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Low HbF expression in HbE-β+-thalassemia may lead to misdiagnosis of HbE heterozygosity. We aimed to characterize the β- and α-globin genes and the modifying factors related to HbF expression in patients with an Hb phenotype similar to that of HbE heterozygotes. Furthermore, screening tools for differentiating HbE-β+-thalassemia from HbE heterozygotes have been investigated. A total of 2133 participants with HbE and HbA with varying HbF levels were recruited. Polymerase chain reaction-based DNA analysis and sequencing were performed to characterize β- and α-globin genes. DNA polymorphism at position −158 nt 5′ to Gγ-globin was performed by XmnI restriction digestion. Receiver operating characteristic (ROC) curves were constructed using the area under the curve (AUC). Cutoff values of HbA2, HbE, and HbF levels for the differentiation of HbE-β+-thalassemia from HbE heterozygotes were determined. Five β+-thalassemia mutations trans to βE-gene (β−87(C>A), β−31(A>G), β−28(A>G), β19(A>G), and β126(T>G)) were identified in 79 patients. Among these, 54 presented with low HbF levels, and 25 presented with high HbF levels. ROC curve analysis revealed an excellent AUC of 1.000 (95% confidence interval:1.000–1.000) for HbE levels, and a cut-off point of ≥35.0% had 100.0% sensitivity, specificity, and Youden's index for differentiating HbE-β+-thalassemia from HbE heterozygotes. The proportion of α-thalassemia mutations was 46.3 and 8.0% among HbE-β+-thalassemia patients with low and high HbF levels, respectively. Two rare α-thalassemia mutations (Cap +14(C>G) and initiation codon (ATG>-TG)) of α2-globin genes were identified. The genotype and allele of the polymorphism at −158 nt 5′ to Gγ-globin was found to be negatively associated with HbF expression. HbE-β+-thalassemia cannot be disregarded until appropriate DNA analysis is performed, and the detection of α-thalassemia mutations should always be performed under these conditions. An HbE level ≥35.0% may indicate screening of samples for DNA analysis for HbE-β+-thalassemia diagnosis. HbE-β+-thalassemia displays a wide range of HbF expression, which may lead to the misdiagnosis of HbE heterozygosity in patients whose Hb analysis shows HbE and HbA. α-Thalassemia may be a major factor associated with decreased secondary activation of HbF expression in the disease. HbE may be a potential indicator for effectively differentiating HbE-β+-thalassemia from HbE heterozygotes. The high proportion and heterogeneity of α-thalassemia mutations found in patients with HbE-β+-thalassemia evoke a complex thalassemia syndrome, requiring complete DNA analysis. [ABSTRACT FROM AUTHOR]

Background: The use of primaquine for mass drug administration (MDA) is being considered as a key strategy for malaria elimination. In addition to being the only drug active against the dormant and relapsing forms of Plasmodium vivax, primaquine is the sole potent drug against mature/infectious Plasmodium falciparum gametocytes. It may prevent onward transmission and help contain the spread of artemisinin resistance. However, higher dose of primaquine is associated with the risk of acute haemolytic anaemia in individuals with a deficiency in glucose-6-phosphate dehydrogenase. In many P. falciparum endemic areas there is paucity of information about the distribution of individuals at risk of primaquine-induced haemolysis at higher dose 45 mg of primaquine. Methods: A retrospective cross-sectional study was carried out using archived samples to establish the prevalence of G6PD deficiency in a malaria hotspot area in Misungwi district, located in Mwanza region, Tanzania. Blood samples collected from individuals recruited between August and November 2010 were genotyped for G6PD deficiency and submicroscopic parasites carriage using polymerase chain reaction. Results: A total of 263 individuals aged between 0 and 87 were recruited. The overall prevalence of the X-linked G6PD A− mutation was 83.7% (220/263) wild type, 8% (21/263) heterozygous and 8.4% (22/263) homozygous or hemizygous. Although, assessment of the enzymatic activity to assign the phenotypes according to severity and clinical manifestation as per WHO was not carried out, the overall genotype and allele frequency for the G6PD deficiency was 16.4% and 13. 2%, respectively. There was no statistically significant difference in among the different G6PD genotypes (p > 0.05). Out of 248 samples analysed for submicroscopic parasites carriage, 58.1% (144/248) were P. falciparum positive by PCR. G6PD heterozygous deficiency were associated with carriage of submicroscopic P. falciparum (p = 0.029). Conclusions: This study showed that 16.4% of the population in this part of North-western Tanzania carry the G6PD A− mutation, within the range of 15–32% seen in other parts of Africa. G6PD gene mutation is widespread and heterogeneous across the study area where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of higher dose of primaquine being associated with the risk of acute haemolytic anaemia (AHA) in individuals with a deficiency in glucose-6-phosphate dehydrogenase and call further research on mapping of G6PD deficiency in Tanzania. Therefore, screening and education programmes for G6PD deficiency is warranted in a programme of malaria elimination using a higher primaquine dose. [ABSTRACT FROM AUTHOR]

Nonlinear optical (NLO) crystals that can generate deep‐ultraviolet (DUV) lasers by the frequency conversion processes play an important role in many basic and frontier research fields. Tetrahedron‐based NLO crystals, which are decent DUV NLO candidates, always exhibit a large DUV transparency window. However, their insufficient birefringence often makes it difficult to satisfy the phase matching condition in the DUV or even UV region. Therefore, some strategies are put forward to improve the phase matching ability of tetrahedron‐based DUV NLO crystals. In this review, the relevant reports are summarized into four categories, including the heterozygosity of tetrahedral groups, the introduction of the planar groups, the combination of the heteroleptic tetrahedrons and the planar groups, and the recombination of polar structures with ferroelectricity. Furthermore, the development tendency of tetrahedron‐based DUV NLO crystals is also discussed. Therefore, this review will be helpful to the exploration of new DUV NLO crystals. [ABSTRACT FROM AUTHOR]

Most population genomic tools rely on accurate single nucleotide polymorphism (SNP) calling and filtering to meet their underlying assumptions. However, genomic complexity, resulting from structural variants, paralogous sequences, and repetitive elements, presents significant challenges in assembling contiguous reference genomes. Consequently, short-read resequencing studies can encounter mismapping issues, leading to SNPs that deviate from Mendelian expected patterns of heterozygosity and allelic ratio. In this study, we employed the ngsParalog software to identify such deviant SNPs in whole-genome sequencing (WGS) data with low (1.5×) to intermediate (4.8×) coverage for four species: Arctic Char (Salvelinus alpinus), Lake Whitefish (Coregonus clupeaformis), Atlantic Salmon (Salmo salar), and the American Eel (Anguilla rostrata). The analyses revealed that deviant SNPs accounted for 22% to 62% of all SNPs in salmonid datasets and approximately 11% in the American Eel dataset. These deviant SNPs were particularly concentrated within repetitive elements and genomic regions that had recently undergone rediploidization in salmonids. Additionally, narrow peaks of elevated coverage were ubiquitous along all four reference genomes, encompassed most deviant SNPs, and could be partially associated with transposons and tandem repeats. Including these deviant SNPs in genomic analyses led to highly distorted site frequency spectra, underestimated pairwise FST values, and overestimated nucleotide diversity. Considering the widespread occurrence of deviant SNPs arising from a variety of sources, their important impact in estimating population parameters, and the availability of effective tools to identify them, we propose that excluding deviant SNPs from WGS datasets is required to improve genomic inferences for a wide range of taxa and sequencing depths. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a genetically and clinically heterogeneous disorder with four described subtypes. Autosomal recessive syndrome of cerebellar ataxia, mental retardation, and disequilibrium type 4 (CAMRQ4) is caused by mutations in the ATP8A2 gene. We report an 8-year-old boy with choreoathetosis, hypotonia, without the ability to keep his head up and profound mental retardation. There was quadrupedal locomotion, as well. MRI of the brain revealed a hypotrophy of the corpus callosum, diffuse white matter reduction, widespread delayed myelination and ventriculomegaly. Trio whole-exome sequencing revealed compound heterozygosity in the ATP8A2 gene consisting of a known variant c.1756C>T (p.Arg586*) inherited from the mother and a novel variant c.691_701delCTGATGAAGTT (p.Leu231fs) inherited from the father. CAMRQ type 4 has been found in about 50 patients. To the best of our knowledge, this is the first reported patient with CAMRQ4 with these gene variants. The clinical presentation is severe. [ABSTRACT FROM AUTHOR]

