Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 37
Filter
1.
PLOS Glob Public Health ; 3(6): e0001555, 2023.
Article in English | MEDLINE | ID: mdl-37267241

ABSTRACT

Serological assays have been used in seroprevalence studies to inform the dynamics of COVID-19. Lateral flow immunoassay (LFIA) tests are a very practical technology to use for this objective; however, one of their challenges may be variable diagnostic performance. Given the numerous available LFIA tests, evaluation of their accuracy is critical before real-world implementation. We performed a retrospective diagnostic evaluation study to independently determine the diagnostic accuracy of 4 different antibody-detection LFIA tests: Now Check (Bionote), CareStart (Access bio), Covid-19 BSS (Biosynex) and OnSite (CTK Biotech). The sample panel was comprised of specimens collected and stored in biobanks; specifically, specimens that were RT-PCR positive for SARS-CoV-2 collected at various times throughout the COVID-19 disease course and those that were collected before the pandemic, during 2018 or earlier, from individuals with upper respiratory symptoms but were negative for tuberculosis. Clinical performance (sensitivity and specificity) was analyzed overall, and subset across individual antibody isotypes, and days from symptoms onset. A very high specificity (98% - 100%) was found for all four tests. Overall sensitivity was variable, ranging from 29% [95% CI: 21%-39%] to 64% [95% CI: 54%-73%]. When considering detection of IgM only, the highest sensitivity was 42% [95% CI: 32%-52%], compared to 57% [95% CI: 47%-66%] for IgG only. When the analysis was restricted to at least 15 days since symptom onset, across any isotype, the sensitivity reached 90% for all four brands. All four LFIA tests proved effective for identifying COVID-19 antibodies when two conditions were met: 1) at least 15 days have elapsed since symptom onset and 2) a sample is considered positive when either IgM or IgG is present. With these considerations, the use of this assays could help in seroprevalence studies or further exploration of its potential uses.

2.
Heliyon ; 9(6): e17138, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37360107

ABSTRACT

Metal-organic frameworks (MOFs) have been an excellent platform for carbon dioxide reduction reactions (CO2RR). In this work, the feasibility of electrochemical reduction of CO2 to obtain C2-deep value-added products was investigated by the preparation of Mg-containing MOF-74 samples combined with transition metal cations (Ni2+, Co2+ and Zn2+). The prepared MOFs were used as electrocatalysts in CO2RR. Chronoamperometric analysis coupled to ATR-FTIR spectroscopy was employed to characterize the CO2 reduction products and subsequently via 1H NMR. Although an isostructural crystalline structure was observed in all synthesized MOFs, the pore diameter distribution was significantly affected due to the Mg coordination along with each transition metal nuclei with the organic ligand to form the MOF-74. Our results showed that Mg-containing MOF-74 electrocatalysts combined with Ni, Co and Zn ions successfully reduced CO2 to C2-deep products, while the monometallic Mg-MOF-74 showed only CO2 mineralization. An ester acetate, isopropyl alcohol, and formic acid were produced by Mg/Ni-MOF-74; isopropyl alcohol was provided by Mg/Co-MOF-74, and ethanol was generated by Mg/Zn-MOF-74. We observed that the change of the transition cation was a key factor in the selectivity of the obtained products, while the degree of Mg ions effectively incorporated into the MOF structure tuned the porosity and the electrocatalytic activity. Among them, Mg/Zn-MFOF-74 showed the highest Mg content loaded after synthesis and thus the most favorable electrocatalytic behavior towards CO2 reduction.

3.
Viruses ; 15(2)2023 02 01.
Article in English | MEDLINE | ID: mdl-36851625

ABSTRACT

Baculoviridae is a large family of arthropod-infective viruses. Recombinant baculoviruses have many applications, the best known is as a system for large scale protein production in combination with insect cell cultures. More recently recombinant baculoviruses have been utilized for the display of proteins of interest with applications in medicine. In the present review we analyze the different strategies for the display of proteins and peptides on the surface of recombinant baculoviruses and provide some examples of the different proteins displayed. We analyze briefly the commercially available systems for recombinant baculovirus production and display and discuss the future of this emerging and powerful technology.


