Genetic Sex Research Articles

Induction of meiotic gynogenesis in Lanzhou catfish ( Silurus lanzhouensis ) with heterologous sperm and evidence for female homogamety

As a critical factor in the sustainability of fisheries, gynogenesis can be used to provide a shortcut for the genetic improvement of the endangered and degraded germplasm resources of the important Yellow River fish Silurus lanzhouensis. In this study, ultraviolet-inactivated yellow catfish Pelteobagrus fulvidraco sperm were used to induce meiotic gynogenesis in S. lanzhouensis through cold shock, and the optimal conditions for the genetic inactivation of the sperm and cold shock treatment were selected. Using microsatellite markers and gonadal histology, the genetic purity and sex determination of the gynogenetic offspring of S. lanzhouensis were analysed. The optimal induction conditions were as follows: treatment with P. fulvidraco sperm with 107- µW/cm2 ultraviolet irradiation for 30 min, fertilization of S. lanzhouensis eggs for 6 min and subsequent cold shock treatment at 4–6°C for 25 min. Flow cytometry and microsatellite markers confirmed the successful induction of meiogynogenesis. The homozygosity of the gynogenetic group (0.63) was higher than that of the normal control group (0.32). The sex ratio was determined through gonad histological observations, and 100% of the offspring in the gynogenetic groups were female, strongly indicating that the sex determination system of S. lanzhouensis is the XX/XY-type. In this study, inactivated heterologous sperm were used to successfully obtain meiogynogenetic individuals of S. lanzhouensis, and the study provides an important basis for the establishment of a pure line of these endangered fish and sex-controlled breeding of S. lanzhouensis.

Development and identification of a sex-specific molecular marker in Dai-qu stock large yellow croaker (Larimichthys crocea)

Dai-qu stock large yellow croaker (Larimichthys crocea) is an important marine economic fish and geographical population in the East China Sea. Traditionally, large yellow croakers can be divided into three geographical populations as follows: Dai-qu, Min-yuedong and Nao-zhou stocks. In the present study, a sex-specific molecular marker in Dai-qu stock was developed from loci between dmrt1 and cfap157. Based on large yellow croaker genome sequence and a well characterized sex-determining region on chromosome 22, 147 pairs of primers were designed for screening the sex-specific markers by PCR amplification. At last, 1 pair of primers were successfully screened and identified. The results showed that the primers only amplified 500 bp bands in females, whereas, 500 bp bands and 390 bp specific bands were amplified in males. Cloning and sequencing analysis of PCR products showed that females and males share the almost same 500 bp sequence, and the males have a specific deletion of 110 bp than females sequence. 276 individuals of Dai-qu stock large yellow croaker were used to verification this sex-specific marker, and compared with gonadal histological results, the accuracy of the specific primer reached 100%, indicating that the primer can effectively and accurately identify the genetic sex of Dai-qu stock large yellow croaker. In this study, a sex-specific marker was developed and identified, which further verified that the Dai-qu stock large yellow croaker also belonged to XX♀-XY♂ type, providing a useful tool for clarifying the molecular mechanism of sex determination and promoting sex-controlled breeding.

Some sexual consequences of being a plant.

Plants have characteristic features that affect the expression of sexual function, notably the existence of a haploid organism in the life cycle, and in their development, which is modular, iterative and environmentally reactive. For instance, primary selection (the first filtering of the products of meiosis) is via gametes in diplontic animals, but via gametophyte organisms in plants. Intragametophytic selfing produces double haploid sporophytes which is in effect a form of clonal reproduction mediated by sexual mechanisms. In homosporous plants, the diploid sporophyte is sexless, sex being only expressed in the haploid gametophyte. However, in seed plants, the timing and location of gamete production is determined by the sporophyte, which therefore has a sexual role, and in dioecious plants has genetic sex, while the seed plant gametophyte has lost genetic sex. This evolutionary transition is one that E.J.H. Corner called 'the transference of sexuality'. The iterative development characteristic of plants can lead to a wide variety of patterns in the distribution of sexual function, and in dioecious plants poor canalization of reproductive development can lead to intrasexual mating and the production of YY supermales or WW superfemales. Finally, plant modes of asexual reproduction (agamospermy/apogamy) are also distinctive by subverting gametophytic processes. This article is part of the theme issue 'Sex determination and sex chromosome evolution in land plants'.