The Yesso scallop Mizuhopecten yessoensis is an important aquaculture species that was introduced to Western Canada from Japan to establish an economically viable scallop farming industry. This highly fecund species has been propagated in Canadian aquaculture hatcheries for the past 40 years, raising questions about genetic diversity and genetic differences among hatchery stocks. In this study, we compare cultured Canadian and wild Japanese populations of Yesso scallop using double-digest restriction site-associated DNA (ddRAD) sequencing to genotype 21,048 variants in 71 wild-caught scallops from Japan, 65 scallops from the Vancouver Island University breeding population, and 37 scallops obtained from a commercial farm off Vancouver Island, British Columbia. The wild scallops are largely comprised of equally unrelated individuals, whereas cultured scallops are comprised of multiple families of related individuals. The polymorphism rate estimated in wild scallops was 1.7%, whereas in the cultured strains, it ranged between 1.35 and 1.07%. Interestingly, heterozygosity rates were highest in the cultured populations, which is likely due to shellfish hatchery practices of crossing divergent strains to gain benefits of heterosis and to avoid inbreeding. Evidence of founder effects and drift was observed in the cultured strains, including high genetic differentiation between cultured populations and between cultured populations and the wild population. Cultured populations had effective population sizes ranging from 9 to 26 individuals whereas the wild population was estimated at 25,048-56,291 individuals. Further, a depletion of low-frequency variants was observed in the cultured populations. These results indicate significant genetic diversity losses in cultured scallops in Canadian breeding programs. [ABSTRACT FROM AUTHOR]

The genetic characterization of the Iranian honey bee was investigated by analyzing 10 polymorphic DNA microsatellite loci in 300 honey bee samples representative of twenty Iranian provinces. This study evaluated the heterozygosity (Ho and He), the Shannon index, the number of observed alleles, and F-statistics among tested populations as genetic parameters. Our finding demonstrated that the Iranian honey bee populations were described by low genetic diversity in terms of the number of observed alleles, Shannon index, and Heterozygosity values. Most populations had significant deviations from Hardy Weinberg equilibrium cause of heterozygote shortage. Low FST and FIS values proposed the absence or very low genetic diversity within and among A. m. meda populations in the present study. The cluster analysis has categorized the honey bee samples gathered from various regions of Iran into two main groups, including honey bees in the North-West (i.e., North, Northwest, and West) provinces and honey bees in the East-South (i.e., Eastern North, Central part, and Southern) provinces of Iran. Our results also revealed lower genetic differentiation and heterozygosity among tested honey bee populations. The results from this study are consistent with previous investigations in Iran, alarming the loss of genetic diversity in the Iranian honey bee populations, which leads to more homozygosity. This study presented new data and reports on genetic structure in investigated native Iranian honey bee populations, and it will benefit future studies on selection, native biodiversity preservation and other conservation breeding projects. [ABSTRACT FROM AUTHOR]

In the present study, two unrelated cases of Hb Q-Thailand heterozygosity unlinked with the (–α4.2/) α+-thalassemia deletion allele were identified by long-read single molecule real-time (SMRT) sequencing in southern China. The aim of this study was to report the hematological and molecular features as well as diagnostic aspects of the rare manifestation. Hematological parameters and hemoglobin analysis results were recorded. A suspension array system for routine thalassemia genetic analysis and long-read SMRT sequencing were applied in parallel for thalassemia genotyping. Traditional methods, including Sanger sequencing, multiplex gap-polymerase chain reaction (gap-PCR) and multiplex ligation-dependent probe amplification (MLPA), were used together to confirm the thalassemia variants. Long-read SMRT sequencing was used to diagnose two Hb Q-Thailand heterozygous patients for whom the hemoglobin variant was unlinked to the (–α4.2/) allele for the first time. The hitherto undescribed genotypes were verified by traditional methods. Hematological parameters were compared with those of Hb Q-Thailand heterozygosity linked with the (–α4.2/) deletion allele in our study. For the positive control samples, long-read SMRT sequencing revealed a linkage relationship between the Hb Q-Thailand allele and the (–α4.2/) deletion allele. Identification of the two patients confirms that the linkage relationship between the Hb Q-Thailand allele and the (−α4.2/) deletion allele is a common possibility but not a certainty. Remarkably, as it is superior to traditional methods, SMRT technology may eventually serve as a more comprehensive and precise method that holds promising prospects in clinical practice, especially for rare variants. [ABSTRACT FROM AUTHOR]

Guinea pigs are a major source of animal protein for Peruvian Andean families. Despite the economic and cultural relevance of guinea pigs, their genomic characterization has been scarcely addressed. Genotyping‐by‐sequencing (GBS) has emerged as an affordable alternative to genotyping of livestock and native animals. Here, we report the use of GBS for single nucleotide polymorphism (SNP) discovery of traditionally raised guinea pigs from six regions of the Peruvian Andes and one group of breeding animals. The paired‐end (2 × 150 bp) sequencing of 40 guinea pig DNA samples generated a mean of 6.4 million high‐quality sequencing reads per sample. We obtained an average sequencing depth of 10× with an 88.5% mapping rate to the Cavia porcellus reference genome. A total of 279 965 SNPs (102 SNPs/Mbp) were identified after variant calling and quality filtering. Based on this SNP set, we assessed the genetic diversity and distance within our selected guinea pig populations. An overall average minor allele frequency of 0.13, an observed heterozygosity of 0.31, an expected heterozygosity of 0.35, and an F‐value of 0.1 were obtained, while the SNP‐based neighbor‐joining tree suggests a closer genetic relationship between individuals from geographically close locations. We showed that GBS is a cost‐effective tool for SNP discovery and genetic characterization of Peruvian guinea pig populations. Therefore, it may be considered as a suitable and affordable tool for genomic characterization of poorly studied native animal species. [ABSTRACT FROM AUTHOR]

In order to study the genetics of local adaptation in all main deserts of northwest China, whole genomes of 169 individuals were resequenced, which covers 20 populations of Zygophyllum loczyi (Zygophyllales: Zygophylaceae). We describe more than 15 million single nucleotide polymorphisms and numerous InDels. The expected heterozygosity and PIC values associated with local adaptation varied significantly across biogeographic regions. Variation in environmental factors contributes largely to the population genetic structure of Z. loczyi. Bayesian analysis performed with STRUCTURE defined four genetic clusters, while the results of principle component analysis were similar. Our results shows that the Qaidam Desert group appears to be diverging into two branches characterized by significant geographic separation and gene flow with two neighboring deserts. Geological data assume that it is possible that the Taklamakan Desert was the original distribution site, and Z. loczyi could have migrated later on and expanded within other desert areas. The above findings provide insights into the processes involved in biogeography, phylogeny, and differentiation within the northwest deserts of China. [ABSTRACT FROM AUTHOR]