Subject(s)
Arthropods , Baculoviridae , Animals , Baculoviridae/genetics , Peptides/genetics , Cell Culture Techniques
4.
Prep Biochem Biotechnol ; 53(5): 488-499, 2023.
Article in English | MEDLINE | ID: mdl-35980820

ABSTRACT

The purpose of the study was to evaluate the production of lignin-modifying enzyme extracts and delignified biomass from agro-industrial wastes using white rot fungi (Inonotus sp. Sp2, Stereum hirsutum Ru-104, Bjerkandera sp. BOS55, Pleurotus eryngii IJFM 169 and Phanerochaete chrysosporium BKM-F-1767). These were screened based on their adaptability and colonization ability on different substrates, as well as by the Laccase, Manganese peroxidase, and Lignin peroxidase enzymatic production. Native strains (Inonotus sp. Sp2 and S. hirsutum Ru-104) showed the highest growth kinetics under the solid-substrate fermentation conditions and the growth rate parameters of the kinetic logistic model for the different substrates were between 0.39-0.81 (1/d) and 0.42-0.83 (1/d), respectively; the determination coefficients were ≥0.99. Inonotus sp. Sp2 was subsequently cultured in static flasks to produce crude enzyme extracts, obtaining manganese peroxidase activity levels of 18.5 and 31.3 (U/g) when growing in corn cob husk and spent tea leaves, respectively. Besides, it was to establish that the best conditions for lignin-modifying enzymes production using corn cob husk are 70% of initial moisture and 2.12 mm of particle size; reaching after 30 incubation days a manganese peroxidase activity of 21 ± 6 (U/g) under these conditions; enzyme that showed a suitable thermostability.


Subject(s)
Industrial Waste , Lignin , Lignin/metabolism , Fermentation , Peroxidases/metabolism , Laccase/metabolism , Plant Extracts
5.
J Adv Vet Anim Res ; 9(1): 59-65, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35445117

ABSTRACT

Objective: Evaluate the effect of arrival weight on feedlot growth performance and carcass characteristics of Holstein steers of similar age. Material and Methods: Three hundred calf-fed Holstein steers (age 113 ± 1-day) were distributed in a completely randomly unbalanced design and divided into five categories (105, 112, 117, 123, and 129 kg) of shrunk initial weight (SIW). Calves were weighed on days 1, 112, 224, and 361. Calves were fed steam-flaked corn-based diets. Growth performance and dietary energy were evaluated for each period and the study as a whole (1-361-day). Results: During the rearing period, average daily gain (ADG) increased (linearly effect, p < 0.01) with increasing birth weight. Birthweight was positively associated (p < 0.05) with feedlot arrival weight (R 2 = 0.47) and final harvest weight (R 2 = 0.36). Overall ADG increased (p < 0.01) with increasing SIW. Dry matter intake increased linearly during the first 224-day but quadratically during the last 137 days. Overall, there was a quadratic effect (p < 0.05) of SIW on gain-to-feed and observed-to-expected dietary NE, with lower efficiencies (4%) for steers in both the lightest and heaviest SIW. Hot carcass weight, Longissimus muscle area, marbling score, and fat thickness increased (linear effect, p ≤ 0.03) as SIW increased, whereas kidney-pelvic-heart fat and yield-grade were unaffected. Conclusions: The initial arrival weight influences the growth performance, energetic efficiency, and carcass characteristics of Holstein steers of similar age. The effect is more pronounced in the lighter (<112 kg) steers.

6.
Mol Biol Evol ; 39(3)2022 03 02.
Article in English | MEDLINE | ID: mdl-35294555

ABSTRACT

Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled ∼9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this data set allows us to fully resolve and date the regional chrY phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region's initial settlement ∼50 kya, and extensive expansions <6 kya. Notably, ∼40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in ISEA, New Guinea, and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ∼25 kya, at the time of the last glacial maximum. This improved chrY topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and ISEA, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the chrY presented here thus enables a detailed exploration of past isolation, interaction, and change in one of the world's least understood regions.


