Heterosis, widely used in plant breeding to enhance yield and quality, is not yet fully understood at the allelic level, particularly in woody plants such as Camellia sinensis, the tea plant. In this study, the first haplotype (HA)-resolved genome of JGY, the most widely cultivated hybrid oolong tea cultivar in China, is presented, and the contribution of its epigenetic and 3D genomic features to heterosis is explored. It was revealed that CHG methylation in gene bodies serves as a key epigenetic predictor of allele-specific expression (ASE), as identified by machine learning models. Additionally, it was shown that allele-specific chromatin accessibility plays a significant role in regulating ASE, with specific chromatin regions in the promoter of CsDXS2, a key enzyme in the methylerythritol phosphate (MEP) terpene biosynthesis pathway, being responsible for the modulation of its expression through CsBZIP48. Furthermore, HA-resolved Hi-C analysis uncovered large-scale chromatin reorganization in the hybrid, including A/B compartment switching and topologically associating domain (TAD) reorganization, which are linked to changes in gene expression, particularly in aroma-related genes. These findings highlight the coordinated reprogramming of parental epigenetic and 3D genomic features during hybridization and provide new insights into the molecular mechanisms underlying heterosis in woody plants.

Advanced genotyping technology has made it feasible for large numbers of individuals to be genotyped resulting in many biobanks across the world. These biobanks are an excellent resource to study haplotype matching at a large scale. Durbin's positional Burrows-Wheeler transform (PBWT) supports efficient haplotype matching and queries given a panel of haplotypes and scales well with large data. It has been widely used for statistical phasing, imputation, and identity-by-descent detection. However, the original PBWT panel does not support updates when haplotypes need to be added or deleted from the panel. Dynamic-PBWT (d-PBWT) solved this problem but is not memory efficient. While the memory constraint problem of the PBWT has been tackled by Syllable-PBWT and -PBWT, these are static data structures that do not allow updates. In addition, Syllable-PBWT only supports long-match query and -PBWT only supports set-maximal match query, limiting their functionality in the compressed form. In this article, we present Dynamic -PBWT (which can also be seen as compressed d-PBWT) that is memory efficient and supports dynamic updates. We run-length compress PBWT to achieve a better compression rate and store the runs in self-balancing trees to enable dynamic updates. We show that the number of updates per insertion or deletion in the tree at each site is constant regardless of the number of haplotypes in the panel and the updates can be made without decompressing the index. Moreover, we use orders of magnitude less memory than d-PBWT. We provide set maximal match and long match query algorithms on Dynamic -PBWT. The long match query algorithm can easily be extended back to the original -PBWT. We benchmark all algorithms on the UK Biobank and 1000 Genomes Project dataset. Overall, the flexibility and space-efficiency of Dynamic -PBWT make it a potential index data structure for biobank-scale genetic data maintenance and analysis.

Bone marrow transplantation and haplotyping Brian Tait, chief scientific officer, Haplomic Technologies Pty Ltd, explores the clinical benefits of haplotyping in single-chromosome sequencing and unrelated donor bone marrow transplantation (HSCT). The principal genes involved in transplant matching are the Human Leukocyte Antigen (HLA) genes, which are located on the short arm of chromosome 6 within the major histocompatibility complex (MHC). (which includes the HLA-A, -B, –C, –DR, -DQ and –DP genes). While HLA matching at individual alleles is a factor determining success in organ transplantation, there is little evidence that HLA haplotype matching improves graft survival.

ObjectiveThis study aims to evaluate the influence of polymorphisms of the HSD11B1, FKBP5 and NR3C1 genes on the outcomes of patients with Takayasu arteritis (TAK).MethodsA retrospective cohort study including 81 TAK patients was carried out. Polymorphisms of the genes HSD11B1 (rs11119328), FKBP5 (rs1360780) and NR3C1 (N363S, Bcll, TthIIII1, ER22/23EK and 9ß) were genotyped by the Sanger technique. Associations between the gene variants and the haplotypes (HT) of the NR3C1 gene with variables related to the outcome of TAK and glucocorticoid (GC)-related adverse events (AEs) were analyzed.ResultsThe polymorphism 9β of the NR3C1 gene, which leads to decreased GC sensitivity, was associated with a higher frequency of GC-related AEs [3.0 (2.0-3.8) vs. 2.0 (1.0-3.0); p = 0.002] and weight gain (37.5% vs. 8.9%; p = 0.012). Worsening glucose tolerance (i.e., a key GC-related AE) was an independent risk factor for acute ischemic events [odds ratio (OR) between 8.9 and 10.2] in all multivariate logistic regression models that included one of the polymorphisms in each model. Moreover, the carriage of 9β in the NR3C1 gene was also an independent risk factor for developing ischemic arterial events (OR: 4.4, 95% confidence interval: 1.1-18.3). None of the other polymorphisms of NR3C1, HSD11B1 and FKBP5 were associated with TAK features or outcomes, nor with GC-related AEs.ConclusionWorsening glucose tolerance and the carriage of 9β of the NR3C1 gene were independent risk factors for acute ischemic events in TAK. The 9β polymorphism of the NR3C1 gene was associated with GC-related AEs in TAK in our patient population. None of the gene variants were predictors of sustained remission or arterial progression.