Establishment of the Y-linked Dmrt1Y as the candidate sex determination gene in spotbanded scat (Selenotoca multifasciata)

Spotbanded scat (Selenotoca multifasciata) has become a valuable marine culturing fish species in the southeast coastal areas of China. Herein, sex-linked markers were developed in spotbanded scat to elucidate its genetic foundation of sex determination. Eighty-four (84) cultured spotbanded scat were randomly chosen and used to screen and test the sex-linked markers. The average weight of the female (249 g, n = 32) is significantly higher than that of the male (212 g, n = 52). The whole genome of a male spotbanded scat was sequenced using next-generation sequencing technology. Phylogenetic analysis showed that spotbanded scat diverged from its closely related species, spotted scat (Scatophagus argus) 13.1 million years ago.Three sex-linked markers (Marker-1, 2 and 3) were obtained in spotbanded scat. Marker-1 and 2 could only amplify 562 bp and 881 bp Dmrt1 specific bands in male fish, while there were no amplified bands in female fish. Marker-3 amplified a single band of 373 bp in all female, and double bands of 373 bp and specific 294 bp in male. Sequence analysis showed that the 294 and 373 bp are Dmrt1 homologous sequences. These results indicate that the spotbanded scat possesses XY sex-determination system (XX females, XY males). Two types of Dmrt1 cDNA sequences were cloned and named Dmrt1X and Dmrt1Y according to their locations on the X and Y chromosomes, respectively. The amino acid (aa) sequences coded by Dmrt1X (309 aa) and Dmrt1Y (305 aa) are highly similar (85.8%). Dmrt1Y mRNA is specifically expressed in testis, with no expression in the ovary. Hence, Dmrt1Y is male-specific and the candidate SD gene. Knowledge of genetic sex determination and the development of sex-linked markers in spotbanded scat, will promote artificial reproduction and breeding in aquaculture.

The Importance of Surgical Sex Reassignment in TheOpinion of Female-To-Male Transsexuals.

<br><b>Introduction:</b> The term transsexualism determines people whose gender identity is contrary to their genetic sex and physical features. This condition leads to a discrepancy between the psychological gender preferred by transsexuals and their biological sex. Transsexuals experience a feeling of being incarcerated in a foreign body and therefore wish to alter their sex by hormone therapy and surgical treatment.</br><br><b>Aim:</b> The aim of this study is to describe the opinions of female-to-male transsexuals concerning sex reassignment surgery with selecting the most important stage.</br><br><b>Method:</b> The questionnaire studies were performed among a group of 82 female-to-male transsexuals with a mean age 25.2 years. Patients were at different stages of treatment. Results: More than 90% of the questionnaired transsexuals expect to complete their treatment with hope. For 86.6% of transsexuals, the most important stage in surgical treatment is the phalloplasty, the second panhysterectomy (70.7%), and the third breast reduction (69.5%).</br><br><b>Conclusions:</b> Phalloplasty is the most important stage in sex reassignment surgery in the opinion of transsexuals. Each stage of treatment improves the mental comfort of female-to-male transsexuals.</br&gt.

Hypothyroidism and Diabetes-Related Dementia: Focused on Neuronal Dysfunction, Insulin Resistance, and Dyslipidemia.

The incidence of dementia is steadily increasing worldwide. The risk factors for dementia are diverse, and include genetic background, environmental factors, sex differences, and vascular abnormalities. Among the subtypes of dementia, diabetes-related dementia is emerging as a complex type of dementia related to metabolic imbalance, due to the increase in the number of patients with metabolic syndrome and dementia worldwide. Thyroid hormones are considered metabolic regulatory hormones and affect various diseases, such as liver failure, obesity, and dementia. Thyroid dysregulation affects various cellular mechanisms and is linked to multiple disease pathologies. In particular, hypothyroidism is considered a critical cause for various neurological problems—such as metabolic disease, depressive symptoms, and dementia—in the central nervous system. Recent studies have demonstrated the relationship between hypothyroidism and brain insulin resistance and dyslipidemia, leading to diabetes-related dementia. Therefore, we reviewed the relationship between hypothyroidism and diabetes-related dementia, with a focus on major features of diabetes-related dementia such as insulin resistance, neuronal dysfunction, and dyslipidemia.