Subject(s)
Asian People , DNA, Mitochondrial , Asia, Southeastern , DNA, Mitochondrial/genetics , Humans , Male , Mitochondria/genetics , Phylogeny
7.
Genes (Basel) ; 13(2)2022 01 25.
Article in English | MEDLINE | ID: mdl-35205264

ABSTRACT

Uniparental genetic systems are unique sex indicators and complement the study of autosomal diversity by providing landmarks of human migrations that repeatedly shaped the structure of extant populations. Our knowledge of the variation of the male-specific region of the Y chromosome in Native Americans is still rather scarce and scattered, but by merging sequence information from modern and ancient individuals, we here provide a comprehensive and updated phylogeny of the distinctive Native American branches of haplogroups C and Q. Our analyses confirm C-MPB373, C-P39, Q-Z780, Q-M848, and Q-Y4276 as the main founding haplogroups and identify traces of unsuccessful (pre-Q-F1096) or extinct (C-L1373*, Q-YP4010*) Y-chromosome lineages, indicating that haplogroup diversity of the founder populations that first entered the Americas was greater than that observed in the Indigenous component of modern populations. In addition, through a diachronic and phylogeographic dissection of newly identified Q-M848 branches, we provide the first Y-chromosome insights into the early peopling of the South American hinterland (Q-BY104773 and Q-BY15730) and on overlying inland migrations (Q-BY139813).


Subject(s)
Chromosomes, Human, Y , Human Migration , Americas , Chromosomes, Human, Y/genetics , Haplotypes , Humans , Male , Phylogeny
8.
Int J Dent Hyg ; 20(2): 301-307, 2022 May.
Article in English | MEDLINE | ID: mdl-34390316

ABSTRACT

OBJECTIVE: To determine the comfort level and reproducibility assessment of the probing pocket depth obtained with three different probes. METHODS: A cross-sectional clinical study was conducted in accordance with the STROBE standards. Three different types of periodontal probes were selected: (1) University of North Carolina (UNC) probe, (2) World health organization (WHO) probe and (3) UNC12 COLORVUE probe. Three experienced and calibrated periodontists performed periodontal clinical assessments (probing depth) and pain assessment with the visual analogue scale (VAS). RESULTS: The clinical evaluations were carried out in 13 volunteers who attended the dental clinic of the Universidad Científica del Sur (Lima, Peru). A total of 2106 periodontal clinical measurements were obtained (702 measurements per examiner). Each examiner evaluated 234 sites for each type of probe. When patient comfort values during the periodontal evaluation performed with the 3 types of probes were compared, the patients evaluated with the UNC12 COLORVUE probe perceived less pain with a mean value of 0.61, followed by the WHO probe and the UNC probe. When evaluating the clinical measurements, the UNC probe was observed to obtain the greatest mean depth on probing 1.4 + 0.5 mm, while with the UNC12 Colorvue probe, the values obtained were 1.1 + 0.3 mm, and with the WHO probe, 1.2 + 0.4 mm. CONCLUSIONS: Based on the periodontal probe used, experience of the examiner and the patient, we can conclude that the UNC12 Colorvue probe was the instrument that promoted the greatest comfort or the slightest response to pain, followed by the WHO probe. However, the use of the WHO probe resulted in obtaining the lowest reproducibility among depths on probing. The UNC probe produced the highest response to pain in the patients.


Subject(s)
Patient Comfort , Periodontics , Cross-Sectional Studies , Humans , Observer Variation , Pain , Periodontal Pocket , Reproducibility of Results
9.
Front Microbiol ; 13: 1074741, 2022.
Article in English | MEDLINE | ID: mdl-36713198