mRNA immunotherapy works by presenting tumor-associated antigens to the patient's immune system, thereby training it to recognize and target cancer cells th at express these antigens. mRNA cancer vaccines have shown remarkable tolerability and safety in both clini cal and preclinical trials. mRNA cancer vaccines produce fewer adverse reactions compared to traditional ca ncer treatments such as chemotherapy and radiotherapy. These vaccines elicit a memory immune response, thereby significantly reducing the risk of cancer recurrence. Notably, in contrast to peptide-based cancer vaccines, mRNA vaccines circumvent the necessity for human leukocyte antigen (HLA) haplot ype matching, offering a broader applicability across diverse patient populations. mRNA vaccines can initiat e antigen expression more rapidly, and they do not carry the genetic risks associated with insertional mutage nesis, which is a concern with DNA vaccine. The therapeutic efficacy of mRNA-based cancer vaccines is fundamentally dependent on their ability to precisely target tumor-associated antigens, consequently eliciting robust cellular immune responses. Tumor antigens can be system atically classified into two distinct categories: tumor-specific antigens (TSAs), which are exclusively expressed on malignant cells and absent in normal tissues, and tumor-associated antigens (TAAs), which exhibit differential expression patterns between neoplastic and normal ce llular populations. Many different types of vaccines were developed to address multiple cancer types, includi ng melanoma, breast cancer, and pancreatic cancer.

Medium-density single nucleotide polymorphism (SNP) profiles enable law enforcement to infer close and distant genetic relationships. Part one of this study demonstrated that the ForenSeq® Kintelligence Kit, which targets 10,230 SNPs, can facilitate extended kinship inference through kinship likelihood ratio (LR) and identical by descent (IBD) segment matching methods. However, if SNPs are not detected, or are incorrectly called, the ability to detect genetic relatives and accurately classify the relationship may be compromised. The Kintelligence profiles for the central individuals of two pedigrees described in Part One were edited to simulate information loss through locus and allele dropout. LRs were calculated with DBLR™ and SNP profiles were uploaded to GEDmatch PRO™ for database searching or direct comparison. The LRs decreased with increasing information loss but still provided strong statistical support for relatedness. LRs exceeded 100,000 for all full sibling to fifth degree relationships for up to 30% locus and allele dropout. Locus dropout did not significantly impact the ability to infer first to fifth degree relationships with IBD segment matching. Allele dropout had a greater impact, with 30% allele dropout impairing the ability to classify relationships to their correct degree. When allele dropout was greater than 10%, the fifth degree relative was no longer detected in the database search. This study highlights the robustness of LR calculations and the GEDmatch PRO™ IBD segment matching algorithms and the suitability of the Kintelligence Kit for medium-range kinship inference, with the algorithm maintaining the ability to infer relationships despite increasing information loss.