Even in the genomics era, the phylogeny of Neotropical small felids comprised in the genus Leopardus remains contentious. We used whole-genome resequencing data to construct a time-calibrated consensus phylogeny of this group, quantify phylogenomic discordance, test for interspecies introgression, and assess patterns of genetic diversity and demographic history. We infer that the Leopardus radiation started in the Early Pliocene as an initial speciation burst, followed by another in its subgenus Oncifelis during the Early Pleistocene. Our findings challenge the long-held notion that ocelot (Leopardus pardalis) and margay (L. wiedii) are sister species and instead indicate that margay is most closely related to the enigmatic Andean cat (L. jacobita), whose whole-genome data are reported here for the first time. In addition, we found that the newly sampled Andean tiger cat (L. tigrinus pardinoides) population from Colombia associates closely with Central American tiger cats (L. tigrinus oncilla). Genealogical discordance was largely attributable to incomplete lineage sorting, yet was augmented by strong gene flow between ocelot and the ancestral branch of Oncifelis , as well as between Geoffroy's cat (L. geoffroyi) and southern tiger cat (L. guttulus). Contrasting demographic trajectories have led to disparate levels of current genomic diversity, with a nearly tenfold difference in heterozygosity between Andean cat and ocelot, spanning the entire range of variability found in extant felids. Our analyses improved our understanding of the speciation history and diversity patterns in this felid radiation, and highlight the benefits to phylogenomic inference of embracing the many heterogeneous signals scattered across the genome. [ABSTRACT FROM AUTHOR]

Whole genome duplication (WGD) is an evolutionary event resulting in a redundancy of genetic material. Different mechanisms of WGD, allo- or autopolyploidization, lead to distinct evolutionary trajectories of newly formed polyploids. Genome studies on such species are important for understanding the early stages of genome evolution. However, assembling neopolyploid is a challenging task due to the presence of 2 homologous (or homeologous) chromosome sets and therefore the existence of the extended paralogous regions in its genome. Post-WGD evolution of polyploids includes cytogenetic diploidization leading to the formation of species, whose polyploid origin might be hidden by disomic inheritance. Earlier we uncovered the hidden polyploid origin of the free-living flatworms of the genus Macrostomum (Macrostomum lignano , M. janickei , and M. mirumnovem). Cytogenetic diploidization in these species is accompanied by intensive chromosomal rearrangements including chromosomes fusions. In this study, we unravel the M. lignano genome organization through generation and sequencing of 2 sublines of the commonly used inbred line of M. lignano (called DV1) differing only in a copy number of the largest chromosome (MLI1). Using nontrivial assembly free comparative analysis of their genomes, we deciphered DNA sequences belonging to MLI1 and validated them by sequencing the pool of microdissected MLI1. Here we presented the uncommon mechanism of genome rediplodization of M. lignano , which consists of (i) presence of 3 subgenomes, which emerged via formation of large fused chromosomes and its variants, and (ii) sustaining their heterozygosity through inter- and intrachromosomal rearrangements. [ABSTRACT FROM AUTHOR]

The use of genomic data makes it possible to examine genetic variability and calculate the genetic parameters of the population in an efficient and precise way. The aim of this research was to analyse linkage disequilibrium (LD), contemporary effective population size (Nec), haplotype block structure, minor allele frequency (MAF), observed (HO) and expected heterozygosity (HE), calculate the genomic relationship matrix and perform a principal component analysis (PCA) in the Serbian Holstein-Friesian cattle population using SNP data from the GGP Bovine 100K chip. After quality control (QC), 83 208 SNPs and 1 575 cows were retained for further analysis. LD on autosomes had an average value of ≥ 0.2 up to a distance of 50--60 kb (r² = 0.211), while on BTX r² ≥ 0.2 was represented at distances of 80--90 kb (r² = 0.211). LD differed between chromosomes. The average HO for autosomes and X chromosome SNPs was 0.412 and 0.422, respectively. 81.30% of SNPs that passed QC had MAF > 0.2. The total number of haplotype blocks in the studied population was 15 642. On average, blocks contained 2.932 SNPs. The average block length was 32.657 kb and ranged from a minimum of 0.019 kb (BTA21 and BTA26) to a maximum of 999.562 kb (BTX). The estimated value of Nec in the this cattle population was 142. The results of PCA showed a significant variability of genotypes in the population, but there was no clear stratification of the population. The obtained results will serve as a basis for future genomic analyses such as the detection of QTLs for important economic traits and the implementation of genomic selection. [ABSTRACT FROM AUTHOR]

Context: Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies. Objective: We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP). Methods: A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis. Results: Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively. Conclusion: LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS. [ABSTRACT FROM AUTHOR]

Abstract Background The population of the Faroe Islands is an isolated population but very little is known about it from whole genome sequencing. The population of about 50000 people has a high incidence of rare diseases e.g., 1:300 for Primary Carnitine Deficiency. A screening programme was implemented, and eleven persons were also whole genome sequenced at x37 coverage for diagnostic purposes of those cases that were not affected by the known mutations. The purpose of our study is to utilize the high coverage data to explore the genomic variation and the ancestral history of the population. We study the SNP heterozygosity, the pairwise relatedness from kinship, the inbreeding from runs of homozygosity ROH, and we find the minor allele frequency distribution. We estimate the population ancestry and the timing of the founding event by using the whole genomes from eight consenting individuals. Results We find the number of SNPs and the heterozygosity for the eight individual samples, and for merged samples, for which we also study the relatedness. We find close relatedness between the supposedly unrelated individuals. From ROH, we interpret the high relatedness as an ancient property of the isolated population. A bottleneck event is estimated starting between years $$\sim 50-300$$ ∼ 50 - 300 with a maximum consanguineous population in year $$\sim 600$$ ∼ 600 and similarly consanguineous between years $$500-700$$ 500 - 700 . The ancestry analysis shows the population descends from founders of $$>99\%$$ > 99 % European and $$

