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459 result(s) for "Brown, Laura G."
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Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X–Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner’s syndrome and in phenotypic differences between the sexes in health and disease. A study comparing the Y chromosome across mammalian species reveals that selection to maintain the ancestral dosage of homologous X–Y gene pairs preserved a handful of genes on the Y chromosome while the rest were lost; the survival of broadly expressed dosage-sensitive regulators of gene expression suggest that the human Y chromosome is essential for male viability. Evolution and function of the Y chromosome Mammalian Y chromosomes, known for their roles in sex determination and male fertility, often contain repetitive sequences that make them harder to assemble than the rest of the genome. To counter this problem Henrik Kaessmann and colleagues have developed a new transcript assembly approach based on male-specific RNA/genomic sequencing data to explore Y evolution across 15 species representing all major mammalian lineages. They find evidence for two independent sex chromosome originations in mammals and one in birds. Their analysis of the Y/W gene repertoires suggests that although some genes evolved novel functions in sex determination/spermatogenesis as a result of temporal/spatial expression changes, most Y genes probably persisted, at least initially, as a result of dosage constraints. In a parallel study, Daniel Bellott and colleagues reconstructed the evolution of the Y chromosome, using a comprehensive comparative analysis of the genomic sequence of X–Y gene pairs from seven placental mammals and one marsupial. They conclude that evolution streamlined the gene content of the human Y chromosome through selection to maintain the ancestral dosage of homologous X–Y gene pairs that regulate gene expression throughout the body. They propose that these genes make the Y chromosome essential for male viability and contribute to differences between the sexes in health and disease.
Independent specialization of the human and mouse X chromosomes for the male germ line
David Page and colleagues report an improved assembly of the human X-chromosome using single haplotype sequencing. They used this assembly to systematically test Ohno's law of X-chromosome conservation by comparison to the mouse X-chromsome and identify 341 X-linked protein coding genes that are not shared between species and therefore violate Ohno's law. We compared the human and mouse X chromosomes to systematically test Ohno's law, which states that the gene content of X chromosomes is conserved across placental mammals 1 . First, we improved the accuracy of the human X-chromosome reference sequence through single-haplotype sequencing of ampliconic regions. The new sequence closed gaps in the reference sequence, corrected previously misassembled regions and identified new palindromic amplicons. Our subsequent analysis led us to conclude that the evolution of human and mouse X chromosomes was bimodal. In accord with Ohno's law, 94–95% of X-linked single-copy genes are shared by humans and mice; most are expressed in both sexes. Notably, most X-ampliconic genes are exceptions to Ohno's law: only 31% of human and 22% of mouse X-ampliconic genes had orthologs in the other species. X-ampliconic genes are expressed predominantly in testicular germ cells, and many were independently acquired since divergence from the common ancestor of humans and mice, specializing portions of their X chromosomes for sperm production.
TEX11 is mutated in infertile men with azoospermia and regulates genome‐wide recombination rates in mouse
Genome‐wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11 , an X‐linked meiosis‐specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non‐obstructive azoospermia and that an analogous mutation in the mouse impairs meiosis. Genetic screening of a large cohort of idiopathic infertile men reveals that TEX11 mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human TEX11 missense mutations in transgenic mouse models identified one mutation (V748A) as a potential infertility allele and found two mutations non‐causative. In the mouse model, an intronless autosomal Tex11 transgene functionally substitutes for the X‐linked Tex11 gene, providing genetic evidence for the X‐to‐autosomal retrotransposition evolution phenomenon. Furthermore, we find that TEX11 protein levels modulate genome‐wide recombination rates in both sexes. These studies indicate that TEX11 alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans. Synopsis Mutations were identified in the X chromosome‐linked germ cell‐specific gene TEX11 in infertile men with non‐obstructive azoospermia. Functional studies of TEX11 protein in mice revealed an unexpected role in the regulation of genome‐wide recombination rates. Sequencing screening of human infertile patients reveals mutations in the TEX11 gene in 1% of non‐obstructive azoospermic men. Infertile men with mutations in TEX11 exhibit meiotic arrest. Experimentally retrotransposed Tex11 on an autosome rescues the fertility of male mice deleted for the X‐linked Tex11 gene. Genetic studies of mice with different Tex11 gene dosages demonstrate a threshold level of TEX11 protein for spermatogenesis. Analysis of crossover formation shows that TEX11 regulates genome‐wide recombination rates in both males and females in a dosage‐dependent manner. Graphical Abstract Mutations were identified in the X chromosome‐linked germ cell‐specific gene TEX11 in infertile men with non‐obstructive azoospermia. Functional studies of TEX11 protein in mice revealed an unexpected role in the regulation of genome‐wide recombination rates.
Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes
The male-specific region of rhesus macaque and human Y chromosome (MSY) are sequenced and compared to the human MSY, showing that during the last 25 million years MSY gene loss in the rhesus and human lineages was limited to the youngest stratum (stratum 5), whereas gene loss in the older strata ceased more than 25 million years ago. The fate of the Y chromosome The mammal sex-determining X and Y chromosomes evolved from a pair of autosomes ('normal' non-sex chromosomes), but as a result of genetic decay, the male-specific region of the human Y chromosome retains only 3% of the ancestral autosomal genes. Here, the authors have sequenced the corresponding region of the rhesus macaque Y, and reconstructed the trajectory of its evolution through an analysis of the rhesus, human and chimpanzee Y chromosomes. The results show that initial rapid loss of genes is followed by strict conservation through purifying selection. This runs counter to the view that the human Y chromosome is destined inevitably for extinction. The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200–300 million years 1 , 2 , 3 . The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes’ genes owing to genetic decay 4 , 5 . This evolutionary decay was driven by a series of five ‘stratification’ events. Each event suppressed X–Y crossing over within a chromosome segment or ‘stratum’, incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over 2 , 6 . The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome 7 , 8 , 9 , 10 , remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.
Application of the Capability, Opportunity, Motivation and Behavior (COM-B) model to identify predictors of two self-reported hand hygiene behaviors (handwashing and hand sanitizer use) to prevent COVID-19 infection among U.S. adults, Fall 2020
Background Handwashing with soap and water is an important way to prevent transmission of viruses and bacteria and worldwide it is estimated handwashing can prevent 1 in 5 viral respiratory infections. Frequent handwashing is associated with a decreased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Using a hand sanitizer with at least 60% alcohol when handwashing is not feasible can also help prevent the transmission of viruses and bacteria. Objective Since early 2020, the public has been encouraged to handwash frequently with soap and water and use alcohol-based hand sanitizer when soap and water are not available to reduce COVID-19 transmission. This study’s objectives were to assess U.S. adults’ perceptions of components of the Capability, Opportunity, Motivation and Behavior (COM-B) Model in relation to these two hand hygiene behaviors and to identify relationships between these components and hand hygiene behaviors. Methods Items assessing capability, opportunity, motivation, and hand hygiene behaviors were included in FallStyles, a survey completed by 3,625 adults in the fall of 2020 through an online panel representative of the U.S. population. We calculated composite capability, opportunity, and motivation measures and descriptive statistics for all measures. Finally, we conducted multiple logistic regressions to identify predictors of handwashing and hand sanitizer use. Results Most respondents reported frequently washing hands with soap and water (89%) and using alcohol-based hand sanitizer (72%) to prevent coronavirus. For capability, over 90% of respondents said that neither behavior takes a lot of effort, but fewer agreed that they knew when, or how, they should engage in handwashing (67%; 74%) and hand sanitizer use (62%; 64%). For opportunity, over 95% of respondents said lack of time didn’t make it hard to engage in either behavior; fewer said visual cues reminded them to engage in the behaviors (handwashing: 30%; sanitizer use: 48%). For motivation, the majority believed the two behaviors were good ways to prevent coronavirus illness (handwashing: 76%; sanitizer use: 59%). Regressions indicated that capability, opportunity, and particularly motivation were positively associated with both hand hygiene behaviors. Conclusions The COM-B model was a helpful framework for increasing understanding of hand hygiene behavior; it identified capability, opportunity, and motivation as predictors of both handwashing and hand sanitizer use.
Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition
Dynamic sex chromosomes Birds and mammals have distinct sex chromosomes. In birds, males have a pair of Z chromosomes and females a Z and a W. In mammals, males are XY and females XX. It has long been assumed that sex-chromosome evolution has involved dramatic modification of the sex-specific (W and Y) chromosomes but only modest changes to the Z and X chromosomes shared by the sexes. Not so, according to a new study reporting the sequence of the chicken Z chromosome and comparing it with the finished sequence of human X. The Z and X chromosomes have changed dramatically from the autosomal (non-sex) chromosomes that gave rise to them. And they seem to have followed convergent evolutionary trajectories, including the acquisition and amplification of testis-expressed gene families, despite having arisen independently from different portions of the ancestral genome. Birds and mammals have distinct sex chromosomes: in birds, males are ZZ and females ZW; in mammals, males are XY and females XX. By sequencing the chicken Z chromosome and comparing it with the human X chromosome, these authors overturn the currently held view that these chromosomes have diverged little from their autosomal progenitors. The Z and X chromosomes seem to have followed convergent evolutionary trajectories, despite evolving with opposite systems of heterogamety. In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex—the W and Y chromosomes 1 , 2 , 3 , 4 , 5 . By contrast, the sex chromosomes found in both sexes—the Z and X chromosomes—are assumed to have diverged little from their autosomal progenitors 2 . Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.