Medium- and long-range kinship analysis using single nucleotide polymorphism (SNP) genotyping allows law enforcement to generate investigative leads by identifying an unknown individual through their close and distant genetic relatives. Short-range kinship inference can be conducted through calculation of likelihood ratios (LRs) using population allele frequency data and the degree of similarity between two DNA profiles but has historically been limited to short tandem repeat (STR) profiles. Alternatively, identical by descent (IBD) segment matching algorithms can be used to detect shared DNA haplotypes between two genetically related individuals that have been inherited from a common ancestor. The ForenSeq® Kintelligence Kit enables law enforcement and forensic laboratories to utilize medium-density SNP sequencing technology for extended kinship inference by analyzing 10,230 SNPs. In this study, DNA from two pedigrees was used to compare the ability of STR profiles, identity-informative SNP (iiSNP) profiles, Kintelligence profiles and Kintelligence and direct-to-consumer profiles available on public genetic genealogy databases to detect and classify genetic relationships. The DNA profiles were analyzed using DBLR™ software to calculate kinship LRs or uploaded to GEDmatch PRO™ for IBD segment matching with either database searching or one-to-one comparisons. The LRs calculated for STR and iiSNP profiles were able to correctly infer first degree relationships (i.e., parent, offspring, and full sibling), with the combined discrimination power able to distinguish between second degree relationships. LRs calculated for the Kintelligence profiles exceeded one million for 93% of full sibling to fifth degree relationships tested. IBD segment matching was effective for detecting first to fifth degree relatives when Kintelligence profiles were searched on the GEDmatch PRO™ database. The results of this study demonstrate that the Kintelligence Kit is a valuable tool for law enforcement and forensic investigators, offering an advanced method for medium-range kinship testing using either LRs or IBD segment matching.

Durbin’s positional Burrows-Wheeler transform (PBWT) supports efficient haplotype matching and queries given a panel of haplotypes. It has been widely used for statistical phasing, imputation and identity-by-descent (IBD) detection. However, the original PBWT panel doesn’t support dynamic updates when haplotypes need to be added or deleted from the panel. Dynamic-PBWT (d-PBWT) solved this problem but it is not memory efficient. While the memory constraint problem of the PBWT has been tackled by Syllable-PBWT and -PBWT, these are static data structures that do not allow updates. Additionally, Syllable-PBWT only supports long-match query and -PBWT only supports set-maximal match query, limiting their functionality in the compressed form. In this paper, we present Dynamic -PBWT (which can also be seen as compressed d-PBWT) that is memory efficient and supports dynamic updates. We run-length compress PBWT to achieve better compression rate and store the runs in the self-balancing trees to enable dynamic updates. We show that the number of updates per insertion or deletion in the tree at each site is constant regardless of the number of haplotypes in the panel and the updates can be made without decompressing the index. In addition, we use orders of magnitude less memory than d-PBWT. We also provide a long match query algorithm that can easily be extended back to the original -PBWT. Overall, the flexibility and space-efficiency of Dynamic -PBWT makes it a potential index data structure for biobank scale genetic data analyses. The source code for Dynamic -PBWT is available at https://github.com/ucfcbb/Dynamic-mu-PBWT.

Traditionally, variations from a linear reference genome were used to represent large sets of haplotypes compactly. In the linear reference genome based paradigm, the positional Burrows-Wheeler transform (PBWT) has traditionally been used to perform efficient haplotype matching. Pangenome graphs have recently been proposed as an alternative to linear reference genomes for representing the full spectrum of variations in the human genome. However, haplotype matches in pangenome graph based haplotype sets are not trivially generalizable from haplotype matches in the linear reference genome based haplotype sets. Work has been done to represent large sets of haplotypes as paths through a pangenome graph. The graph Burrows-Wheeler transform (GBWT) is one such work. The GBWT essentially stores the haplotype paths in a run length compressed BWT with compressed local alphabets. Although efficient in practice count and locate queries on the GBWT were provided by the original authors, the efficient haplotype matching capabilities of the PBWT have never been shown on the GBWT. In this paper, we formally define the notion of haplotype matches in pangenome graph-based haplotype sets by generalizing from haplotype matches in linear reference genome-based haplotype sets. We also describe the relationship between set maximal matches, long matches, locally maximal matches, and text maximal matches on the GBWT, PBWT, and the BWT. We provide algorithms for outputting some of these matches by applying the data structures of the r-index (introduced by Gagie et al.) to the GBWT. We show that these structures enable set maximal match and long match queries on the GBWT in almost linear time and in space close to linear in the number of runs in the GBWT. We also provide multiple versions of the query algorithms for different combinations of the available data structures. The long match query algorithms presented here even run on the BWT in the same time complexity as the GBWT due to their similarity.