Purpose. To study the genetic peculiarities of pedigree tocksof Amur carp and evaluate its genetic variability by analyzing distribution of alleles and genotypes by the specific protein systems and cytogenetic parameters. Methodology. Analysis of polymorphism of protein systems was performed using electrophoresis in polyacrylamide gel. As protein markers to evaluate the genetic structure of Amur carp stocks, the separation of allelic and genotypic frequencies by loci, which encode a number of fish blood proteins, were used: transferrin (TF), albumin (ALB) and esterase (EST, 3.1.1.1). Cytogenetic analysis was performed using the micronucleus test and analysis of apoptosisfrequencies. Collection and processing of biological material of fish as well as statistical processing of the obtained data was performed using generally accepted methods. Findings. A comprehensive analysis of the genetic structure of Amur carp from three farms in Ukraine was carried out by protein systems and cytogenetic markers. The results of the study showed that all pedigree groups of Amur carp were characterized by a deviation towards the predominance of heterozygotes (Fis = from –0.084 to –0.344). A minimal imbalance was observed in the group of carp from the farm “Karpatskyi Vodogray” LLC (Fis = –0.084). The maximum violation of the genetic balance was found in carp from the farm of JSC “Sumyrybhosp” (Fis = –0.308) and in the group from the experimental farm “Veliky Lyubin” (Fis = –0.344). In general, the analysis of the protein systems of fish blood showed a high level of heterogeneity of pedigree stocks of Amur carp from different farms in Ukraine. The analysis of frequencies of cytogenetic parameters of Amur carp from three fish farms showed that fish from fish farms of JSC “Sumyrybhosp” and PFE “Dzherelo” were characterized by a lower frequency of erythrocytes with micronuclei (EMN) (3.3±0.3 ‰), (3.2±0.3 ‰), lymphocytes with micronuclei (LMN) (2.1±0, 2 ‰), (1.9±0.2 ‰), and apoptosis (4.2±0.3‰), (4,3±0,3‰) compared to the group from fish farm “Karpatskyi Vodogray” LLC, where these values were as follows: EMN (4.7±0.3 ‰), LMN (2.4±0.2‰), apoptosis (5.6±0.4‰). These results indicates a lower level of destabilization of chromosomal apparatus of Amur carp from the fish farm JSC “Sumyrybhosp” at the time of the study. Originality. A comprehensive evaluation of the level of variability of the genetic structure of pedigree stocks of Amur carp from different regions of Ukraine was performed for the first time. Practical Value. Pedigree socksof Amur carp have important practical value in selective breeding work with carps, including works for obtaining hybrid lines to increase the resistance of breeding material.

Mung bean (Vigna radiata L. Wilczek) is a self‐pollinating and indispensable pulse crop in Indonesia. While low yield productivity is a major concern, genetic improvement is possible through interspecific hybridization. However, interspecific hybridization is relatively infrequent and produces low recombination exchanges, significantly limiting crop breeding efficiency. Thus, a comprehensive study is needed of the selection and genetic diversity evaluation of progenies in advanced generations derived from interspecific hybridization using a specific molecular marker. This study aims to confirm the heterozygosity in the F2 population and assess the genetic diversity in F3 mung bean populations resulting from interspecific hybridization between the mung bean and common bean. We designed the retrotransposon‐based insertion polymorphism (RBIP) marker by identifying the syntenic regions in the flanking sequences of retrotransposon insertion in common bean and mung bean. The RBIP marker can be applied to distinguish the heterozygote progenies from the homozygote progenies. Six combinations of sequence‐related amplified polymorphism (SRAP) primers were used in the genotyping of F3 mung bean progenies. The SRAP marker showed a high degree of polymorphism of up to 100%, while high genetic variation was observed within the population (71%) of mung bean progenies. The F3.4 population had the greatest number of genotypes and displayed the highest number of effective alleles, private alleles, and percentage of polymorphic loci, suggesting the existence of high genetic diversity within this population. These genetic diversity data are exceptionally critical for future genetic research since it has potentially high yield production. The genomic and marker‐assisted selection studies will support the major goals of the mung bean breeding program.

We describe a case of collodion baby diagnosed prenatally by ultrasound. Classic signs (ectropion, flattened nose, and eclabion) were detected on routine ultrasound at 21 weeks of gestation. At birth, the presence of collodion membrane was confirmed and subsequently, the diagnosis of an autosomal recessive congenital ichthyosis due to compound heterozygosity of the TGM1 gene was made. [ABSTRACT FROM AUTHOR]

This document is an editorial written by David H. Sachs for the 30th anniversary of the journal Xenotransplantation. Sachs reflects on the predictions he made when the journal first began and compares them to the progress made in the field of xenotransplantation over the past 30 years. He discusses the potential of xenografts (transplants between different species) and the challenges that need to be overcome, such as immune responses and non-immunologic differences between species. Sachs also predicts that clinical trials for xenograft organs, particularly for heart and kidney transplants, will begin in the near future. He expresses optimism about the role of xenotransplantation in providing organs to patients in need and reducing the risk to living donors. [Extracted from the article]

This article presents a case report of a 7-month-old female with hyper-IgM syndrome type 3 (HIGM-3), a rare immunodeficiency disorder. The patient had two previously unreported gene defects in CD40, which confirmed the diagnosis of HIGM-3. The article discusses the immunological characteristics and susceptibility to infections in patients with HIGM-3, as well as the treatment options, including immunoglobulin replacement therapy and hematopoietic stem cell transplantation. The authors highlight the importance of thorough evaluation in cases with unknown gene variants and emphasize the need for further research in this area. [Extracted from the article]

The “cost of domestication” hypothesis suggests that the domestication of wild species increases the number, frequency, and/or proportion of deleterious genetic variants, potentially reducing their fitness in the wild. While extensively studied in domesticated species, this phenomenon remains understudied in fungi. Here, we used Saccharomyces cerevisiae, the world’s oldest domesticated fungus, as a model to investigate the genomic characteristics of deleterious variants arising from fungal domestication. Employing a graph-based pan-genome approach, we identified 1,297,761 single nucleotide polymorphisms (SNPs), 278,147 insertion/deletion events (indels; S. cerevisiae showed reduced rates of adaptive evolution relative to the wild S. cerevisiae. In summary, deleterious variants tend to be heterozygous, which may mitigate their harmful effects, but they also constrain breeding potential. Addressing deleterious alleles and minimizing the genetic load are crucial considerations for future S. cerevisiae breeding efforts.

The objective of the present study was to analyze the genetic diversity, individual-based assessment of population structure, and admixture in the Dülmen wild horse population in comparison to warmblood, coldblood, and primitive horse populations. The Dülmen wild horse is kept as a unique horse population in the Merfelder Bruch near Dülmen in Westphalia, Germany, and since 1856 has been managed by the Dukes of Croÿ. The Dülmen wild horse population is exposed to the natural conditions of the Merfelder Bruch all year round without human interventions for feeding and veterinary care. In the present study, genetic diversity was estimated for 101 Dülmen wild horses using multilocus genotypic information from a set of 29 autosomal microsatellites and compared with 587 horses from 17 different horse populations. Dülmen wild horses maintained a high degree of genetic diversity, with an average observed heterozygosity of 0.68, a mean number of 6.17 alleles, and heterozygote deficit of −0.035. Pairwise genetic distances (FST, Nei’s standard, and Cavalli-Sforza distances) were closest to German coldblood breeds, Polish Konik, and Icelandic horses and most divergent from Sorraia and Przewalski’s horses. Neighbor joining dendrogram and PCA plots showed a clear distinction of Dülmen wild horses from other populations, particularly from Przewalski horses. Posterior Bayesian analysis confirmed clear differentiation from other horse populations without an admixture pattern and a high membership index (0.92). It was possible to distinguish Dülmen wild horses from Dülmen and Polish Konik horses. In conclusion, Dülmen wild horses show a notable separation from other German horse breeds and primitive horse populations and may serve as a resource to study evolution of equine domestication.