ABSTRACT

Background: Proteostasis refers to the processes that regulate the biogenesis, folding, trafficking, and degradation of proteins. Any alteration in these processes can lead to cell malfunction. Protein synthesis, a key proteostatic process, is highly-regulated at multiple levels to ensure adequate adaptation to environmental and physiological challenges such as different stressors, proteotoxic conditions and aging, among other factors. Because alterations in protein translation can lead to protein misfolding, examining how protein translation is regulated may also help to elucidate in part how proteostasis is controlled. Codon usage bias has been implicated in the fine-tuning of translation rate, as more-frequent codons might be read faster than their less-frequent counterparts. Thus, alterations in codon usage due to synonymous mutations may alter translation kinetics and thereby affect the folding of the nascent polypeptide, without altering its primary structure. To date, it has been difficult to predict the effect of synonymous mutations on protein folding and cellular fitness due to a scarcity of relevant data. Thus, the purpose of this work was to assess the effect of synonymous mutations in discrete regions of the gene that encodes the highly-expressed enzyme 3-phosphoglycerate kinase 1 (pgk1) in the fission yeast Schizosaccharomyces pombe. Results: By means of systematic replacement of synonymous codons along pgk1, we found slightly-altered protein folding and activity in a region-specific manner. However, alterations in protein aggregation, heat stress as well as changes in proteasome activity occurred independently of the mutated region. Concomitantly, reduced mRNA levels of the chaperones Hsp9 and Hsp16 were observed. Conclusion: Taken together, these data suggest that codon usage bias of the gene encoding this highly-expressed protein is an important regulator of protein function and proteostasis.

10.
Genes (Basel) ; 12(10)2021 10 07.
Article in English | MEDLINE | ID: mdl-34680976

ABSTRACT

A general imbalance in the proportion of disembarked males and females in the Americas has been documented during the Trans-Atlantic Slave Trade and the Colonial Era and, although less prominent, more recently. This imbalance may have left a signature on the genomes of modern-day populations characterised by high levels of admixture. The analysis of the uniparental systems and the evaluation of continental proportion ratio of autosomal and X chromosomes revealed a general sex imbalance towards males for European and females for African and Indigenous American ancestries. However, the consistency and degree of this imbalance are variable, suggesting that other factors, such as cultural and social practices, may have played a role in shaping it. Moreover, very few investigations have evaluated the sex imbalance using haplotype data, containing more critical information than genotypes. Here, we analysed genome-wide data for more than 5000 admixed American individuals to assess the presence, direction and magnitude of sex-biased admixture in the Americas. For this purpose, we applied two haplotype-based approaches, ELAI and NNLS, and we compared them with a genotype-based method, ADMIXTURE. In doing so, besides a general agreement between methods, we unravelled that the post-colonial admixture dynamics show higher complexity than previously described.


Subject(s)
Genetics, Population , Haplotypes/genetics , Human Migration , Black or African American/genetics , Americas , Chromosomes, Human, X/genetics , Female , Genotype , Humans , Male , Maternal Inheritance/genetics , Paternal Inheritance/genetics , White People/genetics
11.
Clinics (Sao Paulo) ; 76: e3015, 2021.
Article in English | MEDLINE | ID: mdl-34614113

ABSTRACT

Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dose-dependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.


Subject(s)
Arthritis, Psoriatic , Biological Products , Psoriasis , Antibodies, Monoclonal , Arthritis, Psoriatic/drug therapy , Biological Products/therapeutic use , Humans , Psoriasis/drug therapy
13.
Rev. Méd. Clín. Condes ; 32(4): 429-441, jul - ago. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1518744

ABSTRACT

En la actualidad, las infecciones de piel y partes blandas forman parte de un alto porcentaje de las consultas en salud. Estas van desde infecciones leves, donde el manejo se realiza con tratamiento tópico, hasta aquellas con severo compromiso sistémico, requiriendo terapia antibiótica sistémica e incluso el desbridaje quirúrgico. En general, son producto de un desbalance entre los mecanismos de defensa de la barrera cutánea y los factores de virulencia y patogenicidad de los microorganismos que la afectan. Se pueden clasificar según distintos criterios, como por ejemplo, profundidad, gravedad, microorganismos involucrados y si estas son purulentas o no. El reconocer estas entidades clínicas es de suma importancia para llevar a cabo un adecuado tratamiento en los pacientes que presentan estas afecciones, ya que los diagnósticos erróneos llevan a las múltiples consultas con el consiguiente aumento de costos asociados en atención en salud.