Aflatoxin contamination of corn can occur when developing kernels are infected by the plant pathogen Aspergillus flavus. One route of infection is from airborne conidia. We executed a series of experiments within the corn canopy during two growing seasons and in two states to document the abundance and dynamics of the airborne A. flavus population. We did not observe any significant diurnal changes in the conidial density (p = 0.171) or any effect of sampler height (p = 0.882) within the canopy. Significant changes (p < 0.001) were noted during the season, with a trend towards increased airborne populations with later stages of corn development and more than a 20-fold increase from July to August. The median aflatoxigenicity of airborne isolates from a corn canopy in Texas was about 50 times higher than the corresponding population in Mississippi. It was also noteworthy that highly aflatoxigenic, weakly sporulating S-morphotypes accounted for 14–30% of the airborne isolates in Mississippi at a site with historically rare abundance of S-morphotypes. The genetic diversity was high among the 140 analyzed airborne isolates, with 76 unique haplotypes identified and 55 haplotypes occurring only in 1 isolate. Even in the context of this highly diverse population, a haplotype matching that of a commercial biocontrol strain was found in 13 of the 70 isolates from Mississippi and 1 of the 70 isolates from Texas. The airborne A. flavus population is genetically diverse (Shannon’s index = 1.4 to 1.6), similar to grain samples in other surveys, and much less aflatoxigenic in Mississippi than in Texas.

Since their domestication, horses have accompanied mankind, and humans have constantly shaped horses according to their needs through stallion-centered breeding. Consequently, the male-specific portion of the Y chromosome (MSY) is extremely uniform in modern horse breeds. The majority of stallions worldwide carry MSY haplotypes (HT) attributed to an only ~1,500-y-old, so-called, "Crown" haplogroup. The predominance of the Crown in modern horse breeds is thought to represent a footprint of the vast impact of stallions of "Oriental origin" in the past millennium. Here, we report the results of a fine-scaled MSY haplotyping of large datasets of patrilines comprising 1,517 males of 189 modern horse breeds, covering a broad phenotypic and geographic spectrum. We can disentangle the multilayered influence of Oriental stallions over the last few hundred years, exposing the intense linebreeding and the wide-ranging impact of Arabian, English Thoroughbred, and Coldblood sires. Iberian and New World horse breeds contain a wide range of diversified Crown lineages. Their broad HT spectrum illustrates the spread of horses of Oriental origin via the Iberian Peninsula after the Middle Ages, which is commonly referred to as the "Spanish influence." Our survey also revealed a second major historical dissemination of horses from Western Asia, attributed to the expansion of the Ottoman Empire. Our analysis shows that MSY analysis can uncover the complex history of horse breeds and can be used to establish the paternal ancestry of modern horse breeds.

Identification of human remains is a challenge in forensic genetics without relatives or personal items available. In Slovenia, a Konfin II mass grave from the Second World War (WWII) was found, containing skeletal remains of 65 victims. The archival documents detailing victims' information describe 45 persons of which 33 could be considered Germanic and 12 Slavic. This study aims to check for concordance between the victim list and actual victims found by using uniparental markers to differentiate between Slavic and non-Slavic origin by attempting to infer ancestry by analyzing the control region (CR) of mitochondrial DNA (mtDNA) and Y-chromosomal STRs. Diaphyses of femurs were used as a DNA source. Next Generation Sequencing (NGS) technology was used for mtDNA- namely HID Ion Chef™ Instrument, Precision ID mtDNA Control Region Panel, and Ion GeneStudio™ S5 System. For the Y-chromosome, PowerPlex® Y23 System (Promega) kit and SeqStudio™ for human identification (HID) were used. European DNA Profiling mtDNA Population Database (EMPOP) and Y-Chromosome STR Haplotype Reference Database (YHRD) were searched for haplotype matches. Closest haplogroups were predicted using EMPOP, Y-DNA Haplogroup Predictor- NevGen, and Whit Athey's Haplogroup Predictor. Despite mitotypes being more diverse than Y-haplotypes, the Y-haplotypes had more database matches and more unequivocal differentiation between populations. 16 victims could be considered Slavic, 15 non-Slavic, and the remaining 34 had a rather scarce informativeness- either unclear or not providing any match. To address ancestry inference more comprehensively, analysis of autosomal ancestry informative markers as well as expansion on haploid markers will be conducted in future research.