Abstract Rapid environmental change presents a significant challenge to the persistence of natural populations. Rapid adaptation that increases population growth, enabling populations that declined following severe environmental change to grow and avoid extinction, is called evolutionary rescue. Numerous studies have shown that evolutionary rescue can indeed prevent extinction. Here, we extend those results by considering the demographic history of populations. To evaluate how demographic history influences evolutionary rescue, we created 80 populations of red flour beetle, Tribolium castaneum, with three classes of demographic history: diverse populations that did not experience a bottleneck, and populations that experienced either an intermediate or a strong bottleneck. We subjected these populations to a new and challenging environment for six discrete generations and tracked extinction and population size. Populations that did not experience a bottleneck in their demographic history avoided extinction entirely, while more than 20% of populations that experienced an intermediate or strong bottleneck went extinct. Similarly, among the extant populations at the end of the experiment, adaptation increased the growth rate in the novel environment the most for populations that had not experienced a bottleneck in their history. Taken together, these results highlight the importance of considering the demographic history of populations to make useful and effective conservation decisions and management strategies for populations experiencing environmental change that pushes them toward extinction.

Abstract Germ cell tumors complicated by hematological malignancy (HM) are a rare clinical phenomenon. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially effective therapy, but graft‐versus‐host disease (GVHD) is a life‐threatening complication. We report a case of a 13‐year‐old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia. After chemotherapy, she received allo‐HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence. However, she developed severe, multiorgan GVHD‐like manifestations. DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.

Abstract Background Moso bamboo (Phyllostachys edulis) is a typical East Asian bamboo that does not flower for > 60 years and propagates without seed reproduction. Thus, Moso bamboo can be propagated vegetatively, possibly resulting in highly heterozygous genetic inheritance. Recently, a draft genome of Moso bamboo was reported, followed by whole genome single nucleotide polymorphisms (SNP) analysis, which showed that the genome of Moso bamboo in China has regional characteristics. Moso bamboo in Japan is thought to have been introduced from China over the sea in 1736. However, it is unclear where and how Moso bamboo was introduced in Japan from China. Here, based on detailed analysis of heterozygosity in genome diversity, we estimate the spread of genome diversity and its pedigree of Moso bamboo. Results We sequenced the whole genome of Moso bamboo in Japan and compared them with data reported previously from 15 regions of China. Only 4.1 million loci (0.37% of the analyzed genomic region) were identified as polymorphic loci. We next narrowed down the number of polymorphic loci using several filters and extracted more reliable SNPs. Among the 414,952 high-quality SNPs, 319,431 (77%) loci were identified as heterozygous common to all tested samples. The result suggested that all tested samples were clones via vegetative reproduction. Somatic mutations may accumulate in a heterozygous manner within a single clone. We examined common heterozygous loci between samples from Japan and elsewhere, from which we inferred that an individual closely related to the sample from Fujian, China, was introduced to Japan across the sea without seed reproduction. In addition, we collected 16 samples from four nearby bamboo forests in Japan and performed SNP and insertion/deletion analyses using a genotyping by sequencing (GBS) method. The results suggested that a small number of somatic mutations would spread within and between bamboo groves. Conclusions High heterozygosity in the genome-wide diversity of Moso bamboo implies the vegetative propagation of Moso bamboo from China to Japan, the pedigree of Moso bamboo in Japan, and becomes a useful marker to approach the spread of genome diversity in clonal plants.

INTRODUCTION: We focused on a sample size of 141 unrelated Rwandan persons to genotype 21 STR loci that were relied up in establishing allele frequencies, heterozygosity and power of exclusion. This study aims at exploring allele frequencies on a representative sample from Rwandan population to determine probability of paternity for sampled families basing on polymorphic STRs loci, using 21 autosomal-STR loci by Genetic Analyzer 3500X. METHODS: This was an experimental study and global filer TM Express PCR Amplification kit was used to amplify 21 autosomal STR loci. RESULTS: The total number of observed alleles was 270; the largest number of different alleles was seen in SE33 and D18S51 loci. The locus with the highest heterozygosity was SE33, while locus TH01 had the lowest heterozygosity. The heterozygosity of the 21 STR loci ranged from 71.3% (TH01) to 91.6% (SE33) with an average of 81.1% a good indicator of high genetic variability. For all microsatellites analyzed the power of exclusion ranged from 43.4% (TH01) to 78.1% (SE33) with an average of 58.2%. For seven of eight cases examined in paternity test alleged father was not excluded as biological father of child. The results found in examination of case 8 indicated that the alleged father was not the biological father of the child. CONCLUSION: Based on calculated statistical parameters, the population of Rwanda may use these 21 STR loci as a vital tool for forensic identification and paternity testing.

A molecular investigation of large-leaved Gunnera growing outside in Britain and Ireland was conducted. Two low-copy nuclear CYCLOIDEA-like genes (CYC-like 1 and CYC-like 2) and two chloroplast DNA regions (matK and psbD-trnT) were sequenced for 271 samples of Gunnera. While it was confirmed that genuine G. tinctoria is growing both in cultivation and in the wild, the results support recently published morphological and historical findings that the species G. manicata appears no longer to be present in Britain and Ireland. Instead, the plant under this name is G. × cryptica, a hybrid between G. manicata and G. tinctoria. The implication of this discovery for legislation on invasive non-native species where G. manicata and G. tinctoria are listed is explored.

Background: The population of the Faroe Islands is an isolated population but very little is known about it from whole genome sequencing. The population of about 50000 people has a high incidence of rare diseases e.g., 1:300 for Primary Carnitine Deficiency. A screening programme was implemented, and eleven persons were also whole genome sequenced at x37 coverage for diagnostic purposes of those cases that were not affected by the known mutations. The purpose of our study is to utilize the high coverage data to explore the genomic variation and the ancestral history of the population. We study the SNP heterozygosity, the pairwise relatedness from kinship, the inbreeding from runs of homozygosity ROH, and we find the minor allele frequency distribution. We estimate the population ancestry and the timing of the founding event by using the whole genomes from eight consenting individuals. Results: We find the number of SNPs and the heterozygosity for the eight individual samples, and for merged samples, for which we also study the relatedness. We find close relatedness between the supposedly unrelated individuals. From ROH, we interpret the high relatedness as an ancient property of the isolated population. A bottleneck event is estimated starting between years ∼ 50 - 300 with a maximum consanguineous population in year ∼ 600 and similarly consanguineous between years 500 - 700 . The ancestry analysis shows the population descends from founders of > 99 % European and < 1 % Admixed American ancestry. A distinct clustering near the central European and British populations of the 1000 Genome Project is likely the result of the population isolation and genetic drift. The minor allele frequency distribution suggests many rare variants. Conclusions: The ancestry is mainly European while the inbreeding is higher compared to European populations and population isolates. The Faroese population has inbreeding more like ancient Europeans. We discovered a bottlenecked and consanguineous population event and estimated it starting in the 1st-4th century as compared to the oldest archaeological findings from the 4th-6th century. [ABSTRACT FROM AUTHOR]

Local sheep in the northeastern Tarim Basin can adapt to dry and low-rainfall regional environments. In this study, three local sheep breeds in the northeastern Tarim Basin, LOP (LOP) sheep, Bayinbuluke (BYK) sheep, and Kunlun (KUN, also known as the Qiemo sheep) sheep, and three introduced sheep breeds, Suffolk (SUF) sheep, Dorset (APD) sheep, and Texel (TEX) sheep, were analyzed for genetic diversity, population structure, and selective signature using the Illumina OvineSNP50K BeadChip. We found that LOP, BYK, and KUN had lower observed heterozygosity and expected heterozygosity than TEX, SUF, and ADP, which were differentiated based on geographic distribution. We performed fixation index (FST) analysis on three local sheep breeds in the northeastern Tarim Basin (LOP, BYK, and KUN) and introduced sheep breeds (TEX, SUF, and ADP) to measure genetic differentiation. Nucleotide diversity (PI) analysis was performed on singlenucleotide polymorphism (SNP) data of LOP, BYK, and KUN. A total of 493 candidate genes were obtained by taking the intersection at a threshold of 5%. Among them, SMAD2, ESR2, and HAS2 were related to reproductive traits. PCDH15, TLE4, and TFAP2B were related to growth traits. SOD1, TSHR, and DNAJB5 were related to desert environmental adaptation. Analyzing the genetic patterns of local sheep in the northeastern Tarim Basin can protect the germplasm resources of local sheep and promote the development and utilization of sheep genetic resources. [ABSTRACT FROM AUTHOR]

