAATGAA haplotype also correlating with hypoadiponectinemia. Our study underscores the importance of the rs17300539 variant and the GGCAATGAA haplotype in the risk of T2D and hypoadiponectinemia. Additionally, the presence of the rs2241766 variant highlights its association with 'diabesity' and hypoadiponectinemia among Tunisian T2D women.

The novel CFTR haplotype E583G/F508del in CFTR-related disorder.

BACKGROUND: CFTR-related disorder (CFTR-RD) is a clinical entity associated to complex diagnostic paths and newly upgraded standard of care. In CFTR-RD, CFTR genotyping represents a diagnostic surrogate marker. In case of novel haplotype, the diagnosis could represents an area of concern. We described the molecular evaluation of the rare CFTR variant E583G identified in trans with the F508del in a novel haplotype. METHODS AND RESULTS: An adult woman was referred to our pulmonary unit for persistent respiratory symptoms. CFTR Next Generation Sequencing was performed to evaluate full-gene mutational status. The variant identified was evaluated for its pathogenicity integrating clinical evidences with dedicated bioinformatics analyses. Clinical evaluation of patient matched with a mono-organ CFTR-RD diagnosis. Genotyping revealed the novel CFTR haplotype F508del/E583G. Multiple evidences of a deleterious effect of the CFTR E583G rare variant emerged from the bioinformatics analyses performed. CONCLUSIONS: Guidelines for CFTR-RD are available with the purpose of harmonizing clinical and molecular investigations. In such context, the identification of novel CFTR haplotype need to a deeper evaluation with a combination of skills. The novel E583G variant could be considered of clinical interest and overall a CFTR-RD Variants of Varying Clinical Consequences.

Evolutionary variation in gene conversion at the avian MHC is explained by fluctuating selection, gene copy numbers and life history.

The major histocompatibility complex (MHC) multigene family encodes key pathogen-recognition molecules of the vertebrate adaptive immune system. Hyper-polymorphism of MHC genes is de novo generated by point mutations, but new haplotypes may also arise by re-shuffling of existing variation through intra- and inter-locus gene conversion. Although the occurrence of gene conversion at the MHC has been known for decades, we still have limited understanding of its functional importance. Here, I took advantage of extensive genetic resources (~9000 sequences) to investigate broad scale macroevolutionary patterns in gene conversion processes at the MHC across nearly 200 avian species. Gene conversion was found to constitute a universal mechanism in birds, as 83% of species showed footprints of gene conversion at either MHC class and 25% of all allelic variants were attributed to gene conversion. Gene conversion processes were stronger at MHC-II than MHC-I, but inter-specific variation at both MHC classes was explained by similar evolutionary scenarios, reflecting fluctuating selection towards different optima and drift. Gene conversion showed uneven phylogenetic distribution across birds and was driven by gene copy number variation, supporting significant role of inter-locus gene conversion processes in the evolution of the avian MHC. Finally, MHC gene conversion was stronger in species with fast life histories (high fecundity) and in long-distance migrants, likely reflecting variation in population sizes and host-pathogen coevolutionary dynamics. The results provide a robust comparative framework for understanding macroevolutionary variation in gene conversion at the avian MHC and reinforce important contribution of this mechanism to functional MHC diversity.

Multiple deletions of candidate effector genes lead to the breakdown of partial grapevine resistance to downy mildew.

Grapevine downy mildew, caused by the oomycete Plasmopara viticola (P. viticola, Berk. & M. A. Curtis; Berl. & De Toni), is a global threat to Eurasian wine grapes Vitis vinifera. Although resistant grapevine varieties are becoming more accessible, P. viticola populations are rapidly evolving to overcome these resistances. We aimed to uncover avirulence genes related to Rpv3.1-mediated grapevine resistance. We sequenced the genomes and characterized the development of 136 P. viticola strains on resistant and sensitive grapevine cultivars. A genome-wide association study was conducted to identify genomic variations associated with resistant-breaking phenotypes. We identified a genomic region associated with the breakdown of Rpv3.1 grapevine resistance (avrRpv3.1 locus). A diploid-aware reassembly of the P. viticola INRA-Pv221 genome revealed structural variations in this locus, including a 30 kbp deletion. Virulent P. viticola strains displayed multiple deletions on both haplotypes at the avrRpv3.1 locus. These deletions involve two paralog genes coding for proteins with 800-900 amino acids and signal peptides. These proteins exhibited a structure featuring LWY-fold structural modules, common among oomycete effectors. When transiently expressed, these proteins induced cell death in grapevines carrying Rpv3.1 resistance, confirming their avirulence nature. This discovery sheds light on the genetic mechanisms enabling P. viticola to adapt to grapevine resistance, laying a foundation for developing strategies to manage this destructive crop pathogen.