Forensic characteristics of 38 Y-STR loci in the Hui population from Shaanxi Province, Northwest China

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single-nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found 2 SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of 4 near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resulting in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

BackgroundSeptoria tritici blotch (STB) is considered to be one of the most destructive foliar wheat diseases and is caused by Zymoseptoria tritici. The yield losses are severe and in Northwestern Europe can reach up to 50%. The efficacy of fungicides is diminishing due to changes in the genetic structure of the pathogen. Therefore, resistance breeding is the most effective strategy of disease management. Recently, genome-wide association studies (GWAS) have become more popular due to their robustness in dissecting complex traits, including STB resistance in wheat. This was made possible by the use of large mapping populations and new sequencing technologies. High-resolution mapping benefits from historical recombination and greater allele numbers in GWAS.ResultsIn our study, 217 wheat genotypes of diverse origin were phenotyped against five Z. tritici isolates (IPO323, IPO88004, IPO92004, IPO86036 and St1-03) and genotyped on the DArTseq platform. In polytunnel tests two disease parameters were evaluated: the percentage of leaf area covered by necrotic lesions (NEC) and the percentage of leaf area covered by lesions bearing pycnidia (PYC). The disease escape parameters heading date (Hd) and plant height (Ht) were also measured. Pearson’s correlation showed a positive effect between disease parameters, providing additional information. The Structure analysis indicated four subpopulations which included from 28 (subpopulation 2) to 79 genotypes (subpopulation 3). All of the subpopulations showed a relatively high degree of admixture, which ranged from 60% of genotypes with less than 80% of proportions of the genome attributed to assigned subpopulation for group 2 to 85% for group 4. Haplotype-based GWAS analysis allowed us to identify 27 haploblocks (HBs) significantly associated with analysed traits with a p-value above the genome-wide significance threshold (5%, which was –log10(p) > 3.64) and spread across the wheat genome. The explained phenotypic variation of identified significant HBs ranged from 0.2% to 21.5%. The results of the analysis showed that four haplotypes (HTs) associated with disease parameters cause a reduction in the level of leaf coverage by necrosis and pycnidia, namely: Chr3A_HB98_HT2, Chr5B_HB47_HT1, Chr7B_HB36_HT1 and Chr5D_HB10_HT3.ConclusionsGWAS analysis enabled us to identify four significant chromosomal regions associated with a reduction in STB disease parameters. The list of valuable HBs and wheat varieties possessing them provides promising material for further molecular analysis of resistance loci and development of breeding programmes.

Seventeen microsatellite loci from the non-recombining region of the human Y chromosome were typed using AmpFlSTR® Yfiler® PCR amplification systems in 404 male subjects belonging to the three largest ethnic groups in Bangladesh. A total of 150 haplotypes from the Chakma, 144 from the Tripura, and 110 from the Khasia were detected with a corresponding discrimination capacity of 73.885%, 65.563%, and 81.250%, respectively. The highest allele frequency of 0.828 was detected in DYS391 locus in the Tripuras, while the lowest allele frequency of 0.009 was detected at the same locus for the Chakma population. The highest gene diversity (0.964) was observed at DYS385a/b locus in the Khasias, while the lowest gene diversity (0.301) was detected at DYS391 locus in Tripuras population. The overall haplotype diversity for the studied populations was 0.986141. Both the Neighbour-Joining tree and pairwise genetic distances showed that Chakma lies closer to a clade consisting of Tripuras (Khagrachari, Bangladesh) and Tripuri (Tripura, India). In contrast, the Khasias demonstrated a close affinity with the Oraon (Chhattisgarh, India), followed by the Santals. The Y-STR haplotype matching probabilities within and between populations demonstrated that the Chakma, Tripura, and Khasia were 100% genetically distinct. The studied ethnic populations exhibited higher frequency for haplogroups L and Q as opposed to haplogroups R1a, H, and L found in the mainstream Bengali population. The Median-joining networking showed haplogroups L and R1a have the most compact clustering within populations, followed by haplogroups Q and H. The presence of haplogroup R1a suggests that Bengali may have originated through west-to-east migration, whereas haplogroups L and Q distribution in the studied tribes reveal a very significant affinity with the South-East Asian populations and may have shared a common ancestral origin with the Mongoloid stock populations. Bioresearch Commu. 10(2): 1482-1488, 2024 (July)