Handwashing and disinfection precautions taken by U.S. adults to prevent coronavirus disease 2019, Spring 2020
Objectives The objectives of this study were to assess self-reported hygiene precautions taken by U.S. adults during spring 2020 to prevent coronavirus disease 2019 (COVID-19) and to identify demographic characteristics associated with these hygiene precautions. Results We obtained data from Porter Novelli Public Services’s national survey, Spring ConsumerStyles , conducted March 19–April 9, 2020 among a nationally representative random sample of 6463 U.S. adults aged 18 years or older. We present data from the survey question: “What, if any, precautions are you taking to prevent coronavirus?”. Respondents replied yes or no to the following precautions: washing hands often with soap and water and disinfecting surfaces at home and work often. Most respondents reported taking hygiene-related precautions to prevent COVID-19; more respondents reported handwashing (93%) than disinfecting surfaces (74%). Men, younger respondents, those with lower income and education levels, and respondents in self-rated poor health had lower reported rates of both handwashing and disinfecting surfaces. Communications about hygiene precautions for COVID-19 prevention may need to target sub-populations with the greatest gaps in hygiene-related practices. Research identifying barriers to these practices and developing effective messaging could inform and improve these communications.
The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men
Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping–sequencing process. A complex of three palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from six distinct families of amplicons, with unit lengths of 115–678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. Deletions of AZFc that cause infertility are remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably served as substrates for homologous recombination.
A State-by-State Assessment of Food Service Regulations for Prevention of Norovirus Outbreaks
Noroviruses are the leading cause of foodborne disease in the United States. Foodborne transmission of norovirus is often associated with contamination of food during preparation by an infected food worker. The U.S. Food and Drug Administration's Food Code provides model food safety regulations for preventing transmission of foodborne disease in restaurants; however, adoption of specific provisions is at the discretion of state and local governments. We analyzed the food service regulations of all 50 states and the District of Columbia (i.e., 51 states) to describe differences in adoption of norovirus-related Food Code provisions into state food service regulations. We then assessed potential correlations between adoption of these regulations and characteristics of foodborne norovirus outbreaks reported to the National Outbreak Reporting System from 2009 through 2014. Of the 51 states assessed, all (100%) required food workers to wash their hands, and 39 (76%) prohibited bare-hand contact with ready-to-eat food. Thirty states (59%) required exclusion of staff with vomiting and diarrhea until 24 h after cessation of symptoms. Provisions requiring a certified food protection manager (CFPM) and a response plan for contamination events (i.e., vomiting) were least commonly adopted; 26 states (51%) required a CFPM, and 8 (16%) required a response plan. Although not statistically significant, states that adopted the provisions prohibiting bare-hand contact (0.45 versus 0.74, P =0.07), requiring a CFPM (0.38 versus 0.75, P =0.09), and excluding ill staff for ≥24 h after symptom resolution (0.44 versus 0.73, P =0.24) each reported fewer foodborne norovirus outbreaks per million person-years than did those states without these provisions. Adoption and compliance with federal recommended food service regulations may decrease the incidence of foodborne norovirus outbreaks.
Characteristics associated with successful foodborne outbreak investigations involving United States retail food establishments (2014–2016)
This study examined relationships between foodborne outbreak investigation characteristics, such as the epidemiological methods used, and the success of the investigation, as determined by whether the investigation identified an outbreak agent (i.e. pathogen), food item and contributing factor. This study used data from the Centers for Disease Control and Prevention's (CDC) National Outbreak Reporting System and National Environmental Assessment Reporting System to identify outbreak investigation characteristics associated with outbreak investigation success. We identified investigation characteristics that increase the probability of successful outbreak investigations: a rigorous epidemiology investigation method; a thorough environmental assessment, as measured by number of visits to complete the assessment; and the collection of clinical samples. This research highlights the importance of a comprehensive outbreak investigation, which includes epidemiology, environmental health and laboratory personnel working together to solve the outbreak.