Exploration of an XX/XY Sex Determination System and Development of PCR-Based Sex-specific Markers in Procambarus clarkii Based on Next-Generation Sequencing Data.

Many economic crustacean species have sex dimorphisms during their growth. Exploring the sex determination system and developing sex-specific molecular marker(s) are very helpful for carrying out sex control breeding, and next-generation sequencing has been used as an efficient way to explore them in recent years. In this study, first, the genetic sex determination system of P. clarkii was explored as an XX/XY system by analyzing the 2b-RAD sequencing data. Furthermore, DNA samples of male and female individuals from a P. clarkii family were pooled separately for whole-genome resequencing. Based on the data of whole-genome resequencing, the 9,163 male- and female-specific bias sites with higher feasibility were obtained based on the assumption of the XX/XY sex determination system, and four sites were selected to design the sex-specific marker primers. One efficient sex-specific marker was identified with a sex discrimination rate of 99.49% (195/196) when applied to five different geographical groups with 196 individuals. The results of this study would provide a foundation for the realization of P. clarkii sex control and could provide some reference for investigating the sex determination system and sex molecular marker(s) of other crustacean species based on next-generation sequencing data.

Novel genetic sex markers reveal unexpected lack of, and similar susceptibility to, sex reversal in free-living common toads in both natural and anthropogenic habitats.

Anthropogenic environmental changes are affecting biodiversity and microevolution worldwide. Ectothermic vertebrates are especially vulnerable because environmental changes can disrupt their sexual development and cause sex reversal, a mismatch between genetic and phenotypic sex. This can potentially lead to sex‐ratio distortion and population decline. Despite these implications, there is scarce empirical knowledge on the incidence of sex reversal in nature. Populations in anthropogenic environments may be exposed to sex‐reversing stimuli more frequently, which may lead to higher sex‐reversal rate or, alternatively, these populations may adapt to resist sex reversal. We developed PCR‐based genetic sex markers for the common toad (Bufo bufo) to assess the prevalence of sex reversal in wild populations living in natural, agricultural and urban habitats, and the susceptibility of the same populations to two ubiquitous oestrogenic pollutants in a common garden experiment. We found negligible sex‐reversal frequency in free‐living adults despite the presence of various endocrine‐disrupting pollutants in their breeding ponds. Individuals from different habitat types showed similar susceptibility to sex reversal in the laboratory: all genetic males developed female phenotype when exposed to 1 µg L−1 17α‐ethinylestradiol (EE2) during larval development, whereas no sex reversal occurred in response to 1 ng L−1 EE2 and a glyphosate‐based herbicide with 3 µg L−1 or 3 mg L−1 glyphosate. The latter results do not support that populations in anthropogenic habitats would have either increased propensity for or higher tolerance to chemically induced sex reversal. Thus, the extremely low sex‐reversal frequency in wild toads compared to other ectothermic vertebrates studied before might indicate idiosyncratic, potentially species‐specific resistance to sex reversal.