Mate-allocation strategies in breeding programs can improve progeny performance by harnessing non-additive genetic effects. These approaches prioritise predicted progeny merit over parental breeding value, making them particularly appealing for clonally propagated crops such as sugarcane. We conducted a comparative analysis of mate-allocation strategies, exploring utilising non-additive and heterozygosity effects to maximise clonal performance with schemes that solely consider additive effects to optimise breeding value. Using phenotypic and genotypic data from a population of 2,909 clones evaluated in final assessment trials of Australian sugarcane breeding programs, we focused on three important traits: tonnes of cane per hectare (TCH), commercial cane sugar (CCS), and Fibre. By simulating families from all possible crosses (1,225) with 50 progenies each, we predicted the breeding and clonal values of progeny using two models: GBLUP (considering additive effects only) and extended-GBLUP (incorporating additive, non-additive, and heterozygosity effects). Integer linear programming was used to identify the optimal mate-allocation among selected parents. Compared to breeding value-based approaches, mate-allocation strategies based on clonal performance yielded substantial improvements, with predicted progeny values increasing by 57% for TCH, 12% for CCS, and 16% for fibre. Our simulation study highlights the effectiveness of mate-allocation approaches that exploit non-additive and heterozygosity effects, resulting in superior clonal performance. However, there was a notable decline in additive gain, particularly for TCH, likely due to significant epistatic effects. When selecting crosses based on clonal performance for TCH, the inbreeding coefficient of progeny was significantly lower compared to random mating, underscoring the advantages of leveraging non-additive and heterozygosity effects in mitigating inbreeding depression. Thus, mate-allocation strategies are recommended in clonally propagated crops to enhance clonal performance and reduce the negative impacts of inbreeding. [ABSTRACT FROM AUTHOR]

Simple Summary: Threatened animal species live in small and isolated populations, often with a reduced number of individuals and reduced genetic diversity. In this review, we summarise studies on amphibian species that examined the effect of genetic diversity on the fitness of individuals or populations. We found evidence for the positive association between genetic diversity and different estimates of fitness where low genetic diversity is associated with lower fitness. Published studies are however scarce, concentrated on a handful species and with a high proportion of non-significant results reported. For the maintenance of amphibian and other animal populations, it is important to increase the research effort in this topic and, for imperilled populations, enhance genetic diversity through different types of conservation measures. Endangered animals suffer from isolation of their habitats. Isolation leads to a reduction in population size as well as a decrease in genetic diversity and a concomitant increase in the risk of extinction. Amphibians are the most endangered vertebrate class. Besides habitat loss, fragmentation and isolation, amphibians are threatened by emerging diseases e.g., chytrid fungus or Ranavirus. By employing experiments, researchers investigate whether changes in genetic diversity within or among isolated populations affect amphibian fitness. While genetic diversity estimates are based on molecular markers, typically microsatellites, fitness is mostly measured as tadpole performance in rearing experiments often under varying environmental conditions. Tadpole performances (e.g., body mass, growth rate and survival) have been found to be negatively affected by low genetic diversity, as several studies have found a positive association between genetic diversity and these fitness traits. Moreover, infection with pathogens also seems to be more likely in individuals or populations with lower genetic diversity. Overall, these genetic–fitness correlations seem to be more pronounced or detectable in smaller, declining populations but not in larger populations. Genomic studies, which sample a larger fraction of the genome, are still scarce in the conservation genetic literature on amphibians. These are likely to increase in upcoming years and may reveal adaptive variants that protect against dangerous pathogens or environmental changes. Altogether, genetic–fitness correlation studies should be a priority in order to develop effective management plans for the genetic rescue of isolated, imperilled amphibian populations. [ABSTRACT FROM AUTHOR]

Background: Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (TP53) and proliferation (CDKN2A, MYC, NOTCH1) has been described as typical aberrations in RT. Results: A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40–60% of cases) were represented by MYC rearrangement/gain, deletions of TP53 and CDKN2A, IGH rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant. Conclusions: Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution. [ABSTRACT FROM AUTHOR]

Objective: Reduced diversity at Human Leukocyte Antigen (HLA) loci may adversely affect the host’s ability to recognize tumor neoantigens and subsequently increase disease burden. We hypothesized that increased heterozygosity at HLA loci is associated with a reduced risk of developing colorectal cancer (CRC). Methods: We imputed HLA class I and II four-digit alleles using genotype data from a population-based study of 5,406 cases and 4,635 controls from the Molecular Epidemiology of Colorectal Cancer Study (MECC). Heterozygosity at each HLA locus and the number of heterozygous genotypes at HLA class -I (A, B, and C) and HLA class -II loci (DQB1, DRB1, and DPB1) were quantified. Logistic regression analysis was used to estimate the risk of CRC associated with HLA heterozygosity. Individuals with homozygous genotypes for all loci served as the reference category, and the analyses were adjusted for sex, age, genotyping platform, and ancestry. Further, we investigated associations between HLA diversity and tumor-associated T cell repertoire features, as measured by tumor infiltrating lymphocytes (TILs; N=2,839) and immunosequencing (N=2,357). Results: Individuals with all heterozygous genotypes at all three class I genes had a reduced odds of CRC (OR: 0.74; 95% CI: 0.56-0.97, p= 0.031). A similar association was observed for class II loci, with an OR of 0.75 (95% CI: 0.60-0.95, p= 0.016). For class-I and class-II combined, individuals with all heterozygous genotypes had significantly lower odds of developing CRC (OR: 0.66, 95% CI: 0.49-0.87, p= 0.004) than those with 0 or one heterozygous genotype. HLA class I and/or II diversity was associated with higher T cell receptor (TCR) abundance and lower TCR clonality, but results were not statistically significant. Conclusion: Our findings support a heterozygote advantage for the HLA class-I and -II loci, indicating an important role for HLA genetic variability in the etiology of CRC. [ABSTRACT FROM AUTHOR]

Cerebral Cavernous Malformations (CCMs) are vascular malformations of the central nervous system which can lead to moderate to severe neurological phenotypes in patients. A majority of CCM lesions are driven by a cancer-like three-hit mutational mechanism, including a somatic, activating mutation in the oncogene PIK3CA, as well as biallelic loss-of-function mutations in a CCM gene. However, standard sequencing approaches often fail to yield a full complement of pathogenic mutations in many CCMs. We suggest this reality reflects the limited sensitivity to identify low-frequency variants and the presence of mutations undetectable with bulk short-read sequencing. Here we report a single-nucleus DNA-sequencing approach that leverages the underlying biology of CCMs to identify lesions with somatic loss-of-heterozygosity, a class of such hidden mutations. We identify an alternative genetic mechanism for CCM pathogenesis and establish a method that can be repurposed to investigate the genetic underpinning of other disorders with multiple somatic mutations. Here the authors establish somatic loss-of-heterozygosity as a genetic underpinning of Cerebral Cavernous Malformations (CCMs): using single-nucleus DNA sequencing, they show homozygosity of chromosomes 7p and/or 7q leads to biallelic inactivation of CCM genes in resected lesions. [ABSTRACT FROM AUTHOR]