Phylogenetic and population genetic analyses of Thrips tabaci Lindeman (Thysanoptera: Thripidae) on Allium host in India.

Background: Onion thrips (Thrips tabaci) is a complex of cryptic species with subtle morphological differences and distinct genetic backgrounds; thus, species identification using traditional methods remains challenging. The existence of different haplotypes and genotypes within a species can significantly influence various aspects of its biology, including host preference, reproductive capacity, resistance to pesticides, and vector competence for plant viruses. Understanding the genetic diversity and population structure of cryptic species within T. tabaci will not only aid in the development of more effective control strategies tailored to specific genetic variants but also in monitoring population dynamics, tracking invasive species, and implementing quarantine measures to prevent the spread of economically damaging thrips biotypes. Methods: This study aims to explore intraspecies genetic diversity and molecular evolutionary relationships of the mitochondrial cytochrome oxidase gene subunit I (mtCOI) in T. tabaci populations from India. To capture diversity within the Indian T. tabaci populations, amplicon sequencing was performed for the thrips mtCOI gene from eight diverse localities in India. A total of 48 sequences retrieved for the mtCOI gene from the NCBI Nucleotide database were analysed. Results: Multiple insertions and deletions were detected at various genomic positions across the populations from different localities, with the highest variation observed in the 300-400 genome position range. Molecular diversity analyses identified 30 haplotypes within the population, with certain subpopulations exhibiting higher gene flow. Analysis of single nucleotide polymorphism patterns within the mtCOI gene across diverse Indian locales revealed significant intrapopulation genetic heterogeneity and its potential repercussions on gene functionality. Elevated F statistics (Fst) values in the northern-western subpopulations suggested high genetic variability, particularly evident in haplotype networks originating mainly from the northern region, notably Delhi. While most populations displayed stable and ancient evolutionary histories, thrips populations from northern, western, and north-eastern regions indicated rapid growth.

MHCtools 1.5: Analysis of MHC Sequencing Data in R.

The genes of the major histocompatibility complex (MHC) play a vital role in the vertebrate immune system and have attracted considerable interest in evolutionary biology. While the MHC has been characterized in detail in humans (human leukocyte antigen, HLA) and in model organisms such as the mouse, studies in non-model organisms often lack prior knowledge about structure, genetic variability, and evolutionary properties of this locus. MHC genotyping in non-model species commonly relies on PCR-based amplicon sequencing, and while several published protocols facilitate generation of MHC sequence data, there is a lack of transparent and standardized tools for downstream data analysis.Here, I present the R package MHCtools version 1.5, which contains 15 tools that (i) assist accurate MHC genotyping from high-throughput amplicon sequencing data, and provide standardized methods to analyze (ii) MHC diversity, (iii) MHC supertypes, and (iv) MHC haplotypes.I hope that MHCtools will be helpful in future studies of the MHC in non-model species and that it may help to advance our understanding of the important roles of the MHC in ecology and evolution.

afila, the origin and nature of a major innovation in the history of pea breeding.

The afila (af) mutation causes the replacement of leaflets by a branched mass of tendrils in the compound leaves of pea - Pisum sativum L. This mutation was first described in 1953, and several reports of spontaneous af mutations and induced mutants with a similar phenotype exist. Despite widespread introgression into breeding material, the nature of af and the origin of the alleles used remain unknown. Here, we combine comparative genomics with reverse genetic approaches to elucidate the genetic determinants of af. We also investigate haplotype diversity using a set of AfAf and afaf cultivars and breeding lines and molecular markers linked to seven consecutive genes. Our results show that deletion of two tandemly arranged genes encoding Q-type Cys(2)His(2) zinc finger transcription factors, PsPALM1a and PsPALM1b, is responsible for the af phenotype in pea. Eight haplotypes were identified in the af-harbouring genomic region on chromosome 2. These haplotypes differ in the size of the deletion, covering more or less genes. Diversity at the af locus is valuable for crop improvement and sheds light on the history of pea breeding for improved standing ability. The results will be used to understand the function of PsPALM1a/b and to transfer the knowledge for innovation in related crops.