A Genetic and Metabolic Staging System for Predicting the Outcome of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver‐related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis‐4 (FIB‐4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation) was used as the outcome. LREs were experienced by 58 patients, only one of whom was in the cohort of patients with a FIB‐4 score < 1.3. Multivariate Cox regression analysis of 229 patients with a FIB‐4 score ≥ 1.3 highlighted clinical variables independently associated with the development of LREs, including older age, low platelet count, low albumin, low high‐density lipoprotein cholesterol, certain genetic factors, and interactions between genetic factors and sex or diabetes. The area under the curve (AUC) for the model was 0.87 at 1, 3, and 5 years. Our novel Genetic and Metabolic Staging (GEMS) scoring system was derived from the Cox model linear predictor, ranked from 0 to 10, and categorized into five classes (0‐5, 5‐6, 6‐7, 7‐8, and 8‐10). The risk of LREs increased from 4% in patients in the best class (GEMS score 0‐5) to 91% in the worst (GEMS score 8‐10). GEMS score was associated with incident severe liver disease in the study population (hazard ratio, 1.56; 95% confidence interval, 1.48‐1.65; P < 0.001) as well as in the UK Biobank cohort where AUCs for prediction of severe liver disease at 1, 3, and 5 years were 0.70, 0.69, and 0.67, respectively. Conclusion: The novel GEMS scoring system has an adequate ability to predict the outcome of patients with NAFLD.

DRPPM-EASY: A Web-Based Framework for Integrative Analysis of Multi-Omics Cancer Datasets.

Simple SummaryWith the influx of multi-omics profiling, effective integration of these data remains the bottleneck for omics-driven discovery. Thus, we developed DRPPM-EASY, an R Shiny framework for integrative multi-omics analysis of cancer datasets. Our tool enables the exploration of multi-omics data by providing a simple user interface that minimizes the need for computational experience. Furthermore, the interface can be deployed locally or on a webserver to facilitate scientific collaboration and discovery.High-throughput transcriptomic and proteomic analyses are now routinely applied to study cancer biology. However, complex omics integration remains challenging and often time-consuming. Here, we developed DRPPM-EASY, an R Shiny framework for integrative multi-omics analysis. We applied our application to analyze RNA-seq data generated from a USP7 knockdown in T-cell acute lymphoblastic leukemia (T-ALL) cell line, which identified upregulated expression of a TAL1-associated proliferative signature in T-cell acute lymphoblastic leukemia cell lines. Next, we performed proteomic profiling of the USP7 knockdown samples. Through DRPPM-EASY-Integration, we performed a concurrent analysis of the transcriptome and proteome and identified consistent disruption of the protein degradation machinery and spliceosome in samples with USP7 silencing. To further illustrate the utility of the R Shiny framework, we developed DRPPM-EASY-CCLE, a Shiny extension preloaded with the Cancer Cell Line Encyclopedia (CCLE) data. The DRPPM-EASY-CCLE app facilitates the sample querying and phenotype assignment by incorporating meta information, such as genetic mutation, metastasis status, sex, and collection site. As proof of concept, we verified the expression of TP53 associated DNA damage signature in TP53 mutated ovary cancer cells. Altogether, our open-source application provides an easy-to-use framework for omics exploration and discovery.

Heterochiasmy and the establishment of gsdf as a novel sex determining gene in Atlantic halibut.

Atlantic Halibut (Hippoglossus hippoglossus) has a X/Y genetic sex determination system, but the sex determining factor is not known. We produced a high-quality genome assembly from a male and identified parts of chromosome 13 as the Y chromosome due to sequence divergence between sexes and segregation of sex genotypes in pedigrees. Linkage analysis revealed that all chromosomes exhibit heterochiasmy, i.e. male-only and female-only meiotic recombination regions (MRR/FRR). We show that FRR/MRR intervals differ in nucleotide diversity and repeat class content and that this is true also for other Pleuronectidae species. We further show that remnants of a Gypsy-like transposable element insertion on chr13 promotes early male specific expression of gonadal somatic cell derived factor (gsdf). Less than 4.5 MYA, this male-determining element evolved on an autosomal FRR segment featuring pre-existing male meiotic recombination barriers, thereby creating a Y chromosome. Our findings indicate that heterochiasmy may facilitate the evolution of genetic sex determination systems relying on linkage of sexually antagonistic loci to a sex-determining factor.

Risk factors for clozapine-induced myocarditis and cardiomyopathy: A systematic review and meta-analysis.