Haplotype phasing, the process of determining which genetic variants are physically located on the same chromosome, is crucial for various genetic analyses. In this study, we first benchmark SHAPEIT and Beagle, two state-of-the-art phasing methods, on two large datasets: > 8 million diverse, research-consented 23andMe, Inc. customers and the UK Biobank (UKB). We find that both perform exceptionally well. Beagle's median switch error rate (SER) (after excluding single SNP switches) in white British trios from UKB is 0.026% compared to 0.00% for European ancestry 23andMe research participants; 55.6% of European ancestry 23andMe research participants have zero non-single SNP switches, compared to 42.4% of white British trios. South Asian ancestry 23andMe research participants have the highest median SER amongst the 23andMe populations, but it is still remarkably low at 0.46%. We also investigate the relationship between identity-by-descent (IBD) and SER, finding that switch errors tend to occur in regions of little or no IBD segment coverage. SHAPEIT and Beagle excel at 'intra-chromosomal' phasing, but lack the ability to phase across chromosomes, motivating us to develop an inter-chromosomal phasing method, called HAPTIC ( HAP lotype TI ling and C lustering), that assigns paternal and maternal variants discretely genome-wide. Our approach uses identity-by-descent (IBD) segments to phase blocks of variants on different chromosomes. HAPTIC represents the segments a focal individual shares with their relatives as nodes in a signed graph and performs bipartite clustering on the signed graph using spectral clustering. We test HAPTIC on 1022 UKB trios, yielding a median phase error of 0.08% in regions covered by IBD segments (33.5% of sites). We also ran HAPTIC in the 23andMe database and found a median phase error rate (the rate of mismatching alleles between the inferred and true phase) of 0.92% in Europeans (93.8% of sites) and 0.09% in admixed Africans (92.7% of sites). HAPTIC's precision depends heavily on data from relatives, so will increase as datasets grow larger and more diverse. HAPTIC enables analyses that require the parent-of-origin of variants, such as association studies and ancestry inference of untyped parents.

In this study, geographic and linguistic distributions of contemporary and ancient matches with the paternal and maternal lineages of two individuals exhumed from the exemplary Pazyryk culture burial site of Ak-Alakha-1 mound 1 were investigated. Using the shared paternal and maternal haplotypes observed in both ancient individuals, extensive database and literature searches were conducted revealing numerous full matches among contemporary Eurasians, majority of whom speak Altaic Languages. Despite the current focus on the two Pazyryk individuals, a rare glimpse into the ancient migrations was gained through the discovery of paternal and maternal haplotype matches across an immense geography that spans from Yakutia to Turkey. In addition to a vast array of archaeological findings in such Scythian “frozen graves” across Central Asia, accumulating archaeogenetic data are expected to shed light on the anthropology of these otherwise mysterious people.

BackgroundThe Kazakhs are one of the biggest Turkic-speaking ethnic groups, controlling vast swaths of land from the Altai to the Caspian Sea. In terms of area, Kazakhstan is ranked ninth in the world. Northern, Eastern, and Western Kazakhstan have already been studied in relation to genetic polymorphism 27 Y-STR. However, current information on the genetic polymorphism of the Y-chromosome of Southern Kazakhstan is limited only by 17 Y-STR and no geographical study of other regions has been studied at this variation.ResultsThe Kazakhstan Y-chromosome Haplotype Reference Database was expanded with 468 Kazakh males from the Zhambyl and Turkestan regions of South Kazakhstan by having their 27 Y-STR loci and 23 Y-SNP markers analyzed. Discrimination capacity (DC = 91.23%), haplotype match probability (HPM = 0.0029) and haplotype diversity (HD = 0.9992) are defined. Most of this Y-chromosome variability is attributed to haplogroups C2a1a1b1-F1756 (2.1%), C2a1a2-M48 (7.3%), C2a1a3-F1918 (33.3%) and C2b1a1a1a-M407 (6%). Median-joining network analysis was applied to understand the relationship between the haplotypes of the three regions. In three genetic layer can be described the position of the populations of the Southern region of Kazakhstan—the geographic Kazakh populations of Kazakhstan, the Kazakh tribal groups, and the people of bordering Asia.ConclusionThe Kazakhstan Y-chromosome Haplotype Reference Database was formed for 27 Y-STR loci with a total sample of 1796 samples of Kazakhs from 16 regions of Kazakhstan. The variability of the Y-chromosome of the Kazakhs in a geographical context can be divided into four main clusters—south, north, east, west. At the same time, in the genetic space of tribal groups, the population of southern Kazakhs clusters with tribes from the same region, and genetic proximity is determined with the populations of the Hazaras of Afghanistan and the Mongols of China.

Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here, we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues throughout aging. We used ultra-sensitive Duplex Sequencing to profile ~2.5 million mt-genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloging ~1.2 million mitochondrial somatic and ultra low frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the Light Strand Origin of Replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared to primates with a surfeit of reactive oxygen species-associated G>T/C>A mutations, and that somatic mutations in protein coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that “re-align” mito-nuclear ancestry within an organism’s lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.