Imputation-Based HLA Typing with GWAS SNPs.

SNP-based imputation approaches for human leukocyte antigen (HLA) typing take advantage of the haplotype structure within the major histocompatibility complex (MHC) region. These methods predict HLA classical alleles using dense SNP genotypes, commonly found on array-based platforms used in genome-wide association studies (GWAS). The analysis of HLA classical alleles can be conducted on current SNP datasets at no additional cost. Here, we describe the workflow of HIBAG, an imputation method with attribute bagging, to infer a sample's HLA classical alleles using SNP data. Two examples are offered to demonstrate the functionality using public HLA and SNP data from the latest release of the 1000 Genomes project: genotype imputation using pre-built classifiers in a GWAS, and model training to create a new prediction model. The GPU implementation facilitates model building, making it hundreds of times faster compared to the single-threaded implementation.

Facilitated introgression from domestic goat into Alpine ibex at immune loci.

Hybridization can result in the transfer of adaptive genetic material from one species to another, known as adaptive introgression. Bottlenecked (and hence genetically depleted) species are expected to be particularly receptive to adaptive introgression, since introgression can introduce new or previously lost adaptive genetic variation. The Alpine ibex (Capra ibex), which recently recovered from near extinction, is known to hybridize with the domestic goat (Capra aegagrus hircus), and signals of introgression previously found at the major histocompatibility complex were suggested to potentially be adaptive. Here, we combine two ancient whole genomes of Alpine ibex with 29 modern Alpine ibex genomes and 31 genomes representing six related Capra species to investigate the genome-wide patterns of introgression and confirm the potential relevance of immune loci. We identified low rates of admixture in modern Alpine ibex through various F statistics and screening for putative introgressed tracts. Further results based on demographic modelling were consistent with introgression to have occurred during the last 300 years, coinciding with the known species bottleneck, and that in each generation, 1-2 out of 100 Alpine ibex had a domestic goat parent. The putatively introgressed haplotypes were enriched at immune-related genes, where the adaptive value of alternative alleles may give individuals with otherwise depleted genetic diversity a selective advantage. While interbreeding with domestic species is a prevalent issue in species conservation, in this specific case, it resulted in putative adaptive introgression. Our findings highlight the complex interplay between hybridization, adaptive evolution, and the potential risks and benefits associated with anthropogenic influences on wild species.

Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ∼2.2-5.5 kb of 100% nucleotide similarity within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci.

A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

High Frequency of Ancestral Haplotype A of Fatty Acid Desaturase Genes in the Yakut Population.

Aims: The purpose of this study was to study the correlation of the body weight of Yakuts with the variability of polymorphisms rs174537, rs174546 and rs3834458 of the FADS1 - FADS2 region to identify the connection of certain genotypes with obesity. Materials and Methods: For genotyping, classical methods of PCR-RFLP analysis were used. A sample of 446 DNA samples from Yakut volunteers without chronic diseases (143 women and 303 men) was studied. Results: The predominance of the ancestral alleles of SNPs rs174537, rs174546 and rs3834458 was established in all of our studied groups. Analysis of the odds ratio of allele and genotype frequencies in patients with normal BMI, high BMI and obesity did not show statistically significant values. We did not find an association between rs174537, rs174546 and rs3834458 with obesity, but we did not take into account the diet of the subjects, which may have had a stronger effect on BMI. Analysis of pairwise linkage disequilibrium and assessment of haplotypes for 3 SNPs in the FADS1 and FADS2 genes showed strong linkage of all three SNPs to each other (r2 = 0.93-0.96). Conclusions: According to the result of genotyping of SNP rs174537, the frequency of haplotype A in the Yakut population was 0.76 and, in comparison with other world data, is quite high. Which in turn is associated with lower conversion of short-chain polyunsaturated fatty acid to long-chain polyunsaturated fatty acid. Accordingly, a shift in nutrition towards more plant foods can negatively impact the health of the Yakuts. At the moment, the exact dosage of polyunsaturated fatty acids (PUFAs) for humans has not yet been established, but judging by the fact that all recommendations are mainly made on the basis of European populations, in connection with the results of the study, the Yakuts have a particularly high need for PUFAs.