Clozapine is the most effective medication for treatment-refractory schizophrenia, but it is associated with severe cardiac adverse events including myocarditis and cardiomyopathy. To aid treatment decision-making for clinicians, patients and their carers, we conducted a systematic review and meta-analysis to identify potential risk factors for clozapine-induced myocarditis and cardiomyopathy. A systematic search was conducted of PubMed, Embase, CINAHL, Web of Science, Cochrane and PsycInfo for studies reporting myocarditis and cardiomyopathy among people on clozapine and potential risk factors. We calculated pooled effect sizes on risk factors using a random-effects meta-analytic model. Risk of publication bias was assessed using the Newcastle-Ottawa scale. Seven studies met the inclusion criteria, of which six studies had quantitative data included in the meta-analysis. The odds of clozapine-induced myocarditis increased with concurrent sodium valproate use (k=6, n=903, pooled OR 3.58, 95% CI 1.81-7.06), but were not significantly greater with the use of quetiapine, lithium or selective serotonin reuptake inhibitors. Our qualitative review identified conflicting results reported for increasing age and higher clozapine dose as risk factors for myocarditis. No other factors, including genetic risk, sex, ethnicity, smoking, alcohol, substance abuse or cardiometabolic disease, were associated with greater odds of myocarditis. No risk factors for cardiomyopathy were identified in the literature. Concurrent use of sodium valproate increases the odds of clozapine-induced myocarditis. Thus, clinicians should consider the temporary cessation of sodium valproate during the initial titration phase of clozapine.

Inheritance of hormonal stress response and temperament in infant rhesus macaques (Macaca Mulatta): Nonadditive and sex-specific effects.

Early life interindividual variation in hypothalamic-pituitary-adrenal (HPA) reactivity to stress is predictive of later life psychological and physical well-being, including the development of many pathological syndromes that are often sex-biased. A complex and interactive set of environmental and genetic causes for such variation has been implicated by previous studies, though little attention has been paid to nonadditive effects (e.g. dominance, X-linked) or sex-specific genetic effects. We used a large pedigreed sample of captive 3-4 months old infant rhesus macaques (N = 2,661, 54% female) to fit univariate and multivariate linear mixed quantitative genetic models for four longitudinal blood cortisol samples and three reliable ratings of infant temperament (nervousness, gentleness, confidence) during a mother-infant separation protocol. Each trait had a moderate narrow-sense heritability (h², 0.26-0.46), but dominance effects caused the first two cortisol samples to have much larger broad-sense heritabilities (H², 0.57 and 0.77). We found no evidence for X-linked variance or common maternal environment variance. There was a sex difference in heritability of the first cortisol sample (hf² < hm²), suggesting differing genetic architecture of perception of maternal separation and relocation during infancy. Otherwise, genetic covariance matrices for the sexes were very similar. Genetic correlations between cortisol levels and temperament were weak (< |0.4|) but stronger than residual or phenotypic correlations. HPA reactivity and temperament had a primarily additive genetic basis in infant macaques, but there were important complexities to the genetic architecture of including genetic dominance and sex differences in heritability at this early life stage. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intensive masculinization caused by chronic heat stress in juvenile Cynoglossus semilaevis: Growth performance, gonadal histology and gene responses

The sea temperature has been observed to chronically increase during the past decades, leaving unpredictable influences to the marine biological resources. Thus, it is of vital significance to study the biological responses of ocean inhabited organisms with the artificially stimulated heat stress environment. Cynoglossus semilaevis provides us with an ideal model to study the influence of chronic heat stress on the sexual differentiation in marine teleosts for its genetic sex determination (GSD) + environmental effected (EE) sex determination system. In this study, the comparative experiment was conducted employing heated seawater (HT group) and ambient seawater (CT group) to cultivate juvenile C. semilaevis respectively. Significant differences were exhibited in growth performance and a delayed germ cell development effect was found in pseudomales formed under chronic heat stress. Using transcriptome analysis, the transcription profile of 55 days post fertilization (dpf) and 100 dpf juveniles’ gonads were studied. A total of 47 libraries were constructed with an average mapping rate of 94.63% after assembling. GO and KEGG enrichment were proceeded using DEGs screened out between (1) pseudomale gonads at 55 dpf and 100 dpf in HT and CT group (2) pseudomale and female gonads at 55 dpf and 100 dpf in HT and CT group. Terms and pathways involved in steroid stimulation, reproduction ability, germ cell proliferation et al. were shed light on. The expression pattern of 29 DEGs including amh, hsp90b1, pgr et al. were also provided to supplement the results of functional enrichment. Weighted gene co-expression networks analysis (WGCNA) was constructed and hspb8-like, histone H2A.V were exhibited to play vital roles in the heat-induced masculinization. Our findings facilitate the understanding for transcriptional variations in intensive masculinization cause by chronic heat stress of C. semilaevis and provide referable study of the influences on the teleosts in elevated sea temperature.

Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation

Pogona vitticeps has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that nr5a1 (Nuclear Receptor Subfamily 5 Group A Member 1), a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-nr5a1 and W-nr5a1), which are both expressed and can recombine. Three transcript isoforms of Z-nr5a1 were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced 16 isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-nr5a1) is likely to produce truncated polypeptides that contain a structurally normal DNA-binding domain and could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosome affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the genetic sex determination (GSD) system of P. vitticeps is a W-borne dominant female-determining gene that may be controlled epigenetically.

Who are you? A framework to identify and report genetic sample mix-ups.

Sample mix-ups occur when samples have accidentally been duplicated, mislabelled or swapped. When samples are subsequently genotyped or sequenced, this can lead to individual IDs being incorrectly linked to genetic data, resulting in incorrect or biased research results, or reduced power to detect true biological patterns. We surveyed the community and found that almost 80% of responding researchers have encountered sample mix-ups. However, many recent studies in the field of molecular ecology do not appear to systematically report individual assignment checks as part of their publications. Although checks may be done, lack of consistent reporting means that it is difficult to assess whether sample mix-ups have occurred or been detected. Here, we present an easy-to-follow sample verification framework that can utilise existing metadata, including species, population structure, sex and pedigree information. We demonstrate its application to a data set representing individuals of a threatened Aotearoa New Zealand bird species, the hihi, genotyped on a 50K SNP array. We detected numerous incorrect genotype-ID associations when comparing observed and genetic sex or comparing to relationships in a verified microsatellite pedigree. The framework proposed here helped to confirm 488 individuals (39%), correct another 20 bird-genotype links, and detect hundreds of incorrect sample IDs, emphasizing the value of routinely checking genetic and genomic data sets for their accuracy. We therefore promote the implementation and reporting of this simple yet effective sample verification framework as a standardized quality control step for studies in the field of molecular ecology.

Association of the top 20 Alzheimer's disease risk genes with [18F]flortaucipir PET.

IntroductionWe previously reported genetic associations of the top Alzheimer's disease (AD) risk alleles with amyloid deposition and neurodegeneration. Here, we report the association of these variants with [18F]flortaucipir standardized uptake value ratio (SUVR).MethodsWe analyzed the [18F]flortaucipir scans of 352 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 54 dementia (DEM) participants from Alzheimer's Disease Neuroimaging Initiative (ADNI)2 and 3. We ran step‐wise regression with log‐transformed [18F]flortaucipir meta—region of interest SUVR as the outcome measure and genetic variants, age, sex, and apolipoprotein E (APOE) ε4 as predictors. The results were visualized using parametric mapping at familywise error cluster‐level–corrected P < .05.Results APOE ε4 showed significant (P < .05) associations with tau deposition across all disease stages. Other significantly associated genes include variants in ABCA7 in CN, CR1 in MCI, BIN1 and CASS4 in MCI and dementia participants.DiscussionWe found significant associations to tau deposition for ABCA7, BIN1, CASS4, and CR1, in addition to APOE ε4. These four variants have been previously associated with tau metabolism through model systems.

An Overview of Noise-Induced Hearing Loss: Systematic Review

The term &quot;noise-induced hearing loss&quot; (NIHL) refers to sensorineural hearing loss brought on by either acute acoustic trauma or prolonged exposure to loud noises. Noise exposure has the potential to permanently change the hearing threshold due to irreparable damage to the inner ear. Many risk factors affect the incidence of NIHL including personal factors; such as genetic factors, age, sex, and lifestyle; and elements relating to the noise; such as the length of exposure, its volume, a

APOE and KLF14 genetic variants are sex-specific for low high-density lipoprotein cholesterol identified by a genome-wide association study.