The whiteleg shrimp (Litopenaeus vannamei) is one of the most economically important aquaculture species in China. Genetic diversity is crucial for maintaining the gene pool of farmed shrimp. In this study, the effects of artificial selection on the genetic structure of four whiteleg shrimp strains were evaluated using microsatellite sequences. The results showed that the observed heterozygosity (Ho), expected heterozygosity (He), and the polymorphism information content (PIC) of the four selected strains ranged from 0.446 to 0.574, 0.450 to 0.566, and 0.435 to 0.509, respectively. All the selected strains maintained a moderate level of genetic diversity. Most inbreeding coefficients (Fis) in the four strains were positive but not significantly different from zero, indicating a relatively low degree of inbreeding within each strain. However, He and PIC in line 5 showed a decreasing trend from the 2017 to the 2019 generations, and Fis in line 10 showed a significant increasing trend across generations, indicating that measures must be taken to maintain the level of genetic diversity for lines 5 and 10. UPGMA cluster trees showed that the four breeding lines had apparent genetic differences, which could provide a genetic basis for studying crossbreeding between selective lines and the utilization of heterosis. This study will be useful for population genetic research and the breeding strategies of whiteleg shrimp. [ABSTRACT FROM AUTHOR]

The aim of the present experiment was to study the genetic diversity in 79 individuals from the Rhodope Shorthorn cattle breed, raised in the region of Smolyan, Bulgaria. For the purpose of the experiment was used a panel of 11 microsatellite markers. A total of 103 alleles were identified and 7 of them were population-specific. The allele number per locus varied from 6 (BM1824) to 14 (TGLA53), with a mean number of 9.36. The highest number of heterozygotes (72) was observed in locus TGLA227 (n = 79). The lowest number of heterozygotes (41) was detected in locus ETH10 (n = 79). Microsatellite markers used in the current experiment showed PIC from 0.52 (ETH10) to 0.88 (ETH3), with a mean value of 0.897. Observed heterozygosity (Ho) varied from 0.767 (locus ETH10) to 0.946 (INRA23). Expected heterozygosity (genetic diversity - He) varied from 0.205 in locus ETH10 to 0.819 in locus TGLA227. Heterozygosity for all investigated loci was Ho = 0.897 and He = 0.586. Effective allele number (N) was between 7 (ETH10, INRA 23) and 14 (TGLA 53). Estimated values (PIC, Ho, He, and MNA) showed that all studied markers were polymorphic. All tested loci were with high Polymorphic information content (>0.5) and Ho > 0.6. [ABSTRACT FROM AUTHOR]

Although current long-read sequencing technologies have a long-read length that facilitates assembly for genome reconstruction, they have high sequence errors. While various assemblers with different perspectives have been developed, no systematic evaluation of assemblers with long reads for diploid genomes with varying heterozygosity has been performed. Here, we evaluated a series of processes, including the estimation of genome characteristics such as genome size and heterozygosity, de novo assembly, polishing, and removal of allelic contigs, using six genomes with various heterozygosity levels. We evaluated five long-read-only assemblers (Canu, Flye, miniasm, NextDenovo and Redbean) and five hybrid assemblers that combine short and long reads (HASLR, MaSuRCA, Platanus-allee, SPAdes and WENGAN) and proposed a concrete guideline for the construction of haplotype representation according to the degree of heterozygosity, followed by polishing and purging haplotigs, using stable and high-performance assemblers: Redbean, Flye and MaSuRCA. [ABSTRACT FROM AUTHOR]

Simple Summary: Population genetic structure and individual multilocus heterozygosity are vital for wildlife management. Traditionally, microsatellite markers have been used to estimate population genetic parameters, but single-nucleotide polymorphisms (SNPs) have gained popularity due to their greater measurement precision. This study compared genetic estimates at the population and individual levels using microsatellite and SNP markers in red deer (Cervus elaphus). The findings revealed correlations between parameters estimated with both markers that were associated with the level of genetic diversity and genetic differentiation. However, microsatellites showed lower accuracy in representing the distribution of genetic diversity among individuals. The analysis of population genetic structure and individual multilocus heterozygosity are crucial for wildlife management and conservation. Microsatellite markers have traditionally been used to assess these genetic parameters. However, single-nucleotide polymorphisms (SNPs) are becoming increasingly popular. Our goal here was to determine to what extent SNPs can provide better insights than microsatellites into the overall genetic status and population genetic processes in the species. To this end, we genotyped 210 red deer (Cervus elaphus) in the Spanish wild population with both 11 microsatellites and 31,712 SNPs. We compared parameters related to population genetic structure and individual multilocus heterozygosity obtained with both types of markers. Our results showed correlations between parameters measured using both microsatellites and SNPs, particularly those related to the level of genetic diversity and genetic differentiation. However, we found notably lower precision of microsatellites in measuring the distribution of genetic diversity among individuals. We conclude that microsatellites can be used to monitor the overall genetic status and detect broad patterns in red deer populations. Nevertheless, the greater precision of SNPs in inferring genetic structure and multilocus heterozygosity leads us to encourage scientists and wildlife managers to prioritize their use whenever possible. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to limited reporting of genomic resources for deep-sea organisms, studies of their adaptive mechanisms for extreme environments have been hindered. A genome survey of the snail Provanna glabra, a representative species in deep-sea chemosynthetic ecosystem, was conducted based on Illumina sequencing. Genome size, repetitive elements, heterozygosity, and other genome features were estimated and characterized. A draft genome and a complete mitochondrial genome were assembled for P. glabra, and candidate molecular markers were identified. Phylogenetic analysis based on mitochondrial genes was performed. The results provide effective genome information for P. glabra and supply a basis for further high-quality genome map construction and biogeography study of this deep-sea chemosynthetic snail. The snail P. glabra is an endemic species in deep-sea chemosynthetic ecosystems of the Northwest Pacific Ocean. To obtain more genetic information on this species and provide the basis for subsequent whole-genome map construction, a genome survey was performed on this snail from the hydrothermal vent of Okinawa Trough. The genomic size of P. glabra was estimated to be 1.44 Gb, with a heterozygosity of 1.91% and a repeated sequence content of 69.80%. Based on the sequencing data, a draft genome of 1.32 Gb was assembled. Transposal elements (TEs) accounted for 40.17% of the entire genome, with DNA transposons taking the highest proportion. It was found that most TEs were inserted in the genome recently. In the simple sequence repeats, the dinucleotide motif was the most enriched microsatellite type, accounting for 53% of microsatellites. A complete mitochondrial genome of P. glabra with a total length of 16,268 bp was assembled from the sequencing data. After comparison with the published mitochondrial genome of Provanna sp. from a methane seep, 331 potential single nucleotide polymorphism (SNP) sites were identified in protein-coding genes (PCGs). Except for the cox1 gene, nad2, nad4, nad5, and cob genes are expected to be candidate markers for population genetic and phylogenetic studies of P. glabra and other deep-sea snails. Compared with shallow-water species, three mitochondrial genes of deep-sea gastropods exhibited a higher evolutionary rate, indicating strong selection operating on mitochondria of deep-sea species. This study provides insights into the genome characteristics of P. glabra and supplies genomic resources for further studies on the adaptive evolution of the snail in extreme deep-sea chemosynthetic environments. [ABSTRACT FROM AUTHOR]