Currently, skin and soft tissue infections are part of a high percentage of health consultations. These range from mild infections, where management is performed with topical treatment, to those with severe systemic compromise requiring systemic antibiotic therapy and even surgical debridement. In general, they are the product of an imbalance between the defense mechanisms of the skin barrier and the virulence and pathogenicity factors of the microorganisms that affect it, which can vary from bacterial, viral, fungal and parasites agents. Skin and soft tissue infections can be classified according to different criteria, such as depth, severity, microorganisms involved and whether they are purulent or not. Recognizing these clinical entities is of utmost importance to carry out adequate treatment in patients with these conditions, since erroneous diagnoses lead to multiple consultations with the consequent increase in costs associated with health care


Subject(s)
Humans , Adult , Middle Aged , Skin Diseases, Infectious/diagnosis , Skin Diseases, Infectious/microbiology , Skin Diseases, Infectious/drug therapy , Skin Diseases, Infectious/classification , Risk Factors , Anti-Bacterial Agents/therapeutic use
14.
Exp Ther Med ; 22(3): 915, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34306189

ABSTRACT

Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309).

15.
Hum Mol Genet ; 30(22): 2123-2134, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34196708

ABSTRACT

American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, even though gene flow could drive adaptive evolution, it is unclear whether and how natural selection acted on the resulting genetic variation in the Americas. In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ~ 6000 admixed individuals from 10 American countries. In doing so, we identified regions characterized by a divergent ancestry profile (DAP), in which a significant over or under ancestral representation is evident. Our results highlighted a series of genomic regions with DAPs associated with immune system response and relevant medical traits, with the longest DAP region encompassing the human leukocyte antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analysing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts and characterized by a high deleteriousness score. Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at a continental scale in the Americas, affecting more often functional and impactful genomic variants.


Subject(s)
Genetics, Population , Genome, Human , Genomics , Racial Groups/genetics , Selection, Genetic , Americas , Computer Simulation , Genomics/methods , Humans , Models, Genetic , Polymorphism, Single Nucleotide
16.
Eur J Hum Genet ; 29(10): 1510-1519, 2021 10.
Article in English | MEDLINE | ID: mdl-33958743

ABSTRACT

The most frequent Y-chromosomal (chrY) haplogroups in northern and eastern Europe (NEE) are well-known and thoroughly characterised. Yet a considerable number of men in every population carry rare paternal lineages with estimated frequencies around 5%. So far, limited sample-sizes and insufficient resolution of genotyping have obstructed a truly comprehensive look into the variety of rare paternal lineages segregating within populations and potential signals of population history that such lineages might convey. Here we harness the power of massive re-sequencing of human Y chromosomes to identify previously unknown population-specific clusters among rare paternal lineages in NEE. We construct dated phylogenies for haplogroups E2-M215, J2-M172, G-M201 and Q-M242 on the basis of 421 (of them 282 novel) high-coverage chrY sequences collected from large-scale databases focusing on populations of NEE. Within these otherwise rare haplogroups we disclose lineages that began to radiate ~1-3 thousand years ago in Estonia and Sweden and reveal male phylogenetic patterns testifying of comparatively recent local demographic expansions. Conversely, haplogroup Q lineages bear evidence of ancient Siberian influence lingering in the modern paternal gene pool of northern Europe. We assess the possible direction of influx of ancestral carriers for some of these male lineages. In addition, we demonstrate the congruency of paternal haplogroup composition of our dataset with two independent population-based cohorts from Estonia and Sweden.