To demonstrate the loci that relate to high-density lipoprotein cholesterol (HDL-C) levels and genetic sex heterogeneity, we enrolled 41,526 participants aged between 30 and 70 years old from the Taiwan Biobank in a genome-wide association study. We applied the Manhattan plot to display the p-values estimated for the relationships between loci and low HDL-C. A total of 160 variants were significantly associated with low HDL-C. The genotype TT of rs1364422 located in the KLF14 gene has 1.30 (95% CI=1.20 - 1.42) times the risk for low-HDL compared to genotype CC in females (log(-p) =8.98). Moreover, the genes APOC1, APOE, PVRL2, and TOMM40 were associated significantly with low-HDL-C in males only. Excluding the variants with high linkage disequilibrium, we revealed the rs429358 located in APOE as the major genetic variant for lowering HDL-C, in which genotype CT has 1.24 (95% CI= 1.16 - 1.32) times the risk. In addition, we also examine 12 genes related to HDL-C in both sexes, including LPL, ABCA1, APOA5, BUD13, ZPR1, ALDH1A2, LIPC, CETP, HERPUD1, LIPG, ANGPTL8, and DOCK6. In conclusion, low-HDL-C is a genetic and sex-specific phenotype, and we discovered that the APOE and KLF14 are specific to low-HDL-C for men and women, respectively.

An Attempt to Extract Ancient DNA from the Petrous Part of the Temporal Bones and Roots of Teeth of Skeletal Remains Found in the Intermediate Climatic Zone in Sri Lanka

Ancient DNA (aDNA) is used to explore the genetic landscape of the past and investigate the movement, mixture, and adaptation events that shaped present-day patterns of human genetic diversity. The present study was designed to explore the genetic composition of the ancient people of Sri Lanka. Despite the low amino acid racemization often found in skeletal remains of Sri Lanka, we attempted to extract DNA from skeletal remains of 5 individuals found from several sites in intermediate climatic zone in Sri Lanka by using methodologies particularly designed for highly damaged and degraded DNA. We attempted to extract and sequence DNA from the petrous part of the temporal bones and tooth roots of remains excavated from Sigiriya <em>Potana, Pellemalala</em> (4,500 YBP) and <em>Mini-atheliya</em> (1,000 – 5,000 YBP) in Sri Lanka. The bone processing, DNA extraction and amplification were performed in three separate rooms with dedicated equipment as accordance to the recommendation for analysis of aDNA. All measures were strictly taken to minimize contamination with modern samples. Using the DNA extracts, we prepared dual-indexed single-stranded libraries treated with uracil-DNA glycosylase (UDG) to reduce the rate of ancient DNA damage. Prior to sequencing, in-solution target hybridization was used to enrich the sequences that overlap the mitochondrial genome and about 1.24 million genome-wide SNPs. Sufficient data passing quality control standards for any of the five individuals studied was not obtained. Coverage of the mitochondrial genome ranged between 0.04-0.45x, with damage rates at the terminal nucleotide that were not indicative of authentic ancient DNA. A range of 453-2,838 SNPs out of ~1.24 million targets were covered across the nuclear genome, translating to a maximum coverage of 0.004x. The damage rates at the terminal nucleotide were not indicative of authentic ancient DNA. The low numbers of SNPs hit on the X and Y chromosomes precluded the confident assessment of genetic sex in all individuals but it is possible that the ancient skeletal sample represented by Sigiriya <em>Potana</em> is a female individual. Although the recent published work on using the petrous part of the temporal bone has generated many times more data than other skeletal elements, even this technique did not work to generate aDNA on this set of prehistoric skeletal remains found in the intermediate climatic zone in Sri Lanka. It is possible that other sites might provide better taphonomic preservation conditions than the sites we analysed, and in addition a priority should be to attempt ancient DNA analysis from skeletal remains found in Sri Lanka’s dry zone.