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The MiniMUGA genotyping array is a popular tool for genetic quality control of laboratory mice and genotyping samples from most experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve the array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA. Here, we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for classical inbred strains and substrains, and increase the number of constructs reliably detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have updated the layout of the report to simplify the interpretation and completeness of the analysis and added a section summarizing the ideogram in table format. These changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

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BACKGROUND: Differences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500-5500, which can increase to 1:200-300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital. METHODS: Descriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City. RESULTS: One hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification. CONCLUSION: The frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.

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Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (ß=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.

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The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research.

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Over the last several decades zebrafish (Danio rerio) has become a major model organism for the study of vertebrate development and physiology. Given this, it may be surprising how little is known about the mechanism that zebrafish use to determine sex. While zebrafish are a gonochoristic species (having two sexes) that do not switch sex as adults, it was appreciated early on that sex ratios obtained from breeding lab domesticated lines were not typically a 1:1 ratio of male and female, suggesting that sex was not determined by a strict chromosomal mechanism. Here we will review the recent progress toward defining the genetic mechanism for sex determination in both wild and domesticated zebrafish.

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With care, it is possible using flow cytometry to create a precise and accurate estimate of the genome size of an insect that is useful for genomics, genetics, molecular/cell biology, or systematics. Genome size estimation is a useful first step in a complete genome sequencing project. The number of sequencing reads required to produce a given level of coverage depends directly upon the 1C amount of DNA per cell, while an even more critical need is an accurate 1C genome size estimate to compare against the final assembly. Here we present a detailed protocol to estimate genome size using flow cytometry. Published genome size estimates should be submitted to genomesize.com so that they are available to all.

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Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α-reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α-reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions. © 2016 Wiley Periodicals, Inc.

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Ovotestis is a rare disorder of sexual differentiation in which the gonads have both ovarian and testicular elements. The patients always present with ambiguous external genitalia, and there are usually with serious disorder between chromosomal sex, gonadal sex, social sex, and psychological sex. The definite diagnosis and gender confirmation, appropriate surgery in internal genitalia and orthomorphia in external genitalia, as well as psychological support are essential for a multidisciplinary medical group in managing this disease. The medical data of two children with ovotestis who were reared as boy or girl respectively were analyzed.