Subject(s)
Chromosomes, Human, Y/genetics , Phylogeny , Polymorphism, Genetic , Estonia , Haplotypes , Human Migration , Humans , Male , Pedigree , Sweden
17.
Sci Rep ; 11(1): 6659, 2021 03 23.
Article in English | MEDLINE | ID: mdl-33758277

ABSTRACT

Human Y chromosome haplogroup J1-M267 is a common male lineage in West Asia. One high-frequency region-encompassing the Arabian Peninsula, southern Mesopotamia, and the southern Levant-resides ~ 2000 km away from the other one found in the Caucasus. The region between them, although has a lower frequency, nevertheless demonstrates high genetic diversity. Studies associate this haplogroup with the spread of farming from the Fertile Crescent to Europe, the spread of mobile pastoralism in the desert regions of the Arabian Peninsula, the history of the Jews, and the spread of Islam. Here, we study past human male demography in West Asia with 172 high-coverage whole Y chromosome sequences and 889 genotyped samples of haplogroup J1-M267. We show that this haplogroup evolved ~ 20,000 years ago somewhere in northwestern Iran, the Caucasus, the Armenian Highland, and northern Mesopotamia. The major branch-J1a1a1-P58-evolved during the early Holocene ~ 9500 years ago somewhere in the Arabian Peninsula, the Levant, and southern Mesopotamia. Haplogroup J1-M267 expanded during the Chalcolithic, the Bronze Age, and the Iron Age. Most probably, the spread of Afro-Asiatic languages, the spread of mobile pastoralism in the arid zones, or both of these events together explain the distribution of haplogroup J1-M267 we see today in the southern regions of West Asia.


Subject(s)
Alleles , Chromosomes, Human, Y , Haplotypes , Bayes Theorem , Evolution, Molecular , Genetics, Population , Humans , Phylogeny , Polymorphism, Single Nucleotide , Spatio-Temporal Analysis
18.
Elife ; 102021 03 30.
Article in English | MEDLINE | ID: mdl-33781384

ABSTRACT

Male infertility is a prevalent condition, affecting 5-10% of men. So far, few genetic factors have been described as contributors to spermatogenic failure. Here, we report the first re-sequencing study of the Y-chromosomal Azoospermia Factor c (AZFc) region, combined with gene dosage analysis of the multicopy DAZ, BPY2, and CDYgenes and Y-haplogroup determination. In analysing 2324 Estonian men, we uncovered a novel structural variant as a high-penetrance risk factor for male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ~1.6 Mb r2/r3 inversion, destabilizing the AZFc region and predisposing to large recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carrier vs non-carrier risk for spermatogenic failure was increased 8.6-fold (p=6.0×10-4). This finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification at young age will facilitate timely counselling and reproductive decision-making.


Subject(s)
Azoospermia/genetics , Chromosome Inversion/genetics , Gene Deletion , Spermatogenesis/genetics , Adolescent , Adult , Azoospermia/epidemiology , Estonia , Humans , Male , Middle Aged , Young Adult
19.
Genome Biol Evol ; 13(4)2021 04 05.
Article in English | MEDLINE | ID: mdl-33638983

ABSTRACT

Detecting natural selection signals in admixed populations can be problematic since the source of the signal typically dates back prior to the admixture event. On one hand, it is now possible to study various source populations before a particular admixture thanks to the developments in ancient DNA (aDNA) in the last decade. However, aDNA availability is limited to certain geographical regions and the sample sizes and quality of the data might not be sufficient for selection analysis in many cases. In this study, we explore possible ways to improve detection of pre-admixture signals in admixed populations using a local ancestry inference approach. We used masked haplotypes for population branch statistic (PBS) and full haplotypes constructed following our approach from Yelmen et al. (2019) for cross-population extended haplotype homozygosity (XP-EHH), utilizing forward simulations to test the power of our analysis. The PBS results on simulated data showed that using masked haplotypes obtained from ancestry deconvolution instead of the admixed population might improve detection quality. On the other hand, XP-EHH results using the admixed population were better compared with the local ancestry method. We additionally report correlation for XP-EHH scores between source and admixed populations, suggesting that haplotype-based approaches must be used cautiously for recently admixed populations. Additionally, we performed PBS on real South Asian populations masked with local ancestry deconvolution and report here the first possible selection signals on the autochthonous South Asian component of contemporary South Asian populations.


Subject(s)
Selection, Genetic , Asian People/genetics , Computer Simulation , Haplotypes , Humans , Polymorphism, Single Nucleotide
SELECTION OF CITATIONS
SEARCH DETAIL
...