Introduction: Factor X deficiency is a rare inherited bleeding disorder. To date, 181 variants are reported in the recently updated F10‐gene variant database. Aim: This study aimed to describe new F10 variants. Method: The F10 gene was analysed in 16 consecutive families with FX deficiency by a targeted high‐throughput sequencing approach, including F10, F9, F8 genes, and 78 genes dedicated to haematological malignancies. Results: We identified 19 variants (17 missense, one nonsense and one frameshift) and two copy number variations. Two patients presenting a combined FVII‐FX deficiency showed a loss of one F10 gene copy (del13q34) associated with a missense variant on the remaining allele, leading to a FX:C significantly lower than the FVII:C level and explaining their unusual bleeding history. We reported five novel variants. Three missense variants (p.Glu22Val affecting the signal peptide cleavage site, p.Cys342Tyr removing the disulphide bond between the FX heavy and light chains, and p.Val385Met located in FX peptidase S1 domain) were detected at compound heterozygosis status in three patients with severe bleeding symptoms and FX:C level below 10 IU/dL. Two truncating variants p.Tyr279* and p.Thr434Aspfs*13 leading to an altered FX protein were found at heterozygous state in two patients with mild bleeding history. Conclusion: This study showed the feasibility and the interest of high‐throughput sequencing approach for rare bleeding disorders, enabling the report of F10 gene screening in a 3‐weeks delay, suitable for clinical use. The description of five new variants may contribute to a better understanding of the phenotype‐genotype correlation in FX deficiency. [ABSTRACT FROM AUTHOR]

We have used Daphnia cucullata (Crustacea: Cladocera) as a model organism for the first time in the four deepest Latvian lakes from the Boreal biogeographical region in order to find the genetic diversity of these populations. During the research, we detected the most appropriate microsatellite markers for future genetic studies of Daphnia cucullata populations of lakes Svente, Riča, Dridzis and Geraņimovas-Ilzas in the Boreal biogeographical region. Based on these microsatellite markers, we determined the genetic diversity of these populations. The loci Dgm105 and Dgm101 had the maximum number of alleles and the maximum number of private alleles. The specific locus Dgm105 had five private alleles (62% of all detected alleles), and locus Dgm101 had four private alleles (57% of all detected alleles) in these loci. We determined the observed heterozygosity (Hobs) and the expected heterozygosity (Hexp) level (via Hardy–Weinberg equilibrium), the number of polymorphic loci, the number of detected alleles in each analyzed microsatellite locus, the average number of alleles at the locus (Na), the average effective number of alleles at the locus (Ne), the FST of the population's genetic differentiation, the genetic distance (D) (following Nei) and the significance (χ2-test) of differences between the levels of observed and expected heterozygosity. It was shown that Daphnia cucullata populations from lakes with a low number of zooplankton taxa (Riča and Geraņimovas-Ilzas) have a higher genetic diversity compared to lakes with a high number of zooplankton taxa (Dridzis and Svente). It was found that Daphnia cucullata populations from lakes Dridzis and Svente have the least genetic distance, and these populations form a single genetic group, as confirmed via clustering. [ABSTRACT FROM AUTHOR]

This study is the first to report the characterization of Carex pumila genomic information. Assembly of the genome generated a draft of C. pumila based on PacBio Sequel II and Illumina paired-end sequencing, which was assembled from 2941 contigs with an estimated genome size of 0.346 Gb. The estimate of repeats in the genome was 31.0%, and heterozygosity ranged from 0.426 to 0.441%. The integrity evaluation of the assembly revealed 1481 complete benchmarked universal single-copy orthologs (BUSCO) (91.76%), indicating the high quality of the draft assembly. A total of 23,402 protein-coding genes were successfully predicted and annotated in the protein database. UpsetR plots showed that 7481 orthogroups were shared by all species. The phylogenetic tree showed that C. pumila is a close but distant relative of Ananas comosus. C. pumila had greater contraction (3154) than expansion (392). Among the extended gene families, aquaporins have been found to be enriched. Primers for microsatellite markers determined 30 polymorphic markers out of 100. The average number of alleles amplified by these 30 polymorphic markers was 4 to 12, with an average polymorphism information content (PIC) value of 0.660. In conclusion, our study provides a useful resource for comparative genomics, phylogeny, and future population studies of C. pumila. [ABSTRACT FROM AUTHOR]

Calcification of the cerebral microvessels in the basal ganglia in the absence of systemic calcium and phosphate imbalance is a hallmark of primary familial brain calcification (PFBC), a rare neurodegenerative disorder. Mutation in genes encoding for sodium‐dependent phosphate transporter 2 (SLC20A2), xenotropic and polytropic retrovirus receptor 1 (XPR1), platelet‐derived growth factor B (PDGFB), platelet‐derived growth factor receptor beta (PDGFRB), myogenesis regulating glycosidase (MYORG), and junctional adhesion molecule 2 (JAM2) are known to cause PFBC. Loss‐of‐function mutations in XPR1, the only known inorganic phosphate exporter in metazoans, causing dominantly inherited PFBC was first reported in 2015 but until now no studies in the brain have addressed whether loss of one functional allele leads to pathological alterations in mice, a commonly used organism to model human diseases. Here we show that mice heterozygous for Xpr1 (Xpr1WT/lacZ) present with reduced inorganic phosphate levels in the cerebrospinal fluid and age‐ and sex‐dependent growth of vascular calcifications in the thalamus. Vascular calcifications are surrounded by vascular basement membrane and are located at arterioles in the smooth muscle layer. Similar to previously characterized PFBC mouse models, vascular calcifications in Xpr1WT/lacZ mice contain bone matrix proteins and are surrounded by reactive astrocytes and microglia. However, microglial activation is not confined to calcified vessels but shows a widespread presence. In addition to vascular calcifications, we observed vessel tortuosity and transmission electron microscopy analysis revealed microangiopathy—endothelial swelling, phenotypic alterations in vascular smooth muscle cells, and thickening of the basement membrane. [ABSTRACT FROM AUTHOR]

Meiotic crossovers can be formed through the interfering pathway, in which one crossover prevents another from forming nearby, or by an independent non-interfering pathway. In Arabidopsis, local sequence polymorphism between homologs can stimulate interfering crossovers in a MSH2-dependent manner. To understand how MSH2 regulates crossovers formed by the two pathways, we combined Arabidopsis mutants that elevate non-interfering crossovers with msh2 mutants. We demonstrate that MSH2 blocks non-interfering crossovers at polymorphic loci, which is the opposite effect to interfering crossovers. We also observe MSH2-independent crossover inhibition at highly polymorphic sites. We measure recombination along the chromosome arms in lines differing in patterns of heterozygosity and observe a MSH2-dependent crossover increase at the boundaries between heterozygous and homozygous regions. Here, we show that MSH2 is a master regulator of meiotic DSB repair in Arabidopsis, with antagonistic effects on interfering and non-interfering crossovers, which shapes the crossover landscape in relation to interhomolog polymorphism. Interhomolog polymorphism, which is detected by MSH2-containing heterodimers, may affect crossover outcomes during meiosis. Here, the authors revealed antagonistic effects of MSH2 on interfering and non-interfering crossover pathways in Arabidopsis. [ABSTRACT FROM AUTHOR]